Fludarabine-Melphalan with Total Body Irradiation or Thiotepa Conditioning Regimens for Adult Patients with Acute Lymphoblastic Leukemia Receiving Allogeneic Stem Cell Transplantation

Le résumé fourni par la source

Background Total body irradiation (TBI) – based regimens have preferentially been used for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We developed a conditioning consisting of fludarabine , melphalan (FM) and low-dose TBI (FMT) or low-dose thiotepa (FMTT) for patients with acute leukemia . This study aimed to evaluate transplant outcomes of ALL patients who received FMT or FMTT. Methods Twenty-nine patients (≥18-year-old) with ALL, who underwent AHSCT between 5/2020-6/2024. Conditioning consisted of fludarabine 40 mg/m 2 /d, melphalan 100-140 mg/m 2 and either TBI 2-4 Gy for patients without central nervous system (CNS) involvement, or thiotepa 5 mg/kg for patients with CNS involvement. All patients with CNS leukemia also received pre-AHSCT craniospinal irradiation (CSI) (18 Gy in 10 daily fractions) and 6 monthly doses of intrathecal (IT) methotrexate after AHSCT. GVHD prophylaxis comprised of post-transplant cyclophosphamide (PTCy), tacrolimus , mycophenolate mofetil, and oral budesonide . Results The median age was 44 years (range 22-72). 24 (83%) patients had B-cell ALL, including 20 patients (70%) with either Ph+ (N=10) or Ph-like ALL (N=10). Donor types were haploidentical (N=17, 59%), HLA match-related (N=11, 38%), and match-unrelated (N=1, 3%). 19 (66%) patients received melphalan 100 mg/m 2 . 24 (83%) patients were in complete remission (CR1), 19 (66%) patients were MRD-negative before AHSCT. 20 and 9 patients received FMT and FMTT regimen, respectively. Median follow-up of survivors was 443 days. All patients achieved neutrophil and platelet engraftment , with median time of 15 and 19 days, respectively. All patients had sustained full donor chimerisms at 1-year post-AHSCT. Two-year overall survival (OS) and progression-free survival (PFS) were 83% (95%CI: 59.9-93.1). Cumulative incidence (CI) of non-relapse mortality and relapse at 2 years were 17.4% (95%CI: 5.4-35.0) and 0%, respectively (Figure 1). All patients had MRD-negative at 100 days after AHSCT. CI of grade 2-4 acute GVHD at 100 days was 3.9% (95%CI: 5.4-35.0), while chronic GVHD at 1 year was 4.2% (95%CI: 0.3-17.6). All 9 patients with CNS disease were alive and disease-free at 1-year post-AHSCT. 11 patients (38%) with high-risk features received blinatumomab maintenance and 5 patients (17%) with Ph+ B-cell ALL received both blinatumomab and ponatinib post-AHSCT with 100% PFS at 1-year. Conclusion The FM-based conditioning regimen with low-dose TBI or thiotepa is effective in adult patients with ALL with very low relapse rate, regardless of donor type. Patients with CNS disease who achieved disease control prior to AHSCT have excellent outcomes. Maintenance therapy for high-risk B-cell ALL patients with blinatumomab ± ponatinib may contribute to the very low relapse rate seen in our study and warrant further investigation.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.