Dose Escalation of Total Marrow and Lymphoid Irradiation Prior to Allogeneic Stem Cell Transplantation treating for Acute Leukemia and Lymphoma

Abstract

Abstract Purpose Hematopoietic stem cell transplantation (HSCT) is a curative option for various hematologic malignancies (HM), however, the risk of relapse hampers favorable HSCT outcomes. Augmentation of irradiation to sites of disease is one potential strategy to overcome this risk. This study evaluated the feasibility of radiation dose escalation of total marrow and lymphoid irradiation (TMLI) as part of the conditioning regimen prior to HSCT. Methods and Materials 53 patients (5 acute myelogenous leukemia (AML), 29 acute lymphoblastic leukemia (ALL), 17 non-Hodgkin’s lymphoma (NHL), 2 mixed acute leukemia (MAL)) received conditioning radiation treatment with TMLI 10 Gy (8 Gy to bone marrow (BM), 10 Gy to involved lymphatic sanctuary sites in 2 fractions per day). 36 patients (5 AML, 26 ALL, 2 NHL, 3 MAL) underwent the radiation treatment with TMLI 12 Gy (8 Gy to BM, 12 Gy to involved lymphatic sanctuary sites in 2 fractions per day) before HSCT. Results The median age of patients receiving TMLI 10 Gy and 12 Gy was 24 (4–47) and 27 (8–55) years old, respectively. Median dose of organs at risk (OARs) was down-regulated by 27% − 79% and 11% − 83% of the prescription dose at TMLI 10 Gy and 12 Gy compared to standard total body irradiation (TBI). Grade 1–2 acute toxicities were primarily observed. The 2 years progression-free survival (PFS) was 73.6% at TMLI 10 Gy and 84.8% at TMLI 12 Gy (95% CI: 0.15, 1.33) and, and the 2 years overall survival (OS) was 79.1% and 65.7% respectively (95% CI: 0.28, 2.15). The 2-year relapse rate was 19% and 11%, and the non-relapse mortality was 9% and 22% at TMLI 10 Gy and 12 Gy, respectively. Conclusions This study suggests that the relapse rate and 2 years PFS of HM are considerably improved when TMLI is performed prior to HSCT, which will offer an effective strategy for treating these diseases.