Allogeneic Hematopoietic Stem Transplantation in Patients with Transfusion Dependent Beta Thalassemia: A Single-Center Experience from India
Authors: Bhat Sunil , Nayak Akshatha , Badiger Shobha , K. S Nataraj , Damodar Sharat 
Published: October 2019

Abstract
Introduction:
The thalassemias are the most common of the inherited abnormalities of hemoglobin, typically characterized by a quantitative defect in the synthesis of either the alpha or beta globin chain, resulting in reduced or absent synthesis of either of the globin chains followed by ineffective erythropoiesis with hemolysis. Beta thalassemia is prevalent in the populations of the Mediterranean region, the Middle East, India, Pakistan, and Southeast Asia.
Patients are treated with red blood cell transfusions and iron chelation to prevent organ iron overload. Currently, the only cure for thalassemia is allogeneic bone marrow transplantation which corrects the genetic defect in the hematopoietic system by the use of allogeneic stem cells.
Methods:
We retrospectively and prospectively analyzed the outcomes in transfusion dependant beta Thalassemia patients, who underwent allogeneic HSCT between June 2004 and June 2014. The patients were classified into Class 1, 2 and 3 as per the Pesaro criteria.
Results:
Sixty seven patients (Males n=40; females n=27) with a median age of 7 years (range 2 to 22 years) underwent HSCT during this time. Fifty seven patients were classified as Class 2, 8 as Class 3 and 2 as Class 1. The conditioning regimens used consisted of Bu-Cy-ATG (n=30), Bu-Cy (n=2), Flu-Bu-Cy-ATG (n=23), Treo-Flu-Thio (n=8), Treo-Flu-Thio-ATG(n=3) and Flu-Bu-Cy-Thio-ATG(n=1) with cyclosporine and methotrexate as GVHD prophylaxis. Stem cell source was marrow, peripheral stem cells and cord in 50, 17 and 1 patients respectively. Sixty four patients had matched sibling transplant and three non-sibling donors (one unrelated cord, one matched unrelated and one haplo-identical ). One patient received both both marrow as well as peripheral stem cells. The median TC cell dose was 6.4x108/kg (range 3 to 16.3 x108/kg) and median CD34 cell dose of 2.4 x106/kg (range 0.6 to 19.6 x106/kg). Hematological recovery was seen in all patients except three patients, who died before engraftment. Neutrophil and platelet engraftment occurred at a median of 14 days (range, 10-22 days) and 22 days (range, 10-35 days), respectively. Twenty four patients developed veno-occlusive disease, 20 patients developed Gr II-IV acute graft-versus-host disease (GVHD), and 3 patients had chronic GVHD. At day +28, thirty five patients showed more than 90% donor chimersim and rest had mixed chimerism. Four patients experienced graft rejection. Treatment-related mortality (TRM) for the whole cohort was 10.4% at 100 days and 14.9% at 6 months post transplant. TRM was 12.28% and 37.5% for Class 2 and class 3 patients respectively. At a median follow up of 416 days, overall survival and thalassemia free survival are 82.1%, and 74.6% respectively.
Conclusion: Similar outcomes have been reported from developed countries. Outcome of Class 3 patients still continues to be poor and VOD rates are high in this patient group.

Disclosures
No relevant conflicts of interest to declare.