The Burden of Survivorship on Hematological Patients-Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation.

Michael Oertel,Georg Lenz,Matthias Stelljes,Kai Kröger,Jan-Henrik Mikesch,Christian Reicherts,Jonas Martel,Hans Theodor Eich,Sergiu Scobioala

doi:10.3390/cancers13225640

Abstract

Simple SummaryTotal body irradiation is an essential large-field technique enabling myeloablation before allogeneic stem cell transplantation. With its field encompassing all organs, a diverse spectrum of toxicities may arise. This work analyzes long-term pulmonary, cardiac, ocular, neurological and renal toxicities in a monocentric patient cohort and identifies possible risk factors. Both the number of patients and the duration of the follow-up period exceed those of many comparable studies in the literature.Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9–89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects.

Highlights

Allogeneic stem cell transplantation has an important role in the treatment of acute leukemia, offering curation in both primary and recurrent/refractory situations [1,2]
Technical and conceptual innovations in radiotherapy (RT) were introduced in previous decades in order to reduce toxicities and, thereby, the burden of disease [3,4]. In spite of this significant progress, the long-term toxicity profile of patients undergoing Allogeneic stem cell transplantation (alloSCT) with Total body irradiation (TBI) is still to be defined as previous works have been limited by the number of patients studied and the duration of the follow-up period
Retrospective analysis was applied to patients with acute leukemia or myelodysplastic syndrome who underwent alloSCT with a conditioning regimen involving TBI at our hematological center between 2001 and 2018 in this monocentric study

Summary

Introduction

Allogeneic stem cell transplantation (alloSCT) has an important role in the treatment of acute leukemia, offering curation in both primary and recurrent/refractory situations [1,2]. Technical and conceptual innovations in radiotherapy (RT) were introduced in previous decades in order to reduce toxicities and, thereby, the burden of (secondary) disease [3,4] In spite of this significant progress, the long-term toxicity profile of patients undergoing alloSCT with TBI is still to be defined as previous works have been limited by the number of patients studied and the duration of the follow-up period. This may have led to a putative underestimation of toxicity rates and the extent of the spectrum of side effects. Toxicity rates and gradings were assessed and analyzed to identify risk factors for the respective organ-specific side effects

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