Clinical Outcomes and Treatment Patterns in Adults With FLT3-ITD(mut+) Acute Myeloid Leukemia Undergoing Allogeneic Hemopoietic Cell Transplantation in the United States and Canada.

Allogeneic hematopoietic cell transplantation (alloHCT) is used to treat patients with acute myeloid leukemia (AML) with internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITDmut+). However, the effect of different characteristics on outcomes after transplant is not fully understood. The aim of this study was to determine the impact of patient, disease, and transplant characteristics on clinical outcomes and trends in maintenance therapy for patients with FLT3-ITDmut+ AML who underwent their first alloHCT. This was an observational cohort study of adults ≥18 years who were recipients of human leukocyte antigen identical sibling, haploidentical, 8/8 or 7/8 unrelated, or cord blood donor alloHCT in the United States and Canada between 2014 and 2019. Patient, disease, and transplant characteristics were collected from Center for International Blood & Marrow Transplant Research between 2014 and 2022. Patients enrolled in the MORPHO clinical trial (NCT02997202) were excluded. Clinical outcomes were measured from the time of alloHCT by disease status: first complete remission (CR1), second or greater complete remission (≥CR2), or relapsed/refractory (R/R). The primary endpoints of this study were overall survival (OS) and leukemia-free survival (LFS). Key secondary endpoints included relapse after alloHCT, nonrelapse mortality (NRM), time from diagnosis to complete remission, time from complete remission to alloHCT, and maintenance therapy before and after alloHCT. Univariate analyses were conducted with Gray's test and log-rank test, while multivariable analyses were conducted using Cox proportional hazards models. A total of 3147 eligible patients (CR1, n = 2389; ≥CR2, n = 340; R/R, n = 418) were included. Most patient, disease, and transplant characteristics were similar between different disease statuses. In univariate analyses, disease status of CR1 compared with ≥CR2 or R/R was significantly (P < .001) associated with improved OS and LFS, and decreased probability of relapse; NRM likely differed across cohorts after alloHCT (P = .003). In multivariable analyses, patients with a disease status of ≥CR2 and R/R compared with CR1 had significantly shorter OS (hazard ratio [HR] 95% confidence interval [CI], 1.43 [1.19 to 1.72], P = .0001, and 2.14 [1.88 to 2.44], P < .0001, respectively). Patients with a disease status of CR1 at ≤2.6 months had better LFS compared with ≥CR2 and R/R (HR [95% CI], 2.03 [1.56 to 2.63], P < .0001 and 3.98 [3.07 to 5.17], P < .0001, respectively). Patients with a ≥CR2 or R/R disease status at ≤2.6 months had an increased likelihood of relapse compared with CR1 (HR [95% CI], 2.46 [1.82 to 3.33], P < .0001 and 4.68 [3.46 to 6.34], P < .0001, respectively). Disease status was not significantly associated with NRM. We also identified several additional patient, disease, and transplant characteristics that may have been associated with inferior OS and/or LFS and greater relapse and/or NRM. Maintenance therapy usage after alloHCT increased from 2014 to 2019 primarily due to increased FLT3 inhibitor use. In this largest study to date of patients from the United States and Canada with FLT3-ITDmut+ AML, disease status of CR1 at the time of alloHCT was associated with better clinical outcomes. Additional factors were identified that may also impact clinical outcomes, and in total, have the potential to inform clinical decision-making.

Pandya BJ ，Burns LJ ，Wang T ，Xie B ，Touya M ，Spalding J ，Block A ，Kuperman G ，Young C ... -  《-》

Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia.

Dillon LW ，Gui G ，Ravindra N ，Andrew G ，Mukherjee D ，Wong ZC ，Huang Y ，Gerhold J ，Holman M ，D'Angelo J ，Miller J ，Higgins J ，Salk JJ ，Auletta JJ ，El Chaer F ，Devine SM ，Jimenez-Jimenez AM ，De Lima MJG ，Litzow MR ，Kebriaei P ，Saber W ，Spellman SR ，Zeger SL ，Page KM ，Hourigan CS ... -  《-》

[Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation].

Xu Y ，Zhang J ，Xue SL ，Miao M ，Wang Y ，Chen SN ，Qiu HY ，Wu DP ... -  《-》

Outcome of FLT3-ITD-positive acute myeloid leukemia: impact of allogeneic stem cell transplantation and tyrosine kinase inhibitor treatment.

Fleischmann M ，Schnetzke U ，Schrenk KG ，Schmidt V ，Sayer HG ，Hilgendorf I ，Hochhaus A ，Scholl S ... -  《-》

Early Mixed Donor Chimerism is a Strong Negative Prognostic Indicator in Allogeneic Stem Cell Transplant for AML and MDS.

Allogeneic bone marrow transplantation remains the most potent curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) due to the graft-versus-tumor effect provided by donor cells. Donor chimerism is utilized early after transplantation to evaluate engraftment and to monitor the persistence of donor hematopoiesis. Literature is conflicting regarding to the prognostic utility of early mixed donor chimerism, chimerism kinetic patterns as well as factors associated with it and we sought to clarify this uncertainty. In this single-centre retrospective analysis, 141 adults aged 18 years of age or older with AML (n = 104) and MDS (n = 37) who received their first transplant from HLA matched related, matched unrelated or mismatched related (haploidentical) donors between 2016 and 2022 and had at least day 30 chimerism measured were included. Approximately 30% received post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis and 67% of subjects received reduced-intensity conditioning. Chimerism was measured using STR-PCR from unfractionated peripheral blood mononuclear cells (whole blood; WB) and CD3+ (T cell; TC) compartment at each time point. Complete donor chimerism was defined as ≥95% whereas <95% defined as mixed. Competing risk analysis was used to estimate cumulative incidence of relapse with kinetic calculations completed using an increment factor. Kaplan-Meier was used for overall survival (OS) and relapse-free survival (RFS). Cox proportional hazards regression was used to explore prognostic factors for OS and RFS. Both day 30 mixed WB and TC donor chimerism were individually associated with an increased risk of relapse and worse overall and relapse-free survival at days 30, 60 and 90 post-transplant. Day 30 mixed WB was more specific for relapse (86%), while mixed TC was more sensitive (67%). Complete day 30 chimerism had a negative predictive value of 63% and 70% and positive predictive value of 57% and 67% for WB and TC, respectively. Day 30 WB and TC donor chimerism of <88.92% and 89.29% had specificities of 79.17% and 82.19% although sensitivities only approximated 50%. Evaluating the kinetics of chimerism over the first 90 days provided additional information for prognosticating relapse than absolute chimerism values at individual time points in both WB day 30 to 90 [HR, 1.75 (95% CI, 1.04 to 2.94); P < .035] and TC day 60 to 90 [HR, 1.32 (95% CI, 1.03, 1.69); P < .29]. Twice as many patients with complete chimerism developed acute GVHD compared to those with mixed chimerism. Factors that were found to be associated with day 30 mixed TC chimerism were donor source, ATG GVHD prophylaxis, myeloablative conditioning and female sex, while only donor source was associated with mixed WB. Both TC and WB day 30 mixed chimerism were associated with an increased risk of relapse. Early mixed WB and TC chimerism is strongly associated with a worse overall and relapse-free survival. The serial measurement of chimerism early post-transplant for monitoring chimerism kinetics provides additional prognostic information beyond the absolute donor chimerism value at a single time point. Haploidentical stem cell transplants were associated with a lower likelihood of mixed chimerism than other donor sources.

Radford M ，Garcia-Horton A ，Badami R ，Jin E ，Usmani N ，Grafodatskaya D ，McCready E ，Khalaf D ，Walker I ，Leber B ，Lepic K ，Pond G ，Berg T ... -  《-》