Excellent Outcome of Myeloablative TBI-Based Allogeneic Stem Cell Transplant in Adult Patients with Acute Lymphocytic Leukemia in MRD Negative CR1: Results from a Retrospective Canadian Cohort
Authors: Ahmed Amani , Cherniawsky Hannah , Chung Shanee , Forrest Donna L. , Lad Deepesh , Kuchenbauer Florian , Nantel Stephen H. , Narayanan Sujaatha , Nevill Thomas J. , Rodrigo Judith Anula , Roy Claudie , Sanford David , Song Kevin , Stubbins Ryan J , Toze Cynthia L. , White Jennifer , Abou Mourad Yasser 
Published: December 2024

Introduction:
Allogeneic stem cell transplantation (Allo-SCT) has emerged as a potential curative option for some patients with ALL, particularly those with high-risk or relapse refractory disease. Implementation of Minimal Residual Disease (MRD) directed therapy has shown an improvement in the outcomes in ALL. Total body irradiation (TBI), when used in conjunction with high-dose chemotherapy, has been a cornerstone of preparative regimens for Allo-SCT in ALL due to its ability to penetrate sanctuary sites and its synergistic effects with chemotherapy. This abstract explores the efficacy of myeloablative (MA) TBI-based conditioning regimens in the context of Allo-SCT for ALL based on pre transplant MRD and other related outcomes.
Methods:
This is a retrospective unicenter analysis of 76 consecutive adult ALL patients who underwent TBI-based Allo-SCT at the Leukemia/Bone Marrow Transplant Program in Vancouver, British Columbia, Canada from January 1, 2015, to September 30, 2022. Baseline demographics, patients' characteristics, type of ALL, status of remission (CR1, 2 or 3), pre-transplant MRD, type of Allo-SCT, clinical outcomes and last follow up data were all collected by reviewing electronic medical records and our Database. MRD negativity was defined as &lt;0.01% leukemic cells and assessed by multicolor flow cytometry for Ph-Negative B-ALL and T-ALL and by molecular studies with PCR for Ph+ B- ALL. Majority of patients 70/76(92%) had MA CyTBI±ATG. Four double cord transplanted patients had MA FluTBI. Overall survival (OS) was calculated from diagnosis to death from any cause and was not censored at the time of Allo-SCT. EFS was calculated from CR to relapse. Patients without an event during the study period were censored at the time of last follow-up. Dichotomous outcomes were compared using Chi-square and Fisher exact tests and continuous variables were compared using two-sample t-test. Kaplan-Meier survival method and log rank test were used to estimate and compare survival.
Results:
76 patients were included. The median duration of follow up of the entire cohort was 36 months (range 1- 108 months). Median age was 34 (range 18-59 years) with majority of patients younger than 40 years (73%). Most patients had Philadelphia negative B-ALL 46 (60.5%) followed by Philadelphia positive B-ALL 18 (23.7%) and T-ALL 12 (15.8%). Remission status prior to transplant as CR1, CR2 and CR3 were in 64/76 (84.2%), 9/76 (11.8%) and 3/76 (4%) respectively. Pre-transplant MRD results were available for 61/76 patients (80%); 48 patients were in MRD negative CR (42/48 in MRD negative CR1; 6/48 in MRD negative CR2 and beyond); 13 patients were in MRD positive CR. Unrelated Allo-SCT was performed in 48/76 (63%), matched sibling in 22/76 (29%), haplo-identical and double cord in six patients (8%). The 5-year OS & EFS rate for the entire cohort were 60% and 58.2% respectively. The 5-year OS rates was higher in MRD negative patients (77%) compared to 27% in MRD positive patients (P&lt;0.001). The 5-year EFS rate was higher in MRD negative (75%) compared to 25% in MRD positive patients (P&lt;0.001). Patients in MRD negative CR1 (42/48) had an excellent 5-year OS (80%) compared to MRD negative patients in CR2 and beyond (6/48) at 50% (P=0.078). 5-year EFS was 78% for patients in MRD negative CR1 compared to 50% for MRD negative CR2 and beyond (p=0.085). Acute GVHD was documented in 52 patients (68%) with 33/52 (64%) being grade I-II. Chronic GVHD was documented in 38 patients (50%) in the whole cohort. Day +100 TRM was 6.6%. At the time of last follow up 31 patients out of 70 evaluable patients died with long-term mortality rate of 54%. Major cause of death was relapse 19/31(61%) followed by infection 6/31(19%), GVHD 3/31(9.5%) and others 3/31(9.5%) including cardiac, respiratory, or neurological events. COVID-19 was documented as the cause of death in 2/6 patients who died from infection.
Conclusions:
Our single institution retrospective results show excellent outcomes of TBI-based myeloablative Allo-SCT in adult ALL patients younger than 60 years with higher OS and EFS for patients in MRD negative CR. The best outcome of Allo-SCT was achieved in MRD negative CR1. These results confirm the clinical implication and importance of MRD monitoring prior to Allo-SCT and that MRD response prior to Allo-SCT is associated with significantly longer OS and EFS. A limitation of this study is the smaller size of the cohort and lack of MRD data for some patients.