Allogeneic stem cell transplantation in chronic myelomonocytic leukemia: analysis of post-transplant survival and risk factors in 138 Mayo Clinic patients

Allogeneic stem cell transplantation in chronic myelomonocytic leukemia: analysis of post-transplant survival and risk factors in 138 Mayo Clinic patients | 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 Article Allogeneic stem cell transplantation in chronic myelomonocytic leukemia: analysis of post-transplant survival and risk factors in 138 Mayo Clinic patients Ayalew Tefferi, Ali Alsugair, Estefania Gauto-Mariotti, Mohammad Alhousani, and 23 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6753879/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Oct, 2025 Read the published version in Blood Cancer Journal → Version 1 posted 9 You are reading this latest preprint version Abstract Allogeneic stem cell transplant (ASCT) remains the only curative option in chronic myelomonocytic leukemia (CMML). We retrospectively analyzed 138 CMML patients who underwent ASCT at the Mayo Clinic. Patients who transitioned to ASCT while in chronic phase (Group A) displayed superior post-transplant survival (PTS), compared to those in whom ASCT was performed after blast transformation (BT; Group B) (median 95 vs. 16 months; p=0.01). In Group A, PTS was superior in patients with <5% bone marrow (BM) blasts at time of ASCT (median 164 vs. 13.5 months; p=0.01). Other predictors of superior PTS included day-100 BM blast <5% or normal cytogenetics (median 164 vs 18 months; p=0.01) or presence of chronic graft-versus-host-disease (GVHD; median 164 vs. 26 months; p=0.01). Pre-ASCT hypomethylating agent exposure (HR=2.03; p=0.03), and receiving more than one line of pre-ASCT chemotherapy (p=0.01) predicted inferior PTS. In multivariable analysis, predictors of superior GVHD-free and relapse-free survival (GRFS) included the use myeloablative conditioning and the absence of morphologically or cytogenetically apparent disease at day-100. The use of post-transplant cyclophosphamide (PTCy) was associated with higher cumulative incidence of relapse (p=0.02) and numerically inferior PTS (p=0.1). Group B patients also appeared to benefit from achieving BM blast <5% at time of ASCT (p=0.4) as well as at day-100 (p=0.01), in terms of PTS, while full chimerism and normal cytogenetics at day-100 were associated with superior GRFS. These observations support the value of ASCT in CMML, especially if performed prior to BT and in the presence of <5% BM blasts at time of ASCT. Additionally, the observed detrimental impact of PTCy requires additional studies to confirm and investigate the underlying mechanisms. Health sciences/Diseases/Haematological diseases/Haematological cancer/Myelodysplastic syndrome Health sciences/Diseases/Haematological diseases/Haematological cancer/Myeloproliferative disease CMML Bone marrow transplantation Blast transformation GVHD post-transplant cyclophosphamide PTC Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by persistent monocytosis in the peripheral blood and features overlapping those of myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDS).( 1 – 3 ) The clinical course of CMML is heterogenous, with a recognized risk of progression to acute myeloid leukemia (AML), referred to as blast transformation (BT).( 4 , 5 ) BT occurs in 15–30% of cases and is associated with poor prognosis, with report of median overall survival (OS) as short as 6 months following transformation, and a five-year survival rate of only about 6%. ( 5 – 8 ) Conventional therapies, including hydroxyurea and hypomethylating agents (HMA), may provide symptomatic benefits but are not curative.( 9 ) Allogeneic stem cell transplantation (ASCT) remains the only potentially curative treatment option.( 10 , 11 ) While the long-term benefits of ASCT in selected patients are well recognized, the risk of transplant-related complications and non-relapse mortality makes patient selection critical.( 12 ) Typically, younger patients have shown better outcomes( 12 ); however, this presents a challenge in CMML patients as the median age at diagnosis is between 70 and 74 years.( 13 , 14 ) In our previous study (N = 70), we demonstrated survival benefit from ASCT, particularly when performed in chronic phase disease compared to undergoing ASCT after BT (5-year OS of 51% vs 19%).( 11 ) The same study also showed that the median graft versus host disease (GVHD)-free relapse-free survival (GRFS) was only 7 months, underscoring both the benefit and morbidity associated with ASCT. The median age in this study, as in most other ASCT studies, was 58 years.( 11 , 15 , 16 ) In the particular study, only abnormal karyotype was adversely prognostic.( 11 ) Gagelmann et al. found that an ASXL1 and/or NRAS -mutated genotype, bone marrow (BM) blasts > 2%, and high hematopoietic cell transplantation comorbidity index (HCT-CI) were independently predictive of worse post-transplant survival (PTS).( 16 ) Reduced-intensity conditioning (RIC) regimens and alternative donor sources such as haploidentical and umbilical cord blood donor, have expanded ASCT eligibility to a broader patient population.( 17 – 20 ) Despite these advances, the decision to proceed with ASCT in CMML remains challenging. Compared with myeloablative conditioning (MAC) regimen, RIC offers the benefit of lower non-relapse mortality but it may be associated with a higher rate of relapse.( 21 ) However, some CMML studies reported no differences in OS between MAC and RIC. ( 12 , 21 ) Implementation of post-transplant cyclophosphamide (PTCy) has improved the GRFS in phase III trials ( 22 , 23 ). However, recent reports observed a tendency toward increased risk of relapse with the use of PTCy.( 24 ) There is lack of prospective data analyzing these risk factors to guide patient selection. In addition, CMML-specific retrospective studies are few, and significant gaps still exist in our understanding of the prognostic impact of various clinical, cytogenetic, molecular risk factors and choice of conditioning regimen in the setting of ASCT for CMML. The aim of the current study was to evaluate PTS and identify risk factors influencing transplant outcomes in CMML patients who underwent ASCT. METHODS This retrospective study was conducted under a Mayo Clinic IRB-approved minimal risk protocol. We identified patients with CMML who underwent ASCT between 1995 and 2024 using the Mayo Clinic electronic databases, which included patients from Mayo Clinic Rochester, Florida, and Arizona, USA. Clinical, laboratory, and outcome data were extracted from these databases. CMML diagnosis and categorization (CMML-1/CMML-2) and myelodysplastic(MD-CMML)/myeloproliferative(MP-CMML) subtypes were made according to the International Consensus Classification (ICC) and confirmed by central review.( 1 ) Mutations/variants in genes associated with myeloid neoplasms were screened by next-generation sequencing in accordance with institutional protocols for clinical use. Cytogenetic findings were reported using the International System for Human Cytogenetic Nomenclature.( 25 ) CMML patients were classified into two groups based on the timing of blast transformation. Group A included patients who underwent ASCT while in chronic phase CMML while Group B included those who had ASCT following BT. Promonocytes were included in the blasts count. Risk stratification was performed using the updated CMML-specific prognostic scoring system that includes molecular abnormalities (CPSS-mol) and BLAST scores, as defined by Elena et al . and Tefferi et al ., respectively.( 26 , 27 ) The BLAST score uses a point-based system, and it includes circulating blasts ≥ 2% (1 point), leukocytes ≥ 13 x 10⁹/L (1 point), and severe (2 points) or moderate (1 point) anemia. Based on the total score, patients were stratified into low-risk (0 points), intermediate-risk (1 point), and high-risk (2–4 points)( 27 ). HCT-CI and Karnofsky performance status (KPS) score were calculated as described by Sorror et al and Karnofsky et al, respectively.( 28 , 29 ) Platelet engraftment was defined as the first of three consecutive days with a platelet count of ≥ 20,000/µL in the absence of platelet transfusion for seven consecutive days.( 30 ) Neutrophil engraftment was defined as the first of three successive days with an absolute neutrophil count ≥ 500/µL after the post-transplantation nadir.( 30 ) Donor chimerism was classified according to the American society for transplantation and cellular therapy (ASTCT) criteria: full donor chimerism if myeloid and lymphoid lineages were > 95%, mixed or partial chimerism if 5–95%, and lost/absent donor chimerism if < 5%.( 30 ) PTS was measured from the date of ASCT to death from any cause. Relapse-free survival (RFS) was defined as the time from ASCT to relapse or death from any cause, whichever occurred first. GRFS was defined as the time from ASCT to grade 3–4 acute GVHD (aGVHD), systemic therapy-requiring chronic GVHD (cGVHD), relapse, or death, whichever occurred first.( 31 ) Non-relapse mortality (NRM) was defined as time from ASCT to death from any cause without a prior relapse or progression. Cumulative incidence of relapse and NRM were estimated using the cumulative incidence method for competing risks. Death and relapse were considered competing risks for relapse and NRM, respectively. Median followed up calculated using reverse kaplan-meier method. Frequencies and percentages were used to summarize categorical variables, while medians and ranges were used for quantitative variables. Time-to-event analyses were performed using Kaplan-Meier estimates, intergroup comparisons assessed with the log-rank test and hazard ratios (HR) were calculated using cox proportional hazards regression. Multivariable analyses (MVA) to identify the impact of risk factors were performed using the Cox proportional hazards regression model. All statistical analyses were conducted using JMP Pro 18.0.0 software (SAS Institute, Cary, NC, USA). RESULTS Presenting clinical and laboratory characteristics A total of 138 Mayo Clinic patients (62% male) with CMML who underwent ASCT were included in the study (Table 1). The median ages at the time of diagnosis and at the time ASCT were 62 (range 18-75) and 63 (range 18-76) years, respectively. Group A comprised 104 patients, while Group B consisted of 34 patients. All patients underwent transplantation between 1995 and 2024. At initial diagnosis, CMML-1/CMML-2 and MD-CMML/MP-CMML phenotypes were seen in 78%/22% and 54%/46% of patients, respectively. Among patients with available molecular data (n=86), the most frequent mutations/variants were ASXL1 (56%), TET2 (44%), and SRSF2 (38%). Abnormal karyotypes were observed in 31% of patients. CPSS-Mol risk categories at diagnosis were low (17%), intermediate-1 (11%), intermediate-2 (40%), and high (32%). BLAST score categories were low risk (38%), intermediate risk (44%), and high risk (18%). Compared to Group B, patients in Group A were more likely to present with RUNX1 mutations/variants (24% vs 0%; p=0.01) and more often received pre-transplant HMA (64% vs 36%; p=0.01). In contrast, Group B patients more frequently received intensive chemotherapy prior to ASCT (79% vs 13%; p=0.01). Other clinical and laboratory characteristics are summarized in Table 1. Pre- and Peri-Transplant Treatment and Disease Status HMAs were used as first-line CMML-directed therapy in 75 (60%) patients, intensive chemotherapy in 29 (23%), other therapies (including hydroxyurea, erythropoietin agonist, danazol, ruxolitinib, or clinical trials) in 16 (13%), and no treatment in 5 (4%; Table 1). Twenty-nine (21%) patients received two or more lines of cytotoxic therapies. Bone marrow assessment at the time of ASCT was available in 126 (91%) patients. In Group A, BM blasts were <5% in 76 (80%), 5-9% in 15 (16%) and 10-19% in 4 (4%) patients. In Group B, BM blasts were <5% in 26 (85%), 5-9% in 2 (6%) and 10-19% in 2 (6%; Table 2) patients. Among patients with BM blasts <5%, abnormal cytogenetics were observed in 20 (30%) patients in Group A and 6 (30%) in Group B. Median KPS score prior to transplant was 90 in both Group A (range: 50-100) and Group B (range: 70-100). HCT-CI scores were 0-1 in 42%, 2-3 in 41%, and ≥4 in 16% of patients. Donor types included matched unrelated (MUD; 58%), matched sibling (MSD; 25%), mismatched unrelated (MMUD; 7%), haploidentical (Hapolo; 9%), and cord blood (1%). RIC was used in 99 patients (73%) and MAC in 36 (26%). Specifically, 17 (13%) patients received busulfan-based MAC, 15 (12%) received cyclophosphamide with total body irradiation (Cy-TBI) MAC, 21 (16%) received busulfan-based RIC, 64 (49%) received melphalan-based RIC, 9 (7%) received Fludarabine-Cy-TBI based RIC (Flu/Cy/TBI), and 4 (3%) received other regimens. GVHD prophylaxis was methotrexate-based in 84 patients (64%) and PTCy-based in 39 (30%). The median donor age was 30 years (range 13-73), and 57% of donors were male (Table 2). Among the 39 patients who received PTCy, 21 (54%) patients received stem cells from MUD, 12 (30%) from Haplo, 5 (13%) from MMUS and 1 (3%) from MSD. In the same group, RIC was used in 35 (90%) and MAC in 4 (10%) patients. Post-transplant survival and risk factors Among 138 patients, 68 (49%) had died at the time of censoring. The median follow-up duration was 71 months (range, 3-212). The median time from diagnosis to ASCT was 11 months (range: 0-201). The median OS from the time of initial diagnosis was 67 months (range, 8-239), and the median PTSwas 54 months (range: 0-212), with 1-, 3-, and 5-year PTS rates of 74%, 57%, and 48%, respectively (supplementary table 1). The median RFS was 34 months, with 1-, 3-, and 5-year RFS rates of 66%, 49%, and 42%, respectively (supplementary table 1). Group B patients had significantly worse PTS compared with those in group A (16 vs 95 months; P=0.01; HR 1.9, 95% CI 1.2-3.2; figure 1). In group A, the median PTS was 95 months (range, 0-212), with 1-, 3-, and 5-year PTS rates of 79%, 62%, and 54%, respectively. The median RFS was 54 months, with 1-, 3-, and 5-year RFS rates of 71%, 52%, and 46%, respectively (supplementary figure 1). In univariate survival analysis (UVA), BM blasts at the time of ASCT of <5%, 5-9%, and 10-19% were associated with median OS of 164, 69 (HR 1.8), and 13.5 (HR 4.3) months, respectively (p=0.01, figure 2a). Group A Patients who received two or more lines of cytotoxic therapies had inferior PTS (median 11 months) compared to those treated with one line (69 months; HR 3.6) or those who did not receive any cytotoxic drugs (95 months; HR 4.6; p=0.01; supplementary figure 2a). Additional factors associated with inferior PTS included abnormal cytogenetics at diagnosis (p=0.02; HR 1.9, 95% CI 1.06-3.6; figure 2c), and pre-ASCT exposure to HMA (p=0.03; HR 2.03, 95% CI 1.02-4; figure 3a). PTS was longest in Group A patients who received busulfan-based MAC and shortest in those who received Flu/Cy/TBI-based conditioning (median not reached vs 22 months; p=0.2; supplementary figure 3A). Compared to other GVHD prophylaxis strategies, PTCy was associated with a shorter median PTS (22 vs 107 months; p=0.1; figure 4a) and significantly higher cumulative incidence of relapse (p=0.02; figure 4b). Group A patients who are in complete morphologic remission (CR) at day100 post-ASCT had better PTS (median 164 vs 18 months; p=0.01, HR 0.2, 95% CI: 0.1–0.5; figure 5a). PTSwas worse in patients with aGVHD grade 2-4 compared to those with grade ≤1 aGVHD (median 21 vs 164 months; p=0.01; HR 2.6, 95% CI: 1.4–4.9; figure 6a). Chronic GVHD of any grade confers better PTS (median 164 vs 26 months; p= 0.01; HR 0.3, 95% CI: 0.1–0.6; figure 6b). We found no association between donor type, age, gender and PTS. Multivariable Cox regression model including BM blasts at the time of ASCT and at day-100 post-ASCT, number chemotherapeutic lines before transplant, cytogenetics at diagnosis and day-100 post-ASCT, pre-ASCT exposure to HMA, conditioning regimen, GVHD prophylaxis, acute GVHD and chronic GVHD identified abnormal cytogenetics at day 100 (p=0.01, HR 5.4, 95% CI: 2.1–13) and aGVHD grade 2-4 (p=0.01, HR 3.6, 95% CI: 1.5–8) to be independently associated with inferior PTS.Conversely, BM blasts <5% at the time of ASCT (p=0.03, HR 0.4, 95% CI: 0.1–0.9) and at day-100 post-ASCT (P=0.08, HR 0.3, 95% CI: 0.8–1.1), and chronic GVHD of any grade (p=0.01, HR 0.2, 95% CI: 0.1–0.5) were independently associated with improved PTS in group A patients. In group B, median PTS was 16 months (range 0-204), with a 1-, 3- and 5-year PTS rates of 57%, 39% and 29%, respectively. The RFS was 10 months, with a 1-, 3- and 5-year RFS rates of 49%, 38% and 29%, respectively. In univariate analysis, relapse at day-100 post ASCT correlated with worse PTS (median 11 vs 39 months; p=0.01, HR 5.3, 95%CI 1.4-20; figure 5b). PTS was longer with BM blasts of 5% at the time of ASCT (median 30 vs 18 months), although this difference was not statistically significant (p=0.4; figure 2b). In group B patients, cGVHD of any grade led to a better PTS (30 vs 18 months; p=0.5). In multivariable analysis, BM blasts at day-100 post-ASCT (p=0.01, HR 0.09, 95%CI 0.01-0.4) was independently associated with better PTS. At last follow-up, 46 patients (44%) in group A and 22 (64%) in group B were dead. The causes of death were relapse/non-relapse related in 36/64% in group A and 39/61% in group B, respectively (supplementary table 1). The most frequent documented causes of non-relapse mortality were GVHD in 12 (30%) patients, infections in 9 (23%), bleeding in 4 (10%) and solid organ malignancy in 4 (10%). Graft-versus-host disease and Graft-versus-host disease-free, relapse-free survival Grade ≥2 aGVHD and moderate to severe cGVHD occurred in 44% and 30% of Group A patients and in 47% and 26% of Group B patients, respectively. Skin was the most frequently involved organ in aGVHD, occurring in 60 (43%) patients, followed by the gut in 44 (32%) and the liver in 18 (13%). Similarly, for cGVHD, skin was most frequently involved occurring in 31 (22%) patients, followed by ocular and oral in 20 (20% each), lung in 22 (16%), liver in 20 (15%), and gut in 10 (7%). In Group A, the median GRFS was 239 days, with 1-, 3-, and 5-year GRFS rates of 41%, 21%, and 16%, respectively (supplementary table 1). MAC was associated with significantly better GRFS compared to RIC (median 622 vs 206 days; p=0.02, HR 2.1, 95% CI: 1.2–3.7; supplementary figure 4a). In contrast, abnormal cytogenetics (median 130 vs 282 days; p=0.01, HR 2.6, 95% CI: 1.3–5.4; supplementary figures 4c) and BM blasts of > 5% at day-100 post-ASCT (median 94 vs 245 days; p=0.01, HR 4.3, 95% CI: 1.5–12.0, supplementary figure 4e) were significantly associated with shorter GRFS. All these variables remained statistically significant in multivariable analysis (p=0.01 in all instances). In Group B, the median GRFS was 169 days, with 1-, 3-, and 5-year GRFS rates of 30%, 16%, and 16%, respectively. Mixed chimerism at day 100 post-ASCT was associated with significantly shorter GRFS compared to full donor chimerism (median 97 vs 195 days; p=0.01, HR 5.3, 95% CI: 1.3–22.0). Similarly, BM blasts of > 5% at day-100 demonstrated a trend toward inferior GRFS (97 vs 195 days; p=0.05, HR 2.8, 95% CI: 0.9–8.9; supplementary figure 4f). DISCUSSION The natural history of CMML is characterized by disease progression and eventual BT, with ASCT considered the only potentially curative therapy.( 3 , 5 , 8 ). In existing retrospective studies, post-transplant outcomes are influenced by HCT-CI, abnormal karyotype, ASXL1 and NRAS mutation, BM blasts and remission status pre-ASCT( 11 , 16 ). In this study, we assessed the impact of baseline characteristics, peri transplant disease status, day-100 assessment, choice of conditioning regimen as well as occurrence of GVHD on PTS. We reported a median PTS of 95 and 16 months with 3-/5-year PTS rates of 62/54% and 39/29% in group A and B, respectively. These outcomes are consistent with findings from the previous Mayo Clinic study( 11 ) and the 3- and 5-year PTS rates of 55% and 50% reported by Gagelmann et al .( 10 ). Similar to earlier reports, PTS was better in patients who had ASCT while in chronic phase supporting the consideration of early transplant( 11 , 32 ). On the other hand, a large retrospective study including 1114 CMML patients have shown shorter PTS in lower risk CMML and no PTS benefit in higher risk CMML patients in comparison to those who did not undergo ASCT.( 12 ) These discrepancies highlight the need for prospective studies to better define the optimal timing of ASCT. Nonetheless, our findings support considering ASCT before BT, particularly in high-risk patients, a group in which the benefits of transplantation have been consistently reported.( 10 – 12 , 33 , 34 ) The BM blast percentages, both at the time of ASCT and at day-100 post-ASCT were independently associated with better PTS. This aligns with findings from Symeonidis et al, in a study of 513 patients with CMML in EBMT database, where achievement of CR, and by inference lower blast percentage, were associated with better PTS.( 32 ) Similarly, in a proposed CMML transplant scoring system, BM blasts > 2% was found to be independently and adversely prognostic and assigned the highest point value.( 16 ) These studies, along with our previous study and the newly proposed BLAST score (circulating blast)( 27 ) demonstrate the dynamic prognostic significance of blast quantity at different stage of CMML and could guide choice of treatment strategies. However, in patients who already experienced BT before transplant, the difference in PTS between those with BM blasts at the time ASCT of < 5% (30 months) and those with BM blasts of ≥ 5% (18 months) did not reach statistical significance. Although ASCT remains a key part of treatment of CMML patient who had BT, the outcome following BT is grim( 6 ) and our study only found PTS benefits and better GRFS in patients who achieved CR at day-100 post-ASCT. Full donor chimerism at day-100 also offers better GFRS but no impact on PTS in this cohort. The busulfan-based MAC regimen was associated with favorable PTS and GRFS in CMML patients who underwent transplant prior to BT. Some studies have reported similar trends while other studies reported no significant difference.( 12 , 35 – 38 ). Given the dual benefit of improved PTS and better GRFS reported in this study, MAC may be a preferred option over RIC when clinically feasible. PTCy has emerged as a new standard of care in ASCT practice based on large randomized clinical trials results demonstrating better GRFS( 22 , 23 ). However, in our study, PTCy correlated with higher cumulative incidence of relapse and numerically shorter PTS which aligns with the results from recently reported real world experiences( 24 , 39 ). In addition, normal cytogenetics at day-100 post-ASCT, grade 0–1 aGVHD (compared with ≥ 2) and any grade of cGVHD were associated with improved outcomes. These findings are consistent with those reported in a cohort of 177 CMML patients from three HSCT registries in Japan.( 40 ) Notably, we found no association between donor type, age and gender. Exposure to HMA before ASCT and receiving two or more lines of chemotherapies were only significant on UVA and not MVA, suggesting they may not be an independent predictor of PTS. We acknowledge that our study is subjected to limitations inherent to retrospective analyses, including but not limited to missing data, heterogeneity arising from data collected across multiple centers, and the long duration over which the data were collected. Additional studies are needed to confirm these findings. In summary, this study suggests that ASCT offers survival benefits in CMML patients, especially if done before BT. We highlighted the prognostic impact of BM blast percentages at the time of ASCT and at Day-100 post-ASCT, with better PTS observed in patients with < 5% BM blasts. MAC regimen and occurrence of Chronic GVHD were also associated with better PTS while abnormal cytogenetics at day-100 post ASCT and aGVHD predict inferior PTS. The use of PTCy conferred higher incidence of relapse. These insights can inform risk-adapted transplant strategies and underscore the need for prospective studies to refine patient selection criteria and guide transplant timing. Declarations Acknowledgements: We acknowledge the Mayo Clinic’s department of hematology for providing us with patient data which is not available commercially. Author Contributions: AT and AS designed the study, collected data, performed analyses, and drafted the paper. 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Abedin S, Lian Q, Martens MJ, Al Malki MHDMM, Elmariah H, Gooptu M, et al. Superiority of Post-Transplant Cyclophosphamide-Based Graft Versus Host Disease (GvHD) Prophylaxis in Patients 70 Years and Older: A BMT CTN 1703 Post-Hoc Analysis. Blood. 2024;144:1042. Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. Journal of Clinical Oncology. 2017;35(11):1154-61. Bolanos-Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, et al. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med. 2023;388(25):2338-48. Broers AEC, de Jong CN, Bakunina K, Hazenberg MD, van Marwijk Kooy M, de Groot MR, et al. Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial. Blood Adv. 2022;6(11):3378-85. Hassan K, Baranwal A, Mangaonkar AA, Hefazi M, Matin A, Litzow MR, et al. Risk of Relapse Post Reduced Intensity Conditioning Allogeneic Stem Cell Transplant in Patients with High-Risk Myeloid Neoplasms Based on Ptcy Vs TAC/MTX Gvhd Prophylaxis. Blood. 2024;144(Supplement 1):4918-. McGowan-Jordan J, Hastings R, Moore S. Re: International System for Human Cytogenetic or Cytogenomic Nomenclature (ISCN): Some Thoughts, by T. Liehr. Cytogenetic and Genome Research. 2021;161(5):225-6. Elena C, Gallì A, Such E, Meggendorfer M, Germing U, Rizzo E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128(10):1408-17. Tefferi A, Fathima S, Abdelmagid M, Alsugair A, Aperna F, Rezasoltani M, et al. BLAST: A Globally Applicable and Molecularly Versatile Survival Model for Chronic Myelomonocytic Leukemia. Blood. 2025. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912-9. Karnofsky DA BJ. The clinical evaluation of chemotherapeutic agents in cancer. Evaluation of chemotherapeutic agents. New York: Columbia University Press. 1949:191-205. Kharfan-Dabaja MA, Kumar A, Ayala E, Aljurf M, Nishihori T, Marsh R, et al. Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy. Transplantation and Cellular Therapy. 2021;27(8):642-9. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-8. Symeonidis A, van Biezen A, de Wreede L, Piciocchi A, Finke J, Beelen D, et al. Achievement of complete remission predicts outcome of allogeneic haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation. Br J Haematol. 2015;171(2):239-46. Patnaik MM, Wassie EA, Padron E, Onida F, Itzykson R, Lasho TL, et al. Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome. Blood Cancer J. 2015;5(1):e270. Liu HD, Ahn KW, Hu ZH, Hamadani M, Nishihori T, Wirk B, et al. Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia. Biol Blood Marrow Transplant. 2017;23(5):767-75. Eissa H, Gooley TA, Sorror ML, Nguyen F, Scott BL, Doney K, et al. Allogeneic Hematopoietic Cell Transplantation for Chronic Myelomonocytic Leukemia: Relapse-Free Survival Is Determined by Karyotype and Comorbidities. Biology of Blood and Marrow Transplantation. 2011;17(6):908-15. Wedge E, Hansen JW, Dybedal I, Creignou M, Ejerblad E, Lorenz F, et al. Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia: Clinical and Molecular Genetic Prognostic Factors in a Nordic Population. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy. 2021;27(12):991.e1-.e9. Abtract: Alyamany R, Alnughmush A, Remberger M, Michelis F, Law AD, Lam W, et al. Strength to Endure: Superiority of MAC over RIC in Patients <65 Years Undergoing Stem Cell Transplantation Using ATG-Ptcy-CSA for Gvhd Prophylaxis. Blood. 2024;144:4863. Scott BL, Pasquini MC, Fei M, Fraser R, Wu J, Devine SM, et al. Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes-Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial. Transplant Cell Ther. 2021;27(6):483 e1- e6. Nagler A, Labopin M, Dholaria B, Wu D, Choi G, Aljurf M, et al. Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation. Transplant Cell Ther. 2022;28(2):86 e1- e8. Itonaga H, Iwanaga M, Aoki K, Aoki J, Ishiyama K, Ishikawa T, et al. Impacts of graft-versus-host disease on outcomes after allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia: A nationwide retrospective study. Leukemia Research. 2016;41:48-55. Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations Yes there is potential conflict of interest. MVS: Research funding to the institution from AbbVie, Astellas, Celgene, KURA Oncology, and Marker Therapeutics. Supplementary Files Supplementarytable1OSGRFSRFS.pdf Supplementary table 1 Supplementaryfigures.pdf Supplementary figure 1, Supplementary figure 2, Supplementary figure 3, Supplementary figure 4, Supplementary figure 5 Table1Baselinecharacteristics.docx Table 1: clinical and laboratory characteristics at the time of initial diagnosis of chronic myelomonocytic leukemia in 138 Mayo Clinic patients who subsequently underwent allogeneic stem cell transplantation stratified by pre-transplant history of blast transformation. Table2BMTclinicalandlabdata.docx Table 2: clinical and laboratory characteristics of 138 Mayo Clinic patients with chronic myelomonocytic leukemia at the time allogeneic stem cell transplantation stratified by pre-transplant history of blast transformation. Cite Share Download PDF Status: Published Journal Publication published 06 Oct, 2025 Read the published version in Blood Cancer Journal → Version 1 posted Editorial decision: revise 02 Jul, 2025 Review # 2 received at journal 20 Jun, 2025 Reviewer # 2 agreed at journal 18 Jun, 2025 Review # 1 received at journal 09 Jun, 2025 Reviewer # 1 agreed at journal 03 Jun, 2025 Reviewers invited by journal 03 Jun, 2025 Editor assigned by journal 27 May, 2025 Submission checks completed at journal 27 May, 2025 First submitted to journal 26 May, 2025 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. 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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-6753879","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":466025188,"identity":"c08c7476-6c52-4e8b-8977-5a55a83c13ff","order_by":0,"name":"Ayalew 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07:07:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":940319,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6753879/v1/788c411f-d094-4f68-9ae3-1e10a1a639a3.pdf"},{"id":84219654,"identity":"53eed103-04a2-4654-a47c-a31ddb294cca","added_by":"auto","created_at":"2025-06-09 11:23:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":41434,"visible":true,"origin":"","legend":"Supplementary table 1","description":"","filename":"Supplementarytable1OSGRFSRFS.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6753879/v1/f0b5a3321aee39ca064b87c1.pdf"},{"id":84219690,"identity":"a9748b04-d41b-4f47-b2cb-752d18bf1018","added_by":"auto","created_at":"2025-06-09 11:24:01","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":299968,"visible":true,"origin":"","legend":"Supplementary figure 1, Supplementary figure 2, Supplementary figure 3, Supplementary figure 4, Supplementary figure 5","description":"","filename":"Supplementaryfigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6753879/v1/b6ce6f556b7ea21f3135e255.pdf"},{"id":84219694,"identity":"4c16929e-4f1c-4792-85d4-3b777917d0d2","added_by":"auto","created_at":"2025-06-09 11:24:01","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":25588,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 1:\u003c/strong\u003e clinical and laboratory characteristics at the time of initial diagnosis of chronic myelomonocytic leukemia in 138 Mayo Clinic patients who subsequently underwent allogeneic stem cell transplantation stratified by pre-transplant history of blast transformation.\u003c/p\u003e","description":"","filename":"Table1Baselinecharacteristics.docx","url":"https://assets-eu.researchsquare.com/files/rs-6753879/v1/12459cd029c98423a17a08b7.docx"},{"id":84219652,"identity":"4eef76d7-7ccb-4a8c-afe1-b4eaca2f7582","added_by":"auto","created_at":"2025-06-09 11:23:55","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":24507,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 2:\u003c/strong\u003e clinical and laboratory characteristics of 138 Mayo Clinic patients with chronic myelomonocytic leukemia at the time allogeneic stem cell transplantation stratified by pre-transplant history of blast transformation.\u003c/p\u003e","description":"","filename":"Table2BMTclinicalandlabdata.docx","url":"https://assets-eu.researchsquare.com/files/rs-6753879/v1/483281dd10c4eb86a6ed81a1.docx"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential conflict of interest.\nMVS: Research funding to the institution from AbbVie, Astellas, Celgene, KURA Oncology, and Marker Therapeutics.","formattedTitle":"Allogeneic stem cell transplantation in chronic myelomonocytic leukemia: analysis of post-transplant survival and risk factors in 138 Mayo Clinic patients","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eChronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by persistent monocytosis in the peripheral blood and features overlapping those of myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDS).(\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) The clinical course of CMML is heterogenous, with a recognized risk of progression to acute myeloid leukemia (AML), referred to as blast transformation (BT).(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) BT occurs in 15\u0026ndash;30% of cases and is associated with poor prognosis, with report of median overall survival (OS) as short as 6 months following transformation, and a five-year survival rate of only about 6%. (\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eConventional therapies, including hydroxyurea and hypomethylating agents (HMA), may provide symptomatic benefits but are not curative.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Allogeneic stem cell transplantation (ASCT) remains the only potentially curative treatment option.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) While the long-term benefits of ASCT in selected patients are well recognized, the risk of transplant-related complications and non-relapse mortality makes patient selection critical.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) Typically, younger patients have shown better outcomes(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e); however, this presents a challenge in CMML patients as the median age at diagnosis is between 70 and 74 years.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn our previous study (N\u0026thinsp;=\u0026thinsp;70), we demonstrated survival benefit from ASCT, particularly when performed in chronic phase disease compared to undergoing ASCT after BT (5-year OS of 51% vs 19%).(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) The same study also showed that the median graft versus host disease (GVHD)-free relapse-free survival (GRFS) was only 7 months, underscoring both the benefit and morbidity associated with ASCT. The median age in this study, as in most other ASCT studies, was 58 years.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) In the particular study, only abnormal karyotype was adversely prognostic.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Gagelmann et al. found that an \u003cem\u003eASXL1\u003c/em\u003e and/or \u003cem\u003eNRAS\u003c/em\u003e-mutated genotype, bone marrow (BM) blasts\u0026thinsp;\u0026gt;\u0026thinsp;2%, and high hematopoietic cell transplantation comorbidity index (HCT-CI) were independently predictive of worse post-transplant survival (PTS).(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eReduced-intensity conditioning (RIC) regimens and alternative donor sources such as haploidentical and umbilical cord blood donor, have expanded ASCT eligibility to a broader patient population.(\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) Despite these advances, the decision to proceed with ASCT in CMML remains challenging. Compared with myeloablative conditioning (MAC) regimen, RIC offers the benefit of lower non-relapse mortality but it may be associated with a higher rate of relapse.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) However, some CMML studies reported no differences in OS between MAC and RIC. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Implementation of post-transplant cyclophosphamide (PTCy) has improved the GRFS in phase III trials (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). However, recent reports observed a tendency toward increased risk of relapse with the use of PTCy.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThere is lack of prospective data analyzing these risk factors to guide patient selection. In addition, CMML-specific retrospective studies are few, and significant gaps still exist in our understanding of the prognostic impact of various clinical, cytogenetic, molecular risk factors and choice of conditioning regimen in the setting of ASCT for CMML. The aim of the current study was to evaluate PTS and identify risk factors influencing transplant outcomes in CMML patients who underwent ASCT.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis retrospective study was conducted under a Mayo Clinic IRB-approved minimal risk protocol. We identified patients with CMML who underwent ASCT between 1995 and 2024 using the Mayo Clinic electronic databases, which included patients from Mayo Clinic Rochester, Florida, and Arizona, USA. Clinical, laboratory, and outcome data were extracted from these databases. CMML diagnosis and categorization (CMML-1/CMML-2) and myelodysplastic(MD-CMML)/myeloproliferative(MP-CMML) subtypes were made according to the International Consensus Classification (ICC) and confirmed by central review.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Mutations/variants in genes associated with myeloid neoplasms were screened by next-generation sequencing in accordance with institutional protocols for clinical use. Cytogenetic findings were reported using the International System for Human Cytogenetic Nomenclature.(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCMML patients were classified into two groups based on the timing of blast transformation. Group A included patients who underwent ASCT while in chronic phase CMML while Group B included those who had ASCT following BT. Promonocytes were included in the blasts count. Risk stratification was performed using the updated CMML-specific prognostic scoring system that includes molecular abnormalities (CPSS-mol) and BLAST scores, as defined by Elena \u003cem\u003eet al\u003c/em\u003e. and Tefferi \u003cem\u003eet al\u003c/em\u003e., respectively.(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) The BLAST score uses a point-based system, and it includes circulating blasts\u0026thinsp;\u0026ge;\u0026thinsp;2% (1 point), leukocytes\u0026thinsp;\u0026ge;\u0026thinsp;13 x 10⁹/L (1 point), and severe (2 points) or moderate (1 point) anemia. Based on the total score, patients were stratified into low-risk (0 points), intermediate-risk (1 point), and high-risk (2\u0026ndash;4 points)(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). HCT-CI and Karnofsky performance status (KPS) score were calculated as described by Sorror et al and Karnofsky et al, respectively.(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePlatelet engraftment was defined as the first of three consecutive days with a platelet count of \u0026ge;\u0026thinsp;20,000/\u0026micro;L in the absence of platelet transfusion for seven consecutive days.(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) Neutrophil engraftment was defined as the first of three successive days with an absolute neutrophil count\u0026thinsp;\u0026ge;\u0026thinsp;500/\u0026micro;L after the post-transplantation nadir.(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) Donor chimerism was classified according to the American society for transplantation and cellular therapy (ASTCT) criteria: full donor chimerism if myeloid and lymphoid lineages were \u0026gt;\u0026thinsp;95%, mixed or partial chimerism if 5\u0026ndash;95%, and lost/absent donor chimerism if\u0026thinsp;\u0026lt;\u0026thinsp;5%.(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePTS was measured from the date of ASCT to death from any cause. Relapse-free survival (RFS) was defined as the time from ASCT to relapse or death from any cause, whichever occurred first. GRFS was defined as the time from ASCT to grade 3\u0026ndash;4 acute GVHD (aGVHD), systemic therapy-requiring chronic GVHD (cGVHD), relapse, or death, whichever occurred first.(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) Non-relapse mortality (NRM) was defined as time from ASCT to death from any cause without a prior relapse or progression. Cumulative incidence of relapse and NRM were estimated using the cumulative incidence method for competing risks. Death and relapse were considered competing risks for relapse and NRM, respectively. Median followed up calculated using reverse kaplan-meier method.\u003c/p\u003e \u003cp\u003eFrequencies and percentages were used to summarize categorical variables, while medians and ranges were used for quantitative variables. Time-to-event analyses were performed using Kaplan-Meier estimates, intergroup comparisons assessed with the log-rank test and hazard ratios (HR) were calculated using cox proportional hazards regression. Multivariable analyses (MVA) to identify the impact of risk factors were performed using the Cox proportional hazards regression model. All statistical analyses were conducted using JMP Pro 18.0.0 software (SAS Institute, Cary, NC, USA).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003ePresenting clinical and laboratory characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 138 Mayo Clinic patients (62% male) with CMML who underwent ASCT were included in the study (Table 1). The median ages at the time of diagnosis and at the time ASCT were 62 (range 18-75) and 63 (range 18-76) years, respectively. Group A comprised 104 patients, while Group B consisted of 34 patients. All patients underwent transplantation between 1995 and 2024. At initial diagnosis, CMML-1/CMML-2 and MD-CMML/MP-CMML phenotypes were seen in 78%/22% and 54%/46% of patients, respectively. Among patients with available molecular data (n=86), the most frequent mutations/variants were \u003cem\u003eASXL1\u003c/em\u003e (56%), \u003cem\u003eTET2\u003c/em\u003e (44%), and \u003cem\u003eSRSF2\u003c/em\u003e (38%). Abnormal karyotypes were observed in 31% of patients. CPSS-Mol risk categories at diagnosis were low (17%), intermediate-1 (11%), intermediate-2 (40%), and high (32%). BLAST score categories were low risk (38%), intermediate risk (44%), and high risk (18%). Compared to Group B, patients in Group A were more likely to present with RUNX1 mutations/variants (24% vs 0%; p=0.01) and more often received pre-transplant HMA (64% vs 36%; p=0.01). In contrast, Group B patients more frequently received intensive chemotherapy prior to ASCT (79% vs 13%; p=0.01). Other clinical and laboratory characteristics are summarized in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePre- and Peri-Transplant Treatment and Disease Status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHMAs were used as first-line CMML-directed therapy in 75 (60%) patients, intensive chemotherapy in 29 (23%), other therapies (including hydroxyurea, erythropoietin agonist, danazol, ruxolitinib, or clinical trials) in 16 (13%), and no treatment in 5 (4%; Table 1). Twenty-nine (21%) patients received two or more lines of cytotoxic therapies.\u003c/p\u003e\n\u003cp\u003eBone marrow assessment at the time of ASCT was available in 126 (91%) patients. In Group A, BM blasts were \u0026lt;5% in 76 (80%), 5-9% in 15 (16%) and 10-19% in 4 (4%) patients. In Group B, BM blasts were \u0026lt;5% in 26 (85%), 5-9% in 2 (6%) and 10-19% in 2 (6%; Table 2) patients. Among patients with BM blasts \u0026lt;5%, abnormal cytogenetics were observed in 20 (30%) patients in Group A and 6 (30%) in Group B. Median KPS score prior to transplant was 90 in both Group A (range: 50-100) and Group B (range: 70-100). HCT-CI scores were 0-1 in 42%, 2-3 in 41%, and ≥4 in 16% of patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDonor types included matched unrelated (MUD; 58%), matched sibling (MSD; 25%), mismatched unrelated (MMUD; 7%), haploidentical (Hapolo; 9%), and cord blood (1%). RIC was used in 99 patients (73%) and MAC in 36 (26%). Specifically, 17 (13%) patients received busulfan-based MAC, 15 (12%) received cyclophosphamide with total body irradiation (Cy-TBI) MAC, 21 (16%) received busulfan-based RIC, 64 (49%) received melphalan-based RIC, 9 (7%) received Fludarabine-Cy-TBI based RIC (Flu/Cy/TBI), and 4 (3%) received other regimens. GVHD prophylaxis was methotrexate-based in 84 patients (64%) and PTCy-based in 39 (30%). The median donor age was 30 years (range 13-73), and 57% of donors were male (Table 2). Among the 39 patients who received PTCy, 21 (54%) patients received stem cells from MUD, 12 (30%) from Haplo, 5 (13%) from MMUS and 1 (3%) from MSD. In the same group, RIC was used in 35 (90%) and MAC in 4 (10%) patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePost-transplant survival and risk factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 138 patients, 68 (49%) had died at the time of censoring. The median follow-up duration was 71 months (range, 3-212). The median time from diagnosis to ASCT was 11 months (range: 0-201). The median OS from the time of initial diagnosis was 67 months (range, 8-239), and the median PTSwas 54 months (range: 0-212), with 1-, 3-, and 5-year PTS rates of 74%, 57%, and 48%, respectively (supplementary table 1). The median RFS was 34 months, with 1-, 3-, and 5-year RFS rates of 66%, 49%, and 42%, respectively (supplementary table 1). Group B patients had significantly worse PTS compared with those in group A (16 vs 95 months; P=0.01; HR 1.9, 95% CI 1.2-3.2; figure 1).\u003c/p\u003e\n\u003cp\u003eIn group A, the median PTS was 95 months (range, 0-212), with 1-, 3-, and 5-year PTS rates of 79%, 62%, and 54%, respectively. The median RFS was 54 months, with 1-, 3-, and 5-year RFS rates of 71%, 52%, and 46%, respectively (supplementary figure 1). In univariate survival analysis (UVA), BM blasts at the time of ASCT of \u0026lt;5%, 5-9%, and 10-19% were associated with median OS of 164, 69 (HR 1.8), and 13.5 (HR 4.3) months, respectively (p=0.01, figure 2a).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGroup A Patients who received two or more lines of cytotoxic therapies had inferior PTS (median 11 months) compared to those treated with one line (69 months; HR 3.6) or those who did not receive any cytotoxic drugs (95 months; HR 4.6; p=0.01; supplementary figure 2a). Additional factors associated with inferior PTS included abnormal cytogenetics at diagnosis (p=0.02; HR 1.9, 95% CI 1.06-3.6; figure 2c), and pre-ASCT exposure to HMA (p=0.03; HR 2.03, 95% CI 1.02-4; figure 3a).\u003c/p\u003e\n\u003cp\u003ePTS was longest in Group A patients who received busulfan-based MAC and shortest in those who received Flu/Cy/TBI-based conditioning (median not reached vs 22 months; p=0.2; supplementary figure 3A). Compared to other GVHD prophylaxis strategies, PTCy was associated with a shorter median PTS (22 vs 107 months; p=0.1; figure 4a) and significantly higher cumulative incidence of relapse (p=0.02; figure 4b). Group A patients who are in complete morphologic remission (CR) at day100 post-ASCT had better PTS (median 164 vs 18 months; p=0.01, HR 0.2, 95% CI: 0.1–0.5; figure 5a). PTSwas worse in patients with aGVHD grade 2-4 compared to those with grade ≤1 aGVHD (median 21 vs 164 months; p=0.01; HR 2.6, 95% CI: 1.4–4.9; figure 6a). Chronic GVHD of any grade confers better PTS (median 164 vs 26 months; p= 0.01; HR 0.3, 95% CI: 0.1–0.6; figure 6b). We found no association between donor type, age, gender and PTS.\u003c/p\u003e\n\u003cp\u003eMultivariable Cox regression model including BM blasts at the time of ASCT and at day-100 post-ASCT, number chemotherapeutic lines before transplant, cytogenetics at diagnosis and day-100 post-ASCT, pre-ASCT exposure to HMA, conditioning regimen, GVHD prophylaxis, acute GVHD and chronic GVHD identified abnormal cytogenetics at day 100 (p=0.01, HR 5.4, 95% CI: 2.1–13) and aGVHD grade 2-4 (p=0.01, HR 3.6, 95% CI: 1.5–8) to be independently associated with inferior PTS.Conversely, BM blasts \u0026lt;5% at the time of ASCT (p=0.03, HR 0.4, 95% CI: 0.1–0.9) and at day-100 post-ASCT (P=0.08, HR 0.3, 95% CI: 0.8–1.1), and chronic GVHD of any grade (p=0.01, HR 0.2, 95% CI: 0.1–0.5) were independently associated with improved PTS in group A patients.\u003c/p\u003e\n\u003cp\u003eIn group B, median PTS was 16 months (range 0-204), with a 1-, 3- and 5-year\u0026nbsp;PTS rates\u0026nbsp;of 57%, 39% and 29%, respectively. The RFS was 10 months, with a 1-, 3- and 5-year RFS rates of 49%, 38% and 29%, respectively. In univariate analysis, relapse at day-100 post ASCT correlated with worse\u0026nbsp;PTS\u0026nbsp;(median 11 vs 39 months; p=0.01, HR 5.3, 95%CI 1.4-20; figure 5b).\u0026nbsp;PTS was longer with BM blasts of \u0026lt;5% compared to BM blasts \u003cu\u003e\u0026gt;\u003c/u\u003e5% at the time of ASCT (median 30 vs 18 months), although this difference was not statistically significant (p=0.4; figure 2b). In group B patients, cGVHD of any grade led to a better\u0026nbsp;PTS\u0026nbsp;(30 vs 18 months; p=0.5). In multivariable analysis, BM blasts at day-100 post-ASCT (p=0.01, HR 0.09, 95%CI 0.01-0.4) was independently associated with better PTS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt last follow-up, 46 patients (44%) in group A and 22 (64%) in group B were dead. The causes of death were relapse/non-relapse related in 36/64% in group A and 39/61% in group B, respectively (supplementary table 1). The most frequent documented causes of non-relapse mortality were GVHD in 12 (30%) patients, infections in 9 (23%), bleeding in 4 (10%) and solid organ malignancy in 4 (10%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGraft-versus-host disease and Graft-versus-host disease-free, relapse-free survival\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGrade ≥2 aGVHD and moderate to severe cGVHD occurred in 44% and 30% of Group A patients and in 47% and 26% of Group B patients, respectively. Skin was the most frequently involved organ in aGVHD, occurring in 60 (43%) patients, followed by the gut in 44 (32%) and the liver in 18 (13%). Similarly, for cGVHD, skin was most frequently involved occurring in 31 (22%) patients, followed by ocular and oral in 20 (20% each), lung in 22 (16%), liver in 20 (15%), and gut in 10 (7%).\u003c/p\u003e\n\u003cp\u003eIn Group A, the median GRFS was 239 days, with 1-, 3-, and 5-year GRFS rates of 41%, 21%, and 16%, respectively (supplementary table 1). MAC was associated with significantly better GRFS compared to RIC (median 622 vs 206 days; p=0.02, HR 2.1, 95% CI: 1.2–3.7; supplementary figure 4a). In contrast, abnormal cytogenetics (median 130 vs 282 days; p=0.01, HR 2.6, 95% CI: 1.3–5.4; supplementary figures 4c) and BM blasts of \u003cu\u003e\u0026gt;\u003c/u\u003e5% at day-100 post-ASCT (median 94 vs 245 days; p=0.01, HR 4.3, 95% CI: 1.5–12.0, supplementary figure 4e) were significantly associated with shorter GRFS. All these variables remained statistically significant in multivariable analysis (p=0.01 in all instances).\u003c/p\u003e\n\u003cp\u003eIn Group B, the median GRFS was 169 days, with 1-, 3-, and 5-year GRFS rates of 30%, 16%, and 16%, respectively. Mixed chimerism at day 100 post-ASCT was associated with significantly shorter GRFS compared to full donor chimerism (median 97 vs 195 days; p=0.01, HR 5.3, 95% CI: 1.3–22.0). Similarly, BM blasts of \u003cu\u003e\u0026gt;\u003c/u\u003e5% at day-100 demonstrated a trend toward inferior GRFS (97 vs 195 days; p=0.05, HR 2.8, 95% CI: 0.9–8.9; supplementary figure 4f).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe natural history of CMML is characterized by disease progression and eventual BT, with ASCT considered the only potentially curative therapy.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In existing retrospective studies, post-transplant outcomes are influenced by HCT-CI, abnormal karyotype, \u003cem\u003eASXL1\u003c/em\u003e and \u003cem\u003eNRAS\u003c/em\u003e mutation, BM blasts and remission status pre-ASCT(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In this study, we assessed the impact of baseline characteristics, peri transplant disease status, day-100 assessment, choice of conditioning regimen as well as occurrence of GVHD on PTS.\u003c/p\u003e \u003cp\u003eWe reported a median PTS of 95 and 16 months with 3-/5-year PTS rates of 62/54% and 39/29% in group A and B, respectively. These outcomes are consistent with findings from the previous Mayo Clinic study(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) and the 3- and 5-year PTS rates of 55% and 50% reported by Gagelmann \u003cem\u003eet al\u003c/em\u003e.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Similar to earlier reports, PTS was better in patients who had ASCT while in chronic phase supporting the consideration of early transplant(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). On the other hand, a large retrospective study including 1114 CMML patients have shown shorter PTS in lower risk CMML and no PTS benefit in higher risk CMML patients in comparison to those who did not undergo ASCT.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) These discrepancies highlight the need for prospective studies to better define the optimal timing of ASCT. Nonetheless, our findings support considering ASCT before BT, particularly in high-risk patients, a group in which the benefits of transplantation have been consistently reported.(\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe BM blast percentages, both at the time of ASCT and at day-100 post-ASCT were independently associated with better PTS. This aligns with findings from Symeonidis et al, in a study of 513 patients with CMML in EBMT database, where achievement of CR, and by inference lower blast percentage, were associated with better PTS.(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) Similarly, in a proposed CMML transplant scoring system, BM blasts\u0026thinsp;\u0026gt;\u0026thinsp;2% was found to be independently and adversely prognostic and assigned the highest point value.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) These studies, along with our previous study and the newly proposed BLAST score (circulating blast)(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) demonstrate the dynamic prognostic significance of blast quantity at different stage of CMML and could guide choice of treatment strategies.\u003c/p\u003e \u003cp\u003eHowever, in patients who already experienced BT before transplant, the difference in PTS between those with BM blasts at the time ASCT of \u0026lt;\u0026thinsp;5% (30 months) and those with BM blasts of \u0026ge;\u0026thinsp;5% (18 months) did not reach statistical significance. Although ASCT remains a key part of treatment of CMML patient who had BT, the outcome following BT is grim(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) and our study only found PTS benefits and better GRFS in patients who achieved CR at day-100 post-ASCT. Full donor chimerism at day-100 also offers better GFRS but no impact on PTS in this cohort.\u003c/p\u003e \u003cp\u003eThe busulfan-based MAC regimen was associated with favorable PTS and GRFS in CMML patients who underwent transplant prior to BT. Some studies have reported similar trends while other studies reported no significant difference.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36 CR37\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Given the dual benefit of improved PTS and better GRFS reported in this study, MAC may be a preferred option over RIC when clinically feasible. PTCy has emerged as a new standard of care in ASCT practice based on large randomized clinical trials results demonstrating better GRFS(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). However, in our study, PTCy correlated with higher cumulative incidence of relapse and numerically shorter PTS which aligns with the results from recently reported real world experiences(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). In addition, normal cytogenetics at day-100 post-ASCT, grade 0\u0026ndash;1 aGVHD (compared with \u0026ge;\u0026thinsp;2) and any grade of cGVHD were associated with improved outcomes. These findings are consistent with those reported in a cohort of 177 CMML patients from three HSCT registries in Japan.(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e) Notably, we found no association between donor type, age and gender. Exposure to HMA before ASCT and receiving two or more lines of chemotherapies were only significant on UVA and not MVA, suggesting they may not be an independent predictor of PTS.\u003c/p\u003e \u003cp\u003eWe acknowledge that our study is subjected to limitations inherent to retrospective analyses, including but not limited to missing data, heterogeneity arising from data collected across multiple centers, and the long duration over which the data were collected. Additional studies are needed to confirm these findings. In summary, this study suggests that ASCT offers survival benefits in CMML patients, especially if done before BT. We highlighted the prognostic impact of BM blast percentages at the time of ASCT and at Day-100 post-ASCT, with better PTS observed in patients with \u0026lt;\u0026thinsp;5% BM blasts. MAC regimen and occurrence of Chronic GVHD were also associated with better PTS while abnormal cytogenetics at day-100 post ASCT and aGVHD predict inferior PTS. The use of PTCy conferred higher incidence of relapse. These insights can inform risk-adapted transplant strategies and underscore the need for prospective studies to refine patient selection criteria and guide transplant timing.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe acknowledge the Mayo Clinic’s department of hematology for providing us with patient data which is not available commercially.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eAT and AS designed the study, collected data, performed analyses, and drafted the paper. EM, MA, SF, NG and MP designed the study, collected data and performed analyses. MY and AB contributed to data abstraction and drafted the paper. JF, AM, ML, HM, LS, JP, WH, MS, SC, NP, NK, LP, AM, SK, MI, EA, JS and HA provided patient care.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting Interests:\u0026nbsp;\u003c/strong\u003eMVS: Research funding to the institution from AbbVie, Astellas, Celgene, KURA Oncology, and Marker Therapeutics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eData Availability Statement:\u0026nbsp;\u003c/strong\u003eThe datasets generated during and/or analyzed during the current study are not publicly available due to Mayo Clinic patients’ confidentiality but are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eArber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka H-M, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. 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Blood Adv. 2022;6(11):3378-85.\u003c/li\u003e\n\u003cli\u003eHassan K, Baranwal A, Mangaonkar AA, Hefazi M, Matin A, Litzow MR, et al. Risk of Relapse Post Reduced Intensity Conditioning Allogeneic Stem Cell Transplant in Patients with High-Risk Myeloid Neoplasms Based on Ptcy Vs TAC/MTX Gvhd Prophylaxis. Blood. 2024;144(Supplement 1):4918-.\u003c/li\u003e\n\u003cli\u003eMcGowan-Jordan J, Hastings R, Moore S. Re: International System for Human Cytogenetic or Cytogenomic Nomenclature (ISCN): Some Thoughts, by T. Liehr. Cytogenetic and Genome Research. 2021;161(5):225-6.\u003c/li\u003e\n\u003cli\u003eElena C, Gall\u0026igrave; A, Such E, Meggendorfer M, Germing U, Rizzo E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128(10):1408-17.\u003c/li\u003e\n\u003cli\u003eTefferi A, Fathima S, Abdelmagid M, Alsugair A, Aperna F, Rezasoltani M, et al. BLAST: A Globally Applicable and Molecularly Versatile Survival Model for Chronic Myelomonocytic Leukemia. Blood. 2025.\u003c/li\u003e\n\u003cli\u003eSorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912-9.\u003c/li\u003e\n\u003cli\u003eKarnofsky DA BJ. The clinical evaluation of chemotherapeutic agents in cancer. Evaluation of chemotherapeutic agents. New York: Columbia University Press. 1949:191-205.\u003c/li\u003e\n\u003cli\u003eKharfan-Dabaja MA, Kumar A, Ayala E, Aljurf M, Nishihori T, Marsh R, et al. Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy. Transplantation and Cellular Therapy. 2021;27(8):642-9.\u003c/li\u003e\n\u003cli\u003eHoltan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-8.\u003c/li\u003e\n\u003cli\u003eSymeonidis A, van Biezen A, de Wreede L, Piciocchi A, Finke J, Beelen D, et al. Achievement of complete remission predicts outcome of allogeneic haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation. Br J Haematol. 2015;171(2):239-46.\u003c/li\u003e\n\u003cli\u003ePatnaik MM, Wassie EA, Padron E, Onida F, Itzykson R, Lasho TL, et al. Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome. Blood Cancer J. 2015;5(1):e270.\u003c/li\u003e\n\u003cli\u003eLiu HD, Ahn KW, Hu ZH, Hamadani M, Nishihori T, Wirk B, et al. Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia. Biol Blood Marrow Transplant. 2017;23(5):767-75.\u003c/li\u003e\n\u003cli\u003eEissa H, Gooley TA, Sorror ML, Nguyen F, Scott BL, Doney K, et al. Allogeneic Hematopoietic Cell Transplantation for Chronic Myelomonocytic Leukemia: Relapse-Free Survival Is Determined by Karyotype and Comorbidities. Biology of Blood and Marrow Transplantation. 2011;17(6):908-15.\u003c/li\u003e\n\u003cli\u003eWedge E, Hansen JW, Dybedal I, Creignou M, Ejerblad E, Lorenz F, et al. Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia: Clinical and Molecular Genetic Prognostic Factors in a Nordic Population. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy. 2021;27(12):991.e1-.e9.\u003c/li\u003e\n\u003cli\u003eAbtract: Alyamany R, Alnughmush A, Remberger M, Michelis F, Law AD, Lam W, et al. Strength to Endure: Superiority of MAC over RIC in Patients \u0026lt;65 Years Undergoing Stem Cell Transplantation Using ATG-Ptcy-CSA for Gvhd Prophylaxis. Blood. 2024;144:4863.\u003c/li\u003e\n\u003cli\u003eScott BL, Pasquini MC, Fei M, Fraser R, Wu J, Devine SM, et al. Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes-Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial. Transplant Cell Ther. 2021;27(6):483 e1- e6.\u003c/li\u003e\n\u003cli\u003eNagler A, Labopin M, Dholaria B, Wu D, Choi G, Aljurf M, et al. Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation. Transplant Cell Ther. 2022;28(2):86 e1- e8.\u003c/li\u003e\n\u003cli\u003eItonaga H, Iwanaga M, Aoki K, Aoki J, Ishiyama K, Ishikawa T, et al. Impacts of graft-versus-host disease on outcomes after allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia: A nationwide retrospective study. Leukemia Research. 2016;41:48-55.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"blood-cancer-journal","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bcj","sideBox":"Learn more about [Blood Cancer Journal](http://www.nature.com/bcj/)","snPcode":"41408","submissionUrl":"https://mts-bcj.nature.com/cgi-bin/main.plex","title":"Blood Cancer Journal","twitterHandle":"@bloodcancerjnl","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"CMML, Bone marrow transplantation, Blast transformation, GVHD, post-transplant cyclophosphamide, PTC","lastPublishedDoi":"10.21203/rs.3.rs-6753879/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6753879/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAllogeneic stem cell transplant (ASCT) remains the only curative option in chronic myelomonocytic leukemia (CMML). We retrospectively analyzed 138 CMML patients who underwent ASCT at the Mayo Clinic. Patients who transitioned to ASCT while in chronic phase (Group A) displayed superior post-transplant survival (PTS), compared to those in whom ASCT was performed after blast transformation (BT; Group B) (median 95 vs. 16 months; p=0.01). In Group A, PTS was superior in patients with \u0026lt;5% bone marrow (BM) blasts at time of ASCT (median 164 vs. 13.5 months; p=0.01). Other predictors of superior PTS included day-100 BM blast \u0026lt;5% or normal cytogenetics (median 164 vs 18 months; p=0.01) or presence of chronic graft-versus-host-disease (GVHD; median 164 vs. 26 months; p=0.01). Pre-ASCT hypomethylating agent exposure (HR=2.03; p=0.03), and receiving more than one line of pre-ASCT chemotherapy (p=0.01) predicted inferior PTS. In multivariable analysis, predictors of superior GVHD-free and relapse-free survival (GRFS) included the use myeloablative conditioning and the absence of morphologically or cytogenetically apparent disease at day-100. The use of post-transplant cyclophosphamide (PTCy) was associated with higher cumulative incidence of relapse (p=0.02) and numerically inferior PTS (p=0.1). Group B patients also appeared to benefit from achieving BM blast \u0026lt;5% at time of ASCT (p=0.4) as well as at day-100 (p=0.01), in terms of PTS, while full chimerism and normal cytogenetics at day-100 were associated with superior GRFS. These observations support the value of ASCT in CMML, especially if performed prior to BT and in the presence of \u0026lt;5% BM blasts at time of ASCT. Additionally, the observed detrimental impact of PTCy requires additional studies to confirm and investigate the underlying mechanisms.\u003c/p\u003e","manuscriptTitle":"Allogeneic stem cell transplantation in chronic myelomonocytic leukemia: analysis of post-transplant survival and risk factors in 138 Mayo Clinic patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-09 11:23:25","doi":"10.21203/rs.3.rs-6753879/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-07-02T14:44:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-20T08:33:14+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-06-18T13:38:19+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-09T17:06:18+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-06-03T19:30:47+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-06-03T18:15:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-27T11:58:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-27T11:58:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Blood Cancer Journal","date":"2025-05-26T22:20:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"blood-cancer-journal","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bcj","sideBox":"Learn more about [Blood Cancer Journal](http://www.nature.com/bcj/)","snPcode":"41408","submissionUrl":"https://mts-bcj.nature.com/cgi-bin/main.plex","title":"Blood Cancer Journal","twitterHandle":"@bloodcancerjnl","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3dfde286-9f6d-4cc8-bdcd-4c7797b8436c","owner":[],"postedDate":"June 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":49477119,"name":"Health sciences/Diseases/Haematological diseases/Haematological cancer/Myelodysplastic syndrome"},{"id":49477120,"name":"Health sciences/Diseases/Haematological diseases/Haematological cancer/Myeloproliferative disease"}],"tags":[],"updatedAt":"2025-10-07T07:07:18+00:00","versionOfRecord":{"articleIdentity":"rs-6753879","link":"https://doi.org/10.1038/s41408-025-01359-w","journal":{"identity":"blood-cancer-journal","isVorOnly":false,"title":"Blood Cancer Journal"},"publishedOn":"2025-10-06 04:00:00","publishedOnDateReadable":"October 6th, 2025"},"versionCreatedAt":"2025-06-09 11:23:25","video":"","vorDoi":"10.1038/s41408-025-01359-w","vorDoiUrl":"https://doi.org/10.1038/s41408-025-01359-w","workflowStages":[]},"version":"v1","identity":"rs-6753879","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6753879","identity":"rs-6753879","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}