Long-Term Toxicity after Total Body Irradiation-Based Conditioning Regimens for Allogeneic Stem Cell Transplantation

Abstract

Total body irradiation (TBI) is an integral component of many conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT). Few studies have investigated long-term sequelae. A large series of patients undergoing myeloablative and non-myeloablative regimens was studied. Adult patients undergoing allogeneic HSCT utilizing TBI-based conditioning regimens from 1995-2020 at our institution were included. Baseline treatment-related factors and long-term toxicities (developing, or persisting beyond, 6 months after HSCT) were collected. The cumulative incidence of long-term toxicities and overall survival (OS) were calculated. Cox regression was used to assess for predictors of toxicity. Five hundred fifty-two patients were analyzed: 378 myeloablative (typically 13.5 Gy/9fx) and 174 non-myeloablative (typically 2 Gy/1fx) TBI recipients. Median follow-up was 7.4 years for surviving patients. Cumulative incidences of long-term toxicities at 5 and 10 years are included in the Table. The most common toxicities were: pulmonary- infectious pneumonia and respiratory failure NOS; cardiac- heart failure and myocardial infarction; other endocrine- adrenal insufficiency and testosterone deficiency. The most common secondary malignancy was non-melanoma skin cancer. The proportion of all toxicities that were high-grade (3-5) for myeloablative and non-myeloablative regimens, respectively, were: pulmonary (65%, 52%), cardiac (66%, 39%), renal (23%, 27%), and other endocrine (3%, 18%). Increasing number of chemotherapy regimens (p = 0.05) and umbilical cord donor (p = 0.02) were associated with long-term pulmonary toxicity. Male sex (p = 0.03), increasing number of chemotherapy regimens (p<0.01), and elevated creatinine after transplant (p<0.01) were associated with long-term renal toxicity. Cataract development was associated with increasing age at transplant (p = 0.02). OS (5 years) was 40% (42% -myeloablative; 33%-non-myeloablative). Allogeneic HSCT, often preceded by TBI-based conditioning regimens, has significant survivorship challenges. Recipients of non-myeloablative regimens are still at risk of significant long-term multisystem toxicity despite much lower doses of TBI and chemotherapy. Pre-transplant factors such as cumulative chemotherapy exposure and age at transplant were associated with some toxicities.