2-year Non-relapse Mortality Research Articles

Allogeneic Stem Cell Transplantation for Patients with Acute Myelogenous Leukemia (AML) in Second Complete Remission (CR2) Transplanted from Unrelated Donors with Post Transplant Cyclophosphamide (PTCy). a Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Background:Post-transplant cyclophosphamide (PTCy) has been shown to significantly reduce transplant related mortality (TRM) post hematopoietic stem cell transplantation (HSCT) and is being increasingly used for acute myelogenous leukemia (AML) patients (pts) undergoing HSCT including from unrelated donors (UD). These publications mainly include pts transplanted in first complete remission (CR1). We recently reported outcome in 1879 AML pts transplanted in second CR (CR2) with conventional graft-versus-host disease (GVHD) prophylaxis (Leukemia 2020). Results may differ in transplantation with PTCy as GVHD prophylaxis, eliminating proliferating alloreactive T cells, and upregulating T regulatory cells while suppressing host natural killer (NK) cells immediately after transplantation, changing the biology and characteristics of the transplantation.Methods: The study aim was to assess outcome of adult AML pts, aged ≥18 years in CR2 undergoing HSCT from a 9-10/10 UD with PTCy, in 2010-2019.Statistics included multivariate analysis (MVA) adjusting for potential confounding factors was performed using a Cox's proportional-hazards regression model for main outcomes.Results: In total, 127 pts were included. Median follow-up was 19.2 (95% CI, 14.7-28) months (mos). Median age was 45.5 (range, 18.2-71.3) years. 54.3% were male. Cytogenetic risk (MRC classification) was favorable, intermediate, and adverse in 15.7%, 55.9%, and 5.5% of pts, respectively (missing data-22.8percentage) Median year of transplantation was 2017. Time from diagnosis to transplantation was 20.4 (range, 4.1-182.4) months. All pts were at CR2 at time of transplantation. Donors were 10/10 and 9/10 UD in 60.6% and 39.4% of pts, respectively. 77.8% and 47.2% of the pts and donors, respectively, were cytomegalovirus (CMV) seropositive. Conditioning was myeloablative in 50.4% and reduced intensity in 49.6%. The most frequent (61.4%) conditioning consisted of busulfan and fludarabine. All pts received PTCy as anti GVHD prophylaxis in combination with immunosuppression, which was cyclosporine A /mycophenolate mofetil (MMF) in 21.3% and MMF/tacrolimus in 23.6%. 33.9% of the pts received In vivo T-cell depletion. Grafts were peripheral blood in 93.7% and bone marrow in 6.3% of transplants. Karnofsky performance score (KPS) was > 90 in 71.2% and the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was zero in 61.5% of the pts. Engraftment was achieved by 97.6% with day (d) 60 absolute neutrophil count (ANC) > 0.5 x 10 9/L in 96.8%, and d 180 incidence of acute (a) GVHD II-IV and III-IV was 26.2% and 9.2%, respectively. The 2-year total and extensive chronic (c) GVHD was 34.3% and 13.8 %, respectively. The 2-year non-relapse mortality (NRM) was 17.2%. The 2-year relapse incidence (RI) was 21.1%. RI was the main cause of death in 41% of pts who died, followed by infections (23.1%) and GVHD (20.5%). The 2-year leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) was 61.7%, 65.2% and 49.3%, respectively (Figure). In MVA time from diagnosis to transplant was significant prognostic factor for RI, LFS, OS and GRFS hazard ratio (HR) =0.19 (95% CI 0.07-0.48, p<0.001), HR=0.3 (95% CI 0.16-0.56, p<10-3) and HR=0.31 (95% CI 0.15-0.61, p< 0.001), HR=0.40 (95% CI 0.24-0.69, p<0.001), respectively. Year of transplant significantly predict GRFS and aGVHD HR =0.87 (95% CI 0.78-0.97, p<0.009) and HR=0.84 (95% CI 0.73-0.98, p=0.027), respectively. Age was prognostic factor for NRM and good risk cytogenetics for OS HR=1.83 (95% CI 1.24-2.69, p=0.002) and HR=0.21 (95% CI 0.05-0.91, p=0.036), respectively. Finally, female to male combination and RIC were prognostic factors for cGVHD HR=0.15 (95% CI 0.03-0.64, p=0.011), and HR=3.74 (95% CI 1.52-9.18, p=0.004), respectively.Conclusions: Outcome of AML pts undergoing HSCT from a 9-10/10 MUD in CR with PTCy as GVHD prophylaxis, are similar to previous reports using conventional GVHD prophylaxis with 26% of pts developing aGVHD ,34% cGVHD and NRM of 17%. These results are also similar to those we previously observed in pts undergoing HSCT from UD with PTCy while in CR1. [Display omitted] DisclosuresLabopin: Jazz Pharmaceuticals: Honoraria. Kulagin: X4 Pharmaceuticals, Alexion, Apellis, Biocad: Research Funding; Novartis, Generium, Sanofi, Roche, Johnson & Johnson, Pfizer: Speakers Bureau. Blaise: Jazz Pharmaceuticals: Honoraria. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

Community Health Status and Long-Term Outcomes in 1-Year Survivors of Autologous and Allogeneic Hematopoietic Cell Transplantation

Background: Race/ethnicity and socioeconomic status (SES) have been associated with access to and outcomes after hematopoietic cell transplantation (HCT). The role of health disparity factors beyond race/SES in HCT outcomes, however, has not been well described. This is especially true for long-term HCT survivors, for whom local socio-demographic factors may have a greater impact on outcomes because patients may no longer be under close monitoring of their transplant center. The County Health Rankings and Roadmaps (CHRR) provides updated aggregated information from several publicly available datasets to comprehensively describe the health status of US counties. A recent report demonstrated an association between community health status and 1-year non-relapse mortality in a CIBMTR cohort of allogeneic HCT recipients (Hong et al., Cancer 2021). We conducted a single-center retrospective cohort study to investigate the association between community health and long-term outcomes in 1-year autologous and allogeneic HCT survivors.Methods: Our study included 1,812 consecutive adult patients from Cleveland Clinic's BMT Program database who received their first allogeneic or autologous HCT between 2003 and 2017 and survived at least 1 year after their transplant. We used patient community risk score (PCS) as the surrogate for community health. PCS was nationally standardized and calculated as the sum of weighted Z-scores of the 23 county-level community health factors considered in CHRR. The 23 factors fell under 4 categories of health factors: health behavior (tobacco and alcohol use, etc.), clinical care (access and quality of care), social and economic factors (education, community safety, etc.), and physical environment (environmental quality and built environment). Higher PCS indicate worse community health. We evaluated the association of PCS with overall survival (OS), relapse, and non-relapse mortality (NRM) with Cox or Fine and Gray regression separately for autologous and allogeneic HCTs. Considered co-variables included pre-transplant sociodemographic data, disease diagnosis, and transplant factors.Results: Autologous HCT recipients (n=1,313) lived in 133 of 3,141 CHRR counties, 90% in Ohio. Similarly, allogeneic recipients (n=499) were from 88 counties, 88% in Ohio. Patient characteristics are shown in Table 1. The median (range) PCS scores for autologous and allogeneic HCT recipients were 0.03 (-0.85, 0.97) and 0.03 (-0.85, 0.58), respectively. For comparison, the PCS for the complete US CHRR dataset ranged from -1.43 to 2.54 and ranged from -1.6 to 2.0 in the prior CIBMTR study that included allogeneic HCT recipients (Hong et al., Cancer 2021). PCS was not associated with OS, relapse, or NRM for autologous or allogeneic HCT recipients in univariable analysis, nor were the four categories of health factors that contribute to the total PCS (Table 2). In addition, race and estimated median household income were not associated with mortality. Similar findings were noted in multivariable analysis.Conclusion: In our single center study, PCS was not associated with OS, relapse, or NRM in allogeneic or autologous HCT recipients who survived at least 1 year after HCT. A limitation of our analysis is that our cohort represented a single center with regional representation, where long-term follow up care is provided through a dedicated survivorship clinic and there is a strong emphasis on psychosocial support. A national cohort with greater geographical diversity is needed to better define the association of community factors and outcomes in long-term HCT survivors. [Display omitted] DisclosuresHamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy.

Post-Transplant Cyclophosphamide Is Associated with Improved Clinical Outcomes in HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation

Post-Transplant Cyclophosphamide Is Associated with Improved Clinical Outcomes in HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation

Single Cord Blood Transplantation Versus HLA-Haploidentical Related Donor Transplantation Using Post-Transplant Cyclophosphamide in Patients with Hematological Malignancies

Introduction: Unrelated cord blood (UCB) and haploidentical related donor transplantation using post-transplant cyclophosphamide (PTCy-haplo) have become alternative options to treat patients with hematological malignancies without a human leukocyte antigen (HLA)-matched donor. Although a previous phase III study showed better outcomes after bone marrow transplantation (BMT) using PTCy-haplo than those after double unit UCB, a donor selection algorithm including peripheral blood stem cell transplant (PBSCT) using PTCy-haplo or high-risk patients remains to be clarified. With the aim to assess the relative efficacies of UCB and PTCy-haplo transplant, we performed a multi-center retrospective analysis to compare the clinical outcomes in patients with hematologic malignancies.Methods: We included 517 patients aged 16 years to 70 years with hematological malignancies who received a first stem cell transplantation using a single UCB unit or PTCy-haplo between 2013 and 2019 in Kyoto Stem Cell Transplantation Group (KSCTG), which is a multi-center group of 18 transplantation centers in Japan. The primary endpoint was to compare overall survival (OS) between the UCB and PTCy-haplo groups. Secondary endpoints were relapse-free survival (RFS), GVHD- and relapse-free survival (GRFS), relapse, non-relapse mortality (NRM), neutrophil engraftment, platelet engraftment, grade II-IV acute graft-versus-host disease (GVHD), grade III-IV acute GVHD, chronic GVHD, and extensive chronic GVHD.Results: Among 517 patients, 460 received single UCB transplant and 57 received PTCy-haplo related donor transplant (53 PBSCT and 4 BMT). The median age of the UCB and PTCy-haplo groups was 55 and 52 years, respectively (P= 0.770). Myeloablative conditioning (MAC) was used more often in the UCB group than in the PTCy-haplo group (P< 0.001). In the PTCy-haplo cohort, the total dose of Cy was 80mg/m 2 (43.9%) or 100mg/m 2 (56.1%), and the median duration of tacrolimus and mycophenolate mofetil use was 173 and 34 days, respectively. The median follow-up periods of survivors were 2.2 and 2.4 years, respectively. OS in the UCB group was comparable to that in the PTCy-haplo group (2-year OS; 53.7%, 53.6%, P= 0.71 and adjusted hazard ratio (aHR) 1.00, P= 0.99), with similar risks of relapse (aHR 0.91, P= 0.99) and NRM (aHR 0.93, P= 0.69). This result was consistent regardless of disease risk. Neutrophil and platelet engraftment were significantly lower (92.2% vs 94.7%, P= 0.042 and 79.8% vs 82.5%, P= 0.003) and the incidence of acute GVHD in the UCB group tended to be higher (gradeⅡ-Ⅳ; aHR 1.64, p= 0.055, grade III-IV; aHR 3.60, P= 0.073) in the UCB group than those in the PTCy-haplo group. However, the incidences of chronic or extensive chronic GVHD after UCB transplant were comparable (chronic; aHR 0.89, p=0.68, extensive chronic; aHR 0.69, P= 0.35) to those after PTCy-haplo transplant. In the subgroup analysis of disease-specific comparison, acute leukemia patients have a significantly lower risk of relapse with UCB transplant (UBC vs PTCy-haplo, HR 0.55, P= 0.030) and lymphoma patients tended to have good results after PTCy-haplo transplant in terms of higher OS (UCB vs PTCy-haplo, aHR 2.13, P= 0.162) and lower relapse (aHR 3.43, P= 0.100). In terms of Cy toxicity in the PTCy-haplo group, transplant with a reduced dose of Cy (80 mg/m 2) tended to show higher OS (2-year OS, 64.8% vs 45.0%) and significantly lower NRM (2-year NRM, 8.0% vs 31.2%) without an increase in gradeⅡ-IV acute GVHD compared to those after standard-dose Cy (100 mg/m 2).Conclusion: Our findings suggest that UCB transplant gives outcomes comparable to PTCy-haplo transplant for patients without an HLA-matched sibling or unrelated donor. DisclosuresKanda: Amgen Astellas BioPharma: Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; Bristol-Myers Squibb Co: Honoraria; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; DAIICHI SANKYO Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co., Ltd.: Honoraria; Megakaryon Co: Honoraria, Membership on an entity's Board of Directors or advisory committees; NextGeM Inc: Patents & Royalties; Novartis Pharma K.K.: Honoraria; Ono Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; SymBio Pharmaceuticals, Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Company Limited: Honoraria, Membership on an entity's Board of Directors or advisory committees; TEIJIN PHARMA LIMITED.: Honoraria. Imada: Celgene Co., Ltd.: Honoraria; Bristol-Myers Squibb K.K.: Honoraria; Astellas Pharma Inc.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co. Ltd.: Honoraria; Takeda Pharmaceutical Co. Ltd.: Honoraria; Novartis Pharma K.K.: Honoraria. Kondo: Asahi Kasei Pharmaceutical: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Chugai Pharma: Honoraria; MSD Pharmaceutical: Honoraria; Sumitomo Dainippon Pharma: Honoraria. Takaori-Kondo: Bristol-Myers K.K.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Research Funding; Celgene: Research Funding.

Incidence and Outcomes of Toxoplasma Reactivation in Patients with Hematologic Diseases after Allogeneic Hematopoietic Stem Cell Transplantation

Incidence and Outcomes of Toxoplasma Reactivation in Patients with Hematologic Diseases after Allogeneic Hematopoietic Stem Cell Transplantation

Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Cell Transplantation for Higher-Risk Myelodysplastic Syndrome

Introduction: Allogeneic hematopoietic cell transplantation is an only potentially curative option for patients with higher-risk myelodysplastic syndrome (MDS). Owing to the advances in treatment strategies including reduced intensity conditioning, graft-versus-host disease (GVHD) prevention and supportive care, more elderly patients or those with comorbidities can proceed to allogeneic HCT. However, the long-term survival rate following allogeneic HCT is reported to be less than 50%, and non-relapse mortality (NRM) rate is still high reaching upto 30%. In this study, we aimed to evaluate the feasibility of using post-transplantation cyclophosphamide (PTCy) as a GVHD prophylaxis in allogeneic HCT for higher-risk MDS patients. We also compared the post-transplantation outcomes of PTCy group and those of historical control who received HCT using anti-thymocyte globulin (ATG).Methods: Patients with higher-risk MDS or MDS/myeloproliferative neoplasm (MPN) with bone marrow blast ≥ 5% were included in this study. Higher-risk MDS was defined by MDS with International Prognostic Scoring System >1.0 or bone marrow blast ≥ 5% at any time points before HCT. Conditioning regimen consists of busulfan (4-days for patients aged <55 years, 2-days for 55 years), fludarabine. For GVHD prophylaxis, PTCy (50 mg/kg on days 3 and 4), cyclosporine, and mycophenolate mofetil were administered. In historical group, patients received 2- or 4-days of busulfan, fludarabine, and ATG with short course of methotrexate and cyclosporine.Results: Ninety-two and 144 patients received allogeneic HCT using PTCy and ATG, respectively. The median overall survival were 47.9 and 44.0 months, respectively (P=.383). Cumulative incidence of total and grade II-IV acute GVHD in PTCy and ATG group were 19.6% vs. 37.5% (P=.002), and 2.6% vs. 21.7% (P<.001), respectively. Incidence of total and extensive chronic GVHD (50.0% vs. 49.1%, P=.567; 32.5% vs. 33.4%, P=.581), 1-year NRM (20.8% vs. 22.9%, P=.702), and 2-year relapse (16.0% vs. 18.1%, P=.605) were not different between two groups. Neutrophil and platelet engraftment was significantly faster with ATG than PTCy (median 12 vs. 15 for neutrophil; median 15 vs. 24 days for platelet).Conclusion: Allogeneic HCT using PTCy as GVHD prophylaxis in higher-risk MDS seems feasible in terms of low rate of acute GVHD and relapse incidence. DisclosuresChoi: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board; AbbVie: Honoraria, Other: Advisory board.

Superior Survival Outcome of Blinatumomab Compared to Mitoxantrone-Etoposide-Cytarabine Salvage for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: A Propensity Score-Matched Cohort Analysis

Background: Complete remission (CR) rate and long-term overall survival (OS) is very poor in patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Previous clinical trials revealed a good remission rate and a safe bridging role to allogeneic-HCT compared to various standard treatments, and several real-world data have been reported.Aim: Here, we analyzed outcome of blinatumomab versus our conventional intensive chemotherapy by propensity score-matched analysis.Methods: From 2009 to 2020, 197 consecutive R/R BCP-ALL were treated with mitoxantrone-etoposide-cytarabine (MEC, n=113) or blinatumomab (n=84), and allogeneic-HCT was planned in patients with CR. For propensity score-matching, the MEC and blinatumomab cohorts were matched in a 1:1 ratio using 5 criteria of age < 35 years old, short CR duration < 12 months, adverse-risk karyotype including Ph-chromosome at relapse, previous allogeneic-HCT, and first-line salvage or not. We compared CR rate, regiment related mortality, and OS with cumulative incidence of relapse (CIR) and non-relapse mortality (NRM).Results: Matched cohort consisted of 52 patients for each salvage group and matched criteria were the same exactly. Median age was 42 years and 34 (65.4%) patients were > 35 years old. There were 22 (42.3%) primary refractoriness, 9 (17.3%) post-chemotherapy relapse and 21 (40.4%) post-HCT relapse. Among 30 relapsed patients, 19 (63.3%) were early relapse with CR duration less than 12 months. There were 25 (48.1%) with poor-risk karyotype at relapse of which 10 were Philadelphia-chromosome. Extramedullary relapse was observed in 14 (26.9%) and 8 (15.4%) were advanced-line salvage. CR rate was significantly higher in blinatumomab (78.8% vs. 53.8%, p=0.012) and more patients proceeded to allo-HCT (80.8% vs. 46.2%, p<0.001). Regimen-related mortality was significantly higher in MEC (40.4% vs. 1.9%, p<0.001). After median follow-up of 32.5 months (range 6.2 to 131.2), 3-year OS of blinatumomab and MEC was 33.2% and 15.4% (p<0.001), and 3-year NRM was 30.3% and 51.9% (p=0.004), respectively. After CR achievement, CIR was not significantly different (46.9% vs. 60.0%). In multivariate analysis, CR duration < 12 months was related with poor OS with high CIR. MEC regimen showed poor OS with high NRM. High NRM was also related with advanced-line salvage.Conclusion: Our matched cohort analysis clearly showed that blinatumomab is superior to MEC salvage regimen. However, we are observing relapse in up to 50% after blinatumomab and following allo-HCT still shows high NRM. Further combinatorial using novel therapeutics are needed for R/R BCP-ALL. [Display omitted] DisclosuresKim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Sequential Conditioning Regimen with Thiotepa in Allogeneic Hematopoietic Cell Transplantation for the Treatment of Refractory Myeloid Malignancies

IntroductionThe outcome of conventional allogeneic hematopoietic cell transplantation (HCT) for the treatment of patients with refractory myeloid malignancies remains poor. Thiotepa-based sequential conditioning has shown promising results for various refractory hematological malignancies (Duléry R et al. Biol Blood Marrow Transplant. 2018; 24(5):1013-1021). However, no study has evaluated the outcome of this sequential approach specifically in refractory myeloid malignancies. The optimal dose of chemotherapeutic agents used in the conditioning regimen and the feasibility of this sequential approach in patients aged 60 years and above also need to be assessed.MethodsAll consecutive patients with refractory myeloid malignancy who underwent allogeneic HCT with a thiotepa-based sequential conditioning regimen in Saint Antoine hospital between April 2013 and October 2020 were included. The sequential approach consisted of a broad spectrum cytoreduction with thiotepa, etoposide, and cyclophosphamide (TEC) from day -15 to -10. Then, after a 3-day rest, a reduced-intensity conditioning (RIC) regimen was administered with fludarabine 150 mg/m 2, intravenous busulfan 6.4 mg/kg and thymoglobulin 5 mg/kg from day -6 to -2. From 2013 to 2018, doses of thiotepa (10 mg/kg), etoposide (400 mg/m 2) and/or cyclophosphamide (1600 mg/m 2) could be reduced in patients older than 60 years or with comorbidities. Since September 2018, the use of a reduced TEC-RIC regimen (thiotepa at 5 mg/kg, etoposide 300 mg/m 2 and cyclophosphamide 1200 mg/m 2 from day -13 to -10) became the new standard of care for all patients. After transplant, patients could receive a hypomethylating agent or targeted therapy to prevent relapse. Prophylactic donor lymphocyte infusions were given to enhance the graft-versus-leukemia effect, in the absence of contraindication. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine A and mycophenolate mofetil for all patients. Post-transplant cyclophosphamide was added in the case of haploidentical HCT.ResultsSeventy-one patients (median age 61 years, range 15-76) were included. Diagnoses comprised acute myeloblastic leukemia (n=65) and myelodysplastic syndrome/chronic myelomonocytic leukemia (n=6). Donors were haploidentical (n=36), matched related (n=13), unrelated (n=21) and umbilical cord blood (n=1). A reduced TEC-RIC was administrated to 43 (61%) patients, a full dose TEC-RIC to 18 (25%), and a TEC-RIC with a dose reduction only for thiotepa to 10 (14%). With a median follow-up of 45.4 months (95% CI: 36.7-63.6), the 2-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM) were 51%, 41%, and 24%, respectively. Patients receiving a reduced TEC-RIC had a lower cumulative incidence of acute and chronic GVHD (acute grade II-IV GVHD: 14%, acute grade III-IV GVHD: 0%, chronic GVHD: 19%) than the other patients (acute grade II-IV GVHD: 29%, acute grade III-IV GVHD: 18%, chronic GVHD: 29%). The outcomes were not significantly different according to the TEC dose in terms of relapse incidence, OS, and PFS, although the NRM was lower with the reduced TEC-RIC (21% versus 28%, p=0.72). Most notably, patients aged 60 years and above had a 2-year OS and PFS of 48% and 39%, respectively, with no significant difference compared to patients younger than 60 years (Figure).ConclusionOur findings endorse the feasibility and efficacy of a thiotepa-based sequential approach for refractory myeloid malignancies undergoing HCT. The dose reduction did not compromise disease control and expanded the transplant option to older patients, ineligible for a higher dose regimen. Thus, a reduced TEC-RIC sequential regimen can be proposed for selected patients older than 60 years and allows promising outcomes for the treatment of refractory myeloid malignancies. [Display omitted] DisclosuresDuléry: Gilead: Other: travel support and meeting fees; Takeda: Consultancy; Novartis: Honoraria. Malard: Therakos/Mallinckrodt: Honoraria; Biocodex: Honoraria; Astellas: Honoraria; JAZZ pharmaceuticals: Honoraria; Sanofi: Honoraria; Janssen: Honoraria. Legrand: Servier: Consultancy. Fenaux: Abbvie: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria. Labopin: Jazz Pharmaceuticals: Honoraria. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

A Phase II Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Efficacy of Cmvpepvax for Preventing CMV Reactivation/Disease after Matched Related/Unrelated Donor Hematopoietic Cell Transplant

A Phase II Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Efficacy of Cmvpepvax for Preventing CMV Reactivation/Disease after Matched Related/Unrelated Donor Hematopoietic Cell Transplant

Impact of Concomitant Genetic Abnormalities on Sorafenib Therapy in FLT3-ITD Positive Acute Myeloid Leukemia Undergoing Allo-HSCT

AimIn this study, we investigated the co-occurring mutation landscape in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (FLT3-ITD), and explored whether post-allogenic hematopoietic stem cell transplantation (allo-HSCT) sorafenib maintenance therapy could improve the outcomes of FLT3-ITD AML patients combined with other co-occurring genetic abnormalities.MethodsA total of 456 FLT3-ITD AML patients receiving first allo-HSCT were included in this study. Gene mutations were detected using direct sequencing or next generation sequencing. Fusion genes were detected using a 53-gene polymerase chain reaction panel. The frequency of each genetic abnormality was investigated, and the mutation landscape was investigated. The primary outcome of this study was 3-year cumulative incidence of relapse. The secondary outcomes were 3-year overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM). The outcomes were compared between patients who received post-HSCT sorafenib maintenance and those who did not in the whole population and in subgroups referring to co-occurring mutations.ResultsA total of 190 patients received post transplantation sorafenib maintenance therapy (sorafenib group) and 266 patients did not (control group). Of the patients receiving sorafenib pre-transplantation, the median duration of sorafenib therapy was 106 days (IQR 68 - 132) in the sorafenib group, and 99 days (IQR 71 - 142) in the control group (p = 0.883). Of the patients receiving post-transplantation sorafenib maintenance therapy, sorafenib was initiated at a median of 30 days (IQR, 30 - 52 days) after allo-HSCT, and continued for a median of 148 days (IQR, 112 - 150).Median follow-up time was 38.7 months (IQR, 28.1 - 47.9). Thirty-four patients in the sorafenib group and 93 patients in the control group relapsed. The 3-year cumulative incidence of relapse was 18.0% (95% CI 13.1% - 24.3%) in the sorafenib group and 36.1% (95% CI 30.5% - 42.3%) in the control group (HR 0.43, 95% CI 0.29 - 0.64; p < 0.001). A total of 126 patients died, including 39 in the sorafenib group and 87 in the control group. Three-year DFS was 75.8% in the sorafenib group and 57.5% in the control group (HR 0.47, 95% CI 0.34 - 0.66; p < 0.001). Three-year OS was 79.5% for patients in the sorafenib group and 68.4% for patients in the control group (HR 0.57, 95% CI 0.39 - 0.83, p = 0.004).Gene mutations were detected using a 12-mutation panel direct sequencing including FLT3-ITD, FLT3-TKD, NPM1, KIT, DNMT3A, CEBPA, ASXL1, TP53, TET2, IDH1, IDH2 and RUNX1 in all patients, and a 127-gene panel new generation sequencing in 188 patients.Except FLT3, a total of 920 co-occurring gene mutations and 147 cytogenetic abnormalties were detected. The co-occurring mutations that presented in at least 10% the cases were NPM1 (31.6%), DNMT3A (15.4%), TET2 (11.4%), and CEBPA (10.5%). There were 10.5% patients presented with both NPM1 and DNMT3A mutations (Triple-mutated AML patients), and 13.8% patients combined with at least one additional genetic abnormality classified as adverse according to the 2017 ELN risk stratification other than FLT3-ITD. Cytogenetic abnormalities presented in more than 1% the patients were RUNX1-RUNX1T1, which occurred in 23 patients (5.0%), followed by +8 (2.9%), complex karyotype (2.6%), CBFB-MYH11 (2.4%), DEK-NUP214 (1.3%) and -y (1.3%).Patients combined with NPM1(p = 0.009 and 0.009), DNMT3A (p = 0.036 and 0.086), triple-mutated AML patients (p = 0.030 and 0.027), and patients with at least one additional adverse abnormality (p = 0.014 and 0.005) benefit significantly in DFS and OS from post-transplantation sorafenib maintenance, but not those with CEBPA (p = 0.669 and 0.576) or TET2 (p = 0.375 and 0.178) mutations.ConclusionPost transplantation sorafenib maintenance therapy can improve the prognosis of FLT3-ITD AML patients combined with DNMT3A or NPM1, patients with triple-mutated AML, and patients combined with at least one additional adverse abnormalities, but not of those combined with CEBPA or TET2 mutations. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of Nelarabine, Intensive L-Asparaginase, and Protracted Intrathecal Therapy on Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia: Results from the Japanese Pediatric Leukemia/Lymphoma Study Group and the Japan Adult Leukemia Study Group

Impact of Nelarabine, Intensive L-Asparaginase, and Protracted Intrathecal Therapy on Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia: Results from the Japanese Pediatric Leukemia/Lymphoma Study Group and the Japan Adult Leukemia Study Group

Haploidentical Versus Cord Blood Stem Cell Transplantation As the Second Transplant for Relapsed Acute Myeloid Leukemia Patients after the First Stem Cell Transplantation

Haploidentical Versus Cord Blood Stem Cell Transplantation As the Second Transplant for Relapsed Acute Myeloid Leukemia Patients after the First Stem Cell Transplantation

Outcomes of patients diagnosed with chronic lymphocytic leukemia after allogeneic hematopoietic stem cell transplantation: Results from a tertiary care center

BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HCT) is currently the only curative treatment for patients with chronic lymphocytic leukemia (CLL). MethodsWe analyzed the outcomes of 93 patients (median age: 52 years) who underwent allo-HCT at our center between 1989 and 2019. ResultsAfter a median follow-up of 35 months, relapse was observed in 15.1% (n = 14) patients. The estimated 2-year non-relapse mortality, relapse-free survival, and overall survival (OS) were 38.1%, 54.2%, and 58.7%, respectively. The ECOG performance status ≥ 2 (hazard ratio [HR]: 4.1; p = .001) and use of total body irradiation (in a myeloablative conditioning regimen; HR: 2.64; p = .005) were predictive of poor OS after multivariable analysis. The occurrence of sinusoidal obstruction syndrome/veno-occlusive disease post-transplant was associated with poor survival (p = .001). ConclusionAlthough the use of kinase and bcl2 inhibitors may result in a decrease in the number and need of transplants, allo-HCT remains a viable option in selected patients with high-risk CLL and good performance status.

Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis

AbstractAllogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P < .001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.

Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era

AbstractGraft-versus-host disease (GVHD) is one of the leading causes of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). Posttransplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicity, and few studies have evaluated the cardiac toxicities that arise after PTCy. We completed a retrospective analysis of patients who underwent matched-donor allo-HCT at our institution and who received PTCy- or non-PTCy–based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after allo-HCT. We included 585 patients in our analysis and found that 38 (6.5%) experienced cardiac toxicity after allo-HCT. The toxicities included arrhythmias (n = 21), heart failure (n = 14), pericardial effusion (n = 10), and myocardial infarction or ischemia (n = 7). Patients who received PTCy had a 7.4% incidence of cardiac toxicity, whereas non-PTCy recipients had an incidence of 5.8% (P = .4). We found that age >55 years (P = .02) and a history of hypertension (P = .01), arrhythmia (P = .003), diabetes (P = .04), and cardiac comorbidities (P < .001) were significant predictors of cardiac toxicity, whereas none of the preparative and GVHD prophylaxis regimens were predictive. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity after allo-HCT. We found that a higher score correlated with an incidence of cardiac toxicity. Furthermore, the development of cardiac toxicity was associated with worse 1-year overall survival (OS) and NRM. The use of PTCy was associated with improvements in 1-year OS and NRM rates.

P-175: Outcomes of autologous-allogeneic vs autologous tandem approach followed by thalidomide maintenance for transplant-eligible patients with newly diagnosed multiple myeloma: a prospective phase II-study

P-175: Outcomes of autologous-allogeneic vs autologous tandem approach followed by thalidomide maintenance for transplant-eligible patients with newly diagnosed multiple myeloma: a prospective phase II-study

Development and validation of a comorbidity index for predicting survival outcomes after allogeneic stem cell transplantation in adult patients with acute leukemia: a Korean nationwide cohort study.

BackgroundAllogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS).MethodsA Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort. A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort.ResultsIn the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17< score ≤0.4), high-risk (0.4< score ≤0.55), and very high-risk (score >0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P<0.001). The developed scoring system yielded discriminatively different 1-year OS rates and 1-year incidence of non-relapse mortality according to the risk group (P=0.085 and P=0.018, respectively). Furthermore, the developed model showed an acceptable performance for predicting 1-year non-relapse mortality with an area under the curve of 0.715.ConclusionThe newly developed predictive scoring system could be a simple and reliable tool helping clinicians to assess risk of alloSCT in adults with acute leukemia.

The Simplified Comorbidity Index: a new tool for prediction of nonrelapse mortality in allo-HCT

AbstractIndividual comorbidities have distinct contributions to nonrelapse mortality (NRM) following allogeneic hematopoietic cell transplantation (allo-HCT). We studied the impact of comorbidities individually and in combination in a single-center cohort of 573 adult patients who underwent CD34-selected allo-HCT following myeloablative conditioning. Pulmonary disease, moderate to severe hepatic comorbidity, cardiac disease of any type, and renal dysfunction were associated with increased NRM in multivariable Cox regression models. A Simplified Comorbidity Index (SCI) composed of the 4 comorbidities predictive of NRM, as well as age >60 years, stratified patients into 5 groups with a stepwise increase in NRM. NRM rates ranged from 11.4% to 49.9% by stratum, with adjusted hazard ratios of 1.84, 2.59, 3.57, and 5.38. The SCI was also applicable in an external cohort of 230 patients who underwent allo-HCT with unmanipulated grafts following intermediate-intensity conditioning. The area under the receiver operating characteristic curve (AUC) of the SCI for 1-year NRM was 70.3 and 72.0 over the development and external-validation cohorts, respectively; corresponding AUCs of the Hematopoietic Cell Transplantation–specific Comorbidity Index (HCT-CI) were 61.7 and 65.7. In summary, a small set of comorbidities, aggregated into the SCI, is highly predictive of NRM. The new index stratifies patients into distinct risk groups, was validated in an external cohort, and provides higher discrimination than does the HCT-CI.

Risk Factors for and the Prognostic Impact of Pericardial Effusion after Allogeneic Hematopoietic Stem Cell Transplantation

Pericardial effusion (PE) is a rare complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the mechanisms underlying the onset of PE remain unclear, patients with PE after allo-HSCT have poor clinical outcomes. However, the prognostic impact of PE remains controversial, and risk factors have varied among studies. Therefore, we examined contributing as well as prognostic factors for PE. We retrospectively examined 243 patients who underwent allo-HSCT at the Faculty of Medicine, Kagawa University and Takamatsu Red Cross Hospital, Kagawa, Japan between 2000 and 2020. Forty-three patients (18%) were excluded owing to a lack of data on PE, and thus we ultimately analyzed 200 patients. We reviewed the findings of computed tomography (CT) scans, including chest CT, and echocardiography after allo-HSCT. Only cases in which a radiologist or echocardiography technician detected PE were assessed. PE was stratified into localized PE and whole-circumference PE. The median age at transplantation was 52 years (range, 16 to 74 years). The study cohort comprised 106 patients (53%) age more than 50 years, 88 females (44%), and 112 males (56%). Primary diseases were myeloid neoplasms in 122 patients (61%) and lymphoid neoplasms in 78 (39%). The conditioning regimen was myeloablative in 142 patients (71%) and nonmyeloablative in 58 (29%). The median duration of follow-up was 47 months (range, 1 to 209 months). Forty patients developed PE within 100 days; localized in 23 (12%) and whole circumference in 17 (9%). In a multivariate analysis, significant risk factors for the development of PE within 100 days were late neutrophil engraftment (hazard ratio [HR], 5.24; 95% CI, 1.92 to 14.30; P < .01) and thrombotic microangiopathy (TMA) (HR, 8.23; 95% CI, 1.42 to 47.60; P=.02). The incidence of whole- circumference PE correlated with a lower overall survival (OS) rate (HR, 3.10; 95% CI, 1.34 to 7.17; P < .01) and higher nonrelapse mortality (NRM) rate (HR, 2.94; 95% CI, 1.18 to 7.32; P=.02). In the subgroup analysis, significant risk factors for the development of PE within 365 days were late neutrophil engraftment (HR, 3.13; 95% CI, 1.08 to 9.02; P=.04), the occurrence of chronic graft-versus-host disease (GVHD) (HR, 3.57; 95% CI, 1.19 to 10.70; P=.02), and disease recurrence (HR, 4.98; 95% CI, 1.43 to 17.30; P=.01). The development of whole-circumference PE also correlated with a lower OS rate (HR, 3.83; 95% CI, 1.65 to 8.89; P < .01) and a higher NRM rate (HR, 83.21; 95% CI, 17.75 to 390.10; P < .01). The overall occurrence of acute (grade II to IV) GVHD, chronic GVHD, and TMA were 36% (72 of 200), 39% (78 of 200), and 10% (19 of 200), respectively. In the entire cohort, the 3-year OS rate was 55%, and 3-year relapse and NRM rates were 37 and 14%, respectively. The present results demonstrate that risk factors for PE varied according to the time after allo-HSCT, and that whole-circumference PE at any time correlated with lower OS and higher NRM rates. A large-scale prospective study is needed to verify risk factors for PE and clarify whether immunosuppressive interventions based on the onset of PE improve the clinical prognosis of patients.

Predictive Factors for Outcome of First Allogeneic Transplant for Elderly Patients With Acute Lymphoblastic Leukemia

Introduction/Background: The treatment of acute lymphoblastic leukemia (ALL) in patients older than 70 is extremely challenging with dismal outcome. Allogeneic stem cell transplantation (alloHCT) has seen many advancements in the last decades showing benefits in younger ALL patients, but this treatment modality is decreasingly used with increasing age due to high treatment-related mortality. Patients and Methods: We identified 84 ALL patients 70 to 84 years old allografted In 2002 to 2019 from a matched related (23%), unrelated (58%), haploidentical (17%), or cord blood (2%) donor at EBMT participating centers with a median follow-up of 23 months. Results: The 2-year relapse incidence (RI) and non-relapse mortality were 37% and 28%, respectively, and 2-year leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 35%, 39% and 23%, respectively. The strongest predictor of outcome was disease status at transplant whereby patients in first complete remission (CR1) had >50% 2-year OS, reflected in multivariate analysis (MVA) with significant improvement in RI, LFS, and GRFS (HR 0.23, 0.49, and 0.54, respectively). Furthermore, karnofsky score ≥90 reflective of good functional status positively influenced non-relapse mortality in both univariate and MVA (HR 0.37), and interestingly, donor CMV positivity appeared to negatively affect RI, LFS and OS in univariate analysis and RI in MVA (HR 2.87). Conclusion: Our data suggest that alloHCT is an option for elderly ALL patients, particularly those carefully selected and transplanted in CR1 especially if failed or without access to novel non-chemotherapy-based approaches.