Total Marrow and Lymphoid Irradiation (TMLI) Is Associated with Good Early Outcomes in Patients Undergoing Matched Sibling Donor and Haplo-identical Transplants for Acute Lymphoblastic Leukemia.

Abstract

Total marrow and lymphoid irradiation (TMLI) can deliver higher doses of irradiation without increased toxicity. This study evaluated TMLI and cyclophosphamide in patients undergoing stem cell transplantation for acute lymphoblastic leukemia (ALL). A total of 58 patients underwent matched related, unrelated, or haplo-identical donor transplantation using TMLI. The graft source was peripheral blood stem cells (PBSCs) in ALL whereas graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine with methotrexate or post-transplant cyclophosphamide. The median age was 20 years (range: 5-49 years) and included 20 children. Engraftment occurred in 56 (96.5%) at a median of 15 days (range: 12-23) with 2 early deaths. Sinusoidal obstruction syndrome (SOS) was seen in 10 patients whereas hemorrhagic cystitis and cardiac dysfunction occurred in 2 patients each. Cumulative incidence (CI) of grades II-IV acute GVHD was 23.6% whereas the CI of grades III-IV was 10.9%. Chronic GVHD was seen in 46.9% whereas relapse was seen in 10 patients (17.2%). The 2-year overall survival (OS) was 65.9% ± 6.8% and the 2-year disease-free survival (DFS) was 59% ± 6.7%. Outcomes were compared with 52 patients who received either Cy/TBI or Flu/Bu4 for conditioning during the same period. Engraftment rates and time to engraftment were similar. Acute GVHD (P = .002), regimen-related toxicity (P = .043) and day 100 non-relapse mortality (P = .020) were significantly lower with TMLI. TMLI was associated with better OS (P = .004) and DFS (P = .005) for haplo-identical transplants. Better DFS was seen with TMLI in patients with high-risk disease (P = .007) and disease status > CR1 (P = .041). The use of TMLI and cyclophosphamide is associated with good outcomes in patients undergoing hematopoietic stem cell transplantation for ALL, especially with haplo-identical stem cell transplants.