Calcineurin inhibitors balance graft-versus-host disease (GvHD) prevention against graft-versus-leukemia (GvL) effects after allogeneic hematopoietic cell transplantation (allo-SCT). Whether the magnitude of early tacrolimus exposure influences relapse or survival remains unclear. We retrospectively studied 122 adults with AML (n = 80) or MDS (n = 42) undergoing 10/10 matched-unrelated donor (MUD) allo-SCT from 2014 to 2021. All received rabbit anti-thymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) for GvHD Prophylaxis. Tacrolimus exposure was quantified as area under the concentration-time curve over days 1-30 (AUC30) and 1-100 (AUC100). Primary endpoints were overall survival (OS) and event-free survival (EFS); secondary endpoints were cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and GvHD. Analyses included median splits, quartiles/deciles, competing-risks models, Cox regression, and smoothed 5-year KM estimates across continuous AUC30. Patients with relapse/death before day + 30/+100 were excluded from the respective AUC analyses. Median follow-up was 61 months; 5-year OS and EFS were 68% and 43%. Neither AUC30 nor AUC100 (median split or quartiles) was associated with OS, EFS, CIR, or NRM. In multivariable models, tacrolimus exposure was not significant; worse outcomes correlated with older age and female donor for OS, and with AML diagnosis and no CR at allo-SCT for EFS. Smoothed survival across continuous AUC30 showed no meaningful gradient. Any-grade and severe aGvHD, and overall/grade ≥ III chronic GvHD, were comparable across exposure groups. Within a homogeneous MUD/ATG/MMF setting, early tacrolimus exposure did not independently predict relapse, NRM, EFS, or OS. Patient and donor factors outweighed tacrolimus AUC. Findings argue against AUC-targeting to improve outcomes; risk-adapted tapering and MRD-guided interventions may offer greater leverage.

Exploration of In Vivo T-cell Depletion protocols in Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies.

The aim of the study was to compare post-transplant cyclophosphamide (PTCY)-based regimens with historical regimens using calcineurin inhibitor and methotrexate (CNI-MTX) for allogeneic hematopoietic stem-cell transplant (HCT) in nonmalignant hematologic disorders. We conducted a single-center, retrospective review of patients with acquired severe aplastic anemia (N = 18) or Diamond-Blackfan anemia (N = 1) who underwent allogeneic HCT from 2011 to 2024. Patients received graft-versus-host disease (GVHD) prophylaxis with either CNI-MTX or PTCY-mycophenolate mofetil-tacrolimus. Primary endpoints were overall survival (OS) and disease-free survival (DFS) without graft failure at 1 year after transplantation. In the CNI-MTX cohort (N = 14) with severe aplastic anemia, 11 patients received fludarabine-cyclophosphamide-thymoglobulin (ATG)-total body irradiation (TBI), while three received cyclophosphamide-ATG allogeneic HCT. Donors were matched-unrelated (N = 7), matched-related (N = 6), or mismatched-unrelated (N = 1). Graft sources included bone marrow (N = 12) or peripheral blood stem cells (N = 2). One patient developed grade 3 skin acute GVHD, and none had chronic GVHD. There was primary graft failure (N = 6), stable mixed T-cell chimerism (N = 4), and 100% donor chimerism (N = 4). Four patients with primary graft failure underwent salvage second transplants at a median of 103 days (35-322) after the first transplant. Five patients with primary graft failure died at a median of 6 months (0.89-9.3) from the first transplant. The PTCY cohort (N = 5) included four patients with severe aplastic anemia and one with Diamond-Blackfan anemia. All underwent fludarabine-cyclophosphamide-ATG-TBI allogeneic HCT. Donors were matched-related (N = 1), matched-unrelated (N = 2), syngeneic (N = 1), or haploidentical (N = 1). Graft source was peripheral blood stem cells (N = 3) for matched-related, matched-unrelated, and syngeneic transplants, and bone marrow (N = 2) for haploidentical and matched-unrelated donor transplants. Donor chimerism was 100% (N = 3) and mixed chimerism (N = 2). All patients became transfusion-independent, and none developed GVHD or graft failure. The 1-year OS rate was 64.29% vs. 100%, the 1-year DFS rate was 57.14% vs. 100%, and the 1-year GVHD-free, graft failure-free survival (GRFS) was 50% vs.100% for the CNI-MTX and PTCY cohorts, respectively. Despite a trend toward better OS, DFS, and GRFS for PTCY, the OS, DFS, and GRFS time distributions were not statistically significantly different (P = 0.1448, 0.0919, and 0.0627, respectively). Allogeneic HCT with uniform conditioning of fludarabine-cyclophosphamide-ATG-TBI with PTCY GVHD prophylaxis is effective for adults with severe aplastic anemia or Diamond-Blackfan anemia across donor types (matched-related, syngeneic, matched-unrelated, haploidentical) and should be prospectively compared with historical regimens using CNI-MTX GVHD prophylaxis.

Peripheral Blood or Bone Marrow Grafts for Mismatched Unrelated Donors with Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis.

Matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) is a viable curative option for children with transfusion-dependent thalassemia major lacking a matched sibling donor. This study aimed to evaluate outcomes of MUD-HSCT in pediatric patients (≤ 12 years) because data on such a cohort are sparse. A retrospective analysis was conducted on 25 patients with thalassemia (≤12 years) who underwent MUD-HSCT. Data on patient demographics, transplant characteristics, post-transplant complications, and survival outcomes were collected. Kaplan-Meier survival analysis was used to estimate overall survival (OS), thalassemia-free survival (TFS), graft-versus-host and relapse-free survival (GRFS), and graft-versus-host and thalassemia-free survival (GTFS). Cox regression analysis was performed to identify predictors of GRFS. Median age at transplantation was 9 years; 60.9% were male. Most patients (68%) were Nanfang Class III. Median ANC and platelet engraftment occurred at 16 and 15 days, respectively. Acute and chronic GVHD were observed in 52% and 16% of patients, respectively. CMV reactivation occurred in 24%. Estimated 5-year OS, TFS, GRFS, and GTFS were 95.8%, 92%, 75.8%, and 92%, respectively. Elevated ferritin levels > 2500 ng/mL were independently associated with inferior GRFS (HR: 0.040; p-value = 0.031). In conclusion, MUD-HSCT yields excellent outcomes for OS and TFS in pediatric patients with thalassemia aged ≤ 12 years. High pre-transplant ferritin adversely impacted GRFS, underscoring the importance of iron control. These findings support MUD-HSCT as a viable option with appropriate pre-transplant optimization and GVHD management.

Post-transplant cyclophosphamide (PTCy) is associated with infectious and organ toxicities. Dose optimization may reduce these risks while maintaining efficacy. We initiated a prospective pilot study in July 2024 evaluating reduced-dose PTCy (35 mg/kg on days +3 and +4; PTCy70) with low-dose anti-thymocyte globulin (ATG) (2 mg/kg) in adults with acute myeloid leukaemia (AML) undergoing matched unrelated donor (MUD) transplantation. Outcomes were compared with a contemporary cohort receiving PTCy100 with ATG 2 mg/kg. Of 173 patients, 41 received PTCy70. Platelet engraftment was faster with PTCy70, 13 vs. 16 days (p < 0.001). In multivariable analysis, PTCy70 was associated with lower risk of bloodstream infections (hazard ratio [HR] 0.39, 95% confidence interval [CI], 0.19-0.78, p = 0.007). At day+100, the incidence of grade II-IV (30.4% vs. 20.3%, p = 0.17), grade III-IV acute graft-versus-host disease (GVHD) (3% vs. 3%, p = 0.08) and non-relapse mortality (3.8% vs. 2.8%, p = 0.67) were similar between groups. Cardiac events were less frequent with PTCy70 (5% vs. 17%; p = 0.06). No cases of sinusoidal obstruction syndrome were observed in the PTCy70 group. At 12 months, relapse (11.1% vs. 15.3%, p = 0.88) and overall survival (79.6% vs. 83.2%, p = 0.87) did not differ between groups. PTCy70 was associated with faster platelet engraftment, fewer bloodstream infections and cardiac events without compromising GVHD, relapse or survival, supporting evaluation in randomized trials.

Hematopoietic stem cell transplantation (HSCT) is a curative option for children with high-risk acute lymphoblastic leukemia (ALL). This retrospective single-center study analyzed 236 pediatric ALL patients in complete remission who underwent allogeneic HSCT using ex-vivo T cell depletion between 2012 and 2021. The majority received haploidentical grafts (n = 202), while the remainder received matched unrelated donor (MUD) grafts (n = 34). At four years, event-free survival (EFS) and overall survival (OS) were 57% and 67%, respectively. Total body irradiation (TBI)-based conditioning was associated with significantly lower relapse rates and superior EFS compared to chemotherapy-based regimens. Non-relapse mortality (NRM) was low (9%), with no significant difference between donor types. Pre-transplant minimal residual disease (MRD) positivity and transplantation beyond first complete remission were independently associated with higher relapse and inferior survival. Chronic GVHD incidence was lower in patients receiving abatacept and tocilizumab instead of ATG. These findings confirm the safety and efficacy of ex-vivo T cell-depleted HSCT in pediatric ALL, with outcomes comparable between haploidentical and MUD donors. TBI-based conditioning and MRD negativity remain key prognostic factors for improved outcome.

Donor evaluation is a vital aspect of hematopoietic stem cell transplantation (HSCT), ensuring both donor suitability and recipient safety.Along with confirmatory human leukocyte antigen (HLA) typing, infectious disease marker (IDM) testing remains crucial.It helps prevent transmissible infections and improves the outcomes of HSCT.In India, while the trend of haploidentical (half-match) donors is increasing, matched unrelated donor (MUD) HSCT is still clinically relevant.However, to the best of our knowledge, no published Indian data exist on IDM profiles specifically for HSCT MUDs.We reviewed IDM testing results of 42 consecutive potential MUDs identified between May 2012 and December 2024 in Northern India.All donors provided written consent, and we collected anonymized data under ethical approval.The evaluation included enhanced chemiluminescence immunoassay (Vitros 3600, Quidel Ortho, United States) for anti-HIV I/II, anti-HCV, HBsAg, anti-HBc (total IgG IgM), anti-CMV IgG and IgM, and syphilis testing; a malaria rapid detection test; and individual donor nucleic acid testing (ID-NAT, Procleix Ultrio Plus, Grifols) for HIV RNA, HBV DNA, and HCV RNA.All 42 potential MUDs tested negative for HIV, HBV, HCV, syphilis, and malaria, including NAT results.Importantly, all were positive for anti-CMV IgG while negative for IgM, as shown in Table 1.This finding suggests prior CMV exposure, which is common in adult populations since CMV seroprevalence increases with age. 1 The mean age of donors in this study was 35.69 years.This universal CMV IgG seropositivity aligns with previous reports of high CMV seroprevalence in Indian adults (98.6%). 1 Given CMV's well-established role as a major infectious complication after HSCT, donor-recipient serological matching assumes clinical significance. 2Among potential recipient (R)-donor (D) combinations, the R /Dscenario carries the

β-thalassemia and sickle cell disease are two inherited hematological diseases due to defective hemoglobin synthesis or to the production of hemoglobin with altered properties. These two conditions have prolonged survival with modern support therapies, albeit life-long, complex, expensive and resource-consuming. Studies carried out in the last three decades have shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) and gene therapy may offer a curative approach for these diseases. Allo-HSCT should be performed early in life to reduce disease-related complications like irreversible tissue damage due to iron overload in patients with transfusion-dependent β-thalassemia (TDT) and systemic vasculopathy in patients with sickle cell disease (SCD). HSCTs from a matched-sibling donor or a matched-unrelated donor represent the best therapeutic option; however, haploidentical HSCT in both TDT and SCD is now increasingly performed as a valuable and viable option for a larger number of these patients. An alternative curative strategy is based on gene therapy. These curative approaches, particularly those of gene therapy, are available only in a part of the world. Gene therapy diffusion is strongly limited by its high technological and infrastructure requirements and its very high cost. Criteria must be defined for the optimal selection of TDT and SCD patients for allo-HSCT or gene therapy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for aplastic anemia (AA). For patients lacking a matched sibling donor (MSD) or matched unrelated donor (MUD), haploidentical HSCT (haplo-HSCT) has become an alternative with comparable efficacy. However, donor-specific anti-HLA antibodies (DSAs) remain the principal barrier. In this study, we compared transplant outcomes in DSA-positive recipients after desensitization with plasma exchange (PE) combined with anti-B-cell therapy.Between January 2019 and December 2023, we enrolled 30 DSA-positive AA patients who underwent haplo-HSCT at our center. All received a desensitization regimen combining PE with anti-B-cell agents. By propensity-score matching (1:2 ratio, caliper 0.02), we additionally enrolled 60 DSA-negative controls matched for key clinical variables to compare therapeutic efficacy and long-term outcomes between the two groups.This study enrolled 90 AA patients who underwent haplo-HSCT: 30 were DSA-positive and 60 were DSA-negative. Baseline characteristics were comparable between the two groups. After desensitization with PE combined with anti-B-cell agents, the DSA-positive group achieved outcomes equivalent to those of the DSA-negative group. Specifically, EBV reactivation (46.7% vs. 68.3%; P = 0.002) was significantly better in the DSA-positive group. Engraftment, aGVHD, Effacacy, OS, and GRFS rates were similar between two groups. However, the risk of cGVHD remains higher in the DSA-positive group (40% vs. 12%; P = 0.009).For DSA-positive AA patients who are candidates for haplo-HSCT and for whom no DSA-negative donor can be identified, desensitization with PE combined with anti-B-cell agents represents an established strategy to improve transplant outcomes; nevertheless, close surveillance for cGVHD is warranted after transplantation.

Safety and Efficacy of CD19 CAR T-Cells Manufactured Post First HSCT and Administered Following a Second HSCT from a Different 10/10 HLA Matched Unrelated Donor to a Child with Multiple Relapsed B-ALL.

The prognostic significance of traditional donor selection criteria for human leukocyte antigen (HLA)-matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) is uncertain in the era of post-transplant cyclophosphamide (PTCy). We re-evaluated the impact of donor age, sex, cytomegalovirus (CMV) serostatus, and ABO compatibility in a large, contemporary cohort of patients receiving PTCy-based graft-versus-host disease (GVHD) prophylaxis. We retrospectively analyzed 699 patients who underwent an 8/8 HLA-matched MUD HCT with PTCy. We assessed the impact of donor characteristics on overall survival (OS), progression-free survival (PFS), relapse, nonrelapse mortality, GVHD, and engraftment. Least absolute shrinkage and selection operator regression confirmed variable selection. Recipient-related factors, specifically the disease risk index and HCT-comorbidity index, were the primary determinants of OS and PFS. By contrast, traditional donor characteristics had a limited impact on survival. Donor age, analyzed as a continuous variable, was not associated with OS (hazard ratio [HR], 0.99 [95% CI, 0.978 to 1.011]; P = .524). Similarly, donor CMV and ABO compatibility did not influence survival. The effect of donor-recipient sex mismatch was primarily limited to modulating GVHD risk. Female-to-male sex mismatch had higher hazard for grade 3-4 acute GVHD (aGVHD) (HR, 3.08 [95% CI, 1.15 to 8.20]; P = .025; adjusted P = .222), whereas male-to-female grafts were associated with a 42% reduction in the hazard for grade 2-4 aGVHD (95% CI, 0.39 to 0.87; P = .009; adjusted P = .045). Major ABO mismatch was associated with delayed neutrophil engraftment in bone marrow grafts but not in peripheral blood grafts. Collectively, these findings suggest that for patients receiving PTCy, the hierarchy of donor selection factors might have evolved, allowing for greater flexibility in donor choice. Our findings provide a solid foundation for future larger external validation studies.

Long-term outcomes of αβ T-cell/CD19 B-cell-depleted peripheral blood stem cell transplantation from unrelated donors in pediatric and adolescent patients with severe aplastic anemia: a single-center study.

Donor Search and Selection Strategy to Facilitate Comparable Transplant Rates across Donor Search Prognosis Groups: A Report from the BMT CTN 1702 Trial.

Cord blood transplantation (CBT) is an alternative donor option for patients lacking suitable matched donors, particularly in high-risk acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). We retrospectively analyzed 76 adults undergoing reduced-intensity conditioning allogeneic transplantation using one of five donor types: CBT with ultra–low-dose methotrexate (uldMTX; n = 47), matched related donor (MRD), matched unrelated donor (MUD), mismatched unrelated donor (MMUD), or mismatched related donor (MMRD) (n = 29 across the four donor types). Two-year overall survival (OS) with uldMTX-CBT (58.8%) was significantly superior to MRD, MUD, and MMRD transplantation, with similar patterns for disease-free survival (DFS). In multivariate analyses, CBT remained independently associated with improved OS and DFS. Neutrophil and platelet recovery were comparable across donor types, as were the incidences of graft-versus-host disease and non-relapse mortality. These findings indicate that CBT provides a safe and effective donor platform with competitive outcomes across diverse alternative donor settings in high-risk AML/MDS.

Introduction CD40 ligand (CD40L) deficiency is a rare X-linked primary immunodeficiency. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment. To date, regional studies have focused on reporting the clinical characteristics of this disease rather than transplant outcomes. This study aims to characterize pediatric patients with CD40L deficiency who have undergone HSCT in centers from Chile, Colombia, Brazil, Mexico, and Argentina. Objectives include describing clinical features, evaluating survival, identifying mortality-associated factors, and reporting major posttransplant complications. Methods We retrospectively reviewed pediatric patients with CD40L deficiency who underwent HSCT between January 2002 and December 2024. We analyzed clinical characteristics, survival outcomes, and complications. Descriptive statistics were used, and overall survival was estimated using Kaplan–Meier analysis. During this period, 27 patients with CD40L deficiency were included in the study. For one patient, data from a second HSCT were also collected. Results Twenty-seven pediatric patients with CD40L deficiency underwent HSCT, with a median age at transplant of 6 years (range 1–18). A confirmed genetic diagnosis was present in 96% of cases, and 12 patients (44%) had a positive family history. Pretransplant complications included pneumonia in 14 patients (52%), gastrointestinal symptoms in 15 patients (56%), neutropenia (26%), and cholangitis (11%). Infectious history included Pneumocystis jirovecii (22%), CMV (7%), Cryptosporidium (15%), and Candida (26%). Intravenous immunoglobulin (IVIG) supplementation was administered before transplant in 96% of patients, and 67% continued IVIG posttransplant. Cotrimoxazole prophylaxis was given prior to HSCT in 93% of cases. Unrelated donors were used in 70% of patients, and most received conditioning with treosulfan/busulfan plus fludarabine. Graft versus host disease (GVHD) prophylaxis included antithymocyte globulin (ATG) in 59% of patients and calcineurin inhibitors in 96%. Engraftment was achieved in 93% of patients, and 3 required a second transplant. Acute GVHD grade III–IV occurred in 30%, and chronic GVHD in 26%. CMV occurred in 10 patients, with one fatal case. A total of four deaths were reported—three were HSCT-related. Overall survival was 83.6% at 1 year, 78.7% at 3 years, and 78.7% at 5 years. Conclusions This multicenter retrospective study analyzed pediatric patients with CD40L deficiency who underwent HSCT. The cohort showed favorable 5-year overall survival. A genetic diagnosis was confirmed in 96% of patients, while one-third had a positive family history. Most patients experienced significant complications prior to transplant, and HSCT was delayed by a median of 5.5 years. Prophylaxis included IVIG in 96% of cases and cotrimoxazole in 93%. Most transplants used matched unrelated donors (MUD), with busulfan/fludarabine-based conditioning regimens. Conditioning approaches varied by center. Serotherapy (mainly ATG) was used in 70% of patients. Engraftment was successful in 93% of cases. Posttransplant complications were frequent. Acute GVHD occurred in 30% of patients, mostly in severe forms (grade III–IV), while 26% developed chronic GVHD. CMV reactivation was reported in 44%, and graft-related complications (“graft problems”), including secondary graft failure and mixed chimerism, were observed in 26% of cases.

Abstract Introduction The American Society of Clinical Oncology recommends discussing infertility risks from gonadotoxic chemotherapy and radiotherapy and offering fertility preservation (FP) options as soon as able. As cancer survival rates rise, flexible, patient-centered strategies become imperative. While semen cryopreservation is straight forward for adult males, it poses challenges for pre or peripubertal boys due to age-related, anatomical and psychosocial factors. In such cases, testicular sperm extraction (TESE) provides a viable option for fertility preservation. Objective We present two cases where TESE was performed before pediatric oncological treatment in exceptional scenarios, highlighting its safety and effectiveness in various clinical settings Methods Two male patients with new urgent oncologic diagnoses required immediate gonadotoxic chemotherapy. The first patient was 14-years-old, Tanner 4, with Hypogammaglobulinemia and CD40 Ligand Deficiency. He underwent chemotherapy and subsequent allogeneic Matched Unrelated Donor Stem Cell Transplant. After two unsuccessful ejaculate sperm-freezing attempts, he underwent an uneventful office-based TESE under local anesthesia. The second patient, a 14-year-old Tanner 5, with Diffuse Large B Cell Lymphoma, had mediastinal lymphadenopathy and underwent intubation and a round of chemo. He then had urgent bedside TESE performed in the ICU after receiving one cycle of cyclophosphamide, as semen collection from ejaculate was not feasible due to intubation and critical condition. Both cases used a horizontal scrotal incision and window technique for testicular tissue retrieval. Extracted tissue was transferred in sperm transport media for FP and cryopreservation. Results In the first case, initial samples yielded one to four non-motile sperm per high-power field (hpf), with final samples revealing 2 non-motile sperm/hpf. Sperm preservation yielded three motile sperm per slide. The patient started chemotherapy the day after. In second case, initial samples revealed approximately three non-motile sperm/hpf, with processed samples showing 5-6 non-motile sperm/hpf, all cryopreserved in three vials. The patient continued chemotherapy right after TESE. There were no infections, hematomas or delays in chemotherapy. The procedure and postoperative recovery were uneventful in both cases. Conclusions These cases demonstrate TESE’s utility in FP for adolescent cancer patients facing gonadotoxic therapies, particularly when ejaculation is not feasible. TESE can be performed under local anesthesia, including in ICU settings for critically ill patients. Collaborative multidisciplinary FP care teams are crucial for optimizing options for pediatric patients requiring rapid oncologic treatment. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Dr. Helen L. Bernie is a consultant for Boston Scientific, Coloplast, and BK Ultrasound

ABSTRACTAllogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for secondary acute myeloid leukemia (sAML). This study compared haploidentical donor (Haplo), matched sibling donor (MSD), and matched unrelated donor (MUD) HSCT in patients with sAML in first complete remission (CR1). Data from 3862 patients (Haplo = 643, MSD = 715, MUD = 2504) transplanted between 2010 and 2022 were analyzed, with a median follow‐up of 3.3 years. Groups differed in patient and donor age, conditioning regimen, stem cell source, and graft‐versus‐host disease (GVHD) prophylaxis. Multivariate analysis showed that MSD‐HSCT had a higher relapse risk than Haplo‐HSCT (hazard ratio [HR]: 1.64) but lower non‐relapse mortality (NRM, HR: 0.32) and acute GVHD risk (HR: 0.54 for grade II–IV), leading to an overall survival (OS) benefit (HR: 0.76). MUD‐HSCT had lower NRM than Haplo‐HSCT (HR: 0.63) but there were no significant differences in OS or GVHD risk. Donor type did not impact leukemia‐free survival (LFS) or GVHD‐free and relapse‐free survival (GRFS). Adverse cytogenetics and reduced‐intensity conditioning were associated with increased relapse risk, while lower Karnofsky scores, older age, and adverse cytogenetics independently predicted worse NRM, LFS, OS, and GRFS outcomes. Female‐to‐male donor‐recipient pairs had an increased risk of chronic GVHD. In this registry‐based analysis, MSD offered the best outcomes for sAML in CR1. Haplo‐HSCT was comparable to MUD‐HSCT, despite a higher NRM, and achieved long‐term disease control in 60% of patients due to a low relapse incidence. In the absence of an MSD, both Haplo and MUD are viable alternatives.

The optimal alternative donor for relapsed/refractory acute lymphoblastic leukemia (R/R ALL) patients remains controversial. We retrospectively analyzed adult R/R ALL patients who underwent a first allogeneic hematopoietic cell transplantation (allo-HCT) between 2010 and 2022 from either a haploidentical donor (Haplo-HCT) or a 10/10 matched unrelated donor (MUD-HCT). The analysis comprised 249 patients (80 Haplo-HCT and 169 MUD-HCT). For graft-versus-host disease (GVHD) prophylaxis, all Haplo-HCT recipients received post-transplant cyclophosphamide (PTCy)-based regimen, whereas all MUD-HCT recipients received anti-thymocyte globulin (ATG) only. After propensity score matching, 47 Haplo-HCT and 69 MUD-HCT recipients were enrolled. No significant differences were observed in the incidence of Day 180 grade II-IV aGVHD (34.4% vs. 26.8%; P = 0.27), or 2-year cGVHD (19.2% vs. 13.8%; P = 0.543). However, the incidence of Day 180 grade III-IV aGVHD was significantly higher in the Haplo-HCT group (23.4% vs. 8%; P = 0.048). Two-year overall survival (31.8% vs. 29.2%; P = 0.742), leukemia-free survival (20.4% vs. 24.4%; P = 0.531), relapse incidence (48.1% vs. 53.1%; P = 0.113), or non-relapse mortality (31.5% vs. 22.5%; P = 0.191) were comparable between Haplo-HCT group and MUD-HCT group, respectively. In conclusion, despite a higher incidence of grade III-IV aGVHD, outcomes for R/R ALL patients receiving Haplo-HCT with PTCy were comparable to those receiving 10/10 MUD-HCT with ATG.

Haploidentical Versus Matched Sibling Donor HCT in Racially Diverse Pediatric and AYA Patients with Hematologic Malignancies: A Single-Center Comparison.