Incidence Of Grade III-IV aGVHD Research Articles

Post-transplant cyclophosphamide at 80 mg/kg with low dose post-engraftment anti-thymocyte globulin in haploidentical transplantation with myeloablative conditioning.

While post-transplant cyclophosphamide (PTCy) is commonly used as graft-versus-host disease (GvHD) prophylaxis in haploidentical stem cell transplantation (haplo-HSCT), its dose remains a matter of debate due to side effect concerns. Standard dose of 100 mg/kg associated with tacrolimus and post-engraftment anti-thymocyte globulin (ATG) was used as the reference GvHD prophylaxis in our center and had demonstrated encouraging results. Though PTCy 80 mg/kg was shown to be feasible in patients in reduced-intensity conditioning, whether it exerts equivalent GvHD prophylactic efficacy in myeloablative conditioning (MAC) setting has not been confirmed. Here, we retrospectively analyzed the efficacy and safety of PTCy 80 mg/kg combined with tacrolimus and post-engraftment ATG as GvHD prophylaxis in patients aged more than 55 years or with cardiac antecedents or HCT-CI score >2 undergoing haplo-HSCT with MAC. The cumulative incidence of grade III-IV aGvHD at day 100 and moderate-to-severe cGvHD at 1 year was 4.8% ± 3.4% and 19.9% ± 7.0%, respectively. When compared with patients receiving the reference regimen, patients from the PTCy 80 mg/kg group had similar incidence of GvHDs and survival as their younger counterparts. Thus, PTCy 80 mg/kg seems to be feasible for patients treated with MAC conditioning regimens in haplo-HSCT, inviting further investigation notably in frail patients.

Efficacy of allogeneic hematopoietic stem cell transplantation based on a total body irradiation conditioning treatment regimen for adult acute lymphocytic leukemia

Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. Methods: The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results: The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (P=0.565), 34.0% and 35.7% (P=0.859), 43.4% and 33.3% (P=0.318), and 20.8% and 50.0% (P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant (HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion: allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

Alemtuzumab, Dual Graft-versus-Host Disease Prophylaxis, and Lower CD3+ T Cell Doses Equalize Rates of Acute and Chronic Graft-versus-Host Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation with Matched Unrelated Donor Peripheral Blood Stem Cells or Bone Marrow Grafts

Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based conditioning are lacking. We investigated whether in vivo T cell depletion using alemtuzumab could reduce the risk of severe acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) after HSCT with matched unrelated donor (MUD) BM or PBSCs. This retrospective multicenter study included 397 children (BM group, n = 202; PBSC group, n = 195) who underwent first MUD HSCT at 9 pediatric centers in the United Kingdom between 2015 and 2019. The median age at transplantation was 7.0 years (range, .1 to 19.3 years), and the median duration of follow-up was 3.1 years (range, .3 to 7.5 years). The 3-year overall survival was 81% for the entire cohort (BM group, 80%; PBSC group, 81%). The incidence of grade II-IV aGVHD was significantly higher in the PBSC group (31%) compared to the BM group (31% versus 19%; P = .003), with no difference in the incidence of grade III-IV aGVHD (BM, 7%; PBSC, 12%; P = .17). CD3+ T cell dose >5 × 108/kg and the use of PBSCs were independent predictors of grade II-IV aGVHD. When considering CD3+ T cell dose and GVHD prophylaxis, PBSC transplantation with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) and a CD3+ T cell dose ≤5 × 108/kg had a comparable grade II-IV aGVHD to BM transplantation plus a CNI (20% versus 18%; P = .52). PBSC transplantation was associated with a lower incidence of cGVHD compared to BM transplantation (6% versus 11%; P = .03). Within the limits of this study, we identified a potential strategy to reduce the risk of severe GVHD in pediatric PBSC recipients that includes a combination of in vivo T cell depletion using alemtuzumab and dual GVHD prophylaxis (with a CNI and MMF) and limiting the CD3+ T cell dose to ≤5 × 108/kg.

New Aplastic Anemia Preconditioned with Fludarabine, Thiotepa, Cyclophosphamide, and Anti-Thymocyte Globulin

Aplastic anemia (AA) is one of life-threatening hematological disorder that can be cured by hematopoietic stem cell transplantation. When the absence of a matched sibling donor, haploidentical stem cell transplantation (haplo-HSCT) becomes an alternative choice for AA patients. We used a prospective study aimed to confirm the feasibility of Thiotepa-based modified post-transplantation cyclophosphamide (PTCY) strategy in haplo-HSCT for AA patients. We analyzed the outcomes of 15 patients who had undergone haplo-HSCT between October 2021-May 2023 in our clinical center. The modified condition regimen consisted of anti-thymoglobulin/antilymphocyte globulin, fludarabine, thiotepa, busulfan and modified low and high-dose cyclophosphamide, mycophenolate mofetil (MMF) and tacrolimus (FK-506)/cyclosporin (CsA) were administered as graft versus host disease (GVHD) prophylaxis after transplantation. The median follow-up time was 267 (range 97-532) days. All 15 patients were successfully implanted (100%), the median times for neutrophil and platelet engraftment were 14 (range 12-19) days and 12 (range 8-25) days, respectively. But one patient developed secondary graft failure because of infected with COVID-19、cytomegalovirus and H1N1. Fortunately, she subsequently underwent a successful secondary haplo-HSCT. The most common regimen-related toxicity was canker sore, hemorrhagic cystitis occurred in 3 patients during transplantation. The cumulative incidence of grade Ⅰ-Ⅱ aGVHD and cGVHD were 13.3% and 6.7% respectively, whereas the incidence of grade Ⅲ-Ⅳ aGVHD was not found so far. All 15 patients are alive, with a failure-free survival rate of 100% and GVHD relapse-free survival rate of 100%. The efficacy evaluation of haplo-HSCT, 14 patients achieved CR and 1 patient achieved PR. Because of 7 patients received the prevention strategy of Letermovir since August 2022, the reactivation rate of cytomegalovirus (CMV) was only 20% and 60% of Epstein-Barr virus (EBV) reactivation, but the CMV diseases and post-transplantation lymphoproliferative disorder (PTLD) were rare. Our study using Thiotepa-based modified haplo-HSCT demonstrated an encouraging result with prolonged survival and reduced complications for aplastic anemia patients.

Post Transplant Cyclophosphamide (PTCY) in Peripheral Blood Stem Cell Transplant Results in Successful Engraftment and Substantially Low Frequency of Chronic Graft Versus Host Disease (GvHD), without Impaired Cellular Immune Reconstitution

The Post-Transplant Cyclophosphamide (PTCY) approach was first studied in the haploidentical transplant setting, and it resulted in high percentages of engraftment and reduced frequency of acute and mainly chronic GvHD as well as non-relapsed mortality. PTCY is now increasingly being used in HLA-partially and fully matched unrelated, as well as matched related donors. The aim of this study was to investigate the impact of PTCY on the incidence of chronic GvHD, disease relapse and infections because of possible cellular immune impairment. Fifty-one consecutive patients who underwent allogeneic hematopoietic stem cell transplant from an unrelated donor were studied. PTCΥ was administered on days +3 and +4 post-transplant at a dose of 50 mg/kg/day. Additional GvHD prophylaxis included tacrolimus and mycophenolate mofetil starting on day +5. In patients with no evidence of GvHD, immunosuppression was gradually tapered, and eventually stopped by day +90. We evaluated the safety and efficacy of PTCY, focusing on toxicity, engraftment, aGvHD and cGvHD frequency, relapse, non-relapse mortality, survival and immune reconstitution. We performed 51 unrelated donor transplants with PTCY from January 2021 to May 2023 in patients with a median age of 52 (18-69) years. The indication for transplant was AML/MDS (n=36), NHL/CLL, (n=2), pMF (n=2), CML (n=2) και ALL (n=9). Disease risk index (DRI) was intermediate for most patients (34/51), 7 had low and 10 had high DRI. Thirty-seven patients received myeloablative conditioning and 14 reduced-intensity. Overall, three patients were transplanted from a matched sibling, 36 from an 8/8 matched unrelated donor and 12 from an 7/8 HLA-matched unrelated donor. All patients received a peripheral blood graft with a median CD34+ cell dose of 6.97×10e6/kg (3.27-15.82). The most common toxicities observed were mucositis (n=34), diarrhea (n=40), vomit (n=12), liver toxicity (n=3) and acute kidney injury (n=4) - which in all cases were grade Ι-ΙΙ. Engraftment, defined as neutrophils >500/μl, was achieved in 46 cases in a median of 16 (13-27) days. Three patients died before day +28 due to NRM and two additional patients with myelofibrosis and MDS respectively had primary graft failure. The cumulative incidence of aGvHD, grade ΙΙ-IV at 100 days was 46.7% (95%CI: 34.1-63.8). However, aGvHD, grade ΙΙΙ-IV was only 3.9% (95%CI: 1.0-15.5). The cumulative incidence of cGvHD at 18 months was 13,4% (95%CI: 5.8-31.0), with only one case of extensive cGvHD. In a median follow-up of 14.5 (1-28) months, disease free (DFS) was 76,8% (95%CI: 65.5-90.0) at 18 months and overall survival (OS) was 76.3% (95%CI: 64.9-89.8) and 71.6% (95%CI: 58.6-88.3) respectively. There was no statistically significant difference in survival rates for patients who received an HLA mismatched and those who received an HLA-matched unrelated-donor transplant. cGvHD-Relapse-Free Survival was 63.5% (95%CI: 50.3-80.1). Two patients died of their disease and non-relapse mortality was 19.1%. Specifically, 6 patients died of Infections, 1 due to primary graft failure, 1 due to heart failure, and 1 due to Idiopathic Pulmonary Syndrome. Immune reconstitution at month 6 was 420 cells/ul (20-2225) and 179 (13-594) for CD8 and CD4 respectively. At month 12 CD8 and CD4 were 552 (55-3002) and 364 (60-787). 31 viral infections were documented in 28 patients (Respiratory viruses n=13, BKV n=11, CMV n=7). In regard with opportunistic infections, 2 patients had fungal infections and 1 patient atypical mycobacterium. We used PTCY for GvHD prophylaxis in mismatched, full-matched unrelated and matched sibling donor transplants with peripheral blood stem cell graft. This approach was well tolerated. Engraftment was documented in most patients, with a low incidence of grade III-IV aGvHD. Importantly cGvHD, which is the most important barrier in unrelated donor transplant, was substantially low with this method. Cellular immune reconstitution was adequate for CD8 but somewhat impaired for CD4. However, the incidence of viral and opportunistic infections was not increased. Overall, there are implications that PTCY may revert the negative impact of HLA mismatch on the outcomes of unrelated donor transplantation, while it is also a viable option for MUD and MSD transplant.

Herombopag, a Second Generation Thrombopoietin-Receptor Agonist, Stimulates Platelet Engraftment after Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: The delayed platelet engraftment is a common complication in allogeneic hematopoietic stem cell transplantation (allo-HSCT), which elevates treatment-related mortality and impairs quality of life. Although some studies reported that platelet engraftment after allo-HSCT was promoted by thrombopoietin-receptor agonists (TPO-RAs), the recommended detailed TPO-RA administration is still lacking. This prospective, single-center, investigator-initiated pilot study aims to explore the efficacy and safety of herombopag, a second-generation TPO-RA, to stimulate platelet engraftment in haploidentical allo-HSCT (haplo-HSCT). Methods: A total of 36 patients (median age 38; range 15-59 years) with anaplastic anemia, myelodysplastic syndrome, acute leukemia, granulocytic sarcoma, or primary hemophagocytic lymphohistiocytosis were enrolled between November 2021 and June 2023. All patients received haplo-HSCT and post-transplant cyclophosphamide for acute graft-versus-host disease (aGVHD) prophylaxis. Patients received herombopag from day+5 post-HSCT until platelet>100,000/µL, disease progression, intolerable toxicity, or withdrawal of informed consent. The dose of herombopag was 5 mg/day initially and reduced to 2.5 mg/day when platelet>75,000/µL. Complete platelet engraftment (CPE) was defined as a platelet count exceeding 50,000/μl for seven consecutive days without transfusion. Partial platelet engraftment (PPE) was defined as a platelet count exceeding 20,000/μl for seven consecutive days without transfusion. The objective response included both CPE and PPE. The primary endpoint was the 21-day cumulative incidence and 28-day cumulative incidence of CPE and objective response after haplo-HSCT. The secondary endpoints were time to CPE, time to objective response, platelet transfusion units, aGVHD, relapse, non-relapse mortality, and safety. Results: The patients received herombopag treatment for a median of 15 days. The 21-day cumulative incidence of CPE was 55.6%, and that of objective response was 77.8%. The 28-day cumulative incidence of CPE was 69.4%, and that of objective response was 80.6%. The median time to objective response was 20.5 (95%CI 17-27) days. The median time to CPE was 23 (95%CI 10-33) days. The mean units of platelet transfusions required within 30 days after HSCT was 6.7. The median follow-up time was 12.1 months. The one-year overall survival rate was 85.3% (95%CI 72.8%-99.8%). Two patients died of aGVHD and two patients died of lung infection. Four Patients (11.1%) experienced molecular relapse. The cumulative incidence of grade III-IV aGVHD was 16.7%. Furthermore, cytomegalovirus reactivation occurred in 13 patients (36.1%). The most common herombopag-related adverse events were hypomagnesemia (61.1%), increased GGT (52.8%), increased ALT (38.9%), and increased bilirubin (19.4%). No grade III/IV adverse events were observed. Conclusion: Herombopag significantly stimulates platelet engraftment in haplo-HSCT patients and has a favorable safety profile. Further research with a larger sample size and longer follow-up period is required to confirm its optimal use.

Outcome improvement over time in reduced intensity conditioning hematopoietic transplantation: a 20-year experience.

The current study includes all consecutive patients (N = 484) who received a reduced-intensity conditioning regimen (RIC) allogeneic hematopoietic stem cell transplantation in our center from 1999 to 2020. Conditioning regimens were based on fludarabine with melphalan or busulfan, with low-dose thiotepa and pharmacological GVHD prophylaxis consisted of cyclosporine A (CsA)-methotrexate (MTX)/mofetil (MMF) (n = 271), tacrolimus-sirolimus (n = 145), and post-transplantation cyclophosphamide (PTCy)-tacrolimus (n = 68). The median time of overall follow-up in survivors was 8years (1-22years) and was at least 3years in all three GVHD prophylaxis groups. Thirty-three percent had a high or very high disease risk index, 56% ≥ 4 European bone marrow transplantation risk, and 65% ≥ 3 hematopoietic stem cell transplantation comorbidity index score-age score. Neutrophil and platelet engraftment was longer for PTCy-tacro (p 0.0001). Cumulative incidence of grade III-IV aGVHD was 17% at 200days, and that of moderate-severe cGvHD was 36% at 8years. GVHD prophylaxis was the only prognostic factor in the multivariable analyses for the development of aGVHD and moderate-severe cGVHD (p 0.0001). NRM and relapse incidences were 29% and 30% at 8years, while OS and PFS rates were 43% and 39% at 8years. At 3years, OS was highest in the PTCy-tacro group (68%) than in the tacro-siro (61%) and CsA-MTX/MMF (49%) cohorts (p < 0.01). In the three groups, respectively, the 200-day incidence of grade III-IV aGvHD (6% vs. 12% vs. 23%) and 3-year moderate-severe cGVHD (8% vs. 40% vs. 38%) were lower in the PTCy cohort. These better outcomes were confirmed in multivariable analyses. Based on our recent results, the PTCy could be considered as a real GvHD prophylaxis in the RIC setting due to improve best 3-year GvHD and survival outcomes.

Thiotepa-busulfan-fludarabine Compared to Treosulfan-based Conditioning for Haploidentical Transplant With Posttransplant Cyclophosphamide in Patients With Acute Myeloid Leukemia in Remission: A Study From the Acute Leukemia Working Party of the EBMT.

We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or treosulfan-based (Treo) conditioning for haplo-hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) between 2010 and 2020. A total of 1123 patients met the inclusion criteria (968 received TBF and 155 received Treo). A 1:1 matched-pair analysis was performed on 142 TBF and 142 Treo patients. In the Treo group, 68% of patients received treosulfan at a dose ≥36 g/m2 and 54% of patients received a second alkylator (thiotepa or melphalan). We observed a trend toward increased incidence of grade II-IV acute (a) graft-versus-host disease (GVHD) at 180 days in the TBF group compared with Treo (29% versus 20%; P = 0.08), while incidence of grade III-IV aGVHD was not statistically different. Similarly, the incidence of chronic (c) GVHD was not statistically different in the 2 groups. Incidence of nonrelapse mortality at 2 years was 19% in TBF and 14% in Treo (P = 0.4). Relapse incidence at 2 years was not statistically different in the 2 groups (16% and 18% in TBF and Treo, respectively; P = 0.9). Leukemia-free survival, overall survival, and GVHD-free, relapse-free survival was 65% versus 68% (P = 0.6), 73% versus 76% (P = 0.5), and 54% versus 53% (P = 0.8) in TBF versus Treo, respectively. In conclusion, we did not find a significant difference between the 2 conditioning in the present study; Treo and TBF represent 2 valid alternative regimens for haplo-HSCT with PTCy for AML in remission.

Treosulfan-Based Conditioning Regimen In Pediatric Hematopoietic Stem Cell Transplantation: A Retrospective Analysis on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC)

Data on treosulfan-based conditioning regimens are little by little increasing, and the benefits of this approach are consistent, particularly regarding acute toxicity. This study aims to describe the results of treosulfan-based conditioning regimens in children, focusing on toxicity and outcomes when used to treat both malignant and non-malignant diseases. Retrospective observational study on pediatric patients treated in Spain with treosulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT), based on data collection from electronic clinical records. One hundred and sixty treosulfan-based conditioning HSCTs to treat non-malignant diseases (n=117) or malignant diseases (n=43) in 158 children and adolescents are reported. Median age at HSCT was 5.1 years (IQR: 2-10). The most frequent diagnoses were primary immunodeficiency (n=42; 36%) and sickle cell disease (n=42; 36%) in the non-malignant cohort and acute lymphoblastic leukemia (n=15; 35%) in the malignant cohort. Engraftment occurred in 97% of the patients. There was a longer median time to neutrophil engraftment (17 vs. 14 days; p=0.008) and platelet engraftment (20 vs. 15 days; p=0.002) in the non-malignant cohort. The 1-year cumulative incidence of VOD was 7.98 (95%CI [4.6-13.6]), with no significant differences between cohorts. The 1-year cumulative incidence of grade III-IV aGvHD was higher in the malignant cohort (18% vs. 3.2%; p=0.011). Overall, cGvHD was more frequently observed in the malignant cohort for both total incidence (9 vs. 3%; p<0.001) and 2-year cumulative incidence of total cGvHD (16 vs. 1.9%; p<0.001). The 2-year cumulative TRM was 15%, with no differences between cohorts. 5-year Overall Survival was 80% (95%CI [72-86]) and was higher in the non-malignant cohort (87 vs. 61%; p=0.01). The 2-year cumulative incidence of relapse in the malignant cohort was 25%. 5-year cumulative GRFS rate was 60% (95%CI [51-70]) and was higher in the non-malignant cohort (72 vs. 22%; p<0.001). The treosulfan-based radiation-free conditioning regimen is feasible, achieving a high engraftment rate and 5-year overall survival. A treosulfan-based conditioning regimen is an emerging option for the first HSCT in non-malignant diseases.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia

To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML). The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d). Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019). Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Abatacept for the Prevention of Gvhd in Pediatric and Adult Patients Receiving 7/8 HLA-Mismatched Unrelated Transplant for Hematologic Malignancies: A Real-World Analysis

Background: Recipients of HLA mismatched unrelated donor (MMURD) hematopoietic cell transplant (HCT) are at increased risk for severe acute graft versus host disease (aGVHD) and treatment related mortality (TRM). Abatacept, CTLA4-Ig was granted FDA approval for the prevention of aGVHD in patients receiving unrelated donor HCT in part based on results of ABA2, a phase II trial evaluating abatacept in addition to standard immunoprophylaxis (calcineurin inhibitor (CNI)/ methotrexate (MTX) for GVHD prevention in either 8/8 MUD or 7/8 MMURD HCT (Watkins et al., 2021). The 7/8 MMURD cohort from ABA2 showed a significant reduction in grade III-IV aGVHD compared with a matched cohort from the CIBMTR receiving CNI/MTX alone (2.3% vs 30.2%, P<0.001). The lower rates of severe aGVHD translated into significant improvements in TRM and overall survival (OS) at 2 years for patients receiving abatacept. While ABA2 included pediatric and adult patients in the analysis, outcomes were not reported separately. Furthermore, there may be selection bias associated with study eligibility and participation that could result in benefits that may not translate into everyday clinical practice. Objectives: To determine the real-world impact of abatacept combined with CNI/MTX on the development of acute and chronic GVHD, survival, and relapse in pediatric and adult patients with hematologic malignancies receiving of 7/8 MMURD HCT as standard of care (off-study). Methods: We conducted a multi-center retrospective analysis of outcomes for pediatric and adult patients receiving a 7/8 MMUD HCT (bone marrow (BM) or peripheral blood stem cells (PBSC)) for hematologic malignancies and received GVHD prophylaxis with abatacept (4 doses on days -1, +5, +14, and +28) combined with CNI/MTX between January 2015 and December 2021. Patients were excluded if they were on ABA2, not in remission at time of HCT, received a prior HCT, or required additional GVHD prophylaxis. The analysis included consecutive adult patients transplanted at Emory University and pediatric patients transplanted at Children's Healthcare of Atlanta and Boston Children's Hospital. Data were analyzed for all patients and for pediatric and adult patients as separate cohorts. Results: A total of 50 consecutive patients (27 pediatric patients and 23 adult patients) met inclusion criteria. Median follow up was 759 days. Twenty-five of 27 pediatric patients received BM grafts while 20 out of 23 adult patients received PBSC. Grade II-IV aGVHD at day 180 was 40%, 48% and 28% for all patients, pediatric patients and adult patients, respectively. Grade III-IV aGVHD at day 180 was 10%, 5% and 15% for all, pediatric and adult patients respectively. Moderate-severe chronic GVHD (cGVHD) at 1 year was 49%, 56% and 42% for all, pediatric and adult patients respectively. TRM at day 180 was 8%, 7% and 9% for all, pediatric and adult patients respectively. OS at 1 year was 82%, 85% and 78% for all, pediatric and adult patients respectively. Relapse at 1 year was 16%, 15% and 17% for all, pediatric and adult patients respectively Disease-free survival (DFS) at 1 year was 73%, 77% and 70% for all, pediatric and adult patients respectively. Grade III-IV aGVHD free, severe cGVHD free, relapse free survival at day 180 was 74%, 70% and 78% for all, pediatric and adult patients respectively. Conclusion: Our real-world results using abatacept prophylaxis for 7/8 MMUD HCT compared favorably with ABA2 results with low incidence of grade III-IV aGVHD and TRM and encouraging DFS. These results are promising given that our off-study patients had more advanced disease compared to the patients on ABA2 (27% vs 13%). This was especially true in our adult patients where 50% had advanced disease and almost all received PBSC grafts. This study was the first to analyze and report outcomes separately for pediatric and adult patients receiving abatacept for GVHD prophylaxis. Our results indicate that both pediatric and adult patients had favorable outcomes with abatacept. Similar to results from ABA2, cGVHD rates were not reduced with the 4 dose abatacept regimen and further studies are needed to evaluate the efficacy of extended dosing abatacept to mitigate this risk. Our real-world results mirrored the results from ABA2 and suggest that the addition of abatacept to standard immunoprophylaxis for our highest risk patients can be effective at substantially improving aGVHD related transplant outcomes in MMUD recipients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Double Filtration Plasmapheresis for Desensitization during Haploidentical Stem Cell Transplantation in Patients with Positive Donor-Specific Anti-HLA Antibodies

Background:Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. Plasma exchange (PE) is an effective treatment widely used for DSA desensitization. However, a large volume of plasma is required. Double filtration plasmapheresis (DFPP) is a semi-selective blood purification modality derived from the PE modality. DFPP avoids the unnecessary loss of plasma proteins, reduces the need for plasma and increases the efficiency of purification. To define the efficacy of DFPP for DSA-positive patients in HaploSCT, we conducted a nested case-control study. Methods: Patients who underwent HaploSCT in the Bone Marrow Transplantation Center of the First Affiliated Hospital of Zhejiang University School of Medicine from March 2017 to November 2021 were enrolled in the study cohort. Thirty-two patients with positive DSA (MFI≥2000) were treated with desensitization protocol including DFPP. Ninety-six patients (1:3) with negative DSA were randomly matched according to gender, age and transplantation time as the control group. DSA positive patients were given alternate-day DFPP twice before starting one week before the beginning of transplant conditioning. DSA was retested after DFPP treatment. A single dose of rituximab (375 mg/m2) was administrated after completion of DFPP. Results: A total of 32 HaploSCT patients with DSAs were included in the study. The majority of patients in the DSA group were female (75%) and a mean age of 41 (13-63) years . 96 DSA negative patients were selected as controls. The two groups had equivalent subject and donor characteristics, including age, gender, underlying diseases, conditioning regimens and GVHD prophylaxis.20 (62.5%) patients presented anti-HLA class I DSAs (4 of them with > 10000 MFI), 9 (28.1%) presented anti-HLA class II DSA (2 with > 10000 MFI) and 3 (9.3%) presented both anti-HLA class I and II DSA (1 with > 10000 MFI). After DFPP treatment, levels of DSA decreased significantly. The mean MFI values before and after treatment were 7189.56 ±4294.01 vs. 2869.57±3454.55 (P < 0.001), respectively. All patients in DSA group achieved hematopoietic reconstitution within 28 day of transplantation. The mean neutrophils and platelets engraftment time was 13.44±2.42 days and 14.03±3.78 days respectively, which were comparable to control group. In the DSA and control groups, the incidence of grade III-IV aGVHD was 9.37% vs. 10.41% (P < 0.05), the 2-year cumulative recurrence rate was 26.35% vs. 15.62% (P < 0.05) and the overall survival (OS) was 77.20% vs. 81.20% (P < 0.05), respectively. Conclusion: DFPP can significantly reduce the level of DSA in patients before transplantation. Treatment with DFPP and rituximab is effective in promoting engraftment for DSA-positive patients in HaploSCT.

Clofarabine and Busulfan Myeloablative Conditioning in Allogeneic Hematopoietic Cell Transplantation for Patients With Active Myeloid Malignancies

Patients with refractory or relapsed and refractory myeloid malignancies have a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning (MAC) in patients with active, chemotherapy-refractory myeloid disease is historically associated with high rates of relapse and nonrelapse mortality (NRM). A MAC regimen combining clofarabine with busulfan (Clo/Bu4) has been reported to exhibit antileukemic activity with acceptable toxicity in patients age ≤70 years. Here we describe the clinical outcomes of a real-world population of patients with active myeloid malignancies undergoing allogeneic HCT with Clo/Bu4 MAC. In a single-center retrospective descriptive analysis, we identified patients who underwent HCT for myeloid malignancies not in remission using Clo/Bu4 MAC between 2012 and 2020. We report event-free survival (EFS) and overall survival (OS), cumulative incidences of relapse and NRM, and the incidence and severity of acute and chronic graft-versus-host disease (GVHD). We identified 69 patients with a median age of 60 years (range, 22 to 70 years). Most patients had relapsed/refractory or primary refractory acute myelogenous leukemia (AML; n=55) or refractory myelodysplastic syndrome (MDS; n=12); 1 patient had chronic myelogenous leukemia, and 1 patient had a blastic plasmacytoid dendritic cell neoplasm. Fifty patients (72.5%) had complete remission at day 100 post-transplantation. Two-year EFS and OS were 30% (95% confidence interval [CI], 20% to 44%) and 40% (95% CI, 29% to 54%), respectively. Patients with AML had a 2-year EFS and OS of 28% (95% CI, 18% to 44%) and 38% (95% CI, 27% to 54%), respectively; those with MDS had a 2-year EFS and OS of 47% (95% CI, 25% to 88%) and 56% (95% CI, 33% to 94%), respectively. The cumulative incidence of relapse at 2 years was 39% (95% CI, 27% to 51%) for all patients, including 45% (95% CI, 31% to 58%) in the patients with AML and 18% (95% CI, 2% to 45%) in those with MDS. NRM at 2 years was 31% (95% CI, 20% to 42%), including 27% (95% CI, 15% to 39%) in patients with AML and 35% (95% CI, 10% to 63%) in those with MDS. The total incidence of acute GVHD (aGVHD) of any severity was 80%, and the incidence of grade III-IV aGVHD was 22%. In patients who achieved remission, those who required systemic immunosuppression for aGVHD (58%) had poorer 2-year EFS (29% versus 54%; P=.05) and 2-year OS (39% versus 70%; P=.04) compared to those who did not. The 2-year cumulative incidence of chronic GVHD was 44% (95% CI, 28% to 58%). Clo/Bu4 MAC followed by allogeneic HCT for patients with active myeloid malignancies is an effective transplantation strategy for patients up to age 70, particularly those with advanced MDS. The high incidence of and poor outcomes associated with aGVHD highlight the importance of optimizing preventative strategies.

Impact of Human Leukocyte Antigen Epitope Matching on Outcomes after Unrelated Bone Marrow Transplantation

Impact of Human Leukocyte Antigen Epitope Matching on Outcomes after Unrelated Bone Marrow Transplantation

Donor source and post-transplantation cyclophosphamide influence outcome in allogeneic stem cell transplantation for GATA2 deficiency.

GATA2 deficiency was described in 2011, and shortly thereafter allogeneic hematopoietic stem cell transplantation (HSCT) was shown to reverse the hematologic disease phenotype. However, there remain major unanswered questions regarding the type of conditioning regimen, type of donors, and graft-versus-host disease (GVHD) prophylaxis. We report 59 patients with GATA2 mutations undergoing HSCT at National Institutes of Health between 2013 and 2020. Primary endpoints were engraftment, reverse of the clinical phenotype, secondary endpoints were overall survival (OS), event-free survival (EFS), and the incidence of acute and chronic GVHD. The OS and EFS at 4 years were 85·1% and 82·1% respectively. Ninety-six percent of surviving patients had reversal of the hematologic disease phenotype by one-year post-transplant. Incidence of grade III-IV aGVHD in matched related donor (MRD) and matched unrelated donor recipients (URD) patients receiving Tacrolimus/Methotrexate for GVHD prophylaxis was 32%. In contrast, in the MRD and URD who received post-transplant cyclophosphamide (PT/Cy), no patient developed grade III-IV aGVHD. Six percent of haploidentical related donor (HRD) recipients developed grade III-IV aGVHD. In summary, a busulfan-based HSCT regimen in GATA2 deficiency reverses the hematologic disease phenotype, and the use of PT/Cy reduced the risk of both aGVHD and cGVHD.

Thiotepa-Busulfan-Fludarabine in Comparison to Busulfan-Cyclophosphamide As Myeloablative Conditioning Regimen Pre Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Background. Busulfan plus Cyclophosphamide (BuCy) is the traditional myeloablative conditioning (MAC) regimen pre allogeneic stem cell transplantation (SCT) for acute myelogenous leukemia (AML). The Thiotepa, Busulfan, Fludarabine (TBF) protocol was initially developed for cord blood SCT and subsequently employed in haploidentical SCT; however, there is limited data assessing the TBF regimen in SCT from sibling (MSD) and unrelated donor (URD) for AML and no comparison between the two preparative protocols has been performed.Patients and methods. We analyzed transplantation outcomes of 2523 adult patients (pts) with AML in remission (CR1, CR2+) aged 18-50 years that underwent a first SCT from MSD or URD between 2007 and 2015 and reported to the ALWP of the EBMT. One hundred and three patients received TBF and 2370 pts received BuCy. Pts who received oral busulfan, manipulated grafts, or transplant from <=8/10 HLA-matched donor were excluded. All pts received MAC regimen (defined by Busulfan dose>=9.6 mg/kg). As compared to BuCy, the TBF group included significantly older pts, who were transplanted more recently, had longer interval from diagnosis to transplant, and were more likely to have received BM as stem cell source and URD as donor type. In order to minimize the bias due to differences in pts characteristics, a 1:3 pair-matched analysis was performed. One hundred and forty-six pts receiving TBF were compared with 438 pts receiving BuCy; matching factors included age, year of SCT, disease status at SCT, interval from diagnosis to SCT, donor type, CMV serostatus of both the donor and patient, stem cell source, GVHD prophylaxis and use of anti-thymocyte globulin.Results. With a median follow-up of 22 months, incidence of grade II-IV and III-IV aGVHD after TBF vs BuCy was 29% vs 23% (p=0.23) and 15% vs 8% (p=0.04), respectively. The 5-year cumulative incidence of cGVHD and severe cGVHD was 36% vs 43% (p=0.66) and 16% vs 22% (p=0.72) for TBF vs BuCy, respectively. The 1-year and 5-year non-relapse mortality (NRM) rates were 10% and 22% for TBF vs 9% and 13% for BuCy, respectively (p=0.36). The 1-year and 5-year relapse incidence (RI) rates were 17% and 25% for TBF vs 21% and 37% for BuCy, respectively (p=0.32). No significant difference was observed in leukemia-free survival (LFS), being the 1-year and 5-year LFS rates 73% and 53% for TBF vs 70% and 50% for BuCy, respectively (p=0.56). Overall survival (OS) was also similar, being 80% and 54% for TBF vs 79% and 59% for BuCy, respectively (p=0.88). The composite endpoint graft-vs-host disease-free, relapse-free survival (GRFS) at 5 years was 48% for TBF and 40% for BuCy (p=0.48). Notably, when the analysis was restricted to pts in CR1, a significant difference in RI rate was observed (1-year and 5-year RI: 10% and 18% for TBF vs 20% and 38% for BuCy, respectively, p=0.003) leading to a trend for better LFS for TBF as compared to BuCy (1-year and 5-year LFS: 78% and 57% for TBF vs 72% and 50% for BuCy, respectively, p=0.07), with no difference in OS. When examining separately pts receiving SCT from MSD or URD, no significant difference was observed between TBF and BuCy regimens in terms of transplant outcome. In multivariate analysis, TBF was associated with lower RI compared to BuCy (HR 0.6, p=0.02), while no difference was observed in terms of NRM, LFS, OS and GRFS (HR 0.8, p=0.12 for GRFS). TBF was also associated with lower incidence of cGVHD (HR 0.7, p=0.04) and a trend for lower incidence of severe cGVHD (HR 0.6, p=0.1); on the contrary we observed a trend for higher incidence of grade III-IV aGVHD following TBF as compared to BuCy (HR 1.79, p=0.06).Conclusions. These results suggest that TBF is a valid myeloablative conditioning pre MSD or URD SCT for AML pts < 50 years of age and in remission, with similar transplantation outcome as compared to the traditional BuCy preparative regimen. These data may serve as the scientific background for a well designed randomized two arm study comparing TBF to BuCy as MAC pre SCT in AML pts below the age of 50 years in CR. [Display omitted] DisclosuresSavani:Jazz Pharmaceuticals: Speakers Bureau.

Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia.

Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78% vs. 37%; p<0.01) and more with complex cytogenetics (44% vs. 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft-versus-host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] vs. 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% vs.11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] vs. 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% vs.11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T vs. the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% vs. 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% vs. 64.1%; p=0.63) and overall survival (OS; 70.2% vs. 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.

Experience Using Anti-Thymocyte Globulin With Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Peripheral Blood Haploidentical Stem Cell Transplantation

Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an updated experience at our center of using in vivo dual T-cell depletion with anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) in peripheral blood haploHCT and report the impact of reducing the dose of ATG from 4.5 mg/kg to 2 mg/kg on post-transplantation complications and outcomes. Ninety-five consecutive adults underwent haploHCT at our center between August 2016 and February 2020, all of whom were included in the study. Nine (9.5%) patients received myeloablative conditioning, and 86 (90.5%) patients underwent reduced-intensity haploHCT. All patients received thymoglobulin, PTCy and cyclosporine (CsA) for graft-versus-host disease (GVHD) prophylaxis: Sixty (63.2%) patients received 4.5 mg/kg, and 35 (36.8%) patients received 2 mg/kg of ATG. Clinical information was collected retrospectively and updated in June 2020. The median age was 57 (18-73), and acute myeloid leukemia was the most prevalent diagnosis (58.9%). The day 100 cumulative incidence of grade II-IV and grade III-IV aGVHD, and 1-year moderate/severe cGVHD were 22.3%, 11.1%, and 20.2%, respectively. Those patients who received 2 mg/kg of ATG had higher incidence of grade III-IV aGVHD (23.9% vs 3.5%, P=.006) and comparable moderate/severe cGVHD (1-year 20.6% vs 19.8%, P=.824) than those patients who received 4.5 mg/kg. Overall, the 18-month overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) were 43.8%, 38.4%, and 40.2%, respectively. The reduction of the ATG dose did not have a significant impact in OS (hazard ratio [HR] 1.06, P=.847), RFS (HR 0.984, P=.955), and in NRM (HR 1.38; P=.348). The reduction of the ATG resulted in a negative impact on aGVHD without conferring any benefit in OS, RFS, and NRM. Consequently, the ATG dose used at our institution in combination with PTCy and CsA for haploHCT continues to be 4.5 mg/kg.

Haploidentical Transplantation with Modified Post-transplantation Cyclophosphamide for Patients with Primary Aplastic Anemia: A Multicenter Experience

Aplastic anemia (AA) is a life-threatening hematological disorder that can be cured by hematopoietic stem cell transplantation. Haploidentical transplantation becomes an alternative choice for patients in the absence of a matched sibling donor. We used a retrospective study aimed to confirm the feasibility of busulfan-based modified post-transplantation cyclophosphamide (PTCY) strategy in haploidentical hematopoietic stem cell transplantation for AA patients. We analyzed the outcomes of 27 patients from 3 clinical centers who had undergone haploidentical transplantation between October 2018 and July 2020. The modified condition regimen consisted of anti-thymoglobulin/antilymphocyte globulin, fludarabine, busulfan and low-dose cyclophosphamide, and high-dose cyclophosphamide, mycophenolate mofetil (MMF) and tacrolimus were administered as graft versus host disease (GVHD) prophylaxis after transplantation. The median follow-up time was 370 (range 65-721) days. One patient developed primary graft failure, and successful engraftment was observed in 96.29% (95% confidence interval [CI], 93.45%-97.91%) of patients. The median times for neutrophil and platelet engraftment were 13 (range 11-18) days and 13 (range 11-28) days, respectively. The most common regimen-related toxicity was bladder toxicity, followed by stomatitis and gastrointestinal toxicity. The cumulative incidence of grade II-IV aGVHD was 25.93% (95% CI, 5.84%-52.64%), whereas the cumulative incidence of grade III-IV aGVHD was 7.4% (95% CI, 0%-52.16%). Chronic GVHD was observed in 3 patients by the end of follow-up. All 27 patients are alive, with a failure-free survival rate of 96.30% (95% CI, 6.49%-99.47%) and GVHD relapse-free survival rate of 88.89% (95% CI, 69.39%-96.28%). Virus reactivation was comparable, with rates of 53.54% for cytomegalovirus (CMV) reactivation and 41.57% for Epstein-Barrvirus, but the CMV diseases and post-transplantation lymphoproliferative disorder were rare. Our study using haploidentical transplantation with modified PTCY demonstrated an encouraging result with prolonged survival and reduced complications for aplastic anemia patients.

Interleukin-7 Receptor Gene Heterozygous Mutations in Recipients Significantly Increase Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Acute graft-versus-host disease (aGVHD) is one of major complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Genetic polymorphisms of interleukin-7 receptor (IL-7R) have an impact on transplant-related mortality (Z Shamim et al. BMT 2006). Our previous studies indicated that hematological and immunological hereditary predisposition genes have potential influence on major complications of allo-HSCT in patients with hematological malignancies (unpublished data). In present study, the influence of hematological and immunological hereditary predisposition genes on aGVHD after allo-HSCT in the patients with hematological malignancies was investigated. Between February 2018 and August 2019, 92 patients with hematological malignancies who underwent allo-HSCT in Beijing Boren Hospital were enrolled. The median age was 17 (1 to 45) years old. The diagnoses included acute myeloid leukemia (37, 40.2%), acute lymphoblastic leukemia (36, 39.1%), non-Hodgkin's lymphoma (13, 14.1%), and myelodysplastic syndrome (6, 6.5%). The disease status before transplant was complete remission in 54 (58.7%), non-remission in 23 (25%), and relapse in 15 (16.3%). Before transplants, blood samples were collected from the patients, their parents and potential related donors to detect hematological and immunological hereditary predisposition genes with whole exon sequencing and validation by sanger sequencing. The donors were from identical siblings (4, 4.3%) or matched unrelated volunteers (8, 8.7%) or haploidentical family members (80, 86.9%). Myeloablative conditioning regimens with either total body irradiation/fludarabine-based or busulfan/fludarabine-based were applied. Anti-thymocyte globulin was used in haploidentical and unrelated transplants. GVHD prophylaxis was with cyclosporine, short-term methotrexate and mycophenolate mofetil. Methylprednisolong 1-2mg/kg daily was used for aGVHD treatment and basiliximab was administrated in severe aGVHD. Forty-eight patients (52.2%) developed aGVHD as aGVHD group and 44 patients (47.8%) have no aGVHD as non-aGVHD group. IL7R gene heterozygous mutations in recipients significantly increased overall aGVHD and also severe aGVHD after allo-HSCT. IL7R gene heterozygous mutations were found in 7/48 patients in aGVHD group, but 0/44 in non-GVHD group (P = 0.041). The incidence of grade III-IV aGVHD in patients with IL7R gene heterozygous mutations was significantly higher than that without IL7R gene heterozygous mutations. (5/7 vs. 7/41, P=0.007). Among the patients with IL7R gene heterozygous mutations in aGVHD group, 5/7 patients (71.4%) had grade III-IV aGVHD. Three of them with grade III aGVHD had the same heterozygous mutation site: c.c1241t; p.t414m and rest 2 patients with grade IV aGVHD had the same heterozygous mutation site: c.g314a; p. S105n. Our preliminary results have shown that IL7R gene heterozygous mutations in recipients have significantly increased the risk of overall aGVHD and severe aGVHD after allo-HSCT in the patients with hematological malignancies. Larger sample size is needed to address this issue. Disclosures No relevant conflicts of interest to declare.