Outcomes of two or more rounds of hematopoietic stem cell transplantation using total body irradiation for hematological malignancies.

Abstract

Relapse after allogeneic hematopoietic stem cell transplantations (allo-HSCT) carries poor outcomes, often necessitating a second transplant. However, toxicity concerns limit repeated total body irradiation (TBI), and its impact in later allo-HSCT is largely unknown. We evaluated outcomes of patients with hematological malignancies who underwent ≥ 2 allo-HSCTs incorporating TBI for graft failure or relapse. We analyzed 37 patients who underwent TBI ≥ 2 times with a cumulative dose > 12 Gy. TBI was delivered using either two-dimensional radiotherapy or intensity-modulated radiation therapy. Myeloablative conditioning consisted of 12 Gy in six fractions, and reduced-intensity conditioning consisted of 3-4 Gy in two fractions. Median follow-up among survivors was 64.9 months. Thirty-one patients received TBI twice and six received TBI three times. The median cumulative dose was 16 Gy. The 1- and 2-year overall survival rates were 48.6% and 27.0%, respectively; the non-relapse mortality rates were 31.4% and 49.9%, respectively. Median cumulative doses to the lungs, kidneys, and liver were 10.8, 11.7, and 16.0 Gy, respectively. After the second allo-HSCT, one patient developed Bearman grade ≥ 3 or late grade ≥ 3 adverse events in the lungs (10.8 Gy), seven in the kidneys (median, 11.7 Gy), and four in the liver (17.2 Gy). No association was observed between cumulative organs-at-risk dose and grade ≥ 3 toxicities. Second or third allo-HSCT incorporating repeated TBI with alternating myeloablative and non-myeloablative doses achieved salvage for a relatively substantial number of patients with tolerable toxicity, given the high-risk status of disease and repeated allo-HSCT.