Conditioning Regimens in Patients with β-Thalassemia Who Underwent Hematopoietic Stem Cell Transplantation: A Scoping Review.

Olga Mulas,Giorgio La Nasa,Giovanni Caocci,Brunella Mola

doi:10.3390/jcm11040907

Abstract

The success of transplant procedures in patients with beta-thalassemia major (β-thalassemia) goes hand-in-hand with improvements in disease knowledge, better supportive care, discoveries in immunogenetics, increase in stem cell sources, and enhancement of conditioning regimens. The aim of this scoping review was to report the evolution of conditioning regimes for β-thalassemia hematopoietic stem cell transplantation. We performed a systematic search for all relevant articles published before July 2021, using the following Medical Subject Headings: “bone marrow transplantation”, “stem cell transplantation”, “allogeneic”, “thalassemia”, “β-thalassemia”, and “thalassemia major”. The final analysis included 52 studies, published between 1988 and 2021, out of 3877 records. The most common conditioning regimen was a combination of busulfan and cyclophosphamide, with successive dose adjustments or remodulation based on patient characteristics. Pre-transplant treatments, reductions in cyclophosphamide dosage, or the adoption of novel agents such as treosulphan all improved overall survival and thalassemia-free survival in transplant-related mortality high-risk patients. Conditioning regimes were modulated for those without a suitable fully matched sibling or unrelated donor, with encouraging results. Hematopoietic stem cell transplantation with haploidentical donors is currently available to virtually all patients with β-thalassemia. However, disparities in outcome are still present around the world. In developing and limited-resource countries, where most diagnoses are focused, transplants are not always available. Therefore, more efforts are needed to close this treatment gap.

Highlights

Beta-thalassemia major (β-thalassemia) is a common monogenic disease characterized by abnormal hemoglobin structure [1]
HSC transplantation (HSCT) were limited to matched sibling donors (MSDs) who provided human were clearly the backbone conditioning regimes in most studies
Graft failure and graft-versus-host disease (GVHD) incidence was not negligible [44,57]. This scoping review aimed to investigate most of the studies that described HSCT in β-thalassemia and analyze the evolution of conditioning regimes in this non-malignant disease, with respect to progressive survival improvement over the past 30 years (Figure 2)

Summary

Introduction

Beta-thalassemia major (β-thalassemia) is a common monogenic disease characterized by abnormal hemoglobin structure [1]. Β-thalassemia occurred predominantly in the region spanning sub-Saharan Africa, the Mediterranean, and the Middle East, stretching to south and southeast Asia [2]. Global migration has spread β-thalassemia worldwide [3]. The most common mutations that cause β-thalassemia are single nucleotide substitutions, small deletions, or insertions within the β-globin gene [1]. These mutations reduce production of β-globin chains and HbA1. The degree of imbalance between αglobin and β-globin chains causes accumulation of defective α-globin complexes that damages red blood cells [4]. This condition determines anemia severity, transfusion dependency, and overall clinical morbidity in β-thalassemia [5]

Methods

Results

Conclusion