Total Marrow and Lymphoid Irradiation in Combination with Post-Transplant Cyclophosphamide-Based Graft Versus Host Disease Prophylaxis Confers Favorable GvHD-Free/Relapse-Free Survival in Patients with Acute Myeloid Leukemia in First or Second Remission
Year: 2025
Type: article
Abstract: Introduction The two main causes of failure of allogeneic hematopoietic cell transplantation (HCT) in patients in first or second complete remission (CR) are relapse and mortality/morbidity associated with chronic graft versus host disease (GvHD). In a randomized trial of 15.75 Gy versus 12 Gy total body irradiation (TBI) in patients with acute myeloid leukemia (AML) who underwent HCT, the higher dose led to decreased relapse but no increase in survival because of radiation-related toxicities (PMID: 2224134). We accordingly used organ-sparing targeted total marrow and lymphoid irradiation (TMLI) to offset the risk of increased toxicity and allow dose escalation to prevent relapse. TMLI was combined with post-transplant cyclophosphamide (PTCy) to prevent chronic GvHD . Methods We present updated trial results of 34 patients (clinicaltrials.gov: NCT03467386). Key eligibility criteria: age 18-60, first or second CR, minimal residual disease negative (by multicolor flow cytometry/molecular markers). TMLI was administered without chemotherapy. High-dose radiation of 20 Gy was targeted to potential disease sites of bone, lymph nodes , and spleen, delivered in 2 Gy fractions twice a day. The radiation dose delivered to brain and liver was capped at 12 Gy. Remaining organs were spared (2.6 Gy to 10.4 Gy). PTCy was given on days plus 3 and 4, 50 mg/kg each day for GvHD prevention followed by tacrolimus , which was tapered starting day 90 in the absence of GvHD . Results The median follow up was 24.1 months (range: 5.6-25.4) for surviving patients (n=30). No grade 3-4 Bearman toxicities or toxicity-related deaths were observed. All patients engrafted. Two-year estimates of overall survival and leukemia-free survival were 84% and 85%, respectively. Disease relapse at 2 years was 15%. The estimate of non-relapse mortality (NRM) at 2 years was 0%. Five patients (15%) developed chronic GvHD . Of these 5 patients, 4 required systemic therapy for their cGvHD, which was administered for a median of 408 days (range:175 – 1095). The 1-year and 2-year estimates of GvHD-/relapse-free survival (GRFS) were 71% and 67%, respectively. Conclusions Dose escalation of organ-sparing whole body radiation using TMLI 20 Gy and PTCy results in low rates of relapse, toxicity, and acute and chronic GvHD , with no NRM. All patients discontinued immunosuppression by 3 years post-transplant, limiting morbidity and mortality associated with transplantation. TMLI and PTCy warrant further study as a replacement for TBI in HCT.
Authors: Anthony S. Stein, Monzr M. Al Malki, Dongyun Yang, Joycelynne Palmer, Ni-Chun Tsai, Ibrahim Aldoss, Haris Ali, Ahmed Aribi, Andrew Artz, Savita Dandapani, Chunhui Han, Leonardo Farol, Susanta Hui, An Liu, Ryotaro Nakamura, Vinod Pullarkat, Amandeep Salhotra, James F Sanchez, Ricardo Spielberger, Stephanie Yoon, Guido Marcucci, Stephen J. Forman, Jeffrey Wong
Institutions: City Of Hope National Medical Center, City of Hope
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W4407977515