Allogeneic Stem Cell Transplantation in Congenital Hemoglobinopathies – A Curative Approach When Performed as a Primary Therapeutic Modality: A Single Center Experience.
Authors: Elhasid Ronit , Zaidman Irina , Khalil Abdalla , Zuckerman Tsila , Haddad Nuhad , Katz Tamar , Arush Myriam Ben , Rowe Jacob M. 
Published: October 2019

Abstract
Abstract 1144
Poster Board I-166
Allogeneic stem cell transplantation (SCT) is the only curative treatment for congenital hemoglobinopathies. To date, hundreds of patients (pts) were transplanted using different conditioning regimens and different sources of stem cells harvested from matched family donor (MFD), matched unrelated donor (MUD) and cord blood. The experience of a single center, the Rambam Medical Center, Haifa, Israel, performing 32 transplants in 31 pts with congenital hemoglobinopathies is presented herein. During the years 2000- 2008, 32 SCT were performed in 31 pts. Median age was 8 years (10 months-22 years). Median follow up was 5.5 years (7 months-9.5 years). Twenty seven pts were transplanted due to thalassemia major, 1 for sickle thalassemia (transplanted twice), 1 with chronic hemolysis, and 2 for sickle cell disease. Distribution of thalassemic pts (including sickle thalassemia) according to the Pesaro risk classification included: 7 in class I, 2 in class II and 20 in class III. There were 29 transplants from MFD while 3 transplants from MUD SCT. Twenty seven pts underwent first transplant while 5 pts received second transplant after rejecting the first one. One patient received 2 transplants in our center while the other 4 received their first transplant in another center. Different conditioning protocols, all based on busulfan (Bu) and cyclophosphamide (Cy), were used according to risk classifications, donor type, first or second transplant and type of disease. Pts with class I thalassemia who had MFD received Bu, Cy, fludarabine and ATG followed by moderate T cell depleted graft (Elhasid et al, 2007). Pts with class III thalassemia received protocol P26 including hydroxyurea, azathioprine, Bu, Cy, fludarabine (Sodani et al, 2004). Protocol P26.1, based on protocol P26 with the addition of thiotepa and ATG, was used for second transplant (Gaziev et al, 2008). Sickle cell disease pts received P26 based protocol. In order to prevent graft versus host disease (GvHD), moderate T cell depletion (TCD) (105/kg T cells) using positive selection of CD34 cells, was planned for all pts who had MFD. Since graft rejection occurred in 2 pts with class III thalassemia receiving protocol P26 and moderate TCD, an amendment modified use of this protocol only in class I thalassemia pts in the setting of MFD transplantation. Twenty eight out of 31 pts survived with overall survival (OS) of 90%. Three pts, all class III thalassemia, died. One patient died after first transplant due to severe hemorrhagic cystitis and multi-organ failure and 2 pts died after second transplant. Twenty six out of 27 pts who had only one transplant survived with OS of 96%. Four pts rejected the graft (12.9%); 1 with sickle cell disease, 2 with class III thalassemia and 1 with class I thalassemia after unrelated CBT. Twenty five out of 28 pts (89%) who survived are ex-thalassemic or sickle cell disease (table 1). No acute GvHD occurred in pts with class I thalassemia who received moderate TCD while the incidence of acute GvHD was 20% in the rest of the pts. Chronic GvHD occurred in 20% of pts regardless of TCD. Although most of our pts were classified as class III thalassemia, OS as well as disease free survival were 90% and 89%, respectively. No acute GvHD occurred in pts with class I thal major transplanted from MFD using moderate TCD. The efficacy and safety of this when used as a primary therapeutic modality is emphasized. Risk-adapted conditioning regimens, including novel ones that do not use post-transplant immunosuppression, improve transplant outcome in congenital hemoglobinopathies.
Table 1 n TRM Overall survival Disease free survival All pts 31 3/31 (9.6%) 28/31 (90%) 25/28 (89%) Class I thalassemia Moderate TCD no GvHD prophylaxis 6 0/6 (0%) 6/6 (100%) 6/6 (100%)

Disclosures
Rowe: Teva Pharmaceuticals: Consultancy; EpiCept Corporation: Consultancy.