Long-Term Toxicity after Non-Myeloablative Conditioning Regimens Using Total Body Irradiation

To evaluate long-term health risks after allogeneic hematopoietic stem cell transplantation (HSCT) using non-myeloablative total body irradiation (TBI).

All adult patients undergoing non-myeloablative allogeneic HSCT using TBI-based conditioning from 1995 to 2020 at our institution were included. Long-term toxicities, defined as events persisting beyond or occurring after 6 months from the date of transplant, were graded per the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. A competing risk analysis was performed to assess the risk of developing long-term toxicities within major organ systems using the Fine-Gray model. Outcomes were compared with a cohort of patients undergoing myeloablative TBI.

A total of 174 patients undergoing nonmyeloablative HSCT were assessed along with 378 myeloablative patients. Nonmyeloablative recipients were older (58 vs 43 years, P < .001), less likely to be transplanted for acute leukemia (35% vs 64%, P < .001), more likely to be transplanted for non-malignant conditions (33% vs 11%, P < .001), and were more likely to have used tobacco (33% vs 22%, P = .009). The median follow-up was 7.4 years. The cumulative incidences of long-term toxicities at 5 years for nonmyeloablative and myeloablative patients, taking into account the competing risk of death, were pulmonary (4% vs 4.8%, P > .9), cardiac (6.8% vs 3.3%, P = .11), renal (4.3% vs 4.1%, P = .9), thyroid (3.6% vs 1.5%, P = .2), other endocrine (3.1% vs 8.8%, P = .04), and cataracts (2.5% vs 2.8%, P = .7). The risk of developing a secondary malignancy was 3.5% vs 1.1% (P = .2) between the 2 cohorts. The proportion of all toxicities that were high-grade (3-5) for nonmyeloablative and myeloablative regimens, respectively, were pulmonary (60% and 69%), cardiac (17% and 45%), renal (27% and 21%), and other endocrine (4% and 2%).

Recipients of nonmyeloablative conditioning regimens, despite receiving much lower doses of TBI and chemotherapy, are at risk of developing significant, long-term medical conditions comparable with those undergoing myeloablative HSCT.