Relapse strategies following first allogeneic hematopoietic stem cell transplantation in adult T-cell lymphoblastic disease  

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Allogeneic hematopoietic stem cell transplantation (allo-HCT) represents a potentially curative option for high-risk or relapsed/refractory (r/r) disease; however, outcomes following relapse after allo-HCT remain poorly defined due to limited real-world data. This retrospective study evaluated post-transplant outcomes, relapse patterns, and salvage strategies in adult T-ALL/LBL patients treated at a single academic center. Methods : We conducted an analysis of 42 adult patients diagnosed and treated with T-ALL/LBL between 2007 and 2025. Survival outcomes, including overall survival (OS), progression-free survival (PFS), relapse-related mortality (RRM), and non-relapse mortality (NRM), were assessed. Kaplan–Meier estimates, Cox proportional hazards models, and competing-risk analyses were applied to evaluate outcomes and prognostic factors following first allo-HCT. Results : Among confirmed T-ALL/LBL patients, 35 (83%) underwent allo-HCT, either in first complete remission (CR1) with high-risk features or in ≥CR2. Median age at transplantation was 32 years. After allo-HCT, median OS was 18.9 months and twelve patients (34%) relapsed. Patients typically relapsed early, with a median time to relapse of 5.3 months. All patients who relapsed post-allo-HCT ultimately died, predominantly from progressive disease. Salvage strategies, including nelarabine-based chemotherapy, donor lymphocyte infusions, daratumumab, experimental agents, or second allo-HCT, resulted in only transient responses. No significant differences in OS were observed between T-ALL and T-LBL or between frontline and salvage allo-HCT. Conclusions : Currently available salvage therapies for T-ALL/LBL patients who relapse after allo-HCT have limited efficacy. This results in fatal outcomes. The findings presented here underscore the urgent need for novel targeted and cellular therapies, such as CAR T-cell based therapies, and support the enrollment of r/r patients into prospective clinical trials. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction T-cell lymphoblastic disease is an uncommon disorder in adult patients and is outnumbered by B-cell precursor leukemias. 1,2 T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) are aggressive malignancies derived from immature T-cell progenitors. 3 T-cell lineage disease accounts for roughly 25% of adult acute lymphoblastic leukemia/lymphoma. 4,5 The World Health Organization (WHO) considers T-ALL and T-LBL as one entity with T-ALL characterized by extensive bone marrow involvement and T-LBL by a mass lesion and less than 25% blasts in the bone marrow. 6,7 T-ALL and T-LBL may be differentiated by distinct immunophenotypic distributions and transcriptomic signatures. 7 The immunophenotype of T-ALL cells reflects the different stages of thymic T-cell differentiation and provides the basis for the subclassification by the German Multicenter Study Group for Adult ALL (GMALL) and European Group for the Immunological Classification of Leukemias (EGIL). 8,9 T-cell lymphoblastic disease is seen more frequently in adolescence and young adulthood and may include hyperleukocytosis, large mediastinal masses and a higher incidence of central nervous system (CNS) involvement compared to B-ALL upon diagnosis. 10 First-line therapy for acute lymphoblastic disease usually comprises different sequences. Patients should be treated within clinical trials and standardized treatment protocols, e.g. in accordance with GMALL recommendations, and minimal residual disease (MRD) monitored thoroughly throughout the course of disease. Although highly aggressive, 5-year overall survival (OS) rates for T-cell lymphoblastic disease are reported to be superior when compared with outcomes from its B-cell counterpart. 4,9,11–13 Regardless, long-term outcomes remain unsatisfactory, with a 5-year OS of only 30-50%. 11,14,15 Although potentially curable by allogeneic hematopoietic stem cell transplantation (allo-HCT), outcomes for relapsed/refractory (r/r) T-ALL/LBL in adults are dismal and the management of r/r disease remains a daunting task. 16 Curative-intent allo-HCT is considered the most effective but also the most toxic anti-leukemic therapy. 9,17 High-risk patients and those experiencing r/r disease may benefit from this procedure. 2,18,19 Thus, allo-HCT is typically recommended for adults with T-ALL/LBL in second or later complete remission (>CR2), but may be offered to patients in first CR (CR1) who also have high-risk features (e.g. age, leukocyte count, immunophenotype, cytogenetics, time to CR, extramedullary disease such as CNS involvement, or MRD). 20 Myeloablative conditioning, especially that which is total body irradiation (TBI)-based, may cause considerable extramedullary toxicity but has improved the outcomes of allo-HCT in T-ALL/LBL. 21 Adult T-ALL/LBL lacks evidence-based treatment algorithms after relapse following allo-HCT. Therefore, we retrospectively evaluated survival outcomes and relapse patterns in a single-center real-world cohort of adult patients, aiming to identify clinically relevant patterns of relapse and clinically relevant prognostic factors. Methods This retrospective, single-center study was performed according to good clinical practice guidelines and approved by the University Medical Center Goettingen Institutional Review Board (UMG 15/6/25) and complied with the Declaration of Helsinki. We enrolled adult patients (aged ≥18 years) with a diagnosis of T-ALL/LBL, confirmed by reference pathologists. These patients underwent allo-HCT at the University Medical Center Goettingen stem cell transplantation program between January 2007 and May 2025 or were deemed transplant-ineligible or deceased prior to intended allo-HCT. Patients eligible for allo-HCT included high-risk patients in CR1 and any patient in ≥CR2 or later relapse. Eligible patients were followed until the 3 rd of December 2025. Allo-HCT recipients and related or unrelated donors were typed at HLA-loci A, B, C, DR, and DQ. At least 9/10 matched loci at HLA A, B, C, D, and DQ was considered eligible for transplantation. Acute and chronic graft-versus-host disease (GvHD) was graded based on the pattern and severity of organ involvement using established international criteria. 22,23 Patients were identified through the institutional transplant database. Patients with missing data on the primary endpoint (i.e., survival status) were excluded. All analyses were performed on a complete-case basis for each endpoint. Clinical and demographic variables were systematically extracted from electronic medical records. These included age, sex, and cytogenetic and molecular risk features where available. Genetic data were included in exploratory analyses when appropriate. Primary outcomes were progression-free survival (PFS) and overall survival (OS) following allo-HCT. Secondary endpoints included cumulative incidence of non-relapse mortality (NRM) and relapse/progressive disease post-allo-HCT as well as associations between clinical or transplant-related factors and survival outcomes. PFS was defined as the time from allo-HCT to disease relapse/progressive disease or death from any cause. OS was calculated as the interval from the date of allo-HCT to the date of death or last follow-up (FU). NRM was defined as death due to complications other than relapse following allo-HCT. Statistical analyses were conducted using Python (version 3.11) and R (version 4.5.2). PFS and OS were calculated using the Kaplan–Meier estimator, and differences between groups (e.g., by disease subtype) were compared using the log-rank test. Prognostic factors for OS were examined using univariate and multivariate Cox proportional hazards regression. Relapse-related mortality (RRM) and NRM were analyzed in a competing risks framework using the Fine and Gray subdistribution hazard model. Results are presented as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). A two-sided p-value < 0.05 was considered statistically significant. Results Clinical and transplant characteristics Overall, we identified 42 consecutive adult patients diagnosed and treated with T-ALL/LBL at our academic center between 2007 and 2025 of whom 35 patients (83%) were subjected to allo-HCT (Figure 1) . Patient and disease characteristics are shown in Table 1 . The overall cohort was predominantly male (76%) and young, with the median age at time of diagnosis being 29 (18-68) years old (Table 1) . The most common sub-entities were Pre-T-ALL (37%) and T-LBL (31%) in the transplanted subgroup (n = 35). The median time from diagnosis to allo-HCT was 7.6 months (range: 3.9 – 58.4 months) and the median age at allo-HCT was 32 years (Table 1) . In regard to remission status at 1 st allo-HCT, 20 patients showed MRD positivity, 5 patients were MRD negative, and MRD status pre-transplant was not available in 10 cases. Nineteen patients (54%) received a front-line allo-HCT for presenting high-risk features or being refractory to induction therapy. The remaining 16 patients (46%) underwent salvage allo-HCT to achieve >CR2. Twenty-four patients (69%) were treated within a myeloablative TBI-based conditioning regimen, and the most common stem cell source was matched unrelated (MUD) in 54% of cases (Table 1) . Clinical outcomes of allo-HCT recipients The median OS (mOS) for the total cohort (n = 42) from diagnosis was 65.2 months (Figure 2A) . The median follow-up from diagnosis was 33.2 months (range: 6.1 – 206.8 months) in the transplant cohort and the median OS (mOS) was 18.9 months from allo-HCT (Table 2) . The mOS from diagnosis for patients who received allo-HCT was 65.2 months versus (vs.) not reached for patients who did not undergo allo-HCT (p = 0.432; Figure 2B, Supplemental table 3) . Twelve transplanted patients (34%) eventually relapsed following 1 st allo-HCT with a median time to relapse of 5.3 months (range: 0.4 – 25.1 months), demonstrating an early pattern of relapse within the first year after allo-HCT. At last follow-up, 19 patients (54.3%) were alive and 16 patients (45.7%) had died (Table 2) . The most frequent cause of death was r/r disease (n = 10; 62.5%). By the end of the study, all patients with relapse post-allo-HCT had died. In total, 18 patients died, and 24 were censored (Supplemental table 1) . Acute GvHD (aGvHD) occurred in 17 patients (49%) and chronic GvHD (cGvHD) in 10 patients (29%), with one subject succumbing to grade IV° pulmonary cGvHD (Table 2) . Finally, the mOS for patients receiving a frontline allo-HCT (n = 19) vs. salvage allo-HCT (n = 16) was not reached for frontline vs. 36 months for salvage allo-HCT, respectively (p = 0.105; Figure 2C) . For all patients, median OS was shorter in T-LBL (42.2 months) compared to T-ALL (not reached), suggesting earlier mortality in the T-LBL group (Supplemental table 2) . However, no statistically significant difference in OS was observed between the two groups in the pairwise log-rank test (p = 0.829; Figure 2D ). The mortality rate was higher in the T-LBL group (50%) than in the T-ALL group (39.3%). Relapse strategies following relapse post-allo-HCT-1 As highlighted above, twelve transplanted patients eventually relapsed post-allo-HCT-1 (Figure 3) . The majority of r/r T-ALL/LBL patients (6; 50%) received a nelarabine-containing salvage therapy, while one patient received nelarabine with cyclophosphamide (Table 3) . T-cells are particularly sensitive to nelarabine, which is approved for r/r T-ALL/LBL following at least two chemotherapy-containing lines of therapy. Two patients (16.7%) received a reinduction therapy in accordance with current GMALL guidelines. Five patients (41.7%) were treated with donor lymphocyte infusions (DLI) with a median number of four infusions (range: 1 – 5) (Table 3) . DLI is a widely used post-relapse intervention intended to enhance the graft-versus-leukemia (GvL) effect. Preemptive DLI is initiated in response to early indicators of relapse, such as MRD or loss of complete donor chimerism (LOC), while therapeutic DLI is administered after overt hematologic relapse, often combined with systemic therapy aimed at reducing tumor burden and allowing for GvL effect. In our analyzed patient cohort, one patient received preemptive DLI (#11, Figure 4 ) and four therapeutic DLI (patients #1, #7, #18, #30). Response rates to DLI were only transient (Figure 4) . Patients #1 and #31 underwent a second allo-HCT to regain remission after the 1 st allo-HCT failure (Table 3) . Patient #1 received an allo-HCT from matched unrelated donor (MUD) while patient #31 underwent haploidentical allo-HCT (mMRD). The median time from relapse after allo-HCT-1 to death in the r/r T-ALL/LBL cohort was 3.4 months (Table 1) . Notably, one patient (#12) was treated with the experimental oral compound nelfinavir for two months and four patients with the anti-CD38 antibody daratumumab. Patients treated with these showed a limited duration of response in all analyzed cases. Factors influencing survival In univariable Cox regression analysis, neither age nor disease type (T-ALL vs. T-LBL) was significantly associated with OS. In the cumulative incidence analysis (Supplemental figure 1) , RRM and NRM exhibited distinct temporal patterns. While NRM initially exceeded RRM for a short time, the curves crossed at approximately twelve months post-diagnosis, after which RRM became the predominant cause of death. Competing risks analysis using the Fine-Gray model revealed no statistically significant differences in the cumulative incidence of either RRM or NRM between T-ALL and T-LBL. However, due to the limited sample size, these findings should be interpreted with caution. A trend toward higher NRM in T-ALL (HR: 1.58; 95% CI, 0.32–7.93) and lower RRM (HR: 0.78; 95% CI, 0.22–2.85) was observed, suggesting potential biological differences that warrant further investigation in larger cohorts. Discussion Beyond the dismal prognosis observed after relapse post-allo-HCT, our data further emphasize the biological aggressiveness of adult T-cell lymphoblastic disease and the narrow therapeutic window available once standard treatment strategies fail. The predominance of early relapses within the first year after transplantation suggests that disease biology rather than transplant-related factors alone may be the major driver of treatment failure. This observation supports the notion that improved pre- and post-transplant disease control, including more sensitive MRD-guided interventions, is critical to improving long-term outcomes. Relapsed or refractory T-cell lymphoblastic disease represents a significant unmet medical need, in both children and adults. Outcomes for adult T-ALL/LBL patients with r/r disease after allo-HCT remain particularly poor compared with newly diagnosed, treatment-naïve patients. Indeed, relapse after allo-HCT was uniformly fatal in our cohort with the majority succumbing to progressive disease, often combined with infectious complications following allo-HCT. This underscores the need for more effective and less toxic treatment strategies for acquired or intrinsic disease resistance in this hard-to-treat population. In line with our single-center, retrospective study the OS of adult r/r ALL disease is estimated at <7% at five years. 16 Still, allo-HCT is considered the most effective anti-leukemic therapy for adults with ALL 17 and 19/35 (54.3%) T-ALL/LBL patients transplanted in our center, whether in the front-line or salvage setting, still enjoy disease control and are potentially cured. However, the limited efficacy of currently available salvage strategies in our cohort underscores the lack of a standardized approach for patients relapsing after allo-HCT-1. The use of nelarabine alone or in combination with other cytotoxic agents like cyclophosphamide has shown encouraging response rates in pediatric r/r T-cell lymphoblastic disease. 24 Nevertheless, these pediatric-inspired protocols resulted only in short-term disease control for the r/r adult population after allo-HCT-1 from our center. B- and T-cell lineage ALL are considered to be rather insusceptible to DLI treatment following molecular relapse or LOC or overt hematologic relapse with measurable blasts after allo-HCT. 25 Five patients from our institution received DLI. On the one hand, this second cellular therapy was able to restore donor chimerism (DC) in some cases, on the other hand the desired graft-versus-leukemia effect was only short-lived. Recently, CD38 has emerged as a novel target for immunotherapy in T-cell lymphoblastic disease with daratumumab demonstrating preclinical activity in human xenograft models. 26 Subsequently, the DELPHINUS study suggested that daratumumab may be an effective bridging strategy to allo-HCT in children and young adults, including in T-cell lineage ALL. 27 In contrast, the role of daratumumab in r/r adult patients, specifically after allo-HCT, remains poorly investigated, with reports limited to smaller single-center experiences. 28 We suggest to assess robust CD38 expression of T-ALL blasts in relapse. Nevertheless, our single-center experience with daratumumab was disappointing with limited responses. At the same time, it should be considered that the four daratumumab-treated patients were already severely ill and experiencing rapid disease progression when the anti-CD38 antibody was administered. Nelfinavir was developed as an antiretroviral compound licensed for the treatment of human immunodeficiency virus (HIV) and is being investigated as an anti-cancer drug. Recently, nelfinavir was shown to suppress T-ALL cell viability in vitro and in a transgenic mouse model, highlighting its potential role as a novel therapeutic candidate for the management of T-cell lymphoblastic disease. 29 Experimental targeting of cellular stress pathways using oral nelfinavir 1250mg twice daily demonstrated temporary restoration of donor chimerism in a heavily pretreated young r/r T-ALL patient, supporting its biological activity in vivo . However, the brevity of response highlights the need for combination strategies and reinforces the concept that monotherapy approaches are unlikely to achieve durable disease control in this setting. Moreover, chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of r/r B-cell ALL resulting in impressive response and survival rates. 30–36 This success has inspired the development of autologous T-cell therapy against T-cell malignancies as well. Currently, the putative role of CAR T-cell therapy in T-cell disease is being investigated intensively, including as a bridging strategy to allo-HCT consolidation. One major challenge for CAR T-cells in T-cell lymphoblastic disease is the lack of specific target antigens. 37 Thus, fratricide in which CAR-T expressing the target antigen, e.g. CD5 or CD7, are eliminated by fellow CAR T-cells, has proven to be a significant obstacle. 37–40 Potentially fatal T-cell aplasia, in which healthy T-cells expressing the target antigens are killed by the CAR T-construct, and the risk of product contamination by malignant lymphoblasts represent other challenges on the path to safe and effective CAR T-cells against T-ALL/LBL. 41–43 Several strategies are implemented to overcome fratricide and to mitigate T-cell aplasia. For instance, targeting specific T-cell subgroups to avoid aplasia, genetic knock-out of target antigens in CAR T-cells, the use of protein expression blockers, natural killer cells as carriers of CARs or even the use of allogeneic T-cells to circumnavigate product contamination are being explored. 44 Various phase 1 and 2 trials have tested the safety and efficacy of CAR-T cells targeting either CD5 or CD7 in T-ALL/LBL with mixed results. 45–52 This study is limited by its retrospective, single-center design and small sample size, which restrict statistical power and generalizability. Incomplete molecular profiling and heterogeneous salvage treatments further limit definitive conclusions regarding optimal therapeutic sequencing. Nevertheless, the strength of this analysis lies in its detailed real-world characterization of relapse patterns and post-transplant outcomes in a rare adult malignancy. In summary, our findings confirm that relapse after allo-HCT-1 in adult T-ALL/LBL remains almost uniformly fatal with currently available therapies. New targeted approaches and patient-tailored therapy regimens are urgently warranted to raise the cure rate for r/r T-ALL/LBL patients that are either not eligible for allo-HCT or who relapse post-allo-HCT and otherwise display dismal prognosis. Future improvements will depend on earlier intervention, biologically informed patient stratification, and the integration of innovative targeted and cellular therapies within prospective clinical trials. Declarations Data availability statement The datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request. Disclosures M.M. has participated in advisory boards from Janssen and Stemline and has received honoraria not related to this manuscript from AbbVie, AstraZeneca, Gilead, Janssen, and Lilly; reports travel support from AbbVie, Gilead, Incyte, Janssen, Sobi, and Stemline. A.A. reports travel grants from Stemline and Gilead not related to this manuscript. All other authors declare no conflicts of interest. Sources of funding The authors declare no sources of funding. Acknowledgements No acknowledgements. Author contributions M.M. and A.A. conceived the project and provided leadership; M.M., G.W., J.B. E.A., M.L., K.T., J.H., L.I., G.W. and A.A. provided patient data; M.M., J.B., M.L. and A.A. analyzed the data. M.M., J.B. and A.A. wrote the main manuscript text and A.A. prepared the figures. J.H., L.I. and G.W. reviewed and edited the manuscript. All authors approved the final manuscript. References Sucre, O., Pamulapati, S., Muzammil, Z. & Bitran, J. 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Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial. Blood 140 , 321–334 (2022). Zhang, X. et al. Analysis of 60 patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma treated with CD7-targeted chimeric antigen receptor-T cell therapy. Am. J. Hematol. 98 , 1898–1908 (2023). Zhang, M. et al. Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma. Clin. Cancer Res. 28 , 2830–2843 (2022). Zhao, L. et al. Autologous CD7 CAR-T cells generated without T cell pre-selection in pediatric patients with relapsed/refractory T-ALL: A phase I trial. Mol. Ther. J. Am. Soc. Gene Ther. 33 , 2753–2767 (2025). Oh, B. L. Z. et al. Fratricide-resistant CD7-CAR T cells in T-ALL. Nat. Med. 30 , 3687–3696 (2024). Pan, J. et al. Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial. J. Clin. Oncol. 39 , 3340–3351 (2021). Chiesa, R. et al. Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia. N. Engl. J. Med. 389 , 899–910 (2023). Hill, L. C. et al. Enhanced anti-tumor activity of CD5 CAR T cells manufactured with tyrosine kinase inhibitors in patients with relapsed/refractory T-ALL. J. Clin. Oncol. 41 , 7002–7002 (2023). Tables Table 1: Baseline and transplant characteristics of T-ALL/LBL patients. Parameter Allo-HCT recipients, n = 35 (%) All patients, n = 42 (%) Gender (M/F), ratio 27/8, 3.4 32/10, 3.2 Median age at diagnosis, years (range) 31 (18-68) 29 (18-68) Disease subclassification Pro-T-ALL Pre-T-ALL ETP-ALL Cortical (thymic) T-ALL Mature T-ALL T-LBL 1 (2.9) 13 (37.1) 4 (11.4) 5 (14.3) 1 (2.9) 11 (31.4) 1 (2.4) 14 (33.3) 4 (9.5) 7 (16.7) 2 (4.8) 14 (33.3) Bulky disease Yes No 19 (54.3) 16 (45.7) 24 (57.1) 18 (42.9) Induction therapy GMALL Protocol GMALL Elderly ALL-BFM High-risk incl. RT CHOEP (partly), followed by GMALL induction/consolidation Hyper-CVAD 28 (80) 3 (8.6) 1 (2.9) 2 (5.7) 1 (2.9) 34 (81) 4 (9.5) 1 (2.4) 2 (4.8) 1 (2.4) Salvage therapy pre-allo-HCT including Nelarabine Re-induction GMALL Hyper-CVAD Radiation 18 (51.4) 4 (11.4) 1 (2.9) 1 (2.9) - - - - Indication to allo-HCT Frontline allo-HCT Salvage allo-HCT 19 (54.3) 16 (45.7) - - Median time from 1 st diagnosis to allo‐HCT, months (range) 7.6 (3.9 – 58.4) - Median age at allo-HCT, years (range) 32 (19 – 69) - Remission status at allo‐HCT-1 MRD negative MRD positive MRD status unknown 5 (14.3) 20 (57.1) 10 (28.6) - - - Conditioning allo-HCT TBI-Flu (8 Gy) TBI-Cy (12 Gy) FBC-12 BuCy TBI-Eto (12 Gy) FBC-8 10 (28.6) 10 (28.6) 5 (14.3) 5 (14.3) 4 (11.4) 1 (2.9) - - - - - - GvHD prophylaxis with ATG 34 (97) - Source of stem cells MUD MRD mMUD mMRD 19 (54.3) 10 (28.6) 5 (14.3) 1 (2.9) - - - - Median day of hematologic engraftment (range) 16 (10 – 29) - T-ALL/LBL= T-cell acute lymphoblastic leukemia/lymphoma; allo-HCT= allogeneic hematopoietic stem cell transplantation; ETP-ALL= early T-cell precursor ALL; GMALL= German Multicenter Study Group for Adult ALL; BFM= Berlin-Frankfurt-Münster (study group); RT= radiotherapy; CHOEP= cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone/prednisolone; Hyper-CVAD= hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; MRD= minimal residual disease; TBI= total body irradiation; Flu= fludarabine; Gy= Gray; Cy= cyclophosphamide; FBC-12= fludarabine, busulfan, cyclophosphamide with myeloablative busulfan exposure, corresponding to a full-dose regimen; BuCy= busulfan, cyclophosphamide; Eto= etoposide; FBC-8= reduced-intensity fludarabine/busulfan/cyclophosphamide; GvHD= graft-versus-host disease; ATG= anti-thymocyte globulin; MUD= matched unrelated donor; MRD= matched related donor; mMUD= mismatched unrelated donor; mMRD= mismatched related donor. Table 2: Clinical outcomes of allo-HCT recipients. Parameter Allo-HCT patients, n = 35 (%) GvHD aGvHD Grade I Grade II Grade III Grade IV cGvHD Mild Moderate Severe 17 (48.6) 6 (17.1) 10 (28.6) 5 (14.3) 1 (2.9) 10 (28.6) 5 (14.3) 0 5 (14.3) Treatment of GvHD Corticosteroids Alemtuzumab ECP Immunosuppression (CsA/Tacrolimus, MMF) Ruxolitinib 18 (51.4) 2 (5.7) 4 (11.4) 5 (14.3) 2 (5.7) Occurrence of hepatic VOD Yes No 3 (8.6) 32 (91.4) Relapse incidence following allo-HCT 12/35 (34.3) Outcomes for relapse after allo-HCT at last follow-up Alive Dead 0 (0) 12 (100) Median time from allo-HCT to relapse, months (range) 5.3 (0.4 – 25.1) Median time from relapse to death, months (range) (n= 12) 3.4 (0.3 – 12.7) Survival status at last follow-up Alive Dead 19 (54.3) 16 (45.7) Causes of death for all deceased patients (n= 16) r/r disease NRM Infection/sepsis GvHD VOD 10 (62.5) 6 (37.5) 4 (25) 1 (6.3) 1 (6.3) Remission status of surviving patients at last FU CR 19 (100) Median follow-up from diagnosis, months (range) 33.2 (6.1 – 206.8) Median follow-up from allo-HCT, months (range) 18.9 (0.8 – 199.3) allo-HCT= allogeneic hematopoietic stem cell transplantation; aGvHD= acute graft-versus-host disease; cGvHD= chronic graft-versus-host disease; ECP= extracorporeal photopheresis; CsA= cyclosporine A; MMF= mycophenolate mofetil; VOD= veno-occlusive disease; r/r= relapsed/refractory; NRM= non-relapse mortality; FU= follow-up; CR= complete remission. Table 3: Relapse strategy following 1 st allo-HCT. Therapy Relapsed patients, n = 12 (%) Reinduction according to GMALL protocols 2 (16.7) Nelarabine 6 (50) Nelarabine/Cyclophosphamide 1 (8.3) DLI Median number of DLI (range) Preemptive DLI Therapeutic DLI 5 (41.7) 4 (1-5) 1 (8.3) 4 (33.3) 2 nd allo-HCT 2 (16.7) Daratumumab 4 (33.3) Radiation therapy 1 (8.3) Romidepsin 1 (8.3) Nelfinavir 1 (8.3) allo-HCT= allogeneic hematopoietic stem cell transplantation; GMALL= German Multicenter Study Group for Adult ALL; DLI= donor lymphocyte infusion. Additional Declarations No competing interests reported. Supplementary Files 4.SupplementarymaterialTALLLBLMM07.04.2026.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 05 May, 2026 Reviewers agreed at journal 03 May, 2026 Reviewers invited by journal 19 Apr, 2026 Editor assigned by journal 16 Apr, 2026 Submission checks completed at journal 16 Apr, 2026 First submitted to journal 12 Apr, 2026 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-9396037","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625781301,"identity":"ed3cb617-24fe-4924-a243-770312667f3d","order_by":0,"name":"Markus Maulhardt","email":"data:image/png;base64,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","orcid":"","institution":"University of Göttingen","correspondingAuthor":true,"prefix":"","firstName":"Markus","middleName":"","lastName":"Maulhardt","suffix":""},{"id":625781302,"identity":"e8fd736e-639d-48f7-b888-2739abf0f2af","order_by":1,"name":"Gina Westhofen","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Gina","middleName":"","lastName":"Westhofen","suffix":""},{"id":625781304,"identity":"b452db0b-c0db-47fb-8c9e-aad44ba12d90","order_by":2,"name":"Judith Büntzel","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Judith","middleName":"","lastName":"Büntzel","suffix":""},{"id":625781315,"identity":"399c9255-7354-490f-8a18-6863a44012ae","order_by":3,"name":"Enver Aydilek","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Enver","middleName":"","lastName":"Aydilek","suffix":""},{"id":625781317,"identity":"941b0a14-d330-4f0c-98a7-8f94862cf007","order_by":4,"name":"Margarete E. Laage","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Margarete","middleName":"E.","lastName":"Laage","suffix":""},{"id":625781324,"identity":"081389b7-09b5-42f5-8a5f-11f13550c034","order_by":5,"name":"Kristian Thomson","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Kristian","middleName":"","lastName":"Thomson","suffix":""},{"id":625781327,"identity":"4ae6e5e2-04d2-42b4-87ad-babe8b105917","order_by":6,"name":"Justin Hasenkamp","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Justin","middleName":"","lastName":"Hasenkamp","suffix":""},{"id":625781329,"identity":"f714a0e5-6c4b-48ce-8663-9c92fa28d34e","order_by":7,"name":"A. Lena Illert","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"Lena","lastName":"Illert","suffix":""},{"id":625781333,"identity":"17ad7cb5-3536-4998-9e95-3b9bf6872cfa","order_by":8,"name":"Wolfram Jung","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Wolfram","middleName":"","lastName":"Jung","suffix":""},{"id":625781335,"identity":"529fb1a5-c100-46fe-a590-3c74c3413469","order_by":9,"name":"Gerald G. Wulf","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Gerald","middleName":"G.","lastName":"Wulf","suffix":""},{"id":625781338,"identity":"df5e16e9-4f3b-47e1-8165-a73f601a3dbe","order_by":10,"name":"Alexander C. Angleitner","email":"","orcid":"","institution":"University of Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"C.","lastName":"Angleitner","suffix":""}],"badges":[],"createdAt":"2026-04-12 17:38:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9396037/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9396037/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108009525,"identity":"8e4da463-d3f1-4dc6-8b67-a613ade06b63","added_by":"auto","created_at":"2026-04-28 13:10:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":95885,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient selection and treatment allocation.\u003c/strong\u003e\u003cbr\u003e\nAdult patients with T-ALL or T-LBL treated at the University Medical Center Goettingen (UMG) between 2007 and 2025 were identified from the institutional database. A total of 42 patients were included in the analysis and stratified according to their allogeneic hematopoietic cell transplantation (allo-HCT) treatment status.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9396037/v1/749baedb8dfcea215bb16df2.png"},{"id":108009541,"identity":"0377259a-bf4f-4a4a-a19b-b7cb4b2167aa","added_by":"auto","created_at":"2026-04-28 13:10:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":146255,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEstimates of overall survival (OS) from first diagnosis.\u003c/strong\u003e\u003cbr\u003e\n(A) OS of the entire cohort. (B) OS stratified by receipt of allogeneic hematopoietic cell transplantation (allo-HCT). (C) OS according to frontline allo-HCT versus salvage allo-HCT. (D) OS stratified by disease entity (T-ALL vs T-LBL). \u003cem\u003eP\u003c/em\u003e values were calculated using the log-rank test.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9396037/v1/642c4e6da12ce051ad262091.png"},{"id":108009533,"identity":"d3ecf3fa-6abd-434c-b2f6-78745e0c30aa","added_by":"auto","created_at":"2026-04-28 13:10:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":96827,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIndividual patient timelines from first diagnosis. \u003c/strong\u003eBars represent the follow-up time from diagnosis in years. Squares indicate first allogeneic hematopoietic cell transplantation (allo-HCT-1), triangles represent relapse after first allo-HCT, diamonds represent second allo-HCT, and red crosses represent patient death.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9396037/v1/9e5457a977f6c17a7b3d051d.png"},{"id":108009526,"identity":"b43b7467-9ec1-41a1-8167-90e6ec5f5d83","added_by":"auto","created_at":"2026-04-28 13:10:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":70389,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSwimmer plot illustrating individual patient timelines from first relapse after allogeneic hematopoietic cell transplantation (allo-HCT-1).\u003c/strong\u003e\u003cbr\u003e\nBars represent the follow-up time from first relapse in months. These are color-coded according to primary salvage strategy. Blue bars represent nelarabine-based therapy, green bars represent other or experimental therapies, and grey bars represent no salvage therapy. Circles indicate the start of first salvage therapy, vertical bars represent donor lymphocyte infusions (DLI), diamonds represent second allo-HCT, and red crosses represent patient death.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9396037/v1/a9e1a989e916b40800dd74f7.png"},{"id":108010950,"identity":"e09db2f4-e272-451d-a267-403462ca221b","added_by":"auto","created_at":"2026-04-28 13:14:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":760644,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9396037/v1/3e22c16b-94c4-42d6-899d-d30105893d8c.pdf"},{"id":108009609,"identity":"7cf1339b-bad8-4363-b3bb-dd949abc7b4e","added_by":"auto","created_at":"2026-04-28 13:10:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":109149,"visible":true,"origin":"","legend":"","description":"","filename":"4.SupplementarymaterialTALLLBLMM07.04.2026.docx","url":"https://assets-eu.researchsquare.com/files/rs-9396037/v1/532505387a0ee1b97f4ca74f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Relapse strategies following first allogeneic hematopoietic stem cell transplantation in adult T-cell lymphoblastic disease ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eT-cell lymphoblastic disease is an uncommon disorder in adult patients and is outnumbered by B-cell precursor leukemias.\u003csup\u003e1,2\u003c/sup\u003e T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) are aggressive malignancies derived from immature T-cell progenitors.\u003csup\u003e3\u003c/sup\u003e T-cell lineage disease accounts for roughly 25% of adult acute lymphoblastic leukemia/lymphoma.\u003csup\u003e4,5\u003c/sup\u003e The World Health Organization (WHO) considers T-ALL and T-LBL as one entity with T-ALL characterized by extensive bone marrow involvement and T-LBL by a mass lesion and less than 25% blasts in the bone marrow.\u003csup\u003e6,7\u003c/sup\u003e T-ALL and T-LBL may be differentiated by distinct immunophenotypic distributions and transcriptomic signatures.\u003csup\u003e7\u003c/sup\u003e The immunophenotype of T-ALL cells reflects the different stages of thymic T-cell differentiation and provides the basis for the subclassification by the German Multicenter Study Group for Adult ALL (GMALL) and European Group for the Immunological Classification of Leukemias (EGIL).\u003csup\u003e8,9\u003c/sup\u003e T-cell lymphoblastic disease is seen more frequently in adolescence and young adulthood and may include hyperleukocytosis, large mediastinal masses and a higher incidence of central nervous system (CNS) involvement compared to B-ALL upon diagnosis.\u003csup\u003e10\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFirst-line therapy for acute lymphoblastic disease usually comprises different sequences. Patients should be treated within clinical trials and standardized treatment protocols, e.g. in accordance with GMALL recommendations, and minimal residual disease (MRD) monitored thoroughly throughout the course of disease. Although highly aggressive, 5-year overall survival (OS) rates for T-cell lymphoblastic disease are reported to be superior when compared with outcomes from its B-cell counterpart.\u003csup\u003e4,9,11\u0026ndash;13\u003c/sup\u003e Regardless, long-term outcomes remain unsatisfactory, with a 5-year OS of only 30-50%.\u003csup\u003e11,14,15\u003c/sup\u003e Although potentially curable by allogeneic hematopoietic stem cell transplantation (allo-HCT), outcomes for relapsed/refractory (r/r) T-ALL/LBL in adults are dismal and the management of r/r disease remains a daunting task.\u003csup\u003e16\u003c/sup\u003e Curative-intent allo-HCT is considered the most effective but also the most toxic anti-leukemic therapy.\u003csup\u003e9,17\u003c/sup\u003e High-risk patients and those experiencing r/r disease may benefit from this procedure.\u003csup\u003e2,18,19\u003c/sup\u003e Thus, allo-HCT is typically recommended for adults with T-ALL/LBL in second or later complete remission (\u0026gt;CR2), but may be offered to patients in first CR (CR1) who also have high-risk features (e.g. age, leukocyte count, immunophenotype, cytogenetics, time to CR, extramedullary disease such as CNS involvement, or MRD).\u003csup\u003e20\u003c/sup\u003e Myeloablative conditioning, especially that which is total body irradiation (TBI)-based, may cause considerable extramedullary toxicity but has improved the outcomes of allo-HCT in T-ALL/LBL.\u003csup\u003e21\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdult T-ALL/LBL lacks evidence-based treatment algorithms after relapse following allo-HCT. Therefore, we retrospectively evaluated survival outcomes and relapse patterns in a single-center real-world cohort of adult patients, aiming to identify clinically relevant patterns of relapse and clinically relevant prognostic factors.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective, single-center study was performed according to good clinical practice guidelines and approved by the University Medical Center Goettingen Institutional Review Board (UMG 15/6/25) and complied with the Declaration of Helsinki. We enrolled adult patients (aged \u0026ge;18 years) with a diagnosis of T-ALL/LBL, confirmed by reference pathologists. These patients underwent allo-HCT at the University Medical Center Goettingen stem cell transplantation program between January 2007 and May 2025 or were deemed transplant-ineligible or deceased prior to intended allo-HCT. Patients eligible for allo-HCT included high-risk patients in CR1 and any patient in \u0026ge;CR2 or later relapse. Eligible patients were followed until the 3\u003csup\u003erd\u003c/sup\u003e of December 2025. Allo-HCT recipients and related or unrelated donors were typed at HLA-loci A, B, C, DR, and DQ. At least 9/10 matched loci at HLA A, B, C, D, and DQ was considered eligible for transplantation. Acute and chronic graft-versus-host disease (GvHD) was graded based on the pattern and severity of organ involvement using established international criteria.\u003csup\u003e22,23\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003ePatients were identified through the institutional transplant database. Patients with missing data on the primary endpoint (i.e., survival status) were excluded. All analyses were performed on a complete-case basis for each endpoint. Clinical and demographic variables were systematically extracted from electronic medical records. These included age, sex, and cytogenetic and molecular risk features where available. Genetic data were included in exploratory analyses when appropriate. Primary outcomes were progression-free survival (PFS) and overall survival (OS) following allo-HCT. Secondary endpoints included cumulative incidence of non-relapse mortality (NRM) and relapse/progressive disease post-allo-HCT as well as associations between clinical or transplant-related factors and survival outcomes. PFS was defined as the time from allo-HCT to disease relapse/progressive disease or death from any cause. OS was calculated as the interval from the date of allo-HCT to the date of death or last follow-up (FU). NRM was defined as death due to complications other than relapse following allo-HCT.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were conducted using Python (version 3.11) and R (version 4.5.2). PFS and OS were calculated using the Kaplan\u0026ndash;Meier estimator, and differences between groups (e.g., by disease subtype) were compared using the log-rank test. Prognostic factors for OS were examined using univariate and multivariate Cox proportional hazards regression. Relapse-related mortality (RRM) and NRM were analyzed in a competing risks framework using the Fine and Gray subdistribution hazard model. Results are presented as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). A two-sided p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eClinical and transplant characteristics\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOverall, we identified 42 consecutive adult patients diagnosed and treated with T-ALL/LBL at our academic center between 2007 and 2025 of whom 35 patients (83%) were subjected to allo-HCT \u003cstrong\u003e(Figure 1)\u003c/strong\u003e. Patient and disease characteristics are shown in \u003cstrong\u003eTable 1\u003c/strong\u003e. The overall cohort was predominantly male (76%) and young, with the median age at time of diagnosis being 29 (18-68) years old \u003cstrong\u003e(Table 1)\u003c/strong\u003e. The most common sub-entities were Pre-T-ALL (37%) and T-LBL (31%) in the transplanted subgroup (n = 35). The median time from diagnosis to allo-HCT was 7.6 months (range: 3.9 – 58.4 months) and the median age at allo-HCT was 32 years \u003cstrong\u003e(Table 1)\u003c/strong\u003e. In regard to remission status at 1\u003csup\u003est\u003c/sup\u003e allo-HCT, 20 patients showed MRD positivity, 5 patients were MRD negative, and MRD status pre-transplant was not available in 10 cases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNineteen patients (54%) received a front-line allo-HCT for presenting high-risk features or being refractory to induction therapy. The remaining 16 patients (46%) underwent salvage allo-HCT to achieve \u0026gt;CR2. Twenty-four patients (69%) were treated within a myeloablative TBI-based conditioning regimen, and the most common stem cell source was matched unrelated (MUD) in 54% of cases \u003cstrong\u003e(Table 1)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eClinical outcomes of allo-HCT recipients \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe median OS (mOS) for the total cohort (n = 42) from diagnosis was 65.2 months \u003cstrong\u003e(Figure 2A)\u003c/strong\u003e. The median follow-up from diagnosis was 33.2 months (range: 6.1 – 206.8 months) in the transplant cohort and the median OS (mOS) was 18.9 months from allo-HCT\u003cstrong\u003e\u0026nbsp;(Table 2)\u003c/strong\u003e. The mOS from diagnosis for patients who received allo-HCT was 65.2 months versus (vs.) not reached for patients who did not undergo allo-HCT (p = 0.432;\u003cstrong\u003e\u0026nbsp;Figure 2B, Supplemental table 3)\u003c/strong\u003e. Twelve transplanted patients (34%) eventually relapsed following 1\u003csup\u003est\u003c/sup\u003e allo-HCT with a median time to relapse of 5.3 months (range: 0.4 – 25.1 months), demonstrating an early pattern of relapse within the first year after allo-HCT. At last follow-up, 19 patients (54.3%) were alive and 16 patients (45.7%) had died \u003cstrong\u003e(Table 2)\u003c/strong\u003e. The most frequent cause of death was r/r disease (n = 10; 62.5%). By the end of the study, all patients with relapse post-allo-HCT had died. In total, 18 patients died, and 24 were censored \u003cstrong\u003e(Supplemental table 1)\u003c/strong\u003e. Acute GvHD (aGvHD) occurred in 17 patients (49%) and chronic GvHD (cGvHD) in 10 patients (29%), with one subject succumbing to grade IV° pulmonary cGvHD \u003cstrong\u003e(Table 2)\u003c/strong\u003e. Finally, the mOS for patients receiving a frontline allo-HCT (n = 19) vs. salvage allo-HCT (n = 16) was not reached for frontline vs. 36 months for salvage allo-HCT, respectively (p = 0.105;\u003cstrong\u003e\u0026nbsp;Figure 2C)\u003c/strong\u003e. For all patients, median OS was shorter in T-LBL (42.2 months) compared to T-ALL (not reached), suggesting earlier mortality in the T-LBL group \u003cstrong\u003e(Supplemental table 2)\u003c/strong\u003e. However, no statistically significant difference in OS was observed between the two groups in the pairwise log-rank test (p = 0.829; \u003cstrong\u003eFigure 2D\u003c/strong\u003e). The mortality rate was higher in the T-LBL group (50%) than in the T-ALL group (39.3%).\u003c/p\u003e\n\u003cp\u003eRelapse strategies following relapse post-allo-HCT-1\u003c/p\u003e\n\u003cp\u003eAs highlighted above, twelve transplanted patients eventually relapsed post-allo-HCT-1 \u003cstrong\u003e(Figure 3)\u003c/strong\u003e. The majority of r/r T-ALL/LBL patients (6; 50%) received a nelarabine-containing salvage therapy, while one patient received nelarabine with cyclophosphamide \u003cstrong\u003e(Table 3)\u003c/strong\u003e. T-cells are particularly sensitive to nelarabine, which is approved for r/r T-ALL/LBL following at least two chemotherapy-containing lines of therapy. Two patients (16.7%) received a reinduction therapy in accordance with current GMALL guidelines. Five patients (41.7%) were treated with donor lymphocyte infusions (DLI) with a median number of four infusions (range: 1 – 5) \u003cstrong\u003e(Table 3)\u003c/strong\u003e.\u0026nbsp;DLI is a widely used post-relapse intervention intended to enhance the graft-versus-leukemia (GvL) effect. Preemptive DLI is initiated in response to early indicators of relapse, such as MRD or loss of complete donor chimerism (LOC), while therapeutic DLI is administered after overt hematologic relapse, often combined with systemic therapy aimed at reducing tumor burden and allowing for GvL effect. In our analyzed patient cohort, one patient received preemptive DLI (#11, \u003cstrong\u003eFigure 4\u003c/strong\u003e) and four therapeutic DLI (patients #1, #7, #18, #30). Response rates to DLI were only transient \u003cstrong\u003e(Figure 4)\u003c/strong\u003e. Patients #1 and #31 underwent a second allo-HCT to regain remission after the 1\u003csup\u003est\u003c/sup\u003e allo-HCT failure \u003cstrong\u003e(Table 3)\u003c/strong\u003e. Patient #1 received an allo-HCT from matched unrelated donor (MUD) while patient #31 underwent haploidentical allo-HCT (mMRD). The median time from relapse after allo-HCT-1 to death in the r/r T-ALL/LBL cohort was 3.4 months \u003cstrong\u003e(Table 1)\u003c/strong\u003e. Notably, one patient (#12) was treated with the experimental oral compound nelfinavir for two months and four patients with the anti-CD38 antibody daratumumab. Patients treated with these showed a limited duration of response in all analyzed cases.\u003c/p\u003e\n\u003cp\u003eFactors influencing survival \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn univariable Cox regression analysis, neither age nor disease type (T-ALL vs. T-LBL) was significantly associated with OS. In the cumulative incidence analysis \u003cstrong\u003e(Supplemental figure 1)\u003c/strong\u003e, RRM and NRM exhibited distinct temporal patterns. While NRM initially exceeded RRM for a short time, the curves crossed at approximately twelve months post-diagnosis, after which RRM became the predominant cause of death.\u003c/p\u003e\n\u003cp\u003eCompeting risks analysis using the Fine-Gray model revealed no statistically significant differences in the cumulative incidence of either RRM or NRM between T-ALL and T-LBL. However, due to the limited sample size, these findings should be interpreted with caution. A trend toward higher NRM in T-ALL (HR: 1.58; 95% CI, 0.32–7.93) and lower RRM (HR: 0.78; 95% CI, 0.22–2.85) was observed, suggesting potential biological differences that warrant further investigation in larger cohorts.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBeyond the dismal prognosis observed after relapse post-allo-HCT, our data further emphasize the biological aggressiveness of adult T-cell lymphoblastic disease and the narrow therapeutic window available once standard treatment strategies fail. The predominance of early relapses within the first year after transplantation suggests that disease biology rather than transplant-related factors alone may be the major driver of treatment failure. This observation supports the notion that improved pre- and post-transplant disease control, including more sensitive MRD-guided interventions, is critical to improving long-term outcomes.\u003c/p\u003e\n\u003cp\u003eRelapsed or refractory T-cell lymphoblastic disease represents a significant unmet medical need, in both children and adults. Outcomes for adult T-ALL/LBL patients with r/r disease after allo-HCT remain particularly poor compared with newly diagnosed, treatment-na\u0026iuml;ve patients. Indeed, relapse after allo-HCT was uniformly fatal in our cohort with the majority succumbing to progressive disease, often combined with infectious complications following allo-HCT. This underscores the need for more effective and less toxic treatment strategies for acquired or intrinsic disease resistance in this hard-to-treat population. In line with our single-center, retrospective study the OS of adult r/r ALL disease is estimated at \u0026lt;7% at five years.\u003csup\u003e16\u003c/sup\u003e Still, allo-HCT is considered the most effective anti-leukemic therapy for adults with ALL\u003csup\u003e17\u003c/sup\u003e and 19/35 (54.3%) T-ALL/LBL patients transplanted in our center, whether in the front-line or salvage setting, still enjoy disease control and are potentially cured. However, the limited efficacy of currently available salvage strategies in our cohort underscores the lack of a standardized approach for patients relapsing after allo-HCT-1.\u003c/p\u003e\n\u003cp\u003eThe use of nelarabine alone or in combination with other cytotoxic agents like cyclophosphamide has shown encouraging response rates in pediatric r/r T-cell lymphoblastic disease.\u003csup\u003e24\u003c/sup\u003e Nevertheless, these pediatric-inspired protocols resulted only in short-term disease control for the r/r adult population after allo-HCT-1 from our center. B- and T-cell lineage ALL are considered to be rather insusceptible to DLI treatment following molecular relapse or LOC or overt hematologic relapse with measurable blasts after allo-HCT.\u003csup\u003e25\u003c/sup\u003e Five patients from our institution received DLI. On the one hand, this second cellular therapy was able to restore donor chimerism (DC) in some cases, on the other hand the desired graft-versus-leukemia effect was only short-lived.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRecently, CD38 has emerged as a novel target for immunotherapy in T-cell lymphoblastic disease with daratumumab demonstrating preclinical activity in human xenograft models.\u003csup\u003e26\u003c/sup\u003e Subsequently, the DELPHINUS study suggested that daratumumab may be an effective bridging strategy to allo-HCT in children and young adults, including in T-cell lineage ALL.\u003csup\u003e27\u003c/sup\u003e In contrast, the role of daratumumab in r/r adult patients, specifically after allo-HCT, remains poorly investigated, with reports limited to smaller single-center experiences.\u003csup\u003e28\u003c/sup\u003e We suggest to assess robust CD38 expression of T-ALL blasts in relapse. Nevertheless, our single-center experience with daratumumab was disappointing with limited responses. At the same time, it should be considered that the four daratumumab-treated patients were already severely ill and experiencing rapid disease progression when the anti-CD38 antibody was administered.\u003c/p\u003e\n\u003cp\u003eNelfinavir was developed as an antiretroviral compound licensed for the treatment of human immunodeficiency virus (HIV) and is being investigated as an anti-cancer drug. Recently, nelfinavir was shown to suppress T-ALL cell viability \u003cem\u003ein vitro\u003c/em\u003e and in a transgenic mouse model, highlighting its potential role as a novel therapeutic candidate for the management of T-cell lymphoblastic disease.\u003csup\u003e29\u003c/sup\u003e Experimental targeting of cellular stress pathways using oral nelfinavir 1250mg twice daily demonstrated temporary restoration of donor chimerism in a heavily pretreated young r/r T-ALL patient, supporting its biological activity \u003cem\u003ein vivo\u003c/em\u003e. However, the brevity of response highlights the need for combination strategies and reinforces the concept that monotherapy approaches are unlikely to achieve durable disease control in this setting.\u003c/p\u003e\n\u003cp\u003eMoreover, chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of r/r B-cell ALL resulting in impressive response and survival rates.\u003csup\u003e30\u0026ndash;36\u003c/sup\u003e This success has inspired the development of autologous T-cell therapy against T-cell malignancies as well. Currently, the putative role of CAR T-cell therapy in T-cell disease is being investigated intensively, including as a bridging strategy to allo-HCT consolidation. One major challenge for CAR T-cells in T-cell lymphoblastic disease is the lack of specific target antigens.\u003csup\u003e37\u003c/sup\u003e Thus, fratricide in which CAR-T expressing the target antigen, e.g. CD5 or CD7, \u0026nbsp;are eliminated by fellow CAR T-cells, has proven to be a significant obstacle.\u003csup\u003e37\u0026ndash;40\u003c/sup\u003e Potentially fatal T-cell aplasia, in which healthy T-cells expressing the target antigens are killed by the CAR T-construct, and the risk of product contamination by malignant lymphoblasts represent other challenges on the path to safe and effective CAR T-cells against T-ALL/LBL.\u003csup\u003e41\u0026ndash;43\u003c/sup\u003e Several strategies are implemented to overcome fratricide and to mitigate T-cell aplasia. For instance, targeting specific T-cell subgroups to avoid aplasia, genetic knock-out of target antigens in CAR T-cells, the use of protein expression blockers, natural killer cells as carriers of CARs or even the use of allogeneic T-cells to circumnavigate product contamination are being explored.\u003csup\u003e44\u003c/sup\u003e Various phase 1 and 2 trials have tested the safety and efficacy of CAR-T cells targeting either CD5 or CD7 in T-ALL/LBL with mixed results.\u003csup\u003e45\u0026ndash;52\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThis study is limited by its retrospective, single-center design and small sample size, which restrict statistical power and generalizability. Incomplete molecular profiling and heterogeneous salvage treatments further limit definitive conclusions regarding optimal therapeutic sequencing. Nevertheless, the strength of this analysis lies in its detailed real-world characterization of relapse patterns and post-transplant outcomes in a rare adult malignancy.\u003c/p\u003e\n\u003cp\u003eIn summary, our findings confirm that relapse after allo-HCT-1 in adult T-ALL/LBL remains almost uniformly fatal with currently available therapies. New targeted approaches and patient-tailored therapy regimens are urgently warranted to raise the cure rate for r/r T-ALL/LBL patients that are either not eligible for allo-HCT or who relapse post-allo-HCT and otherwise display dismal prognosis. Future improvements will depend on earlier intervention, biologically informed patient stratification, and the integration of innovative targeted and cellular therapies within prospective clinical trials.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eM.M.\u003c/strong\u003e has participated in advisory boards from Janssen and Stemline and has received honoraria not related to this manuscript from AbbVie, AstraZeneca, Gilead, Janssen, and Lilly; reports travel support from AbbVie, Gilead, Incyte, Janssen, Sobi, and Stemline. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA.A.\u003c/strong\u003e reports travel grants from Stemline and Gilead not related to this manuscript.\u003c/p\u003e\n\u003cp\u003eAll other authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSources of funding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no sources of funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo acknowledgements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eM.M. and A.A. conceived the project and provided leadership; M.M., G.W., J.B. E.A., M.L., K.T., J.H., L.I., G.W. and A.A. provided patient data; M.M., J.B., M.L. and A.A. analyzed the data. M.M., J.B. and A.A. wrote the main manuscript text and A.A. prepared the figures. J.H., L.I. and G.W. reviewed and edited the manuscript. All authors approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSucre, O., Pamulapati, S., Muzammil, Z. \u0026amp; Bitran, J. Advances in Therapy of Adult Patients with Acute Lymphoblastic Leukemia. \u003cem\u003eCells\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 371 (2025).\u003c/li\u003e\n\u003cli\u003eJabbour, E. \u003cem\u003eet al.\u003c/em\u003e The evolution of acute lymphoblastic leukemia research and therapy at MD Anderson over four decades. \u003cem\u003eJ. Hematol. Oncol.J Hematol Oncol\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, 22 (2023).\u003c/li\u003e\n\u003cli\u003eBassan, R., Maino, E. \u0026amp; Cortelazzo, S. 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Med.\u003c/em\u003e \u003cstrong\u003e30\u003c/strong\u003e, 3687\u0026ndash;3696 (2024).\u003c/li\u003e\n\u003cli\u003ePan, J. \u003cem\u003eet al.\u003c/em\u003e Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial. \u003cem\u003eJ. Clin. Oncol.\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 3340\u0026ndash;3351 (2021).\u003c/li\u003e\n\u003cli\u003eChiesa, R. \u003cem\u003eet al.\u003c/em\u003e Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia. \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e \u003cstrong\u003e389\u003c/strong\u003e, 899\u0026ndash;910 (2023).\u003c/li\u003e\n\u003cli\u003eHill, L. C. \u003cem\u003eet al.\u003c/em\u003e Enhanced anti-tumor activity of CD5 CAR T cells manufactured with tyrosine kinase inhibitors in patients with relapsed/refractory T-ALL. \u003cem\u003eJ. Clin. Oncol.\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 7002\u0026ndash;7002 (2023).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Baseline and transplant characteristics of T-ALL/LBL patients.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAllo-HCT recipients,\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 35 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll patients,\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 42 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eGender (M/F), ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e27/8, 3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e32/10, 3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eMedian age at diagnosis, years (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e31 (18-68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e29 (18-68)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eDisease subclassification\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003ePro-T-ALL\u003c/li\u003e\n \u003cli\u003ePre-T-ALL\u003c/li\u003e\n \u003cli\u003eETP-ALL\u003c/li\u003e\n \u003cli\u003eCortical (thymic) T-ALL\u003c/li\u003e\n \u003cli\u003eMature T-ALL\u003c/li\u003e\n \u003cli\u003eT-LBL\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003cp\u003e13 (37.1)\u003c/p\u003e\n \u003cp\u003e4 (11.4)\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003cp\u003e11 (31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (2.4)\u003c/p\u003e\n \u003cp\u003e14 (33.3)\u003c/p\u003e\n \u003cp\u003e4 (9.5)\u003c/p\u003e\n \u003cp\u003e7 (16.7)\u003c/p\u003e\n \u003cp\u003e2 (4.8)\u003c/p\u003e\n \u003cp\u003e14 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eBulky disease\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eYes\u003c/li\u003e\n \u003cli\u003eNo\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (54.3)\u003c/p\u003e\n \u003cp\u003e16 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (57.1)\u003c/p\u003e\n \u003cp\u003e18 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eInduction therapy\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eGMALL Protocol\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGMALL Elderly\u003c/li\u003e\n \u003cli\u003eALL-BFM High-risk incl. RT\u003c/li\u003e\n \u003cli\u003eCHOEP (partly), followed by GMALL induction/consolidation\u003c/li\u003e\n \u003cli\u003eHyper-CVAD\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 (80)\u003c/p\u003e\n \u003cp\u003e3 (8.6)\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34 (81)\u003c/p\u003e\n \u003cp\u003e4 (9.5)\u003c/p\u003e\n \u003cp\u003e1 (2.4)\u003c/p\u003e\n \u003cp\u003e2 (4.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eSalvage therapy pre-allo-HCT including\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eNelarabine\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRe-induction GMALL\u003c/li\u003e\n \u003cli\u003eHyper-CVAD\u003c/li\u003e\n \u003cli\u003eRadiation\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 (51.4)\u003c/p\u003e\n \u003cp\u003e4 (11.4)\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eIndication to allo-HCT\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eFrontline allo-HCT\u003c/li\u003e\n \u003cli\u003eSalvage allo-HCT\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (54.3)\u003c/p\u003e\n \u003cp\u003e16 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eMedian time from 1\u003csup\u003est\u003c/sup\u003e diagnosis to allo‐HCT, months (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e7.6 (3.9 \u0026ndash; 58.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eMedian age at allo-HCT, years (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e32 (19 \u0026ndash; 69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eRemission status at allo‐HCT-1\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eMRD negative\u003c/li\u003e\n \u003cli\u003eMRD positive\u003c/li\u003e\n \u003cli\u003eMRD status unknown\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e20 (57.1)\u003c/p\u003e\n \u003cp\u003e10 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eConditioning allo-HCT\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eTBI-Flu (8 Gy)\u003c/li\u003e\n \u003cli\u003eTBI-Cy (12 Gy)\u003c/li\u003e\n \u003cli\u003eFBC-12\u003c/li\u003e\n \u003cli\u003eBuCy\u003c/li\u003e\n \u003cli\u003eTBI-Eto (12 Gy)\u003c/li\u003e\n \u003cli\u003eFBC-8\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (28.6)\u003c/p\u003e\n \u003cp\u003e10 (28.6)\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e4 (11.4)\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eGvHD prophylaxis with ATG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e34 (97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eSource of stem cells\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eMUD\u003c/li\u003e\n \u003cli\u003eMRD\u003c/li\u003e\n \u003cli\u003emMUD\u003c/li\u003e\n \u003cli\u003emMRD\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (54.3)\u003c/p\u003e\n \u003cp\u003e10 (28.6)\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48.3444%;\"\u003e\n \u003cp\u003eMedian day of hematologic engraftment (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.49%;\"\u003e\n \u003cp\u003e16 (10 \u0026ndash; 29)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eT-ALL/LBL= T-cell acute lymphoblastic leukemia/lymphoma; allo-HCT= allogeneic hematopoietic stem cell transplantation; ETP-ALL= early T-cell precursor ALL; GMALL= German Multicenter Study Group for Adult ALL; BFM= Berlin-Frankfurt-M\u0026uuml;nster (study group); RT= radiotherapy; CHOEP= cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone/prednisolone; Hyper-CVAD= hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; MRD= minimal residual disease; TBI= total body irradiation; Flu= fludarabine; Gy= Gray; Cy= cyclophosphamide; FBC-12= fludarabine, busulfan, cyclophosphamide with myeloablative busulfan exposure, corresponding to a full-dose regimen; BuCy= busulfan, cyclophosphamide; Eto= etoposide; FBC-8= reduced-intensity fludarabine/busulfan/cyclophosphamide; GvHD= graft-versus-host disease; ATG= anti-thymocyte globulin; MUD= matched unrelated donor; MRD= matched related donor; mMUD= mismatched unrelated donor; mMRD= mismatched related donor.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Clinical outcomes of allo-HCT recipients.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAllo-HCT patients,\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 35 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eGvHD\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eaGvHD\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eGrade I\u003c/p\u003e\n \u003cp\u003eGrade II\u003c/p\u003e\n \u003cp\u003eGrade III\u003c/p\u003e\n \u003cp\u003eGrade IV\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003ecGvHD\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (48.6)\u003c/p\u003e\n \u003cp\u003e6 (17.1)\u003c/p\u003e\n \u003cp\u003e10 (28.6)\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003cp\u003e10 (28.6)\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eTreatment of GvHD\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eCorticosteroids\u003c/li\u003e\n \u003cli\u003eAlemtuzumab\u003c/li\u003e\n \u003cli\u003eECP\u003c/li\u003e\n \u003cli\u003eImmunosuppression (CsA/Tacrolimus, MMF)\u003c/li\u003e\n \u003cli\u003eRuxolitinib\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 (51.4)\u003c/p\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003cp\u003e4 (11.4)\u003c/p\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eOccurrence of hepatic VOD\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eYes\u003c/li\u003e\n \u003cli\u003eNo\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (8.6)\u003c/p\u003e\n \u003cp\u003e32 (91.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eRelapse incidence following allo-HCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e12/35 (34.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eOutcomes for relapse after allo-HCT at last follow-up\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eAlive\u003c/li\u003e\n \u003cli\u003eDead\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e12 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eMedian time from allo-HCT to relapse, months (range)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e5.3 (0.4 \u0026ndash; 25.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eMedian time from relapse to death, months (range) (n= 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e3.4 (0.3 \u0026ndash; 12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eSurvival status at last follow-up\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eAlive\u003c/li\u003e\n \u003cli\u003eDead\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (54.3)\u003c/p\u003e\n \u003cp\u003e16 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eCauses of death for all deceased patients (n= 16)\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003er/r disease\u003c/li\u003e\n \u003cli\u003eNRM\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eInfection/sepsis\u003c/p\u003e\n \u003cp\u003eGvHD\u003c/p\u003e\n \u003cp\u003eVOD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (62.5)\u003c/p\u003e\n \u003cp\u003e6 (37.5)\u003c/p\u003e\n \u003cp\u003e4 (25)\u003c/p\u003e\n \u003cp\u003e1 (6.3)\u003c/p\u003e\n \u003cp\u003e1 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eRemission status of surviving patients at last FU\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eCR\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eMedian follow-up from diagnosis, months (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e33.2 (6.1 \u0026ndash; 206.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 415px;\"\u003e\n \u003cp\u003eMedian follow-up from allo-HCT, months (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e18.9 (0.8 \u0026ndash; 199.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eallo-HCT= allogeneic hematopoietic stem cell transplantation; aGvHD= acute graft-versus-host disease; cGvHD= chronic graft-versus-host disease; ECP= extracorporeal photopheresis; CsA= cyclosporine A; MMF= mycophenolate mofetil; VOD= veno-occlusive disease; r/r= relapsed/refractory; NRM= non-relapse mortality; FU= follow-up; CR= complete remission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Relapse strategy following 1\u003csup\u003est\u003c/sup\u003e allo-HCT.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelapsed patients, n = 12 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eReinduction according to GMALL protocols\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e2 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eNelarabine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e6 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eNelarabine/Cyclophosphamide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e1 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eDLI\u003c/p\u003e\n \u003cp\u003eMedian number of DLI (range)\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003ePreemptive DLI\u003c/li\u003e\n \u003cli\u003eTherapeutic DLI\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e5 (41.7)\u003c/p\u003e\n \u003cp\u003e4 (1-5)\u003c/p\u003e\n \u003cp\u003e1 (8.3)\u003c/p\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003e2\u003csup\u003end\u003c/sup\u003e allo-HCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e2 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eRadiation therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e1 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eRomidepsin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e1 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eNelfinavir\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e1 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eallo-HCT= allogeneic hematopoietic stem cell transplantation; GMALL= German Multicenter Study Group for Adult ALL; DLI= donor lymphocyte infusion.\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9396037/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9396037/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: Adult acute T-cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive malignancy. Allogeneic hematopoietic stem cell transplantation (allo-HCT) represents a potentially curative option for high-risk or relapsed/refractory (r/r) disease; however, outcomes following relapse after allo-HCT remain poorly defined due to limited real-world data. This retrospective study evaluated post-transplant outcomes, relapse patterns, and salvage strategies in adult T-ALL/LBL patients treated at a single academic center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We conducted an analysis of 42 adult patients diagnosed and treated with T-ALL/LBL between 2007 and 2025. Survival outcomes, including overall survival (OS), progression-free survival (PFS), relapse-related mortality (RRM), and non-relapse mortality (NRM), were assessed. Kaplan–Meier estimates, Cox proportional hazards models, and competing-risk analyses were applied to evaluate outcomes and prognostic factors following first allo-HCT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Among confirmed T-ALL/LBL patients, 35 (83%) underwent allo-HCT, either in first complete remission (CR1) with high-risk features or in ≥CR2. Median age at transplantation was 32 years. After allo-HCT, median OS was 18.9 months and twelve patients (34%) relapsed. Patients typically relapsed early, with a median time to relapse of 5.3 months. All patients who relapsed post-allo-HCT ultimately died, predominantly from progressive disease. Salvage strategies, including nelarabine-based chemotherapy, donor lymphocyte infusions, daratumumab, experimental agents, or second allo-HCT, resulted in only transient responses. No significant differences in OS were observed between T-ALL and T-LBL or between frontline and salvage allo-HCT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Currently available salvage therapies for T-ALL/LBL patients who relapse after allo-HCT have limited efficacy. This results in fatal outcomes. The findings presented here underscore the urgent need for novel targeted and cellular therapies, such as CAR T-cell based therapies, and support the enrollment of r/r patients into prospective clinical trials.\u003c/p\u003e","manuscriptTitle":"Relapse strategies following first allogeneic hematopoietic stem cell transplantation in adult T-cell lymphoblastic disease ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-28 12:55:26","doi":"10.21203/rs.3.rs-9396037/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"294483684494201583293772572729168837917","date":"2026-05-05T16:29:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"35946914086829597090869969283831056370","date":"2026-05-03T19:50:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-19T17:10:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-16T13:23:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-16T13:23:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2026-04-12T17:32:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6552ed88-3f2b-4c5d-bc64-f14ba5ba6e40","owner":[],"postedDate":"April 28th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"294483684494201583293772572729168837917","date":"2026-05-05T16:29:07+00:00","index":18,"fulltext":""},{"type":"reviewerAgreed","content":"35946914086829597090869969283831056370","date":"2026-05-03T19:50:31+00:00","index":17,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T12:55:26+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-28 12:55:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9396037","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9396037","identity":"rs-9396037","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}