Allogeneic Hematopoietic Stem Cell Transplantation Research Articles

Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia.

FMS-like tyrosine kinase 3 (FLT3) mutations are genetic changes found in approximately thirty percent of patients with acute myeloid leukemia (AML). FLT3 mutations in AML represent a challenging clinical scenario characterized by a high rate of relapse, even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The advent of FLT3 tyrosine kinase inhibitors (TKIs), such as midostaurin and gilteritinib, has shown promise in achieving complete remission. However, a substantial proportion of patients still experience relapse following TKI treatment, necessitating innovative therapeutic strategies. This review critically addresses the current landscape of TKI treatments for FLT3+ AML, with a particular focus on gilteritinib. Gilteritinib, a highly selective FLT3 inhibitor, has demonstrated efficacy in targeting the mutant FLT3 receptor, thereby inhibiting aberrant signaling pathways that drive leukemic proliferation. However, monotherapy with TKIs may not be sufficient to eradicate AML blasts. Specifically, we provide evidence for integrating gilteritinib with mammalian targets of rapamycin (mTOR) inhibitors and interleukin-15 (IL-15) complexes. The combination of gilteritinib, mTOR inhibitors, and IL-15 complexes presents a compelling strategy to enhance the eradication of AML blasts and enhance NK cell killing, offering a potential for improved patient outcomes.

Impact of “day 90” CD4+ T cells on clinical outcomes in children with relapsed/refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

BackgroundThe severity of complications after hematopoietic stem cell transplantation (HSCT) is dictated by the degree of immune reconstitution. However, the connection between immune reconstitution and the prognosis of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. Therefore, the aim of this study was to evaluate the impact of lymphocyte subsets in children diagnosed with refractory or relapsed acute myeloid leukemia (R/R-AML) after allo-HSCT. MethodsWe retrospectively investigated the prognosis and lymphocyte subsets at d 90 (D90) post-allo-HSCT in 130 children diagnosed with R/R-AML between September 2019 and October 2022 at the Children's Hospital of Soochow University. Lymphocyte subgroups were assessed by flow cytometric analysis on D90 and compared among human leukocyte antigen (HLA)-matched sibling donor HSCT (MSD) (n = 14), haploidentical donor HSCT (n = 94), and HLA-matched unrelated donor HSCT (n = 22) groups. The associations between the counts and frequencies of lymphocyte subgroups and prognosis were assessed. ResultsIn the MSD group, CD4+ T cell frequency and count were the highest (P < 0.001). Among the examined lymphocyte subsets, a lower proportion of CD4+ T cells (<14.535 %) at D90 correlated with a higher risk of cytomegalovirus infection (P = 0.002). A higher CD4+ T cell count (>121.39/μL) at D90 after HSCT was the single predictor of a lower fatality risk across all lymphocyte subgroups (univariate: P = 0.038 cut-off: 121.39/μL; multivariate: P = 0.036). No association with relapse was observed. ConclusionsCD4+ T cell count may be used to identify pediatric patients with R/R-AML with a greater mortality risk early after HSCT.

Deciphering bone marrow engraftment after allogeneic stem cell transplantation in humans using single-cell analyses.

BACKGROUNDDonor cell engraftment is a prerequisite of successful allogeneic hematopoietic stem cell transplantation. Based on peripheral blood analyses, it is characterized by early myeloid recovery and T and B cell lymphopenia. However, cellular networks associated with bone marrow engraftment of allogeneic human cells have been poorly described.METHODSMass cytometry and CITE-Seq analyses were performed on bone marrow cells 3 months after transplantation in patients with acute myelogenous leukemia.RESULTSMass cytometric analyses in 26 patients and 20 healthy controls disclosed profound alterations in myeloid and B cell progenitors, with a shift toward terminal myeloid differentiation and decreased B cell progenitors. Unsupervised analysis separated recipients into 2 groups, one of them being driven by previous graft-versus-host disease (R2 patients). We then used single-cell CITE-Seq to decipher engraftment, which resolved 36 clusters, encompassing all bone marrow cellular components. Hematopoiesis in transplant recipients was sustained by committed myeloid and erythroid progenitors in a setting of monocyte-, NK cell-, and T cell-mediated inflammation. Gene expression revealed major pathways in transplant recipients, namely, TNF-α signaling via NF-κB and the IFN-γ response. The hallmark of allograft rejection was consistently found in clusters from transplant recipients, especially in R2 recipients.CONCLUSIONBone marrow cell engraftment of allogeneic donor cells is characterized by a state of emergency hematopoiesis in the setting of an allogeneic response driving inflammation.FUNDINGThis study was supported by the French National Cancer Institute (Institut National du Cancer; PLBIO19-239) and by an unrestricted research grant by Alexion Pharmaceuticals.

Recent advances in acute gastrointestinal graft versus host disease (aGvHD): aspects of steroid-resistant disease.

Acute Graft versus Host Disease (aGvHD) is a common immunological complication occurring in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Moreover, aGvHD is associated with a higher risk of infections and metabolic complications, affecting non-relapse mortality. Progress in transplantation has changed the prophylactic and therapeutic strategies of aGvHD and improved patient outcomes. The standard first-line therapy remains steroids, with a response rate of about 50%. The Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, is an effective second-line therapy. The management of patients who developed a disease that is refractory to steroids and ruxolitinib, especially in the severe gastrointestinal forms of aGvHD, is not validated and remains an unmet medical need. In the article, we present the current clinical practice, as well as the latest advances targeting pathophysiological pathways of GvHD and gut microbiota, which may be a potential future of aGvHD therapy.

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n= 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B.ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B.ovatus.

Utilization of allogeneic hematopoietic stem cell transplantation among patients with newly diagnosed acute myeloid leukemia in California: a population-based linked dataset study.

Acute myeloid leukemia (AML) often requires allogeneic hematopoietic cell transplantation (alloHCT) for cure, but historically alloHCT has been strikingly underutilized. Reasons for this remain uncertain at the population level. We examined alloHCT utilization over time and explored associations between demographic/healthcare factors and use of alloHCT by age group (AYA 15-39y, adult 40-64y, older adult 65-79y) using a linked dataset merging the Center for International Blood and Marrow Transplant Research, California Cancer Registry, and California Patient Discharge Database. Eligibility included patients newly diagnosed with AML in California between 2001-2016 who received induction therapy and had no prior HCT. Multivariable Fine-Gray regression analyses were fitted separately across age groups. Among 7,925 patients with AML, alloHCT utilization increased over time across all age groups; however, in the most recent time period studied (2011-2016), utilization within 2 years of diagnosis remained lowest in older adults (13%) relative to adults (41%) and AYAs (49%). Factors statistically significantly associated with lower alloHCT utilization: (1) AYAs: female sex, lower neighborhood socioeconomic status (nSES), uninsured or Indian Health Services (IHS) coverage; (2) adults: older age, male sex, non-Hispanic Black or Asian race and ethnicity, unmarried, lower nSES, uninsured or covered by Medicaid, Medicare, or IHS, higher comorbidity, and living 100+ miles from a transplant center; and (3) older adults: older age, Asian race, and unmarried. In conclusion, using a population-based linked dataset, we demonstrate that utilization of alloHCT among older patients newly diagnosed with AML remains low in California, and factors associated with utilization vary by age group.

Real-World Impact of Routine Addition of Antithymocyte Globulin to Standard GVHD Prophylaxis in Myeloablative Unrelated Donor Transplants: Important Gains in Graft-versus-Host Disease Prevention though No Difference in Overall Survival

Introduction: Antithymocyte globulin (ATG) has been demonstrated to reduce the incidence of graft-versus-host disease (GVHD); however, it remains controversial whether these gains are offset by an increase in relapse. Methods: We conducted a retrospective historical control study consisting of patients (n = 210) who underwent myeloablative allogeneic hematopoietic stem-cell transplantation (HSCT) from 2014 to 2020. Results: The incidence of acute GVHD was lower in the ATG group (51.4%) than the non-ATG group (control) (70.0%, p = 0.010). The incidence of chronic GVHD was also lower in the ATG group at 1-year (36.4% vs. 62.9%, p < 0.001) and 2-year (40.0% vs. 65.7%, p < 0.001) post-HSCT. The mortality due to GVHD was higher in the control (18.5%) than the ATG group (4.3%; p = 0.024). The severe GVHD-relapse-free survival was higher in the ATG group (36.4%) than the control (12.9%; p < 0.001). Nevertheless, the 2-year overall survival was similar. Conclusion: Our results confirm the effectiveness of ATG in prevention of GVHD in the real-world setting and enhanced GVHD-free survival. An important result is the equalization of overall survival between the ATG and control groups at 1- and 2-year post-HSCT and implies that earlier GVHD-associated mortality may be offset by later relapse mortality producing similar overall survival over time.

Clinical impact of airflow obstruction after allogeneic hematopoietic stem cell transplantation

Criteria for airflow obstruction (AFO) at one year after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pulmonary function tests (PFTs) are more stringent than the bronchiolitis obliterans syndrome (BOS) criteria of the National Institutes of Health. This single-center, retrospective cohort study evaluated the clinical impact of the AFO criteria at any time after transplantation. In 132 patients who underwent allo-HSCT from 2006 to 2016, the 2-year cumulative incidence of AFO was 35.0%, and the median time to diagnosis of AFO was 101 days after transplantation (range 35–716 days). Overall chronic graft-versus-host disease (cGVHD) incidence was significantly higher in patients with AFO than in those without AFO (80.4% vs. 47.7%, P < 0.01); notably, 37.0% of patients with AFO developed cGVHD after AFO diagnosis. AFO patients developed BOS with a 5-year cumulative incidence of 49.1% after AFO onset. The 5-year cumulative incidence of non-relapse mortality in the AFO group was higher than that in the non-AFO group (24.7% vs. 7.1%, P < 0.01). These results suggest that closely monitoring PFTs within two years after allo-HSCT, regardless of cGVHD status, is important for early detection of AFO and prevention of progression to BOS. (192words).

Feasibility of intravenous vitamin C supplementation in allogeneic hematopoietic cell transplant recipients.

Intravenous vitamin C was administered following hematopoietic stem cell transplant to mitigate nonrelapse mortality (NRM) in a Phase II clinical trial. Patients with advanced hematologic malignancies received IV vitamin C, 50mg/kg/day, in three divided doses on days 1-14 after HSCT, followed by 500mg bid oral until 6 months. All patients enrolled (55) were deficient in vitamin C at day 0 and had restoration to normal levels. Vitamin C recipients had a trend for lower nonrelapse mortality (NRM, 11%vs. 25%, p-value=0.07) compared with propensity score-matched historical controls. A similar trend toward improved survival was observed (82%vs. 62% p=0.06), with no attributable grade 3 and 4 toxicities to vitamin C. In patients undergoing allogeneic HSCT, repletion of vitamin C is feasible and may reduce NRM and improve overall survival. Randomized trials in large uniform cohorts of patients are needed to confirm the utility of this easily available and inexpensive therapy.

Seven-years post allogeneic hematopoietic stem cell transplantation pure red cell aplastic anemia cured with daratumumab: A case report and review of literature

BACKGROUND Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is currently the only viable method of curing patients with acute myeloid leukaemia. In 30% to 50% of patients, donors and recipients have some level of ABO blood group incompatibility. ABO blood group incompatibility can cause antibodies against the donor's red blood cells to persist in the recipient's body, resulting in a delay of several months in the recovery of red blood cells. A number of different treatments have been reported for post-transplant pure red cell aplastic anaemia (PRCA), such as plasmapheresis, donor lymphocyte infusions, anti-thymocyte globulin, rituximab and steroids. CASE SUMMARY A 41-year-old female diagnosed with acute myeloid leukaemia underwent peripheral blood allogeneic haematopoietic stem cell transplantation in November 2013 from an HLA matched unrelated donor. The donor was AB-positive and the recipient was O-positive. The patient was diagnosed with PRCA three months after receiving the donor stem cell transplant. After failing multiple lines of therapy, the patient applied for daratumumab. After receiving three doses of daratumumab, the patient developed a reticulocyte response and no longer required blood transfusions. CONCLUSION The use of daratumumab anti-CD38 for the remove of plasma cells is safe and effective and may be tried for refractory patients with PRCA after undergoing allo-HSCT for ABO incompatibility.

CT-634 Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation and Its Association With Donor Virus-Specific Cellular Immunity

CT-634 Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation and Its Association With Donor Virus-Specific Cellular Immunity

Vitality and Engraftment Times in Allogeneic Hematopoietic Stem Cell Transplantations Made With Frozen and Fresh Product

Vitality and Engraftment Times in Allogeneic Hematopoietic Stem Cell Transplantations Made With Frozen and Fresh Product

Prognostic Value of EASIX Score in Allogeneic Hematopoietic Stem Cell Transplantation

Prognostic Value of EASIX Score in Allogeneic Hematopoietic Stem Cell Transplantation

Effects of donor-engrafted clonal hematopoiesis in allogeneic and autologous stem cell transplantation: a systematic review and meta-analysis.

Donor stem cell health may be critically important to the success of hematopoietic stem cell transplantation (HSCT). Herein, we performed this systematic review and meta-analysis including meta-regression to assess the impact of donor-engrafted clonal hematopoiesis (CH) in allogeneic HSCT (allo-HSCT) and impact of pre-transplant CH in autologous HSCT (auto-HSCT). We applied random-effects models to analyze 5 allo-HSCT studies with 3192 donor-recipient pairs and 9 auto-HSCT studies with 2854 patients. We found that donor-engrafted CH after allo-HSCT decreased the risk of disease relapse [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI): (0.67, 0.93)], but did not affect overall survival (OS) [HR = 0.91, 95% CI: (0.75, 1.11)], progression-free survival (PFS) [HR = 0.94, 95% CI: (0.63, 1.41)], or non-relapse mortality [HR = 1.06, 95% CI: (0.81, 1.39)]. In contrast, pre-transplant CH in auto-HSCT recipients resulted in inferior OS [HR = 1.30, 95% CI: (1.16, 1.46)], inferior PFS [HR = 1.35, 95% CI: (1.18, 1.54)], and higher risk for therapy-related myeloid neoplasm [HR = 4.85, 95% CI: (2.39, 9.82)] when compared to auto-HSCT recipients without CH. This study sheds light onto the debate about prospective "CHIP screening" for stem cell donors and addresses the impact of CH as a transmissible phenomenon.

Sysmex XN-HPC: study of reference intervals and clinical decision limits in healthy allogeneic donors mobilised with G-CSF

The Sysmex XN series haematopoietic progenitor cell (XN-HPC) is a novel tool for assessing stem cell yield before allogeneic haematopoietic stem cell transplantation. This study aimed to establish a reference interval (RI) for XN-HPC in peripheral blood allogeneic transplant donors following granulocyte colony-stimulating factor (G-CSF) stimulation and determine its clinical significance. All specimens were analysed using Sysmex XN-20. Samples were collected and analysed using non-parametric percentile methods to define the RIs. Quantile regression was used to explore the dependency of the RIs on sex and age. Samples were included in clinical decision limits for apheresis based on receiver operating characteristic curve analysis. The non-parametrically estimated RI for XN-HPC was 623.50 (90% confidence interval [CI90%] 510.00–657.00) to 4,144.28 (CI90% 3,761.00–4,547.00). The RIs for the XN-HPC were not age-dependent but were sex-dependent. The RI for males was 648.40 (CI90% 582.00–709.00)–4,502.60 (CI90% 4,046.00–5,219.00) and for females was 490.90 (CI90% 311.00–652.00)–3,096.90 (CI90% 2,749.00–3,782.00). Comparisons based on XN-HPC values between the poor and less-than-optimal groups, good and less-than-optimal groups, and good and non-good groups had areas under the curve of 0.794 (P < 0.001), 0.768 (P < 0.001), and 0.806 (P < 0.001), respectively, indicating a good predictive value for mobilisation effectiveness. XN-HPC data exceeding 3974 × 106/L suggested that a sufficient number of stem cells could be collected clinically. Values > 5318 < 106/L indicated 100% mobilisation effectiveness. We established an RI for XN-HPC in peripheral blood allogeneic transplant donors following G-CSF stimulation and determined clinical decision thresholds for mobilisation efficiency.

Risk factors of HBV reactivation in leukemia patients with resolved HBV infection after allogeneic hematopoietic stem cell transplantation

BackgroundThe hepatitis B surface antigen (HBsAg)–negative and antibody to hepatitis B core antigen (anti-HBc)–positive patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of HBV reactivation (HBVr). MethodsTo analyze the risk factors for HBVr, a total of 1,042 leukemia patients(≥18years of age), who underwent allo-HSCT from January 2016 to April 2022 in The First Affiliated Hospital of Soochow University, were enrolled in the study. Finally, 193 leukemia patients with resolved HBV infection were included into the study. ResultsHBVr occurred in 22 patients (11.39 %), and the median time to HBVr was 24 months (with a range of 11-51months). Hepatitis flares developed in 22.73 % of patients with HBVr, and hepatic failure occurred in 1 patient. During the follow-up period, only 1(1.3 %) patient experienced HBVr among 79 patients with antiviral prophylaxis. While 21(18.42 %) patients experienced HBVr among 114 patients without antiviral prophylaxis. The cumulative incidence of HBV reactivation at 3 years was 44.4. % for anti-HBs-negative donors/recipients with a low anti-HBs titer (<100IU/L) and 7.1 % for anti-HBs-positive donors/recipients with a high anti-HBs titer (≥100IU/L) respectively. In addition, univariate and multivariate Cox regression analyses confirmed the use of rituximab as a risk factor for HBV reactivation. ConclusionThe univariate and multivariate analyses confirmed that the anti-HBs titer in both recipients and donors are protective indicators to prevent incidence of HBVr. In addition, antiviral prophylaxis can significantly reduce the incidence of HBVr.

Chemokine receptors are required for effector T-cell trafficking to GVHD tissues but not to bone marrow

AbstractIn allogeneic hematopoietic stem cell transplantation (allo-SCT), alloreactive donor T cells mediate the graft-versus-leukemia effect but also attack nonhematopoietic tissues, causing graft-versus-host disease (GVHD). Reducing alloreactive T-cell trafficking to GVHD target tissues while allowing their access to bone marrow (BM) and spleen, major sites of malignant hematopoiesis, is a rational strategy for reducing the GVHD risk when using alloreactive T cells as a therapeutic. Here, we show that effector T-cell (Teff) entry into BM and spleen in unmanipulated mice and in mice that received transplantation without alloreactive T cells is augmented by pertussis toxin (PTX)-sensitive chemokine receptor signaling. However, unexpectedly, in the presence of a GVH response, chemokines no longer draw T cells into BM and spleen but remain critical for their recruitment to GVHD target tissues. Consistent with this, PTX-treated Teff cells were as efficacious as untreated T cells in killing leukemia cells in BM and spleen in mice with a concurrent GVHD response. These results suggest a strategy to improve the safety of alloreactive T-cell therapeutics in treating leukemias in the context of an allo-SCT.

The Road More or Less Traveled- Examining the Role of Consolidative Allogeneic Hematopoietic Stem Cell Transplantation After Chimeric Antigen Receptor T Cell Therapy in B-cell ALL

Treatment with CD19-targeted chimeric antigen receptor T cell therapy (CD19-CART) has improved salvage rates in children and adults with relapsed and/or refractory B-cell acute lymphoblastic leukemia (ALL). However, not all patients treated with CD19-CAR T cells achieve long-term remission. The role of allogeneic hematopoietic stem cell transplantation as consolidative therapy remains undefined. We aim to review the current literature published to date regarding prognostic markers indicating durable ALL response to CD19-CART and risk factors for relapse after CD19-CART to identify patient cohorts who may benefit from consolidative hematopoietic stem cell transplantation.

Cost-effectiveness of blinatumomab for the treatment of B‑precursor acute lymphoblastic leukemia pediatric patients with high‑risk first‑relapse in Mexico

BackgroundBlinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule that engages T cells to lyse CD19-expressing B cells. Based on a multicenter, open-label, phase 3, randomized clinical trial (Clinical Trials ID: NCT02393859), we aimed to evaluate the cost-effectiveness (CE) of blinatumomab compared to standard consolidation chemotherapy (SC) for the treatment of pediatric patients with high-risk first-relapsed Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) from a Mexico healthcare payer perspective. MethodsA decision-analytic model, a partitioned survival model, was used to estimate the life-years (LYs) and costs over a lifetime horizon. We assumed that patients who remained alive beyond a 5-year period were cured. To account for the lingering impacts of cancer treatment, an excess mortality rate was incorporated into the model. Event-free survival (EFS) and overall survival (OS) were estimated by fitting mixture-cure and standard parametric survival distributions to the time-to-event data from the phase 3 trial. The model accounted for treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT) costs, and subsequent treatment costs. ResultsBlinatumomab was associated with a lifetime gained of 5.11 years at an incremental cost of $621,111 MXN, relative to SC. The ICER for blinatumomab vs Standard of care was estimated to be $121,526 MXN/LY gained in the base case. Cost-effectiveness was sensitive to varying the time horizon. Blinatumomab had a probability of 99 % of being cost-effective, relative to SC, at the willingness to pay threshold defined in Mexico. LimitationsHealth-related quality of life values were not included in the analysis and therefore we did not estimate the quality-adjusted life-years gained. ConclusionsBlinatumomab was associated with greater benefit in terms of OS and EFS relative to SC. Probabilistic, deterministic, and scenario analyses indicate that blinatumomab represents the best value for money. Therefore, blinatumomab administered as part of consolidation therapy in B-ALL pediatric patients with high-risk first relapse is a cost-effective option.

Graft Versus Host Disease Prophylaxis in Matched Donor Stem Cell Transplantation: Post-transplantation Cyclophosphamide Combinations Versus Methotrexate/Tacrolimus

BackgroundThe use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft versus host disease (GVHD) for haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is limited data on the role of PTCy as GVHD prophylaxis in matched-sibling and fully matched-unrelated donor (MSD/MUD) allo-HSCT. MethodsOur single-center retrospective study aims to compare outcomes of PTCy alone or in combination with mycophenolate mofetil and tacrolimus (PTCy/MMF/TAC) relative to methotrexate and tacrolimus (MTX/TAC). The primary endpoint of our study was GVHD-free, relapse free survival (GRFS). Secondary endpoints were overall survival (OS), disease free survival (DFS), and incidence of severe acute and chronic GVHD. We identified 74 adult patients who underwent MSD/MUD allo-HSCT at our institution from 2015 to 2023. ResultsWithin our cohort, 33.8% (n = 25) received MTX/TAC, while 54.0% (n = 40) received PTCy/MMF/TAC, and 12.2% (n = 9) received PTCy alone. Patients receiving PTCY had the longest time to neutrophil engraftment relative to MTX/TAC (15 days vs. 12 days, P = .010). PTCy/MMF/TAC was associated with improved GRFS relative to MTX/TAC (hazard ratio [HR] = HR 0.42, 95% CI 0.19-0.93, P = .031), which persisted when controlling for age. Incidence of chronic GVHD was lower in the PTCy/MMF/TAC group compared to MTX/TAC (1-year 9.0% vs. 30.1%, HR 0.19, 95% CI 0.06-0.59, P = .005). However, OS and DFS were comparable across all groups. ConclusionsOur results demonstrate decreased rates of severe chronic GVHD resulting in improved GRFS when using PTCy/TAC/MTX as GVHD prophylaxis compared to MTX/TAC in MSD/MUD.