We compared the presence of additional chromosomal abnormalities (ACAs, n = 345) with a referent group with no ACAs (n = 169) (noACAs) in patients with Ph+ ALL receiving TKI before transplantation. The groups did not differ significantly in age, gender, or interval from diagnosis to transplantation. More patients with ACAs received PB grafts (86.4% vs. 78.1%, p = 0.03), while more patients in the noACAs group received myeloablative conditioning (87% vs. 75.9%, p = 0.003). Day 30 ANC (≥109/L) was 97.9% vs. 98.2%, and day 60 platelet count (≥20 × 109/L) was 93.9% vs. 95.5%. Day 100 acute GVHD grades II-IV was 26.4% vs. 31%, and of grades III-IV was 8.6% vs. 9.7%. 4-year chronic GVHD was 40.5% vs. 39.9%, and the proportion of extensive chronic GVHD was 19.3% vs. 20.1%. 4-year NRM was 13.1% vs. 13.5%, and 4-year RI was 19.2% vs. 21.1%; 4-year LFS and OS were 67.7% vs. 65.4% and 76.3% vs. 78.5%. 4-year GRFS was 48.5% vs. 45%, respectively. In multivariable analysis, having ACAs and the number of ACAs did not significantly affect transplant outcomes. Administration of a TKI upfront, followed by transplantation, may overcome the poor prognostic influence of ACAs in Ph+ ALL.

Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) may occur after allo-HSCT. This retrospective study of 793 allo-HSCT performed in adult patients analyzes the impact of clinical risk factors and the EASIX score on the incidence and outcomes of SOS/VOD using Real-World data (GETH-TC registry). Severity and clinical risk factors were defined according to the EBMT-2023 criteria. The EASIX score was calculated at three time points after allo-HSCT (EASIX-day 0, d + 7, d + 14). SOS/VOD developed in 79 patients (10%), at a median time of 15 days. The cumulative incidence of SOS/VOD at 30 and 90 days post-HSCT was 8.58% and 9.97%, respectively. Defibrotide was used in 44 patients (56%) who developed SOS/VOD. Patients with SOS/VOD experienced an increased risk of NRM (HR 5.56; p < 0.001). Multivariate analysis confirmed the prognostic value for SOS/VOD incidence of second or subsequent HSCT, use of parenteral nutrition, high tacrolimus/sirolimus levels, INR > 1.5 before SOS, as well as day 0 EASIX ≥ 2 (sHR 1.67; p = 0.036), d + 7 EASIX ≥ 6 (sHR 2.86; p < 0.001), and d + 14 EASIX ≥ 6 (sHR 2.87; p = 0.003). In conclusion, SOS/VOD incidence is similar to previous series and significantly impacts NRM. EASIX score was validated as a risk factor of SOS/VOD.

For patients with high-risk acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (HCT) remains standard of care. In the setting of an HLA-matched unrelated donor HCT, in vivo T-cell depletion (TCD) for prophylaxis of graft versus host disease (GVHD) relies on anti-thymocyte globulin (ATG) in Europe and alemtuzumab in the UK. In a retrospective study from the EBMT registry, we pair-matched 90 ALL patients aged ≥40 years transplanted in CR1 according to age (median 56 years) and ALL subtype (37.8% Ph-negative B-ALL, 46.7% Ph-positive B-ALL, 15.6% T-ALL). Reduced-intensity conditioning included fludarabine/melphalan (94.4%) in the alemtuzumab and fludarabine/busulfan (36.7%), fludarabine/total body irradiation (21.1%), fludarabine/melphalan (14.4%) and thiotepa/busulfan/fludarabine (13.3%) in the ATG group. Two-year leukemia-free and overall survival were similar between groups (Alemtuzumab: 56.4% vs ATG: 50.7%, HR 0.82, p = 0.34, and 62.7% vs 62.9%, HR 0.91, p = 0.67), as were cumulative incidence of relapse (23.7% vs 23.9%, HR 0.89, p = 0.69) and non-relapse mortality (19.9% vs 25.4%, HR 0.75, p = 0.32), resulting in similar GVHD- and relapse-free survival (GRFS) of 48.9% vs 42.1%, HR 0.8, p = 0.24. With GVHD and infections as main reasons for death in both groups, we conclude that both IS strategies are both safe for RIC HCT of these ALL patients.

Chronic graft-versus-host disease (cGVHD) remains a leading cause of late morbidity after allogeneic hematopoietic cell transplantation (HCT), but its phenotype under modern prophylaxis with post-transplant cyclophosphamide (PTCy) is not well characterized. We conducted a prospective, single-center study of 600 consecutive adults undergoing HCT with PTCy- based prophylaxis to assess incidence, clinical manifestations, treatment response, prognostic factors, and outcomes. Donors included matched siblings (36%), matched unrelated (34%), haploidentical (24%), and mismatched unrelated (6%). The 1-year cumulative incidence of moderate-to-severe cGVHD was 22% (95% confidence interval [CI]: 19-26%). The mouth was the most frequently involved organ (64%), with lichen planus-like changes as the predominant diagnostic feature, whereas sclerotic forms were uncommon. Notably, 27% of moderate-to-severe cases were managed successfully without systemic corticosteroids. The cumulative incidence of systemic therapy requirement was 15% at 1 year, with risk significantly higher in donors ≥30 years and in female-to-male transplants. Among 105 patients requiring systemic steroids, 64% achieved complete response, 32% discontinued immunosuppression, yet 18% developed cGVHD-related sequelae. Mouth ulcers and erythema, as well as a lung score ≥2 at steroid initiation independently predicted shorter failure-free survival. At 2 years, overall survival, cGVHD-free relapse-free survival, and GVHD-free relapse-free survival were 76% (95% CI: 72-79), 63% (95% CI: 60-68), and 57% (95% CI: 53-62), respectively. In conclusion, after HCT with PTCy-based prophylaxis, systemic therapy was required in only a minority of patients, with risk influenced by donor age and sex mismatch rather than donor type. While corticosteroids were generally effective, a substantial subset required salvage therapy, underscoring the burden of refractory cGVHD and the need for steroid-sparing approaches and novel interventions.

It remains uncertain whether lower CD19 expression is clinically relevant for outcomes of CD19 CAR-T therapy of large B-cell lymphoma (LBCL). We conducted an integrative analysis of tumor CD19 levels with centralized quantitative assessment by flow cytometry (FC), immunohistochemistry and RNA-sequencing in a LBCL cohort (n=301). Pre-treatment CD19 by FC correlated with 1-year progression-free survival following axicabtagene ciloleucel or lisocabtagene maraleucel (16%, 53% and 64% for CD19low, CD19intermediate and CD19high, respectively; p=0.005). After CAR-T relapse, proportion of CD19low tumors increased (from 17% to 35%). Concordant associations were observed by immunohistochemistry and RNA-sequencing. Transcriptomic profiling linked lower CD19 to inflammatory pathways, validated in an external LBCL cohort (n=1,017). Genetic loss of the CD19 locus was observed in 8% of pre-CAR-T and 11% of post-CAR-T tumors (p=0.82), while no CD19 coding mutations were identified. Overall, CD19 expression is a clinically meaningful determinant of CAR-T outcomes, supporting quantitative assessment to improve risk stratification.

Chronic graft-versus-host disease (cGVHD) remains the leading cause of late morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation, despite major advances in transplant techniques and supportive care. This European position statement provides a comprehensive and forward-looking synthesis of the evolving biology, epidemiology, diagnosis, and management of cGVHD, while highlighting critical unmet needs that impede progress. cGVHD arises from a complex interplay of immune dysregulation, aberrant tissue repair, and progressive fibrosis, resulting in a heterogeneous clinical spectrum that profoundly impairs quality of life and functional status. Although recent therapeutic innovations-including JAK inhibition, ROCK2 inhibition, and CSF-1R-directed therapies-have expanded options beyond corticosteroids, treatment responses remain variable, and optimal sequencing, biomarkers of activity, and organ-specific strategies are lacking. Persistent challenges in diagnosis, staging reproducibility, integration of patient-reported outcomes, and harmonized clinical trial endpoints further limit clinical and regulatory advancement. The substantial pharmaco-economic burden of cGVHD underscores the urgency of developing more effective, durable, and accessible interventions. This review outlines a collaborative roadmap centered on biomarker-driven precision medicine, harmonized assessment tools, integrated supportive care, and international research networks, aiming to transform cGVHD from a debilitating complication into a predictable, preventable, and ultimately curable condition.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML), and outcomes are strongly influenced by disease status at transplantation. In transplants using conventional graft-versus-host disease (GVHD) prophylaxis, outcomes also depend on the number of induction courses required to achieve first complete remission (CR1); however, this has not been evaluated in patients receiving post-transplant cyclophosphamide (PTCy). We retrospectively analyzed 677 adult AML patients transplanted in CR1 between 2012 and 2022 using PTCy-based GVHD prophylaxis. Outcomes were compared between patients achieving CR1 after one induction course (n = 518) and those requiring two courses (n = 159). Baseline characteristics, donor type, conditioning intensity, graft source, engraftment, and rates of acute and chronic GVHD were comparable between groups. Patients requiring two inductions had a higher 2-year cumulative incidence of relapse (27% vs. 19.3%; HR 1.75, p = 0.003). However, no significant differences were observed in 2-year overall survival (62.8% vs. 69%), leukemia-free survival (61.1% vs. 65%), GVHD-free/relapse-free survival (46.3% vs. 50.4%), or non-relapse mortality (11.9% vs. 15.7%). In AML patients receiving alloHSCT with PTCy, outcomes were largely similar regardless of whether CR1 was achieved after one or two-induction courses, with relapse incidence being higher in patients requiring 2 inductions.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for secondary acute myeloid leukemia (sAML). Post-transplant cyclophosphamide has improved graft-versus-host disease (GVHD) prophylaxis, enabling the broader use of alternative donors. For patients lacking a human leukocyte antigen (HLA)-matched donor, haploidentical donor (Haplo) or 9/10 HLA mismatched unrelated donor (MMUD) HSCTs are widely used, yet their relative effectiveness in sAML is uncertain. We retrospectively compared outcomes after Haplo versus MMUD HSCT in adults with sAML in first complete remission transplanted between 2010 and 2022. Among 711 patients, 602 received Haplo and 109 MMUD grafts. Patient and transplant characteristics differed between cohorts, including donor age, conditioning intensity, graft source, and transplant year. Neutrophil recovery was faster after MMUD transplantation, while platelet recovery was comparable. Rates of acute and chronic GVHD, relapse incidence, non-relapse mortality, overall survival, leukemia-free survival, and GVHD-free/relapse-free survival were similar. Reduced intensity conditioning lowered acute GVHD risk, while peripheral blood grafts increased chronic GVHD. Lower Karnofsky score, older age and adverse-risk cytogenetics were adverse prognostic factors. Haplo and MMUD transplantation demonstrated comparable efficacy and safety with post-transplant cyclophosphamide, supporting both approaches as viable alternatives in the absence of an HLA-matched donor.

Introduction Infections are the leading cause of TRM following CAR-T. The severity of infectious episodes is graded using CTCAE in clinical trials, whereas the BMT CTN grading system was developed to better reflect severity and clinical impact in allo-HCT. Neither system has been systematically validated in the CAR-T setting. Objectives We aimed to validate the BMT CTN criteria in a large CAR-T population and to compare prognostic performance between the BMT CTN and CTCAE systems. Methods This retrospective study included adult patients who received commercial CAR-T therapy at a large-volume academic center between 2018 and 2024. Infectious episodes occurring from lymphodepletion until next treatment, death or end-of-follow up, were graded by CTCAE v5.0 (grades 1–5; grade 5 excluded) and BMT CTN (grades 1–3; fatal infections excluded). Overall survival up to day 180 was the primary endpoint. Cox proportional hazards models were constructed with infection severity as a time-dependent covariate. Model discrimination was assessed by time-dependent concordance index (CTD) using a 5-fold cross-validation, adjusted for age, CAR-T product, disease, and KPS (dichotomized at 90). Results We identified 636 infectious episodes within the first 180 days post-CAR-T among 563 patients (median age 65 years, IQR 56–72). Most patients (82%) received CD19 CAR-T for lymphoma, and 18% received BCMA CAR-T for myeloma; 65% were male. 78% received bridging, 59% had a HEMATOX score ≥2, 54% developed grade ≥2 N-ICAHT, and 37% had CRS grade ≥2. Overall, 63% of patients developed ≥1 infection of any grade during the 180-day period.By CTCAE, 28% of infections were grade 1, 34% grade 2, 36% grade 3, and 3% grade 4. Using the BMT CTN criteria, 75% were grade 1, 20% grade 2, and 5% grade 3.Low-grade infections (CTCAE grades 1–2 or BMT CTN grade 1) were not associated with excess mortality up to 180 days. Neither were CTCAE grade 3 (adjusted HR=1.6, p=0.11) or BMT CTN grade 2 (adjusted HR=1.9, p=0.056). In contrast, CTCAE grade 4 (adjusted HR=12, p<0.001) and BMT CTN grade 3 (adjusted HR=9, p<0.001) were associated with OS.In five-fold cross-validation, the BMT CTN model had a median CTD of 0.63 (IQR 0.60–0.64) versus 0.74 (IQR 0.72–0.75) for CTCAE. CTCAE outperformed BMT CTN across all five cross-validation splits, implying better discriminative performance. Conclusion This represents the first and largest application of the BMT CTN grading to the CAR-T context. Only BMT CTN grade 3 infections were associated with excess mortality. Similarly, only CTCAE grade 4 infections were associated with mortality. While CTCAE appeared superior to BMT CTN, in both cases only a small number of patients had high grade infections highlighting limitations of applying these grading systems in CAR-T relative to allo-HCT recipients. Future studies should evaluate which specific infections drive mortality and if further refinements are necessary.

BACKGROUND:Secondary malignancies (SM) are a well-recognized long-term complication after hematopoietic cell transplantation (HCT), increasingly contributing to morbidity and mortality as post-transplant survival improves. However, the incidence, spectrum, and outcomes of SM remain incompletely defined in the context of evolving transplant practices and a growing population of long-term survivors. OBJECTIVE:To evaluate the incidence, risk factors, and outcomes of SM in a contemporary cohort of autologous and allogeneic HCT recipients. STUDY DESIGN:Observational, retrospective, single-center study including all consecutive patients undergoing a first autologous or allogeneic HCT from any donor type at the Hospital Universitario y Politécnico La Fe (Valencia, Spain) between January 2007 and December 2024. RESULTS:Among 2098 patients, 103 (4.9%) developed non-cutaneous SM, including 56 solid tumors (ST), 25 post-transplant lymphoproliferative disorders (PTLD), 15 therapy-related myelodysplastic syndromes/acute myeloid leukemia (t-MDS/AML), 2 donor cell leukemia, and 5 other hematologic malignancies. PTLD occurred earlier after allogeneic transplantation (median 3.9 months) than t-MDS/AML (median 47.0 months) and ST (median 51.5 months). Risk factors for ST included a history of prior malignancy (hazard ratio [HR] 2.96, 95% confidence interval [CI] 1.46 to 6.00; p = .003), allogeneic HCT (HR 2.44, 95% CI 1.29 to 4.60), and patient age ≥50 years (HR 1.89, 95% CI 1.07 to 3.35), whereas the risk of t-MDS/AML was higher among patients with a prior malignancy (HR 2.96, 95% CI 1.47 to 5.98). In the allogeneic setting, the use of post-transplant cyclophosphamide as graft-versus-host disease prophylaxis did not affect the risk of SM in multivariate analysis. SM ranked as the second and third leading causes of death after autologous and allogeneic HCT, respectively. Overall survival (OS) differed among SM subtypes entities, being particularly adverse for PTLD (1-year OS 19%, 95% CI 9 to 43) and better for solid tumors (5-year OS 43%, 95% CI 29 to 64). CONCLUSION:SM are a significant determinant of post-transplant mortality, with risk shaped by prior malignancy, older age, and transplant type, and outcomes varying markedly according to subtype.

CAR T-cell therapy has transformed relapsed/refractory large B-cell lymphoma (LBCL) treatment, yet durable remissions remain challenging. In this retrospective multicenter study, 479 LBCL patients treated with commercial CD19 CAR-T products, axicabtagene ciloleucel (axi-cel, n = 262), tisagenlecleucel (tisa-cel, n = 131), and lisocabtagene maraleucel (liso-cel, n = 86), were evaluated using serial landmark analyses, with median follow-ups of 23, 34, and 16 months, respectively. Progression-free survival (PFS) was assessed at Day 28 and at 3, 6, 12, 18 and 24 months post-infusion to determine when relapse risk declines and sustained disease-free remission is achieved. Patients who attained a complete response (CR) at early time points had significantly improved PFS. In multivariable analyses, elevated pre-lymphodepletion lactate dehydrogenase (LDH) levels were independently associated with inferior PFS across several landmarks (HR 2.67, P < .001 at Day 28; HR 1.83, P = .044 at 3 months; HR 2.19, P = .016 at 6 months) and showed consistent association with inferior overall survival (OS) at these same time points. Cumulative relapse and non-relapse mortality (NRM) estimates supported the prognostic value of sustained CR. This landmark-based analysis advances understanding of durable remission kinetics following CAR T-cell therapy, indicating a trend toward cure, though longer follow-up is needed to confirm durable remission.

PURPOSE For patients with hematologic malignancies, relapse is the leading cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). Frequently, relapses are explained by immune evasion through alterations of human leukocyte antigens (HLAs), but determinants and clinical consequences remain poorly defined. METHODS We analyzed 533 relapses of hematologic cancers after allo-HCT from different donor types, conducted at 27 centers worldwide. Genomic loss of mismatched HLA (HLA loss) was assessed using a newly developed next-generation sequencing pipeline. Clinical and immunogenetic factors associated with HLA loss were evaluated. Using HLA data from approximately 5 million individuals, a web-based tool to infer HLA incompatibility phasing was developed. RESULTS HLA loss occurred in 15.6% of relapses, with significant variation according to donor type (28.7% haploidentical family, 7.2% unrelated adult, 2.7% cord blood, P < .0001). The distribution of HLA mismatches across the patient's haplotypes, predicted through the phasing tool, was strongly associated with HLA loss, with an incidence of 27.6% when HLA mismatches were in the same haplotype, compared with 5.4% if present on different haplotypes ( P < .0001). HLA loss affected postrelapse outcomes, abrogating the efficacy of original donor lymphocyte infusions, with significant survival advantage by second allo-HCT from a different donor. CONCLUSION The likelihood of HLA loss varies significantly according to the number and positioning of HLA mismatches between patient and donor. A newly developed phasing tool enables reliable prediction of its risk, supporting informed donor selection. Routine assessment of HLA loss at relapse is warranted, as it critically affects the success of immunologic salvage therapies.

Bispecific antibodies (BsAb) targeting CD20 and CD3 have shown efficacy for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), but their impact on outcomes following allogeneic hematopoietic cell transplantation (alloHCT) remains unclear. In this international, retrospective study, we compared outcomes of adult patients with R/R B-NHL undergoing first alloHCT after BsAb exposure (n=47) versus a historical BsAb-naïve cohort (n=101). Baseline imbalances were addressed using inverse probability of treatment weighting (IPTW) and propensity score matching (PSM). The primary endpoint was non-relapse mortality (NRM); secondary endpoints included overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), graft-versus-host disease (GVHD), engraftment, and GVHD/relapse-free survival (GRFS). In the overall cohort, 2-year NRM did not differ significantly between BsAb-exposed and BsAb-naïve groups (IPTW: 29.1% vs. 31.4%, p=0.80; PSM: 35.8% vs. 27.9%, p=0.43). CIR was significantly lower in BsAb-exposed patients after IPTW (7.4% vs. 20.0%, p=0.01), but not in PSM (9.5% vs. 23.4%, p=0.06). OS, GVHD, GRFS, and engraftment were comparable. In a pre-specified subanalysis limited to large B-cell lymphomas, CIR differences were consistent across IPTW (6.1% vs. 21.1%, p=0.01) and PSM (9.2% vs. 33.3%, p=0.03), reinforcing a potential benefit of prior BsAb therapy. A significant improvement in PFS was observed in this subgroup with IPTW (55.5% vs. 36.6%; p=0.04), but not in PSM (p=0.20). Prior BsAb exposure does not adversely impact alloHCT safety and may be associated with improved disease control. Prospective studies are warranted to define optimal sequencing in this high-risk population.

Acute myeloid leukemia (AML) with translocation (6;9)(p23;q34) is a rare and high-risk disease, frequently co-occurring with FLT3-ITD alteration. We retrospectively analyzed 544 patients with t(6;9) AML undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and reported to the EBMT registry, between 2000 and 2022. At 2-years, overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), non-relapse mortality (NRM) and GVHD-free/relapse-free survival (GRFS) were 65.7%, 59.1%, 23.0%, 17.9% and 45.6% respectively. The 431 patients transplanted in first complete remission (CR1) had more favorable OS (71.7%), LFS (65.8%) and RI (18.2%). Pediatric and adolescent/young adult (AYA, ≤ 39 years) patients in CR1 had improved outcomes. In patients ≥ 40 years old, OS, LFS, and NRM gradually worsened, whereas significant increase in RI and decrease in GRFS were observed after 53 years. In a matched-pair analysis performed on 76 FLT3-ITD positive and 76 negative CR1 patients, FLT3-ITD was associated with an approximately three-fold higher RI risk, without differences in OS. In conclusion, allo-HSCT in t(6;9) AML provides relatively favorable outcomes especially when performed in CR1. Pediatric and AYA patients derived the greatest benefit from transplant. FLT3-ITD positivity remains a relevant risk factor for relapse, though without impact on OS.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). Although post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG) have reshaped prophylactic strategies, contemporary real-world data on GVHD incidence under current practice are limited. We conducted a nationwide retrospective study including 1 544 alloHSCTs performed in Spain (2018-2020) to characterize current prophylaxis patterns and the epidemiology of GVHD. PTCy-based prophylaxis was used in 65.6% of transplants, being nearly universal in haploidentical donors (96.9%) and predominant in mismatched unrelated (72.4%), matched unrelated (58.6%), and matched related donors (43.5%). The cumulative incidence of acute GVHD grades II-IV was 28.4% at day +100 and 30.7% at 1 year; grade III-IV occurred in 6.9% and 8.0%, respectively. Chronic GVHD at 2 years was 36.7%, with 23.5% moderate-to-severe cases. Acute GVHD was independently associated with inferior survival (HR 2.40, p<0.001), particularly grade III-IV disease (HR 4.34, p<0.001). These findings define the contemporary real-world burden of GVHD in a high-volume European country and provide an updated epidemiologic framework to inform preventive strategies, clinical trial design, and healthcare planning in modern alloHSCT.

Haploidentical stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) is a therapeutic option for secondary acute myeloid leukemia (sAML). The study aimed to compare peripheral blood stem cells (PBSC) vs. bone marrow (BM) as a graft source for haplo-HSCT with PTCy in patients with sAML in first complete remission. A total of 554 patients were included, BM = 136, PBSC = 418. Median follow-up was 3 years. The median year of transplant was 2018 (range, 2010-2021). The antecedent hematological disease was myelodysplastic syndrome /myeloproliferative neoplasms in most patients. Patients in the BM group were younger, median age 59.2 vs. 61.7 years (p = 0.008), and received myeloablative conditioning more frequently (66.4% vs. 47.4%, p < 0.001). Time from diagnosis to haplo-HSCT was 5.3 vs. 4.8 months, respectively (p = 0.019). Performance status, cytogenetic risk, gender, cytomegalovirus serostatus, and donor age did not differ. There were no differences between the groups with respect to main transplantation outcomes. In conclusion, outcomes of haplo-HSCT with PTCy in sAML with either PBSC or BM grafts are similar, with no differences in major transplantation outcomes.

Limited data is available on outcomes of mixed phenotype acute leukemia (MPAL) following allogeneic stem cell transplantation (HCT), and the impact of haploidentical HCT with post-transplant cyclophosphamide in this setting is lacking. We retrospectively analyzed 195 adults with MPAL undergoing HCT in first complete remission from 2014 to 2023. The 2-year overall survival (OS) and leukemia free survival (LFS) were 70.7% and 56.4%. Relapse incidence (RI) was 29.8% and non-relapse mortality was 13.8% at 2 years. The cumulative incidence of grade II-IV and III-IV acute graft versus host disease (GvHD) was 28.8% and 9.3% at 100 days. The 2-year cumulative incidence of chronic GvHD was 36.6%. The 2-year GvHD-free-relapse free survival was 37.6% (95%CI 29.9-45.3%). In multivariate analysis, patients undergoing myeloablative conditioning had better OS (HR 0.5, 95%CI 0.27-0.93, p = 0.03) and LFS (HR 0.49, 95%CI 0.26-0.94, p = 0.03). The use of peripheral blood was associated with better LFS (HR 0.36, 95%CI 0.17-0.76, p = 0.008) and lower RI (HR 0.33, 95%CI 0.12-0.93, p = 0.04). In vivo T-cell depletion was associated with lower incidence of chronic GvHD (HR 0.32, 95%CI 0.17-0.63, p < 0.001). These findings highlight that conditioning intensity, graft source, and T-cell depletion strategies are critical factors in optimizing transplant outcomes for MPAL.

The approval of CD19 chimeric antigen receptor T-cell (CAR-T) therapy in the second-line (2L) setting for large B-cell lymphoma (LBCL) has reshaped treatment sequencing and the population at risk for post-CAR-T relapse; however, management after failure of early-line CAR-T therapy remains informed largely by later-line cohorts. We conducted an international, multicenter retrospective study of adults with LBCL treated with 2L or third-line (3L) CAR-T therapy to evaluate clinical characteristics, salvage strategies, and outcomes following relapse or progression. Among 545 patients, the 1-year cumulative incidence of relapse or progression after CAR-T was 40%. Of 235 patients who relapsed or progressed, 193 received salvage therapy, with an overall response rate (ORR) of 47%. One-year event-free survival (EFS) and overall survival (OS) after salvage were 18% and 44%, respectively. Outcomes were comparable after 2L and 3L CAR-T therapy, with no independent association between CAR-T line and EFS or OS in multivariable analyses. Relapse within 3 months of CAR-T infusion was strongly associated with inferior response and survival. Post-CAR-T salvage therapy consisted of heterogeneous regimens, most commonly polatuzumab-bendamustine-rituximab and CD20 × CD3 bispecific antibody monotherapy. Response rates and short-term survival varied across approaches, with bispecific antibody monotherapy having the highest ORR (65%) and favorable 1-year outcomes (OS 56%; EFS 43%). In this contemporary multicenter cohort, salvage therapy after CAR-T failure achieved objective but often short-lived responses, with outcomes driven by relapse timing after CAR-T infusion rather than the line of prior CAR-T therapy, supporting individualized treatment selection in this high-risk setting.