Long-term toxicities after allogeneic hematopoietic stem cell transplantation with or without total body irradiation: a population-based study in Korea

Abstract

Purpose: To compare long-term toxicity incidences, including secondary cancer (SC) with or without total body irradiation (TBI), in Asian patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using a nationwide database.

Materials and methods: We identified 4,554 patients receiving HSCT for leukemic disease from 2009 to 2016 using the healthcare bigdata system of Korea. Incidence rate ratios (IRRs) for SC, cataracts, hypothyroidism, chronic kidney disease (CKD), myocardial infarction, or strokes were compared, and standardized incidence ratios (SIR) of SC was also estimated.

Results: TBI was conducted on 1,409 patients (30.9%). No overall survival differences based on TBI were observed. With a median follow-up duration of 58.2 months, 143 patients were diagnosed with subsequent SC (3.4%). Incidence rates per 1,000 person-year were 6.56 (95% confidence interval [CI], 4.8-8.8) and 7.23 (95% CI, 5.9-8.8) in the TBI and no-TBI groups, respectively (p = 0.594). Also, the SIR (95% CI) was not significantly increased by TBI (1.32 [0.86-1.94] vs. 1.39 [1.08-1.77] in the no-TBI group). In the young age group (0-19 years), SIRs were increased in both groups regardless of TBI (8.60 vs. 11.96). The IRRs of cataracts (1.60; 95% CI, 1.3-2.0), CKD (1.85; 95% CI, 1.3-2.6), and hypothyroidism (1.50; 95% CI, 1.1-2.1) were significantly increased after TBI. However, there were no significant differences in the occurrence of myocardial infarction and stroke according to TBI.

Conclusion: Our results suggest that modern TBI may not additionally increase the risk of SC after allogeneic HSCT, although increased risks of other diseases were noted. Physicians should carefully consider individualized risks and benefits of TBI, with a particular focus by age group.

Keywords: Cataract; Chronic renal insufficiency; Hematopoietic stem-cell transplantation; Secondary malignancy; Total body irradiation; Whole-body irradiation.

Fig. 1.

(A) Cumulative incidence of secondary cancers by cancer type depending on whether total body irradiation (TBI) was received after allogeneic hematopoietic stem-cell transplantation in leukemia patients and (B) overall cumulative incidence curve of secondary cancers.

Fig. 2.

Cumulative incidence curves of (A) cataracts, (B) chronic kidney disease, and (C) hypothyroidism after allogeneic hematopoietic stem-cell transplantation in leukemia patients. TBI, total body irradiation.