Viral Reactivation after T-Cell Replete Haploidentical Transplantation Using Myeloablative Conditioning and Post-Transplant Cyclophosphamide

Abstract

TXThalassemia, a hemoglobinopathy which is common in Asian descendants, in its severe forms, has a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) in severe thalassemia patients is an only way to cure the disease, however available HLA-matched donors for the patients were hardly identified. We recently reported an alternative strategy, pre-transplant immunosuppression (PTIS), combination of fludarabine (Flu) and dexamethasone (Dxm), would immunosuppress the patients to facilitate engraftment when followed by a reduced-toxicity conditioning (RTC) regimen, antithymocyte globulin (ATG), Flu and IV busulfan (Bu), to prepare high risk thalassemia patients for allo-SCT. We explored the use of an alternative, mismatched related ("haplo-"), donor in thalassemia patients. We enrolled severe thalassemia patients including a high risk group, so called class 3 Lucarelli classification, aged more than 7 years old and had a liver size more than 5 cms below the costal margin. All patients received two courses of PTIS, 40 mg/m 2 /day of IV Flu and 25 mg/m 2 /day of IV Dxm on day -68 to -64 and day -40 to -36, followed by RTC regimen, 1.5 mg/kg/ day of ATG on day -12 to -10, 35 mg/m 2 /day of Flu on day -8 to -3 and 130 mg/m 2 /day of Bu on day -8 to -5, was administered followed by unmanipulated peripheral blood stem cell (PBSC) from haploidentical donors. Graft-versus-host disease (GVHD) prophylaxis consisted of 50 mg/kg/day of cyclophosphamide (PTCy) on day +3 and +4 and tacrolimus or sirolimus was started together with a short course of mycophenolate mofetil. Twenty five patients received haplo-SCT at the median age of 10 (2-20) years. Twenty one patients had beta-thalassemia/hemoglobin E while the rest of patients had homozygous beta-thalassemia. Twelve patients had class 3 disease, their median age at the time of haplo-SCT was 14 (10-20) years. One of the patients had haplo-SCT as a second transplant after a matched-related allo-HSCT complicated with primary graft failure with autologous reconstitution. Sixteen patients received PBSC from the mother while the rest received from the father, the median CD34+ cell dose at 11.6 (4.0-19.0) x 10 6 cells/kg of body weight of recipients. The median time of neutrophil engraftment and platelet engraftment were 14 (11-18) and 30 (20-45) days, respectively. Two patients who suffered from primary graft failure had anti-HLA antibodies. Nine patients developed grade II acute GVHD, while four patients developed mild reversible veno-occlusive disease. Only three patients developed limited chronic GVHD. One patient died of GVHD complications. The 2-year overall and thalassemia-free survival rates are 93% and 88%, respectively, at the median follow up time was 11 (6-30) months. We concluded our new program, PTIS followed by RTC regimen and PTCy-based GVHD prophylaxis, had rapid and durable engraftment, yet a low risk of serious GVHD in the severe thalassemia patients.Background: Allogeneic Hematopoietic Cell Transplantation (HCT) is currently the only treatment modality to res...