Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

Yu‐Chun Chiang ,Woei Tsay,Shang-Yi Huang,Ming Yao,Bor-Sheng Ko,Yu-Hsuan Chen,Sheng Chieh Chou ,Chi Cheng Li ,Chieh‐Yu Liu ,Jia Hau Liu ,Hsien Tang Chou ,Ming Chih Liu ,Dong‐Tsamn Lin ,Shih Ping Hsu ,Xiu Wen Liao ,Hwei‐Fang Tien ,Jian Wu ,Chien Yuan Chen ,Cheng‐Hong Tsai ,Yao Chang Chen ,Sung‐Hsin Kuo ,Shipher Wu ,Yung‐Li Yang ,Wei‐Lung Chou ,Jen-Ruey Tang ,Chieh Lung Cheng ,Chang Hsin Lin ,Hsin An Hou ,Ming‐Chi Lu ,Hui Hua Chang ,Kai Hsin Lin

doi:10.1038/srep36730

Abstract

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

Highlights

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases
The Co-Total body irradiation (TBI) and IM-TBI groups were comparable in terms of age, sex, and the proportion of cases with complete remission (CR) at the time of hematopoietic stem cell transplantation (HSCT) (P = 0.375, 0.907, and 0.811, respectively)
As compared with the conventional lung-shielding TBI technique (Co-TBI) group, more of the patients in the IM-TBI group had acute leukemia (86% vs. 75%, P = 0.022), initial central nervous system (CNS) involvement (30% vs. 5%, P < 0.001), and graft-versus-host disease (GvHD) of either the acute or chronic type (66% vs. 35%, P < 0.001 and 39% vs. 24%, P = 0.004, respectively)

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. Total body irradiation (TBI) has an established role in the conditioning regimens that are administered before allogeneic hematopoietic stem cell transplantation (HSCT)[1,2,3,4]. Previous studies of conditioning regimens for acute leukemia have found that, as compared with chemotherapy alone, the combination of TBI and chemotherapy provided non-inferior outcomes[5,6,7,8,9,10,11,12,13] and a lower CNS relapse rate[9], even without cranial boost[14]. Since 2007, linear accelerators have become predominant, and we have developed a bilateral TBI technique that uses rice-bag compensators as intensity modulators (IM-TBI). Both techniques were delivered with a hyperfractionation schedule and a fixed dose of 12 Gray (Gy). The aim of this study is to evaluate the efficacy and complication rate of the newly developed TBI method

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Results

Conclusion