Romiplostim N01 accelerates platelet engraftment in autologous stem cell transplantation using non-cryopreserved peripheral blood stem cells for plasma cell neoplasms

Romiplostim N01 accelerates platelet engraftment in autologous stem cell transplantation using non-cryopreserved peripheral blood stem cells for plasma cell neoplasms | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Romiplostim N01 accelerates platelet engraftment in autologous stem cell transplantation using non-cryopreserved peripheral blood stem cells for plasma cell neoplasms Xianfu Sheng, Qijia Zheng, Jingjing Xiang, Nanxi Dong, Yuechao Zhao, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8603508/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Delayed platelet engraftment remains a major limitation of autologous stem cell transplantation (ASCT) for plasma-cell neoplasms. Romiplostim N01, a thrombopoietin receptor agonist, may enhance early megakaryocytic recovery, while the use of non-cryopreserved peripheral blood stem cells (PBSCs) eliminates dimethyl-sulfoxide–related toxicity and reduces procedural cost. This retrospective study evaluated 15 patients receiving non-cryopreserved PBSCs and early Romiplostim N01 after ASCT and compared them with 21 historical controls who received cryopreserved PBSCs and recombinant human thrombopoietin. We tried to compare time to engraftment, transfusion burden, hospitalization duration and cost, safety, hematologic responses and survival outcomes. Platelet engraftment occurred significantly earlier in the Romiplostim N01 cohort (median 11 vs. 13 days; P = 0.008), and complete platelet recovery by day + 30 was higher (100% vs. 66.7%; P = 0.027). Neutrophil recovery, transfusion requirements, and hospitalization duration were comparable between groups. Total hospitalization cost was markedly lower with Romiplostim N01 (77,609 ± 21,624 vs. 106,188 ± 14,910 CNY; P < 0.001). The two patient groups also demonstrated comparable safety profiles, treatment responses, and survival outcomes. Romiplostim N01 safely accelerates thrombopoietic recovery and substantially reduces cost when combined with non-cryopreserved PBSCs. This strategy represents a practical and economically favorable supportive-care model for ASCT. Romiplostim N01 Thrombopoietin receptor agonist Multiple myeloma Systemic light-chai amyloidosis Autologous hematopoietic stem cell transplantation Non-cryopreserved stem cells Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Autologous stem cell transplantation (ASCT) remains a cornerstone of treatment for transplant-eligible multiple myeloma (MM) and systemic light-chain (AL) amyloidosis[ 1 – 3 ]. High-dose melphalan (HD-Mel) conditioning reliably deepens hematologic responses; however, it often induces prolonged cytopenias[ 4 – 6 ]. Among these, delayed platelet engraftment is particularly consequential, increasing the risk of hemorrhage, prolonging transfusion dependence, necessitating extended hospitalization, and elevating overall healthcare cost[ 7 ]. Despite its clinical relevance, strategies optimized specifically to enhance thrombopoietic recovery after ASCT remain limited. Current supportive measures rely primarily on platelet transfusion and, in select centers, short-term administration of recombinant human thrombopoietin (rhTPO)[ 8 , 9 ]. Platelet transfusion is effective for acute bleeding prevention but imposes significant logistic and cost burdens, and repetitive exposure increases the risk of alloimmunization and transfusion reactions[ 8 ]. rhTPO, while theoretically attractive, has a short half-life, variable efficacy in the post-HD-Mel setting, and risks related to antibody formation[ 10 – 12 ]. These limitations underscore the need for more effective, sustained, and biologically targeted thrombopoietic support. Thrombopoietin receptor agonists (TPO-RAs) directly stimulate the c-Mpl receptor, activating downstream signaling pathways—including JAK-STAT, PI3K-AKT, and MAPK—that drive megakaryocyte proliferation, endomitosis, and proplatelet formation[ 13 – 15 ]. Romiplostim N01, a domestically manufactured TPO-RA lacking sequence homology to endogenous thrombopoietin[ 13 ], offers theoretical advantages in mitigating HD-Mel–related marrow suppression. Yet evidence supporting its use in ASCT remains limited. In parallel, renewed clinical interest has emerged regarding non-cryopreserved peripheral blood stem cells (PBSCs)[ 16 , 17 ]. Cryopreservation requires controlled-rate freezing, dimethyl-sulfoxide (DMSO) handling, and long-term liquid-nitrogen storage; DMSO infusion itself carries risks of nausea, hypertension, bradycardia, and rare neurotoxicity[ 18 ]. Non-cryopreserved PBSCs, when infused within short intervals after collection, can provide hematopoietically competent grafts while reducing toxicity, shortening processing time, and significantly lowering cost[ 19 , 20 ]. Integrating early Romiplostim N01 with non-cryopreserved PBSCs represents a biologically and operationally synergistic strategy: pharmacologic acceleration of megakaryopoiesis coupled with simplified graft workflow. However, this combined approach has not been formally evaluated. Therefore, we conducted a retrospective cohort study to evaluate the efficacy and safety between patients receiving Romiplostim N01 plus non-cryopreserved PBSCs and historical controls receiving cryopreserved PBSCs and rhTPO. Patients and methods Study design and setting This single-center retrospective cohort study included adult patients diagnosed with multiple MM or AL amyloidosis who underwent their first ASCT at the First Affiliated Hospital of Zhejiang Chinese Medical University. In the observation group, we collected data from consecutive patients who received non-cryopreserved PBSCs and prophylactic Romiplostim N01, between May 2024 and July 2025. Meanwhile, patients who underwent ASCT from January 2022 to December 2024 were included as historical controls, selecting those receiving cryopreserved PBSCs with rhTPO as supportive therapy. This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (Approval No. 2025-KLS-945-01) and complied with the principles of the Declaration of Helsinki. Given the retrospective design and the use of anonymized clinical data only, the ethics committee approved a waiver of informed consent, as the study posed minimal risk and re-contacting all participants was not feasible. Patient eligibility Patients were eligible if they were ≥ 18 years old, had confirmed MM or AL amyloidosis, and were deemed appropriate candidates for ASCT based on institutional criteria. Adequate hepatic, renal, and cardiopulmonary function was required. Patients were excluded for uncontrolled active infection, pregnancy, a history of thromboembolic events within the preceding 3 months, prior exposure to TPO-RAs, or incomplete medical records. Baseline clinical characteristics—including disease subtype, remission status, cytogenetic or FISH risk, induction regimen, comorbidity profile, and organ involvement—were abstracted from electronic medical documentation. Mobilization, apheresis, and graft handling Stem-cell mobilization for the Romiplostim N01 cohort consisted of granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 5–6 days. Plerixafor (20 mg) was administered if peripheral CD34⁺ counts were < 20 /µL on the anticipated day of apheresis. Apheresis was performed using continuous-flow cell separators, with the goal of collecting ≥ 2.0 × 10⁶ CD34⁺ cells/kg. Mobilized PBSCs were stored at 4 ℃ and reinfused within 24–48 hours without cryopreservation. Mobilization regimens in the historical cohort included G-CSF alone or cyclophosphamide plus G-CSF, depending on practices during the corresponding period. PBSCs were processed using standard DMSO cryopreservation. Products were frozen in controlled-rate freezers and stored in vapor-phase liquid nitrogen until infusion. Cryopreserved graft infusion involved standard premedication protocols to mitigate DMSO-related reactions. Conditioning regimen and supportive care All patients received HD-Mel, administered at 200 mg/m² for eligible patients or 140 mg/m² for individuals with renal impairment or advanced age, per institutional guidelines. Stem-cell infusion occurred on day 0. Supportive care included antibacterial, antifungal, and antiviral prophylaxis; antiemetics; tumor lysis prevention when clinically indicated; oral cryotherapy; and aggressive intravenous hydration. G-CSF was restarted on day + 5 and continued until neutrophil recovery. Red-cell and platelet transfusions followed institutional thresholds and were administered based on clinical status rather than prespecified numeric triggers. Romiplostim N01 and rhTPO administration Romiplostim N01 was initiated on day + 1 at a weekly dose of 5 µg/kg. Dose escalation to 10 µg/kg was permitted if platelet engraftment (≥ 20 × 10⁹/L) had not occurred by day + 14, and treatment continued until platelet counts surpassed 75 × 10⁹/L or a maximum of four doses was given. In the historical cohort, rhTPO (300 U/kg/day) was administered subcutaneously when platelet counts dropped below 75 × 10⁹/L and was continued for up to 14 days if needed. No other TPO-RAs were used during the study. Definitions and outcome measures The primary endpoint was time to platelet engraftment, defined as the first of three consecutive days with platelet counts ≥ 20 × 10⁹/L without transfusion for at least seven days. Secondary endpoints included time to neutrophil engraftment (ANC ≥ 0.5 × 10⁹/L for three consecutive days), complete platelet recovery (≥ 100 × 10⁹/L by day + 30), duration of severe thrombocytopenia (< 20 × 10⁹/L), transfusion burden (single-donor platelet units and packed red cells), hospital length of stay, hospitalization cost, adverse events, hematologic responses and survival outcomes. Response assessments followed International Myeloma Working Group criteria and Mayo criteria[ 21 , 22 ], evaluated at baseline, post-induction, and day + 90 post-ASCT. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of ASCT to the time of disease progression, relapse, death, or last follow-up. Cumulative incidence of relapse was estimated with non-relapse mortality as a competing risk. Statistical analysis Continuous variables were summarized as median (range) and compared using the Mann–Whitney U test. Categorical variables were compared using Fisher’s exact test. Time-to-event endpoints were analyzed using Kaplan–Meier curves, compared using the log-rank test. Competing-risk analyses used Gray’s test. A two-sided P < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS (version 26.0) and R (version 4.2.2). Results Patient characteristics A total of 15 patients underwent non-cryopreserved PBSC ASCT with Romiplostim N01 support (Romiplostim N01 group), while 21 historical controls received cryopreserved PBSC ASCT with rhTPO (Control group). Baseline demographic and disease-related variables—including age, sex, disease subtype, International Staging System (ISS) or Mayo stage, disease status prior to transplantation, hematopoietic cell transplant comorbidity index (HCT-CI) score, plerixafor use and single day apheresis—were generally comparable between the two groups (Table 1 ). Patients in the Romiplostim N01 cohort tended to proceed to transplantation earlier in their disease course, with a shorter median interval from diagnosis to ASCT (5.5 vs. 7.0 months; P = 0.002) and fewer induction cycles prior to transplantation (median 4 vs. 5 cycles; P = 0.024) (Table 1 ), reflecting earlier disease control and transplantation timing rather than differences in disease biology. The CD34⁺ cell dose infused was similar between the cohorts, measuring 4.53 ×10⁶/kg (range 1.26–10.05) in the Romiplostim N01 group and 5.60 ×10⁶/kg (range 1.24–22.04) in controls ( P = 0.499) (Table 1 ), confirming comparable graft quality. Conditioning intensity and melphalan dosing strategies were identical between groups, ensuring consistent transplant-related toxicity exposure (Table 1 ). Table 1 Characteristics of plasma cell neoplasms patients and grafts Variable Romiplostim N01 group (N=15) Control Group (N=21) P value Median age, years (range) 59.8 (50-79) 61 (45-78) 0.849 Sex, no. (%) Male Female 11 (73.3) 4 (26.7) 13 (61.9) 8 (38.1) 0.721 Diagnosis, no. (%) MM AL amyloidosis 12 (80) 3 (20) 20 (95.2) 1 (4.8) 0.287 ISS stage of MM, no. (%) I II III N=12 4 (33.3) 4 (33.3) 4 (33.3) N=20 7 (35) 6 (30) 7 (35) 1.000 Mayo 2012 stage of AL amyloidosis, no. (%) I II III IV N=3 0 1 (33.3) 2 (66.7) 0 N=1 0 0 0 1 (100) 0.500 Median time from diagnosis to ASCT, months, (range) 5.5 (3-9) 7 (5-32) 0.002 Median number of induction cycles (range) 4 (2-6) 5 (4-16) 0.024 Disease status before ASCT, no. (%) SD PR VGPR CR 1 (6.7) 3 (20) 7 (46.7) 4 (26.7) 1 (4.8) 6 (28.6) 9 (42.9) 5 (23.8) 0.954 HCT-CI score, no. (%) 0 1-2 3 9 (60) 5 (33.3) 1 (6.7) 11 (52.4) 9 (42.9) 1 (4.8) 0.838 Plerixafor use, no. (%) 9 (60) 7 (33.3) 0.175 Single day apheresis, no. (%) 5 (33.3) 4 (19) 0.443 Dose of Melphalan, no. (%) 200mg/m 2 140mg/m 2 9 (60) 6 (40) 14 (66.7) 7 (33.3) 0.736 Stem cells CD34 + , ×10 6 /kg, median (range) 4.53 (1.26-10.05) 5.60 (1.24-22.04) 0.499 MM: Multiple myeloma; AL: Immunoglobulin light-chain; ISS: International Staging System; ASCT: Autologous hematopoietic stem cell transplantation; SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: Complete response; HCT-CI: hematopoietic cell transplantcomorbidity index; n: Number Hematopoietic engraftment All patients in both cohorts achieved hematopoietic engraftment. By day + 30, Median time to neutrophil engraftment were similar between groups (11 days [range 10–17]) vs. controls (11 days [range 9–13]; P = 0.899) (Table 2 ). The neutrophil engraftment kinetics were also similar (Fig. 1 a), indicating equivalent early myeloid reconstitution. In contrast, platelet engraftment occurred significantly earlier in the Romiplostim N01 group, with a median of 11 days (range 8–16) compared with 13 days (range, 9–20) in controls ( P = 0.008) (Table 2 ). This advantage was consistent across individual patients and was reflected in a left-shifted cumulative recovery curve (Fig. 1 b). Moreover, the quality of platelet reconstitution differed substantially. By day + 30, all patients in the Romiplostim N01 cohort (100%) achieved complete platelet recovery (≥ 100 ×10⁹/L), whereas only 66.7% of controls reached this threshold ( P = 0.027) (Table 2 ). This divergence in sustained thrombopoietic improvement highlights the biological impact of Romiplostim N01 on megakaryocyte maturation beyond mere early engraftment. Despite these improvements, the duration of severe thrombocytopenia (< 20 ×10⁹/L) was similar between cohorts (median 5 days [0–8] vs. 4 days [0–14]; P = 0.800) (Table 2 ), suggesting that Romiplostim N01 primarily accelerated recovery after nadir rather than modifying nadir depth. Table 2 Comparisons of engraftment, transfusion burden, and hospitalization metrics post-ASCT Variable Romiplostim N01 group (N = 15) Control group (N = 21) P value Median neutrophil engraftment, days (range) 11 (10–17) 11 (9–13) 0.899 Median platelet engraftment, days (range) 11 (8–16) 13 (9–20) 0.008 Graft failure, no. (%) 0 0 Platelet counts ≥ 100 × 10 9 /L, no. (%) 15 (100) 14 (66.7) 0.027 Median duration of severe thrombocytopenia (platelet counts < 20 × 10⁹/L), days (range) 5 (0–8) 4 (0–14) 0.800 Platelet transfusion requirements, no. (%) 14 (93.3) 18 (85.7) 0.626 Number of SDP transfusion, (range) 1 (0–3) 1 (0–3) 0.924 Volume of transfused platelet, units 22 (0–56) 18 (0–59) 0.704 RBC transfusion requirements, no. (%) 2 (13.3) 0 0.167 Length of hospital stay, days (range) 30 (22–49) 32 (25–45) 0.693 Total cost of ASCT (CNY) – mean ± SD 77609 ± 21624 106188 ± 14910 < 0.001 ASCT: Autologous hematopoietic stem cell transplantation; SDP: Single donor platelet; RBC: Red blood cell; CNY: Chinese Yuan;n: Number Time-to-event analysis was used to calculate the cumulative incidence of neutrophil (a) and platelet (b) engraftment with death in aplasia as competing risks. ASCT: Autologous hematopoietic stem cell transplantation Transfusion burden and hospitalization outcomes Platelet transfusion requirements were comparable between groups. 93.3% of patients receiving Romiplostim N01 and 85.7% of controls required at least one platelet transfusion ( P = 0.626). The number of single-donor platelet (SDP) units administered per patient (median 1 unit [0–3] vs. 1 unit [0–3]) and the total units of platelets transfused (22 units [0–56] vs. 18 units [0–59]) did not differ significantly ( P = 0.924 and P = 0.704, respectively) (Table 2 ). These findings were consistent with the similar depth and duration of severe thrombocytopenia observed in each group. Red-blood-cell transfusion was required in two patients in the Romiplostim N01 cohort and none in the control cohort, a difference not statistically significant ( P = 0.167) (Table 2 ). The median length of hospitalization was comparable, measuring 30 days (range 22–49) in the Romiplostim N01 cohort and 32 days (25–45) in controls ( P = 0.693). However, total hospitalization cost showed a marked and clinically meaningful reduction in the Romiplostim N01 group. The mean total cost was 77,609 ± 21,624 CNY compared with 106,188 ± 14,910 CNY in the control cohort ( P < 0.001) (Table 2 ), reflecting a nearly 27% reduction. The largest contributions to cost reduction were elimination of cryopreservation-related processing expenses and reduced reliance on rhTPO, despite the added cost of Romiplostim N01. Collectively, these findings underscore the economic efficiency of combining Romiplostim N01 with non-cryopreserved PBSCs. Safety Romiplostim N01 demonstrated a favorable safety profile, with no unexpected adverse events observed. The frequency and grade of common non-hematologic toxicities—including mucositis, gastrointestinal symptoms (nausea, vomiting, and diarrhea), and febrile neutropenia—were similar across cohorts and consistent with those typically encountered following HD-Mel ASCT (Table 3 ). Bacteremia occurred in 8.3% of patients receiving Romiplostim N01 and 23.8% of controls ( P = 0.379), and elevations in hepatic transaminases occurred in 12.5% vs. 33.3% ( P = 0.248) (Table 3 ), respectively. Although numerically lower in the Romiplostim N01 group, these differences did not reach statistical significance. No thromboembolic events, severe infusion-related reactions, acute cardiovascular instability, or ICU admissions were reported in either group. Importantly, no cases of symptomatic marrow fibrosis or romiplostim-associated hypersensitivity reactions were observed. Together, these findings support the safety and tolerability of early Romiplostim N01 administration following ASCT. Table 3 Comparisons of safety profiles Variable Romiplostim N01 group (N = 15) Control group (N = 21) P value Gastrointestinal adverse events Mucositis, no. (%) 9 (60) 15 (71.4) 0.499 Nausea/vomiting, no. (%) 15 (100) 20 (95.2) 1.000 Diarrhea, no. (%) 11 (73.3) 20 (95.2) 0.138 Infectious adverse events Febrile neutropenia, no. (%) 15 (100) 20 (95.2) 1.000 Bacteremia, no. (%) 1 (8.3) 5 (23.8) 0.379 Other adverse events Hepatic injury, no. (%) 2 (12.5) 7 (33.3) 0.248 Cardiovascular events 0 0 Severe infusion-related reactions 0 0 Thromboembolic events 0 0 ICU admission 0 0 ICU: Intensive care unit; n: Number Post-transplant responses and survival Firstly, at the 3-month post-transplant efficacy assessment, no significant differences were observed between the Romiplostim N01 and control groups in terms of partial response (PR) rate, very good partial response (VGPR) rate, complete response (CR) rate, overall response rate (ORR, CR + VGPR + PR), or deep response rate (DRR, CR + VGPR) (Fig. 2 a), indicating that Romiplostim N01 did not impair disease control. To evaluate transplantation's impact on disease control, we pooled patients from both the Romiplostim N01 and control groups and compared pre- versus post-transplant responses. The CR rate increased from 25% pre-ASCT to 67.7% post-ASCT ( P < 0.001), resulting in significantly higher DRR post-ASCT (91.7% vs. 69.4%, P = 0.035), consistent with the deepened response from HD-Mel conditioning. However, ORR failed to improve (94.4% vs. 94.4%, P = 1.000) as non-remission rates remained unchanged (Fig. 2 b). We compared hematological endpoints (PR, VGPR, CR, ORR, DRR) between the Romiplostim N01 and control groups at 3 months post-ASCT (a). To evaluate the impact of transplantation itself, we then pooled both groups to compare these endpoints before and 3 months after ASCT (b). ASCT: Autologous hematopoietic stem cell transplantation; TPO-RAs: Thrombopoietin receptor agonists; PR: Partial response; VGPR: Very good partial response; CR: Complete response; ORR: Overall response rate; DRR: Deep response rate. * P < 0.05 and ** P < 0.01 With a median follow-up of 13.5 months, early survival outcomes were comparable between groups. Estimated 2-year OS was 92.3% ± 7.4% in the Romiplostim N01 group and 84.8% ± 8.1% in the control cohort ( P = 0.855) (Fig. 3 a). Estimated 2-year PFS was 93.3% ± 6.4% vs. 51.7% ± 15.2% ( P = 0.501) (Fig. 3 b), with the wider confidence interval in controls reflecting greater heterogeneity and fewer events. The cumulative incidence of relapse with death as a competing risk did not differ significantly (7.14% ± 0.51% vs. 43.42% ± 2.74%; P = 0.744) (Fig. 4 ). No transplant-related mortality within the first 100 days occurred in either cohort. a: The comparison of estimated 2-year OS between Romiplostim N01 and control groups (92.3% ± 7.4% vs. 84.8% ± 8.1%, P = 0.855). b: The comparison of estimated 2-year PFS between Romiplostim N01 and control groups (93.3% ± 6.4% vs. 51.7% ± 15.2%, P = 0.501). ASCT: Autologous hematopoietic stem cell transplantation; OS: Overall survival; PFS: Progression-free survival Comparison of cumulative relapse rates between the Romiplostim N01 group and the control group. ASCT: Autologous hematopoietic stem cell transplantation Discussion This retrospective cohort study demonstrates that early administration of Romiplostim N01 following ASCT, combined with the use of non-cryopreserved PBSCs, leads to significantly accelerated platelet engraftment, more consistent complete platelet recovery, and substantially reduced hospitalization cost, while maintaining an excellent safety profile. These findings collectively highlight the feasibility, clinical value, and economic advantages of integrating a TPO-RA–based thrombopoietic support strategy into routine ASCT practice for plasma-cell neoplasms. Recent studies present conflicting evidence regarding the ability of non-cryopreserved PBSCs to shorten engraftment time[ 19 , 23 , 24 ]. A Worldwide Network for Blood & Marrow Transplantation meta-analysis of 1,686 patients confirmed the feasibility and safety of non-cryopreserved PBSCs transplantation. This analysis reported a median platelet engraftment time of 15.3 days, aligning with the 15-day median reported by Jacinth et al. in Blood [ 16 , 25 ]. In contrast, our study demonstrated a significantly shorter median platelet engraftment time of 11 days. Given comparable median CD34 + cell counts across the studies, the accelerated platelet recovery observed in our cohort may be attributable to the administration of Romiplostim N01. The two-day improvement in platelet engraftment observed in the Romiplostim N01 cohort is clinically meaningful and aligns with the known pharmacologic activity of TPO-Ras[ 7 ]. HD-Mel induces profound megakaryocytic suppression by impairing stromal integrity, damaging vascular niches, and temporally arresting megakaryocyte endomitosis[ 26 , 27 ]. Endogenous TPO levels, though increased during cytopenia, remain insufficient to overcome this transient marrow injury. Romiplostim N01, through c-Mpl receptor binding and activation of JAK-STAT, PI3K-AKT, and MAPK pathways, provides a supraphysiologic stimulus that restores megakaryopoiesis during this vulnerable post-conditioning window[ 13 ]. The improvement in both the speed and quality of thrombopoietic recovery—evidenced by universally achieved complete platelet recovery by day + 30—is consistent with this mechanistic rationale and suggests a coordinated enhancement of megakaryocyte maturation and proplatelet formation. These findings expand the existing body of evidence for TPO-RAs in transplantation. Previous studies evaluating romiplostim or eltrombopag in hematopoietic cell transplantation have largely focused on salvage therapy for poor graft function or delayed engraftment, often requiring prolonged administration over several weeks[ 14 , 28 – 32 ]. In contrast, our data demonstrate that proactive, early, short-course Romiplostim N01 can significantly shift the platelet recovery trajectory even in patients receiving uniformly intensive conditioning. This distinction is important because reactive use of TPO-RAs typically occurs after substantial marrow compromise has occurred, whereas early use leverages intact megakaryocyte progenitor pools present immediately after PBSCs reinfusion. The economic advantage observed in the Romiplostim N01 cohort is another compelling aspect of this strategy. Hospitalization cost was reduced by nearly 27%, driven primarily by elimination of cryopreservation-related expenses, including DMSO handling, controlled-rate freezing, liquid-nitrogen storage, Cryoprotective equipment, infusion-related monitoring, and management of DMSO-associated adverse events[ 16 , 19 , 20 ]. The use of non-cryopreserved PBSCs avoids these steps entirely and simplifies the logistical framework of ASCT processing. Notably, this cost reduction was achieved despite the addition of Romiplostim N01, indicating that the savings associated with simplified graft handling outweighed the cost of pharmacologic thrombopoietic support. The safety profile of Romiplostim N01 observed in this study is consistent with prior experience in immune thrombocytopenia and chemotherapy-induced thrombocytopenia[ 28 , 33 – 35 ]. No thromboembolic complications, infusion reactions, exacerbations of mucositis or gastrointestinal events, hepatic toxicity, or marrow fibrosis was observed. The absence of cardiovascular or pro-thrombotic signals is especially reassuring, given concern for thrombopoietic overstimulation in the peri-engraftment period. Importantly, there was no evidence that Romiplostim N01 adversely affected disease control; depth of hematologic response increased appropriately after ASCT, and early PFS and OS outcomes were comparable to those in the control cohort. The clinical implications of these findings are noteworthy. In many transplant centers—particularly those with high patient volume or limited cryopreservation infrastructure—simplifying the PBSCs workflow could significantly reduce resource strain[ 18 ]. Non-cryopreserved PBSCs infusion eliminates DMSO-associated toxicities, supports more predictable scheduling, and reduces dependence on cryopreservation facilities[ 25 ]. When paired with Romiplostim N01, this approach provides a coherent and rational framework for reducing the medical and financial burden of ASCT without structurally altering conditioning strategies or transfusion practices. Nevertheless, this study has limitations. Its retrospective nature introduces inherent risks of selection bias, although baseline characteristics were comparable between cohorts. The modest sample size limits the power to detect rare adverse events, small differences in survival outcomes, or subgroup-specific effects (e.g., MM vs. AL). Follow-up duration remains relatively short, precluding assessment of late relapses, long-term marrow stability, or delayed fibrotic changes. Additionally, although the control group reflected contemporaneous institutional practice, evolving supportive-care protocols may have introduced unmeasured confounders. Future prospective studies should evaluate optimal timing and dosing of Romiplostim N01. Despite these limitations, the strengths of the study are notable: uniform conditioning regimens, consistent definitions of engraftment and toxicity, stable institutional transplant practices across the study period, and integration of both clinical and economic endpoints. The internal consistency across engraftment acceleration, improved platelet recovery quality, and substantial cost reduction strongly supports the biological and operational validity of this combined strategy. Conclusions This study demonstrates that early administration of Romiplostim N01 accelerates platelet recovery, enhances the quality of thrombopoiesis, and significantly reduces hospitalization cost without compromising safety when used in combination with non-cryopreserved PBSCs during ASCT for plasma-cell neoplasms. These findings support the integration of Romiplostim N01 into routine thrombopoietic support for ASCT, particularly in centers seeking to streamline graft processing and reduce resource utilization. Declarations Acknowledgments The authors would like to extend their sincere gratitude to Professor Jindan Yu for her language polishing of this paper. Author contributions Xianfu Sheng was responsible for direct patient care, data extraction and data analysis, interpreting the finally results and writing the manuscript. Qijia Zheng was responsible for data analysis, writing the manuscript, updated the reference list. Jingjing Xiang and Nanxi Dong were responsible for data extraction, data analysis and making charts. Yuechao Zhao and Huijin Hu were responsible for direct patient care and manuscript review. Lili Qian was responsible for statistical analysis and quality control. Wenbin Liu and Jianping Shen designed the protocol and conducted the apheresis procedures and stem cell harvest. Baodong Ye and Yu Zhang designed the protocol, were responsible for patient care, protocol supervision, interpreted the finally results, helped writing the manuscript and reviewed the manuscript. Funding This work was supported by the Special Project for the Modernization of Traditional Chinese Medicine in Zhejiang Province (No. 2020ZX007); National Major and Difficult Diseases (Lymphoma) Clinical Collaboration Project of Traditional Chinese and Western Medicine (No. ZDYN-2024-A-024); Zhejiang Provincial Natural Science Foundation (No. LY19H270004, LTGY23H270004, LQ24H290001). Data availability The original data is available upon special request to Yu Zhang, E-mail: [email protected] . Competing interests The authors declare no competing interests. Open Acess Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. References Moreno V, Saba L, Tama-Shekan S, Chaulagain CP (2024) Current and Emerging Immunotherapies for Systemic AL Amyloidosis. Discov Med 36:1761–1771. https://doi.org/10.24976/Discov.Med.202436188.162 Grieb N, Oeser A, Ferle M, Hanke F, Flossdorf S, Sauer S, Goldschmidt H, Muller-Tidow C, Salwender HJ, Fenk R, Engelhardt M, Zeiser R, Vucinic V, Franke GN, Blau IW, Teschner D, Einsele H, Kimmich C, Kull M, Besemer B, Gagelmann N, Kroger N, Neumuth T, Platzbecker U, Merz M, German Registry for Hematopoietic Stem Cell T, and, Cell T (2025) Single versus tandem autologous stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transplant 60: 335–345. https://doi.org/10.1038/s41409-024-02490-1 Parmar H, Doucette K, Vesole D (2024) Role of Autologous Stem Cell Transplantation in Systemic Light Chain Amyloidosis. Clin Lymphoma Myeloma Leuk 24:770–777. https://doi.org/10.1016/j.clml.2024.06.009 Rajkumar SV (2024) Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol 99:1802–1824. https://doi.org/10.1002/ajh.27422 Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, Hulin C, Antonioli E, Leleu X, Mangiacavalli S, Perrot A, Cavo M, Belotti A, Broijl A, Gay F, Mina R, Nijhof IS, van de Donk N, Katodritou E, Schjesvold F, Sureda Balari A, Rosinol L, Delforge M, Roeloffzen W, Silzle T, Vangsted A, Einsele H, Spencer A, Hajek R, Jurczyszyn A, Lonergan S, Ahmadi T, Liu Y, Wang J, Vieyra D, van Brummelen EMJ, Vanquickelberghe V, Sitthi-Amorn A, de Boer CJ, Carson R, Rodriguez-Otero P, Blade J, Moreau P, Investigators PT (2024) Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 390:301–313. https://doi.org/10.1056/NEJMoa2312054 Villar S, Zapata E, Rifon J (2025) The role of stem cell transplantation in the modern management of multiple myeloma. Curr Opin Hematol 32:321–326. https://doi.org/10.1097/MOH.0000000000000896 Elsayed A, Elsayed B, Elmarasi M, Elsabagh AA, Elsayed E, Elmakaty I, Yassin M (2024) Thrombopoietin Receptor Agonists in Post-Hematopoietic Cell Transplantation Complicated by Prolonged Thrombocytopenia: A Comprehensive Review. Immunotargets Ther 13:461–486. https://doi.org/10.2147/ITT.S463384 Kaufman RM, Assmann SF, Triulzi DJ, Strauss RG, Ness P, Granger S, Slichter SJ (2015) Transfusion-related adverse events in the Platelet Dose study. Transfusion 55:144–153. https://doi.org/10.1111/trf.12791 Society of Chemotherapy CA-CA and Committee of Neoplastic Supportive-Care CA-CA (2023) [Consensus on the clinical diagnosis, treatment and prevention of cancer treatment-induced thrombocytopenia in China (2023 edition)]. Zhonghua Yi Xue Za Zhi 103:2579–2590. https://doi.org/10.3760/cma.j.cn112137-20230409-00575 Xu X, Yang R, Jia Y, Gao G, Huang T, He A, Wang F (2025) Comparison of Thrombopoietin Receptor Agonists Plus Recombinant Human Thrombopoietin versus Recombinant Human Thrombopoietin Alone for Hematopoietic Reconstruction in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation. Transplant Cell Ther 31: 84 e1-84 e8. https://doi.org/10.1016/j.jtct.2024.12.015 Qiu X, Jiang H, Xiao X, Huang L, Xu Y (2024) Recombinant human thrombopoietin improves platelet engraftment after autologous hematopoietic stem cell transplantation in patients with aggressive lymphoma. Transfus Apher Sci 63:103972. https://doi.org/10.1016/j.transci.2024.103972 Feng D, Liu Q, Gao H, Cao Y, Chen X, Zhang R, Zhai W, Yang D, Wei J, He Y, Pang A, Feng S, Han M, Ma Q, Jiang E (2025) Increasing the dose of recombinant human thrombopoietin can enhance platelet engraftment after allogeneic haematopoietic stem cell transplantation: A NICHE cohort study. Br J Haematol 206:769–772. https://doi.org/10.1111/bjh.19954 Bussel JB, Soff G, Balduzzi A, Cooper N, Lawrence T, Semple JW (2021) A Review of Romiplostim Mechanism of Action and Clinical Applicability. Drug Des Devel Ther 15:2243–2268. https://doi.org/10.2147/DDDT.S299591 Pasvolsky O, Shargian L, Rozovski U, Wolach O, Ram R, Shapira MY, Avni B, Stepensky P, Israeli M, Vidal-Fisher L, Shpilberg O, Raanani P, Yeshurun M (2021) Eltrombopag for enhancement of platelet engraftment in patients undergoing allogeneic cord blood transplantation. Leuk Lymphoma 62:2747–2754. https://doi.org/10.1080/10428194.2021.1929957 Liesveld JL, Phillips GL 2nd, Becker M, Constine LS, Friedberg J, Andolina JR, Milner LA, DeBolt J, Smudzin T, Hyrien O, Erickson-Miller CL, Johnson BM, Dawson KL, Chen Y (2013) A phase 1 trial of eltrombopag in patients undergoing stem cell transplantation after total body irradiation. Biol Blood Marrow Transpl 19:1745–1752. https://doi.org/10.1016/j.bbmt.2013.10.002 Bekadja MA, Niederwieser D, Kharfan-Dabaja MA, El Fakih R, Garderet L, Yakoub-Agha I, Greinix H, Weisdorf DJ, Galeano S, Ahmed SO, Chabanon C, Hashmi SK, Ruggeri A, Gergis U, Bazarbachi A, Hamad N, Albeihany A, Pasquini M, Hanbali A, Szer J, Kodera Y, Kumar A, Elhassan T, McLornan D, Worel N, Greco R, Mohty M, Atsuta Y, Koh M, Sureda A, Rondelli D, Aljurf M, Rasheed W (2025) Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation. Bone Marrow Transpl 60:19–27. https://doi.org/10.1038/s41409-024-02431-y Bekadja MA, Boumendil A, Blaise D, Chevallier P, Peggs KS, Salles G, Giebel S, Marks R, Arcese W, Milpied N, Finel H, Gorin NC (2021) Non-cryopreserved hematopoietic stem cells in autograft patients with lymphoma: a matched-pair analysis comparing a single center experience with the use of cryopreserved stem cells reported to the European Society for Blood and Marrow Transplantation registry. Cytotherapy 23:483–487. https://doi.org/10.1016/j.jcyt.2020.12.016 Noiperm P, Julamanee J, Viboonjuntra P, Lekhakula A (2023) Non-Cryopreserved Peripheral Blood Stem Cell Graft for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma and Lymphoma Patients. Ann Transpl 28:e938595. https://doi.org/10.12659/AOT.938595 Araujo AB, Soares TB, Schmalfuss T, Angeli MH, Furlan JM, Salton GD, Burin MM, Rohsig LM (2022) Non-cryopreserved peripheral blood stem cells as a safe and effective alternative for autologous transplantation in multiple myeloma. Transfusion 62:1967–1972. https://doi.org/10.1111/trf.17090 Jennane S, Hasnaoui N, Mahtat EM, Merimi F, Bougar S, El Maaroufi H, Belmekki A, Zafad S, Essakalli M, Mikdame M, Doghmi K (2020) Non-cryopreserved peripheral blood stem cells autologous transplantation in multiple myeloma: Bicentric study. Transfus Clin Biol 27:152–156. https://doi.org/10.1016/j.tracli.2020.03.006 Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17:e328–e346. https://doi.org/10.1016/S1470-2045(16)30206-6 Kumar SK, Callander NS, Adekola K, Anderson LD Jr., Baljevic M, Campagnaro E, Castillo JJ, Costello C, D'Angelo C, Devarakonda S, Elsedawy N, Garfall A, Godby K, Hillengass J, Holmberg L, Htut M, Huff CA, Hultcrantz M, Kang Y, Larson S, Lee HC, Liedtke M, Martin T, Omel J, Rosenberg A, Sborov D, Valent J, Berardi R, Kumar R (2023) Systemic Light Chain Amyloidosis, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 21:67–81. https://doi.org/10.6004/jnccn.2023.0001 Pessoa JM, da Rosa EL, Americo AD, Motta CL, de Oliveira CZ, Concilio RR, Amigo Filho JU, Marret ACF, Lazar AE, De Gusmao BM, Scheinberg P, Kerbauy FR (2022) Cryopreserved versus non-cryopreserved stem cell autografts in multiple myeloma a restrospective cohort study. Bone Marrow Transpl 57:1313–1318. https://doi.org/10.1038/s41409-022-01718-2 Piriyakhuntorn P, Tantiworawit A, Rattanathammethee T, Hantrakool S, Chai-Adisaksopha C, Rattarittamrong E, Norasetthada L (2020) Outcomes of Non-Cryopreserved Versus Cryopreserved Peripheral Blood Stem Cells for Autologous Stem Cell Transplantation in Multiple Myeloma. Ann Transpl 25:e927084. https://doi.org/10.12659/AOT.927084 Joseph J, Wookey V, Randolph B, Chandler JC, Marjoncu D, Holman K, Peeler D, Armstrong M, Khaled Y (2020) Fresh Versus Cryopreserved Peripheral Stem Cell for Autologous Transplantation in Multiple Myeloma: An Analysis of Short-Term Outcomes. Blood 136:9–10. https://doi.org/10.1182/blood-2020-143049 Kemp K, Morse R, Sanders K, Hows J, Donaldson C (2011) Alkylating chemotherapeutic agents cyclophosphamide and melphalan cause functional injury to human bone marrow-derived mesenchymal stem cells. Ann Hematol 90:777–789. https://doi.org/10.1007/s00277-010-1141-8 Soff GA, Al-Samkari H, Leader A, Eisen M, Saad H (2024) Romiplostim in chemotherapy-induced thrombocytopenia: A review of the literature. Cancer Med 13:e7429. https://doi.org/10.1002/cam4.7429 Mahat U, Rotz SJ, Hanna R (2020) Use of Thrombopoietin Receptor Agonists in Prolonged Thrombocytopenia after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transpl 26:e65–e73. https://doi.org/10.1016/j.bbmt.2019.12.003 Peffault de Latour R, Chevret S, Ruggeri AL, Suarez F, Souchet L, Michonneau D, Sicre de Fontbrune F, Coman T, Dhedin N, Rubio MT, Nguyen S, Mohty M, Socie G (2020) Romiplostim in patients undergoing hematopoietic stem cell transplantation: results of a phase 1/2 multicenter trial. Blood 135:227–229. https://doi.org/10.1182/blood.2019000358 Zaninetti C, Gresele P, Bertomoro A, Klersy C, De Candia E, Veneri D, Barozzi S, Fierro T, Alberelli MA, Musella V, Noris P, Fabris F, Balduini CL, Pecci A (2020) Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial. Haematologica 105:820–828. https://doi.org/10.3324/haematol.2019.223966 Halahleh K, Al-Ya'Goub M, Ma'koseh M, Al-Far R, Da'na W, Pharm RA, Taqash A, Muradi I, Sughayer M, Abu-Jazar H (2025) Eltrombopag Enhances Recovery from Cytopenias Due to Poor Graft Function after Hematopoietic Cell Transplantation. Blood Cell Ther 8:160–166. https://doi.org/10.31547/bct-2024-017 Bayram N, Yaman Y, Ozdilli K, Nepesov S, Al IO, Elli M, Anak S (2025) Eltrombopag for Treatment of Thrombocytopenia After Autologous Stem Cell Transplantation in Children: Single Center Experience. J Pediatr Hematol Oncol 47:e10–e14. https://doi.org/10.1097/MPH.0000000000002971 Chen F, McDonald V, Newland A (2021) Experts' review: the emerging roles of romiplostim in immune thrombocytopenia (ITP). Expert Opin Biol Ther 21:1383–1393. https://doi.org/10.1080/14712598.2021.1960979 Liu P, Dong E, Jiang Y, Chen L, Xie B, Ling J (2025) Successful treatment of refractory cancer therapy-induced thrombocytopenia in a breast cancer patient using romiplostim N01: A case report. Med (Baltim) 104:e43665. https://doi.org/10.1097/MD.0000000000043665 Melikyan AL, Protsenko EA, Salogub GN, Bakirov BA, Davydkin IL, Kovalik VV, Gefen ML, Matvienko YD, Saparova VB, Khokhlov AL, Makarenko IE, Drai RV (2025) Multicenter Single-Blind Randomized Controlled Trial of the Romiplostim Biosimilar. EJHaem 6: e70105. https://doi.org/10.1002/jha2.70105 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8603508","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":578840028,"identity":"70d12df7-31c3-4642-b8a7-9fd8da8e0e3f","order_by":0,"name":"Xianfu Sheng","email":"","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Xianfu","middleName":"","lastName":"Sheng","suffix":""},{"id":578840030,"identity":"94b9da72-87d7-40e1-bcd1-0b5b3ea7a2b2","order_by":1,"name":"Qijia Zheng","email":"","orcid":"","institution":"The First Medical College of Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qijia","middleName":"","lastName":"Zheng","suffix":""},{"id":578840032,"identity":"16934f50-30e1-408b-892f-7f1a6f88230c","order_by":2,"name":"Jingjing Xiang","email":"","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Xiang","suffix":""},{"id":578840037,"identity":"0acdbe52-9e4d-4e26-8281-7df202530899","order_by":3,"name":"Nanxi Dong","email":"","orcid":"","institution":"The First Medical College of Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Nanxi","middleName":"","lastName":"Dong","suffix":""},{"id":578840038,"identity":"44c4bada-4031-4023-84b8-61551adf4b9d","order_by":4,"name":"Yuechao Zhao","email":"","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Yuechao","middleName":"","lastName":"Zhao","suffix":""},{"id":578840039,"identity":"21b37050-438d-460b-8c66-17702a3804f0","order_by":5,"name":"Huijin Hu","email":"","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Huijin","middleName":"","lastName":"Hu","suffix":""},{"id":578840040,"identity":"6fade954-c0dc-4f9b-8054-e6420bebed85","order_by":6,"name":"Lili Qian","email":"","orcid":"","institution":"Department of Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"Qian","suffix":""},{"id":578840044,"identity":"6d525fc1-0234-4901-b50f-8c20f6351053","order_by":7,"name":"Wenbin Liu","email":"","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Wenbin","middleName":"","lastName":"Liu","suffix":""},{"id":578840045,"identity":"a4c972f8-2edc-415c-a407-e5b19b7c8a80","order_by":8,"name":"Jianping Shen","email":"","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Jianping","middleName":"","lastName":"Shen","suffix":""},{"id":578840046,"identity":"ffcfab8b-7f35-4777-94f7-48794a053e29","order_by":9,"name":"Baodong Ye","email":"","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Baodong","middleName":"","lastName":"Ye","suffix":""},{"id":578840048,"identity":"e6e07a86-188c-49a0-aef4-23cbd66df005","order_by":10,"name":"Yu Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIie3QMWvCUBDA8XscXJaHrhdS6ld4EEgdHn4WRXguGTq5NiA4CV2FlvoVnJxjj7p27eDi4hywlAxFGt26JBkLff/hpvsNdwA+31+Mr9PeEmKeF8YO2hIXdwIabZf3btyWyOilq2PRxavKmkTvaXY8fIJTcwQj1uQIgbyt64h63t3FN2CREIaSmn0HtHMfdQR5mETh2VFF8oocEVgntYR48hUxiCZUmfSNqKyJaE6TsADh6skg0IYwp9OoerIhJNgujBtT0y295WQTlmAfVo/vp6L8toNuILtacgn1r+ua1i+pss2Wz+fz/d9+AHupQu87vlUnAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":true,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2026-01-14 15:53:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8603508/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8603508/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101273685,"identity":"04740686-975c-4aed-8f36-5fc7d25ddfba","added_by":"auto","created_at":"2026-01-28 03:07:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":87302,"visible":true,"origin":"","legend":"\u003cp\u003eThe cumulative incidence of neutrophil and platelet engraftment after transplantation.\u003c/p\u003e\n\u003cp\u003eTime-to-event analysis was used to calculate the cumulative incidence of neutrophil (a) and platelet (b) engraftment with death in aplasia as competing risks. ASCT: Autologous hematopoietic stem cell transplantation\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8603508/v1/f9ebcbe1cdae259efd06a828.png"},{"id":101297667,"identity":"bdcb4623-e6b1-4209-ad0d-53800213c1f0","added_by":"auto","created_at":"2026-01-28 09:28:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":74187,"visible":true,"origin":"","legend":"\u003cp\u003eThe hematologic responses to ASCT.\u003c/p\u003e\n\u003cp\u003eWe compared hematological endpoints (PR, VGPR, CR, ORR, DRR) between the Romiplostim N01 and control groups at 3 months post-ASCT (a). To evaluate the impact of transplantation itself, we then pooled both groups to compare these endpoints before and 3 months after ASCT (b). ASCT: Autologous hematopoietic stem cell transplantation; TPO-RAs: Thrombopoietin receptor agonists; PR: Partial response; VGPR: Very good partial response; CR: Complete response; ORR：Overall response rate; DRR: Deep response rate. *\u003cem\u003eP \u003c/em\u003e\u0026lt;0.05 and ** \u003cem\u003eP\u003c/em\u003e\u0026lt;0.01\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8603508/v1/8ccaf73240605cf7c7f15a2a.png"},{"id":101273684,"identity":"b4631eed-230b-4bd7-8b3e-ddaca3deb0f1","added_by":"auto","created_at":"2026-01-28 03:07:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":97152,"visible":true,"origin":"","legend":"\u003cp\u003eThe survival outcomes after ASCT.\u003c/p\u003e\n\u003cp\u003ea: The comparison of estimated 2-year OS between Romiplostim N01 and control groups (92.3% ± 7.4% vs. 84.8% ± 8.1%, \u003cem\u003eP \u003c/em\u003e= 0.855). b: The comparison of estimated 2-year PFS between Romiplostim N01 and control groups (93.3% ± 6.4% vs. 51.7% ± 15.2%, \u003cem\u003eP \u003c/em\u003e= 0.501). ASCT: Autologous hematopoietic stem cell transplantation; OS: Overall survival; PFS: Progression-free survival\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8603508/v1/367eab0304436c3ef3a8c072.png"},{"id":101273683,"identity":"f6b358ed-2e14-4da1-a7b2-135274a10d92","added_by":"auto","created_at":"2026-01-28 03:07:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":50244,"visible":true,"origin":"","legend":"\u003cp\u003eThe cumulative incidence of relapse, with death as competing risk.\u003c/p\u003e\n\u003cp\u003eComparison of cumulative relapse rates between the Romiplostim N01 group and the control group. ASCT: Autologous hematopoietic stem cell transplantation\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8603508/v1/f849df4381b141c16f8652bb.png"},{"id":102567498,"identity":"4c6f7580-7c4b-4137-8c8c-76170f0992e1","added_by":"auto","created_at":"2026-02-13 06:10:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1082027,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8603508/v1/a7f9d59d-9475-4c16-95b8-b886a811321f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Romiplostim N01 accelerates platelet engraftment in autologous stem cell transplantation using non-cryopreserved peripheral blood stem cells for plasma cell neoplasms","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAutologous stem cell transplantation (ASCT) remains a cornerstone of treatment for transplant-eligible multiple myeloma (MM) and systemic light-chain (AL) amyloidosis[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. High-dose melphalan (HD-Mel) conditioning reliably deepens hematologic responses; however, it often induces prolonged cytopenias[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Among these, delayed platelet engraftment is particularly consequential, increasing the risk of hemorrhage, prolonging transfusion dependence, necessitating extended hospitalization, and elevating overall healthcare cost[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Despite its clinical relevance, strategies optimized specifically to enhance thrombopoietic recovery after ASCT remain limited.\u003c/p\u003e \u003cp\u003eCurrent supportive measures rely primarily on platelet transfusion and, in select centers, short-term administration of recombinant human thrombopoietin (rhTPO)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Platelet transfusion is effective for acute bleeding prevention but imposes significant logistic and cost burdens, and repetitive exposure increases the risk of alloimmunization and transfusion reactions[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. rhTPO, while theoretically attractive, has a short half-life, variable efficacy in the post-HD-Mel setting, and risks related to antibody formation[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These limitations underscore the need for more effective, sustained, and biologically targeted thrombopoietic support.\u003c/p\u003e \u003cp\u003eThrombopoietin receptor agonists (TPO-RAs) directly stimulate the c-Mpl receptor, activating downstream signaling pathways\u0026mdash;including JAK-STAT, PI3K-AKT, and MAPK\u0026mdash;that drive megakaryocyte proliferation, endomitosis, and proplatelet formation[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Romiplostim N01, a domestically manufactured TPO-RA lacking sequence homology to endogenous thrombopoietin[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], offers theoretical advantages in mitigating HD-Mel\u0026ndash;related marrow suppression. Yet evidence supporting its use in ASCT remains limited.\u003c/p\u003e \u003cp\u003eIn parallel, renewed clinical interest has emerged regarding non-cryopreserved peripheral blood stem cells (PBSCs)[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Cryopreservation requires controlled-rate freezing, dimethyl-sulfoxide (DMSO) handling, and long-term liquid-nitrogen storage; DMSO infusion itself carries risks of nausea, hypertension, bradycardia, and rare neurotoxicity[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Non-cryopreserved PBSCs, when infused within short intervals after collection, can provide hematopoietically competent grafts while reducing toxicity, shortening processing time, and significantly lowering cost[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIntegrating early Romiplostim N01 with non-cryopreserved PBSCs represents a biologically and operationally synergistic strategy: pharmacologic acceleration of megakaryopoiesis coupled with simplified graft workflow. However, this combined approach has not been formally evaluated. Therefore, we conducted a retrospective cohort study to evaluate the efficacy and safety between patients receiving Romiplostim N01 plus non-cryopreserved PBSCs and historical controls receiving cryopreserved PBSCs and rhTPO.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eThis single-center retrospective cohort study included adult patients diagnosed with multiple MM or AL amyloidosis who underwent their first ASCT at the First Affiliated Hospital of Zhejiang Chinese Medical University. In the observation group, we collected data from consecutive patients who received non-cryopreserved PBSCs and prophylactic Romiplostim N01, between May 2024 and July 2025. Meanwhile, patients who underwent ASCT from January 2022 to December 2024 were included as historical controls, selecting those receiving cryopreserved PBSCs with rhTPO as supportive therapy. This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (Approval No. 2025-KLS-945-01) and complied with the principles of the Declaration of Helsinki. Given the retrospective design and the use of anonymized clinical data only, the ethics committee approved a waiver of informed consent, as the study posed minimal risk and re-contacting all participants was not feasible.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient eligibility\u003c/h3\u003e\n\u003cp\u003ePatients were eligible if they were \u0026ge;\u0026thinsp;18 years old, had confirmed MM or AL amyloidosis, and were deemed appropriate candidates for ASCT based on institutional criteria. Adequate hepatic, renal, and cardiopulmonary function was required. Patients were excluded for uncontrolled active infection, pregnancy, a history of thromboembolic events within the preceding 3 months, prior exposure to TPO-RAs, or incomplete medical records. Baseline clinical characteristics\u0026mdash;including disease subtype, remission status, cytogenetic or FISH risk, induction regimen, comorbidity profile, and organ involvement\u0026mdash;were abstracted from electronic medical documentation.\u003c/p\u003e\n\u003ch3\u003eMobilization, apheresis, and graft handling\u003c/h3\u003e\n\u003cp\u003eStem-cell mobilization for the Romiplostim N01 cohort consisted of granulocyte colony-stimulating factor (G-CSF) 10 \u0026micro;g/kg/day for 5\u0026ndash;6 days. Plerixafor (20 mg) was administered if peripheral CD34⁺ counts were \u0026lt;\u0026thinsp;20 /\u0026micro;L on the anticipated day of apheresis. Apheresis was performed using continuous-flow cell separators, with the goal of collecting\u0026thinsp;\u0026ge;\u0026thinsp;2.0 \u0026times; 10⁶ CD34⁺ cells/kg. Mobilized PBSCs were stored at 4 ℃ and reinfused within 24\u0026ndash;48 hours without cryopreservation.\u003c/p\u003e \u003cp\u003eMobilization regimens in the historical cohort included G-CSF alone or cyclophosphamide plus G-CSF, depending on practices during the corresponding period. PBSCs were processed using standard DMSO cryopreservation. Products were frozen in controlled-rate freezers and stored in vapor-phase liquid nitrogen until infusion. Cryopreserved graft infusion involved standard premedication protocols to mitigate DMSO-related reactions.\u003c/p\u003e\n\u003ch3\u003eConditioning regimen and supportive care\u003c/h3\u003e\n\u003cp\u003e All patients received HD-Mel, administered at 200 mg/m\u0026sup2; for eligible patients or 140 mg/m\u0026sup2; for individuals with renal impairment or advanced age, per institutional guidelines. Stem-cell infusion occurred on day 0. Supportive care included antibacterial, antifungal, and antiviral prophylaxis; antiemetics; tumor lysis prevention when clinically indicated; oral cryotherapy; and aggressive intravenous hydration. G-CSF was restarted on day\u0026thinsp;+\u0026thinsp;5 and continued until neutrophil recovery. Red-cell and platelet transfusions followed institutional thresholds and were administered based on clinical status rather than prespecified numeric triggers.\u003c/p\u003e\n\u003ch3\u003eRomiplostim N01 and rhTPO administration\u003c/h3\u003e\n\u003cp\u003eRomiplostim N01 was initiated on day\u0026thinsp;+\u0026thinsp;1 at a weekly dose of 5 \u0026micro;g/kg. Dose escalation to 10 \u0026micro;g/kg was permitted if platelet engraftment (\u0026ge;\u0026thinsp;20 \u0026times; 10⁹/L) had not occurred by day\u0026thinsp;+\u0026thinsp;14, and treatment continued until platelet counts surpassed 75 \u0026times; 10⁹/L or a maximum of four doses was given. In the historical cohort, rhTPO (300 U/kg/day) was administered subcutaneously when platelet counts dropped below 75 \u0026times; 10⁹/L and was continued for up to 14 days if needed. No other TPO-RAs were used during the study.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions and outcome measures\u003c/h2\u003e \u003cp\u003eThe primary endpoint was time to platelet engraftment, defined as the first of three consecutive days with platelet counts\u0026thinsp;\u0026ge;\u0026thinsp;20 \u0026times; 10⁹/L without transfusion for at least seven days. Secondary endpoints included time to neutrophil engraftment (ANC\u0026thinsp;\u0026ge;\u0026thinsp;0.5 \u0026times; 10⁹/L for three consecutive days), complete platelet recovery (\u0026ge;\u0026thinsp;100 \u0026times; 10⁹/L by day\u0026thinsp;+\u0026thinsp;30), duration of severe thrombocytopenia (\u0026lt;\u0026thinsp;20 \u0026times; 10⁹/L), transfusion burden (single-donor platelet units and packed red cells), hospital length of stay, hospitalization cost, adverse events, hematologic responses and survival outcomes.\u003c/p\u003e \u003cp\u003eResponse assessments followed International Myeloma Working Group criteria and Mayo criteria[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], evaluated at baseline, post-induction, and day\u0026thinsp;+\u0026thinsp;90 post-ASCT. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of ASCT to the time of disease progression, relapse, death, or last follow-up. Cumulative incidence of relapse was estimated with non-relapse mortality as a competing risk.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were summarized as median (range) and compared using the Mann\u0026ndash;Whitney U test. Categorical variables were compared using Fisher\u0026rsquo;s exact test. Time-to-event endpoints were analyzed using Kaplan\u0026ndash;Meier curves, compared using the log-rank test. Competing-risk analyses used Gray\u0026rsquo;s test. A two-sided \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistical analyses were performed using SPSS (version 26.0) and R (version 4.2.2).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eA total of 15 patients underwent non-cryopreserved PBSC ASCT with Romiplostim N01 support (Romiplostim N01 group), while 21 historical controls received cryopreserved PBSC ASCT with rhTPO (Control group). Baseline demographic and disease-related variables\u0026mdash;including age, sex, disease subtype, International Staging System (ISS) or Mayo stage, disease status prior to transplantation, hematopoietic cell transplant comorbidity index (HCT-CI) score, plerixafor use and single day apheresis\u0026mdash;were generally comparable between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatients in the Romiplostim N01 cohort tended to proceed to transplantation earlier in their disease course, with a shorter median interval from diagnosis to ASCT (5.5 vs. 7.0 months; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) and fewer induction cycles prior to transplantation (median 4 vs. 5 cycles; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), reflecting earlier disease control and transplantation timing rather than differences in disease biology. The CD34⁺ cell dose infused was similar between the cohorts, measuring 4.53 \u0026times;10⁶/kg (range 1.26\u0026ndash;10.05) in the Romiplostim N01 group and 5.60 \u0026times;10⁶/kg (range 1.24\u0026ndash;22.04) in controls (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.499) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), confirming comparable graft quality. Conditioning intensity and melphalan dosing strategies were identical between groups, ensuring consistent transplant-related toxicity exposure (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eCharacteristics of\u0026nbsp;plasma cell neoplasms\u0026nbsp;patients and grafts\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eRomiplostim N01 group\u0026nbsp;(N=15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eControl Group (N=21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eMedian age, years (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e59.8 (50-79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e61 (45-78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eSex, no. (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Male\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (73.3)\u003c/p\u003e\n \u003cp\u003e4 (26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (61.9)\u003c/p\u003e\n \u003cp\u003e8 (38.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eDiagnosis, no. (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; MM\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp;AL amyloidosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (80)\u003c/p\u003e\n \u003cp\u003e3 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (95.2)\u003c/p\u003e\n \u003cp\u003e1 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eISS stage of MM, no. (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; I\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; II\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eN=12\u003c/p\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eN=20\u003c/p\u003e\n \u003cp\u003e7 (35)\u003c/p\u003e\n \u003cp\u003e6 (30)\u003c/p\u003e\n \u003cp\u003e7 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eMayo 2012 stage of AL\u0026nbsp;amyloidosis,\u0026nbsp;no. (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; I\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; II\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; III\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eN=3\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003cp\u003e2 (66.7)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eN=1\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eMedian time from diagnosis to ASCT, months, (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e5.5 (3-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e7 (5-32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eMedian number of\u0026nbsp;induction cycles\u0026nbsp;(range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4 (2-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e5 (4-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eDisease status before ASCT,\u0026nbsp;no. (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; SD\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; PR\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; VGPR\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; CR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (6.7)\u003c/p\u003e\n \u003cp\u003e3 (20)\u003c/p\u003e\n \u003cp\u003e7 (46.7)\u003c/p\u003e\n \u003cp\u003e4 (26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (4.8)\u003c/p\u003e\n \u003cp\u003e6 (28.6)\u003c/p\u003e\n \u003cp\u003e9 (42.9)\u003c/p\u003e\n \u003cp\u003e5 (23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eHCT-CI score, no. (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 1-2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (60)\u003c/p\u003e\n \u003cp\u003e5 (33.3)\u003c/p\u003e\n \u003cp\u003e1 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (52.4)\u003c/p\u003e\n \u003cp\u003e9 (42.9)\u003c/p\u003e\n \u003cp\u003e1 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.838\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003ePlerixafor use, no. (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e9 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e7 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eSingle day apheresis, no. (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e5 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e4 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.443\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eDose of Melphalan, no. (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 200mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 140mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (60)\u003c/p\u003e\n \u003cp\u003e6 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (66.7)\u003c/p\u003e\n \u003cp\u003e7 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.736\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 260px;\"\u003e\n \u003cp\u003eStem cells\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp;CD34\u003csup\u003e+\u003c/sup\u003e, \u0026times;10\u003csup\u003e6\u003c/sup\u003e/kg, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.53 (1.26-10.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.60 (1.24-22.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMM: Multiple myeloma; AL: Immunoglobulin light-chain; ISS: International Staging System; ASCT: Autologous hematopoietic stem cell transplantation; SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: Complete response; HCT-CI: hematopoietic cell transplantcomorbidity index; n: Number\u003c/p\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eHematopoietic engraftment\u003c/h2\u003e \u003cp\u003eAll patients in both cohorts achieved hematopoietic engraftment. By day\u0026thinsp;+\u0026thinsp;30, Median time to neutrophil engraftment were similar between groups (11 days [range 10\u0026ndash;17]) vs. controls (11 days [range 9\u0026ndash;13]; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.899) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The neutrophil engraftment kinetics were also similar (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea), indicating equivalent early myeloid reconstitution. In contrast, platelet engraftment occurred significantly earlier in the Romiplostim N01 group, with a median of 11 days (range 8\u0026ndash;16) compared with 13 days (range, 9\u0026ndash;20) in controls (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This advantage was consistent across individual patients and was reflected in a left-shifted cumulative recovery curve (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). Moreover, the quality of platelet reconstitution differed substantially. By day\u0026thinsp;+\u0026thinsp;30, all patients in the Romiplostim N01 cohort (100%) achieved complete platelet recovery (\u0026ge;\u0026thinsp;100 \u0026times;10⁹/L), whereas only 66.7% of controls reached this threshold (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This divergence in sustained thrombopoietic improvement highlights the biological impact of Romiplostim N01 on megakaryocyte maturation beyond mere early engraftment.\u003c/p\u003e \u003cp\u003eDespite these improvements, the duration of severe thrombocytopenia (\u0026lt;\u0026thinsp;20 \u0026times;10⁹/L) was similar between cohorts (median 5 days [0\u0026ndash;8] vs. 4 days [0\u0026ndash;14]; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.800) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), suggesting that Romiplostim N01 primarily accelerated recovery after nadir rather than modifying nadir depth.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparisons of engraftment, transfusion burden, and hospitalization metrics post-ASCT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRomiplostim N01 group (N\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003egroup (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian neutrophil engraftment, days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (10\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9\u0026ndash;13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.899\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian platelet engraftment, days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (8\u0026ndash;16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (9\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGraft failure, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet counts\u0026thinsp;\u0026ge;\u0026thinsp;100 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian duration of severe thrombocytopenia (platelet counts\u0026thinsp;\u0026lt;\u0026thinsp;20 \u0026times; 10⁹/L), days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (0\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet transfusion requirements, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.626\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of SDP transfusion, (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.924\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume of transfused platelet, units\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (0\u0026ndash;56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (0\u0026ndash;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.704\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBC transfusion requirements, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay, days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (22\u0026ndash;49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (25\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.693\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cost of ASCT (CNY) \u0026ndash; mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77609\u0026thinsp;\u0026plusmn;\u0026thinsp;21624\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106188\u0026thinsp;\u0026plusmn;\u0026thinsp;14910\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eASCT: Autologous hematopoietic stem cell transplantation; SDP: Single donor platelet; RBC: Red blood cell; CNY: Chinese Yuan;n: Number\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTime-to-event analysis was used to calculate the cumulative incidence of neutrophil (a) and platelet (b) engraftment with death in aplasia as competing risks. ASCT: Autologous hematopoietic stem cell transplantation\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTransfusion burden and hospitalization outcomes\u003c/h2\u003e \u003cp\u003ePlatelet transfusion requirements were comparable between groups. 93.3% of patients receiving Romiplostim N01 and 85.7% of controls required at least one platelet transfusion (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.626). The number of single-donor platelet (SDP) units administered per patient (median 1 unit [0\u0026ndash;3] vs. 1 unit [0\u0026ndash;3]) and the total units of platelets transfused (22 units [0\u0026ndash;56] vs. 18 units [0\u0026ndash;59]) did not differ significantly (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.924 and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.704, respectively) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These findings were consistent with the similar depth and duration of severe thrombocytopenia observed in each group. Red-blood-cell transfusion was required in two patients in the Romiplostim N01 cohort and none in the control cohort, a difference not statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.167) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe median length of hospitalization was comparable, measuring 30 days (range 22\u0026ndash;49) in the Romiplostim N01 cohort and 32 days (25\u0026ndash;45) in controls (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.693). However, total hospitalization cost showed a marked and clinically meaningful reduction in the Romiplostim N01 group. The mean total cost was 77,609\u0026thinsp;\u0026plusmn;\u0026thinsp;21,624 CNY compared with 106,188\u0026thinsp;\u0026plusmn;\u0026thinsp;14,910 CNY in the control cohort (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), reflecting a nearly 27% reduction. The largest contributions to cost reduction were elimination of cryopreservation-related processing expenses and reduced reliance on rhTPO, despite the added cost of Romiplostim N01. Collectively, these findings underscore the economic efficiency of combining Romiplostim N01 with non-cryopreserved PBSCs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSafety\u003c/h2\u003e \u003cp\u003eRomiplostim N01 demonstrated a favorable safety profile, with no unexpected adverse events observed. The frequency and grade of common non-hematologic toxicities\u0026mdash;including mucositis, gastrointestinal symptoms (nausea, vomiting, and diarrhea), and febrile neutropenia\u0026mdash;were similar across cohorts and consistent with those typically encountered following HD-Mel ASCT (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBacteremia occurred in 8.3% of patients receiving Romiplostim N01 and 23.8% of controls (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.379), and elevations in hepatic transaminases occurred in 12.5% vs. 33.3% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.248) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), respectively. Although numerically lower in the Romiplostim N01 group, these differences did not reach statistical significance. No thromboembolic events, severe infusion-related reactions, acute cardiovascular instability, or ICU admissions were reported in either group. Importantly, no cases of symptomatic marrow fibrosis or romiplostim-associated hypersensitivity reactions were observed. Together, these findings support the safety and tolerability of early Romiplostim N01 administration following ASCT.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparisons of safety profiles\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRomiplostim N01 group (N\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003egroup (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucositis, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.499\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea/vomiting, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhea, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfectious adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFebrile neutropenia, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacteremia, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.379\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatic injury, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere infusion-related reactions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThromboembolic events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eICU: Intensive care unit; n: Number\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePost-transplant responses and survival\u003c/h2\u003e \u003cp\u003eFirstly, at the 3-month post-transplant efficacy assessment, no significant differences were observed between the Romiplostim N01 and control groups in terms of partial response (PR) rate, very good partial response (VGPR) rate, complete response (CR) rate, overall response rate (ORR, CR\u0026thinsp;+\u0026thinsp;VGPR\u0026thinsp;+\u0026thinsp;PR), or deep response rate (DRR, CR\u0026thinsp;+\u0026thinsp;VGPR) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea), indicating that Romiplostim N01 did not impair disease control. To evaluate transplantation's impact on disease control, we pooled patients from both the Romiplostim N01 and control groups and compared pre- versus post-transplant responses. The CR rate increased from 25% pre-ASCT to 67.7% post-ASCT (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), resulting in significantly higher DRR post-ASCT (91.7% vs. 69.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035), consistent with the deepened response from HD-Mel conditioning. However, ORR failed to improve (94.4% vs. 94.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000) as non-remission rates remained unchanged (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe compared hematological endpoints (PR, VGPR, CR, ORR, DRR) between the Romiplostim N01 and control groups at 3 months post-ASCT (a). To evaluate the impact of transplantation itself, we then pooled both groups to compare these endpoints before and 3 months after ASCT (b). ASCT: Autologous hematopoietic stem cell transplantation; TPO-RAs: Thrombopoietin receptor agonists; PR: Partial response; VGPR: Very good partial response; CR: Complete response; ORR: Overall response rate; DRR: Deep response rate. *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and ** \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003cp\u003eWith a median follow-up of 13.5 months, early survival outcomes were comparable between groups. Estimated 2-year OS was 92.3% \u0026plusmn; 7.4% in the Romiplostim N01 group and 84.8% \u0026plusmn; 8.1% in the control cohort (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.855) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Estimated 2-year PFS was 93.3% \u0026plusmn; 6.4% vs. 51.7% \u0026plusmn; 15.2% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.501) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb), with the wider confidence interval in controls reflecting greater heterogeneity and fewer events. The cumulative incidence of relapse with death as a competing risk did not differ significantly (7.14% \u0026plusmn; 0.51% vs. 43.42% \u0026plusmn; 2.74%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.744) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). No transplant-related mortality within the first 100 days occurred in either cohort.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ea: The comparison of estimated 2-year OS between Romiplostim N01 and control groups (92.3% \u0026plusmn; 7.4% vs. 84.8% \u0026plusmn; 8.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.855). b: The comparison of estimated 2-year PFS between Romiplostim N01 and control groups (93.3% \u0026plusmn; 6.4% vs. 51.7% \u0026plusmn; 15.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.501). ASCT: Autologous hematopoietic stem cell transplantation; OS: Overall survival; PFS: Progression-free survival\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComparison of cumulative relapse rates between the Romiplostim N01 group and the control group. ASCT: Autologous hematopoietic stem cell transplantation\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective cohort study demonstrates that early administration of Romiplostim N01 following ASCT, combined with the use of non-cryopreserved PBSCs, leads to significantly accelerated platelet engraftment, more consistent complete platelet recovery, and substantially reduced hospitalization cost, while maintaining an excellent safety profile. These findings collectively highlight the feasibility, clinical value, and economic advantages of integrating a TPO-RA\u0026ndash;based thrombopoietic support strategy into routine ASCT practice for plasma-cell neoplasms.\u003c/p\u003e \u003cp\u003eRecent studies present conflicting evidence regarding the ability of non-cryopreserved PBSCs to shorten engraftment time[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A Worldwide Network for Blood \u0026amp; Marrow Transplantation meta-analysis of 1,686 patients confirmed the feasibility and safety of non-cryopreserved PBSCs transplantation. This analysis reported a median platelet engraftment time of 15.3 days, aligning with the 15-day median reported by Jacinth et al. in \u003cem\u003eBlood\u003c/em\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In contrast, our study demonstrated a significantly shorter median platelet engraftment time of 11 days. Given comparable median CD34\u003csup\u003e+\u003c/sup\u003e cell counts across the studies, the accelerated platelet recovery observed in our cohort may be attributable to the administration of Romiplostim N01.\u003c/p\u003e \u003cp\u003eThe two-day improvement in platelet engraftment observed in the Romiplostim N01 cohort is clinically meaningful and aligns with the known pharmacologic activity of TPO-Ras[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. HD-Mel induces profound megakaryocytic suppression by impairing stromal integrity, damaging vascular niches, and temporally arresting megakaryocyte endomitosis[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Endogenous TPO levels, though increased during cytopenia, remain insufficient to overcome this transient marrow injury. Romiplostim N01, through c-Mpl receptor binding and activation of JAK-STAT, PI3K-AKT, and MAPK pathways, provides a supraphysiologic stimulus that restores megakaryopoiesis during this vulnerable post-conditioning window[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The improvement in both the speed and quality of thrombopoietic recovery\u0026mdash;evidenced by universally achieved complete platelet recovery by day\u0026thinsp;+\u0026thinsp;30\u0026mdash;is consistent with this mechanistic rationale and suggests a coordinated enhancement of megakaryocyte maturation and proplatelet formation.\u003c/p\u003e \u003cp\u003eThese findings expand the existing body of evidence for TPO-RAs in transplantation. Previous studies evaluating romiplostim or eltrombopag in hematopoietic cell transplantation have largely focused on salvage therapy for poor graft function or delayed engraftment, often requiring prolonged administration over several weeks[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29 CR30 CR31\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In contrast, our data demonstrate that proactive, early, short-course Romiplostim N01 can significantly shift the platelet recovery trajectory even in patients receiving uniformly intensive conditioning. This distinction is important because reactive use of TPO-RAs typically occurs after substantial marrow compromise has occurred, whereas early use leverages intact megakaryocyte progenitor pools present immediately after PBSCs reinfusion.\u003c/p\u003e \u003cp\u003eThe economic advantage observed in the Romiplostim N01 cohort is another compelling aspect of this strategy. Hospitalization cost was reduced by nearly 27%, driven primarily by elimination of cryopreservation-related expenses, including DMSO handling, controlled-rate freezing, liquid-nitrogen storage, Cryoprotective equipment, infusion-related monitoring, and management of DMSO-associated adverse events[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The use of non-cryopreserved PBSCs avoids these steps entirely and simplifies the logistical framework of ASCT processing. Notably, this cost reduction was achieved despite the addition of Romiplostim N01, indicating that the savings associated with simplified graft handling outweighed the cost of pharmacologic thrombopoietic support.\u003c/p\u003e \u003cp\u003eThe safety profile of Romiplostim N01 observed in this study is consistent with prior experience in immune thrombocytopenia and chemotherapy-induced thrombocytopenia[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. No thromboembolic complications, infusion reactions, exacerbations of mucositis or gastrointestinal events, hepatic toxicity, or marrow fibrosis was observed. The absence of cardiovascular or pro-thrombotic signals is especially reassuring, given concern for thrombopoietic overstimulation in the peri-engraftment period. Importantly, there was no evidence that Romiplostim N01 adversely affected disease control; depth of hematologic response increased appropriately after ASCT, and early PFS and OS outcomes were comparable to those in the control cohort.\u003c/p\u003e \u003cp\u003eThe clinical implications of these findings are noteworthy. In many transplant centers\u0026mdash;particularly those with high patient volume or limited cryopreservation infrastructure\u0026mdash;simplifying the PBSCs workflow could significantly reduce resource strain[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Non-cryopreserved PBSCs infusion eliminates DMSO-associated toxicities, supports more predictable scheduling, and reduces dependence on cryopreservation facilities[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. When paired with Romiplostim N01, this approach provides a coherent and rational framework for reducing the medical and financial burden of ASCT without structurally altering conditioning strategies or transfusion practices.\u003c/p\u003e \u003cp\u003eNevertheless, this study has limitations. Its retrospective nature introduces inherent risks of selection bias, although baseline characteristics were comparable between cohorts. The modest sample size limits the power to detect rare adverse events, small differences in survival outcomes, or subgroup-specific effects (e.g., MM vs. AL). Follow-up duration remains relatively short, precluding assessment of late relapses, long-term marrow stability, or delayed fibrotic changes. Additionally, although the control group reflected contemporaneous institutional practice, evolving supportive-care protocols may have introduced unmeasured confounders. Future prospective studies should evaluate optimal timing and dosing of Romiplostim N01.\u003c/p\u003e \u003cp\u003eDespite these limitations, the strengths of the study are notable: uniform conditioning regimens, consistent definitions of engraftment and toxicity, stable institutional transplant practices across the study period, and integration of both clinical and economic endpoints. The internal consistency across engraftment acceleration, improved platelet recovery quality, and substantial cost reduction strongly supports the biological and operational validity of this combined strategy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study demonstrates that early administration of Romiplostim N01 accelerates platelet recovery, enhances the quality of thrombopoiesis, and significantly reduces hospitalization cost without compromising safety when used in combination with non-cryopreserved PBSCs during ASCT for plasma-cell neoplasms. These findings support the integration of Romiplostim N01 into routine thrombopoietic support for ASCT, particularly in centers seeking to streamline graft processing and reduce resource utilization.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003eThe authors would like to extend their sincere gratitude to Professor Jindan Yu for her language polishing of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003eXianfu Sheng was responsible for direct patient care, data extraction and data analysis, interpreting the finally results and writing the manuscript. Qijia Zheng was responsible for data analysis, writing the manuscript, updated the reference list. Jingjing Xiang and Nanxi Dong were responsible for data extraction, data analysis and making charts. Yuechao Zhao and Huijin Hu were responsible for direct patient care and manuscript review. Lili Qian was responsible for statistical analysis and quality control. Wenbin Liu and Jianping Shen designed the protocol and conducted the apheresis procedures and stem cell harvest. Baodong Ye and Yu Zhang designed the protocol, were responsible for patient care, protocol supervision, interpreted the finally results, helped writing the manuscript and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis work was supported by the Special Project for the Modernization of Traditional Chinese Medicine in Zhejiang Province (No. 2020ZX007);\u0026nbsp;National Major and Difficult Diseases (Lymphoma) Clinical Collaboration Project of Traditional Chinese and Western Medicine (No. ZDYN-2024-A-024);\u0026nbsp;Zhejiang Provincial Natural Science Foundation (No. LY19H270004, LTGY23H270004, LQ24H290001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003eThe original data is available upon special request to Yu Zhang, E-mail: [email protected].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOpen Acess\u0026nbsp;\u003c/strong\u003eOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article\u0026rsquo;s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u0026rsquo;s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMoreno V, Saba L, Tama-Shekan S, Chaulagain CP (2024) Current and Emerging Immunotherapies for Systemic AL Amyloidosis. Discov Med 36:1761\u0026ndash;1771. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.24976/Discov.Med.202436188.162\u003c/span\u003e\u003cspan address=\"10.24976/Discov.Med.202436188.162\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrieb N, Oeser A, Ferle M, Hanke F, Flossdorf S, Sauer S, Goldschmidt H, Muller-Tidow C, Salwender HJ, Fenk R, Engelhardt M, Zeiser R, Vucinic V, Franke GN, Blau IW, Teschner D, Einsele H, Kimmich C, Kull M, Besemer B, Gagelmann N, Kroger N, Neumuth T, Platzbecker U, Merz M, German Registry for Hematopoietic Stem Cell T, and, Cell T (2025) Single versus tandem autologous stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transplant 60: 335\u0026ndash;345. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-024-02490-1\u003c/span\u003e\u003cspan address=\"10.1038/s41409-024-02490-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParmar H, Doucette K, Vesole D (2024) Role of Autologous Stem Cell Transplantation in Systemic Light Chain Amyloidosis. Clin Lymphoma Myeloma Leuk 24:770\u0026ndash;777. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clml.2024.06.009\u003c/span\u003e\u003cspan address=\"10.1016/j.clml.2024.06.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRajkumar SV (2024) Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol 99:1802\u0026ndash;1824. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/ajh.27422\u003c/span\u003e\u003cspan address=\"10.1002/ajh.27422\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, Hulin C, Antonioli E, Leleu X, Mangiacavalli S, Perrot A, Cavo M, Belotti A, Broijl A, Gay F, Mina R, Nijhof IS, van de Donk N, Katodritou E, Schjesvold F, Sureda Balari A, Rosinol L, Delforge M, Roeloffzen W, Silzle T, Vangsted A, Einsele H, Spencer A, Hajek R, Jurczyszyn A, Lonergan S, Ahmadi T, Liu Y, Wang J, Vieyra D, van Brummelen EMJ, Vanquickelberghe V, Sitthi-Amorn A, de Boer CJ, Carson R, Rodriguez-Otero P, Blade J, Moreau P, Investigators PT (2024) Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 390:301\u0026ndash;313. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMoa2312054\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa2312054\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVillar S, Zapata E, Rifon J (2025) The role of stem cell transplantation in the modern management of multiple myeloma. Curr Opin Hematol 32:321\u0026ndash;326. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/MOH.0000000000000896\u003c/span\u003e\u003cspan address=\"10.1097/MOH.0000000000000896\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElsayed A, Elsayed B, Elmarasi M, Elsabagh AA, Elsayed E, Elmakaty I, Yassin M (2024) Thrombopoietin Receptor Agonists in Post-Hematopoietic Cell Transplantation Complicated by Prolonged Thrombocytopenia: A Comprehensive Review. Immunotargets Ther 13:461\u0026ndash;486. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/ITT.S463384\u003c/span\u003e\u003cspan address=\"10.2147/ITT.S463384\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaufman RM, Assmann SF, Triulzi DJ, Strauss RG, Ness P, Granger S, Slichter SJ (2015) Transfusion-related adverse events in the Platelet Dose study. Transfusion 55:144\u0026ndash;153. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/trf.12791\u003c/span\u003e\u003cspan address=\"10.1111/trf.12791\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSociety of Chemotherapy CA-CA and Committee of Neoplastic Supportive-Care CA-CA (2023) [Consensus on the clinical diagnosis, treatment and prevention of cancer treatment-induced thrombocytopenia in China (2023 edition)]. Zhonghua Yi Xue Za Zhi 103:2579\u0026ndash;2590. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3760/cma.j.cn112137-20230409-00575\u003c/span\u003e\u003cspan address=\"10.3760/cma.j.cn112137-20230409-00575\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu X, Yang R, Jia Y, Gao G, Huang T, He A, Wang F (2025) Comparison of Thrombopoietin Receptor Agonists Plus Recombinant Human Thrombopoietin versus Recombinant Human Thrombopoietin Alone for Hematopoietic Reconstruction in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation. Transplant Cell Ther 31: 84 e1-84 e8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jtct.2024.12.015\u003c/span\u003e\u003cspan address=\"10.1016/j.jtct.2024.12.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQiu X, Jiang H, Xiao X, Huang L, Xu Y (2024) Recombinant human thrombopoietin improves platelet engraftment after autologous hematopoietic stem cell transplantation in patients with aggressive lymphoma. Transfus Apher Sci 63:103972. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.transci.2024.103972\u003c/span\u003e\u003cspan address=\"10.1016/j.transci.2024.103972\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeng D, Liu Q, Gao H, Cao Y, Chen X, Zhang R, Zhai W, Yang D, Wei J, He Y, Pang A, Feng S, Han M, Ma Q, Jiang E (2025) Increasing the dose of recombinant human thrombopoietin can enhance platelet engraftment after allogeneic haematopoietic stem cell transplantation: A NICHE cohort study. Br J Haematol 206:769\u0026ndash;772. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/bjh.19954\u003c/span\u003e\u003cspan address=\"10.1111/bjh.19954\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBussel JB, Soff G, Balduzzi A, Cooper N, Lawrence T, Semple JW (2021) A Review of Romiplostim Mechanism of Action and Clinical Applicability. Drug Des Devel Ther 15:2243\u0026ndash;2268. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/DDDT.S299591\u003c/span\u003e\u003cspan address=\"10.2147/DDDT.S299591\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePasvolsky O, Shargian L, Rozovski U, Wolach O, Ram R, Shapira MY, Avni B, Stepensky P, Israeli M, Vidal-Fisher L, Shpilberg O, Raanani P, Yeshurun M (2021) Eltrombopag for enhancement of platelet engraftment in patients undergoing allogeneic cord blood transplantation. Leuk Lymphoma 62:2747\u0026ndash;2754. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/10428194.2021.1929957\u003c/span\u003e\u003cspan address=\"10.1080/10428194.2021.1929957\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiesveld JL, Phillips GL 2nd, Becker M, Constine LS, Friedberg J, Andolina JR, Milner LA, DeBolt J, Smudzin T, Hyrien O, Erickson-Miller CL, Johnson BM, Dawson KL, Chen Y (2013) A phase 1 trial of eltrombopag in patients undergoing stem cell transplantation after total body irradiation. Biol Blood Marrow Transpl 19:1745\u0026ndash;1752. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bbmt.2013.10.002\u003c/span\u003e\u003cspan address=\"10.1016/j.bbmt.2013.10.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBekadja MA, Niederwieser D, Kharfan-Dabaja MA, El Fakih R, Garderet L, Yakoub-Agha I, Greinix H, Weisdorf DJ, Galeano S, Ahmed SO, Chabanon C, Hashmi SK, Ruggeri A, Gergis U, Bazarbachi A, Hamad N, Albeihany A, Pasquini M, Hanbali A, Szer J, Kodera Y, Kumar A, Elhassan T, McLornan D, Worel N, Greco R, Mohty M, Atsuta Y, Koh M, Sureda A, Rondelli D, Aljurf M, Rasheed W (2025) Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation. Bone Marrow Transpl 60:19\u0026ndash;27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-024-02431-y\u003c/span\u003e\u003cspan address=\"10.1038/s41409-024-02431-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBekadja MA, Boumendil A, Blaise D, Chevallier P, Peggs KS, Salles G, Giebel S, Marks R, Arcese W, Milpied N, Finel H, Gorin NC (2021) Non-cryopreserved hematopoietic stem cells in autograft patients with lymphoma: a matched-pair analysis comparing a single center experience with the use of cryopreserved stem cells reported to the European Society for Blood and Marrow Transplantation registry. Cytotherapy 23:483\u0026ndash;487. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jcyt.2020.12.016\u003c/span\u003e\u003cspan address=\"10.1016/j.jcyt.2020.12.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoiperm P, Julamanee J, Viboonjuntra P, Lekhakula A (2023) Non-Cryopreserved Peripheral Blood Stem Cell Graft for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma and Lymphoma Patients. Ann Transpl 28:e938595. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.12659/AOT.938595\u003c/span\u003e\u003cspan address=\"10.12659/AOT.938595\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAraujo AB, Soares TB, Schmalfuss T, Angeli MH, Furlan JM, Salton GD, Burin MM, Rohsig LM (2022) Non-cryopreserved peripheral blood stem cells as a safe and effective alternative for autologous transplantation in multiple myeloma. Transfusion 62:1967\u0026ndash;1972. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/trf.17090\u003c/span\u003e\u003cspan address=\"10.1111/trf.17090\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJennane S, Hasnaoui N, Mahtat EM, Merimi F, Bougar S, El Maaroufi H, Belmekki A, Zafad S, Essakalli M, Mikdame M, Doghmi K (2020) Non-cryopreserved peripheral blood stem cells autologous transplantation in multiple myeloma: Bicentric study. Transfus Clin Biol 27:152\u0026ndash;156. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.tracli.2020.03.006\u003c/span\u003e\u003cspan address=\"10.1016/j.tracli.2020.03.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17:e328\u0026ndash;e346. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S1470-2045(16)30206-6\u003c/span\u003e\u003cspan address=\"10.1016/S1470-2045(16)30206-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar SK, Callander NS, Adekola K, Anderson LD Jr., Baljevic M, Campagnaro E, Castillo JJ, Costello C, D'Angelo C, Devarakonda S, Elsedawy N, Garfall A, Godby K, Hillengass J, Holmberg L, Htut M, Huff CA, Hultcrantz M, Kang Y, Larson S, Lee HC, Liedtke M, Martin T, Omel J, Rosenberg A, Sborov D, Valent J, Berardi R, Kumar R (2023) Systemic Light Chain Amyloidosis, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 21:67\u0026ndash;81. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.6004/jnccn.2023.0001\u003c/span\u003e\u003cspan address=\"10.6004/jnccn.2023.0001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePessoa JM, da Rosa EL, Americo AD, Motta CL, de Oliveira CZ, Concilio RR, Amigo Filho JU, Marret ACF, Lazar AE, De Gusmao BM, Scheinberg P, Kerbauy FR (2022) Cryopreserved versus non-cryopreserved stem cell autografts in multiple myeloma a restrospective cohort study. Bone Marrow Transpl 57:1313\u0026ndash;1318. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-022-01718-2\u003c/span\u003e\u003cspan address=\"10.1038/s41409-022-01718-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiriyakhuntorn P, Tantiworawit A, Rattanathammethee T, Hantrakool S, Chai-Adisaksopha C, Rattarittamrong E, Norasetthada L (2020) Outcomes of Non-Cryopreserved Versus Cryopreserved Peripheral Blood Stem Cells for Autologous Stem Cell Transplantation in Multiple Myeloma. Ann Transpl 25:e927084. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.12659/AOT.927084\u003c/span\u003e\u003cspan address=\"10.12659/AOT.927084\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoseph J, Wookey V, Randolph B, Chandler JC, Marjoncu D, Holman K, Peeler D, Armstrong M, Khaled Y (2020) Fresh Versus Cryopreserved Peripheral Stem Cell for Autologous Transplantation in Multiple Myeloma: An Analysis of Short-Term Outcomes. Blood 136:9\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/blood-2020-143049\u003c/span\u003e\u003cspan address=\"10.1182/blood-2020-143049\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKemp K, Morse R, Sanders K, Hows J, Donaldson C (2011) Alkylating chemotherapeutic agents cyclophosphamide and melphalan cause functional injury to human bone marrow-derived mesenchymal stem cells. Ann Hematol 90:777\u0026ndash;789. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00277-010-1141-8\u003c/span\u003e\u003cspan address=\"10.1007/s00277-010-1141-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoff GA, Al-Samkari H, Leader A, Eisen M, Saad H (2024) Romiplostim in chemotherapy-induced thrombocytopenia: A review of the literature. Cancer Med 13:e7429. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cam4.7429\u003c/span\u003e\u003cspan address=\"10.1002/cam4.7429\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMahat U, Rotz SJ, Hanna R (2020) Use of Thrombopoietin Receptor Agonists in Prolonged Thrombocytopenia after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transpl 26:e65\u0026ndash;e73. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bbmt.2019.12.003\u003c/span\u003e\u003cspan address=\"10.1016/j.bbmt.2019.12.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeffault de Latour R, Chevret S, Ruggeri AL, Suarez F, Souchet L, Michonneau D, Sicre de Fontbrune F, Coman T, Dhedin N, Rubio MT, Nguyen S, Mohty M, Socie G (2020) Romiplostim in patients undergoing hematopoietic stem cell transplantation: results of a phase 1/2 multicenter trial. Blood 135:227\u0026ndash;229. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/blood.2019000358\u003c/span\u003e\u003cspan address=\"10.1182/blood.2019000358\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZaninetti C, Gresele P, Bertomoro A, Klersy C, De Candia E, Veneri D, Barozzi S, Fierro T, Alberelli MA, Musella V, Noris P, Fabris F, Balduini CL, Pecci A (2020) Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial. Haematologica 105:820\u0026ndash;828. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3324/haematol.2019.223966\u003c/span\u003e\u003cspan address=\"10.3324/haematol.2019.223966\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHalahleh K, Al-Ya'Goub M, Ma'koseh M, Al-Far R, Da'na W, Pharm RA, Taqash A, Muradi I, Sughayer M, Abu-Jazar H (2025) Eltrombopag Enhances Recovery from Cytopenias Due to Poor Graft Function after Hematopoietic Cell Transplantation. Blood Cell Ther 8:160\u0026ndash;166. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.31547/bct-2024-017\u003c/span\u003e\u003cspan address=\"10.31547/bct-2024-017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBayram N, Yaman Y, Ozdilli K, Nepesov S, Al IO, Elli M, Anak S (2025) Eltrombopag for Treatment of Thrombocytopenia After Autologous Stem Cell Transplantation in Children: Single Center Experience. J Pediatr Hematol Oncol 47:e10\u0026ndash;e14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/MPH.0000000000002971\u003c/span\u003e\u003cspan address=\"10.1097/MPH.0000000000002971\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen F, McDonald V, Newland A (2021) Experts' review: the emerging roles of romiplostim in immune thrombocytopenia (ITP). Expert Opin Biol Ther 21:1383\u0026ndash;1393. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/14712598.2021.1960979\u003c/span\u003e\u003cspan address=\"10.1080/14712598.2021.1960979\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu P, Dong E, Jiang Y, Chen L, Xie B, Ling J (2025) Successful treatment of refractory cancer therapy-induced thrombocytopenia in a breast cancer patient using romiplostim N01: A case report. Med (Baltim) 104:e43665. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/MD.0000000000043665\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000043665\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelikyan AL, Protsenko EA, Salogub GN, Bakirov BA, Davydkin IL, Kovalik VV, Gefen ML, Matvienko YD, Saparova VB, Khokhlov AL, Makarenko IE, Drai RV (2025) Multicenter Single-Blind Randomized Controlled Trial of the Romiplostim Biosimilar. EJHaem 6: e70105. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jha2.70105\u003c/span\u003e\u003cspan address=\"10.1002/jha2.70105\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Romiplostim N01, Thrombopoietin receptor agonist, Multiple myeloma, Systemic light-chai amyloidosis, Autologous hematopoietic stem cell transplantation, Non-cryopreserved stem cells","lastPublishedDoi":"10.21203/rs.3.rs-8603508/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8603508/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDelayed platelet engraftment remains a major limitation of autologous stem cell transplantation (ASCT) for plasma-cell neoplasms. Romiplostim N01, a thrombopoietin receptor agonist, may enhance early megakaryocytic recovery, while the use of non-cryopreserved peripheral blood stem cells (PBSCs) eliminates dimethyl-sulfoxide\u0026ndash;related toxicity and reduces procedural cost.\u003c/p\u003e \u003cp\u003eThis retrospective study evaluated 15 patients receiving non-cryopreserved PBSCs and early Romiplostim N01 after ASCT and compared them with 21 historical controls who received cryopreserved PBSCs and recombinant human thrombopoietin. We tried to compare time to engraftment, transfusion burden, hospitalization duration and cost, safety, hematologic responses and survival outcomes.\u003c/p\u003e \u003cp\u003ePlatelet engraftment occurred significantly earlier in the Romiplostim N01 cohort (median 11 vs. 13 days; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008), and complete platelet recovery by day\u0026thinsp;+\u0026thinsp;30 was higher (100% vs. 66.7%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027). Neutrophil recovery, transfusion requirements, and hospitalization duration were comparable between groups. Total hospitalization cost was markedly lower with Romiplostim N01 (77,609\u0026thinsp;\u0026plusmn;\u0026thinsp;21,624 vs. 106,188\u0026thinsp;\u0026plusmn;\u0026thinsp;14,910 CNY; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The two patient groups also demonstrated comparable safety profiles, treatment responses, and survival outcomes.\u003c/p\u003e \u003cp\u003eRomiplostim N01 safely accelerates thrombopoietic recovery and substantially reduces cost when combined with non-cryopreserved PBSCs. This strategy represents a practical and economically favorable supportive-care model for ASCT.\u003c/p\u003e","manuscriptTitle":"Romiplostim N01 accelerates platelet engraftment in autologous stem cell transplantation using non-cryopreserved peripheral blood stem cells for plasma cell neoplasms","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-28 03:07:01","doi":"10.21203/rs.3.rs-8603508/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dee9db0f-ba47-4b21-9c9d-208c48fbcf48","owner":[],"postedDate":"January 28th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-13T06:10:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-28 03:07:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8603508","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8603508","identity":"rs-8603508","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}