Abstract
Allogeneic stem cell transplant (aSCT) which remains the only curative option for patients with β thalassemia major (TM) is often limited by a lack of ideal donors. The role of alternative (related phenotypic donor- RD and Unrelated donor -UD) donor hematopoietic cell transplantation in thalassemia is not well established. Use of conventional myeloablation with busulphan and cyclophosphamide in alternative RDs (either phenotypically identical or 1-antigen-mismatched donors) has been associated with higher graft failure and acute graft versus host disease (aGvHD) prompting novel approaches (Gaziev et al., 2000, 2013). We undertook a retrospective analysis of patients who underwent aSCT from alternative donors in TM.
From February, 2009 to June, 2016, 51 HLA matched transplants for TM was done at our center. Among them 19 (37.3%) used alternate donors. In this cohort, the median age was 9 years (range: 2-18) and there were 13 (68.4%) males. Thirteen (68.4%) were Pesaro Class III and 8 (42.1%) were in the Class III higher risk group as defined earlier (Mathews et al., 2007). All 19 received a treosulfan based regimen. PBSC (Peripheral Blood Stem Cell) was the source of stem cells in 78% and bone marrow in the rest. All patients received a cyclosporin (CSA) plus short course methotrexate GvHD prophylaxis regimen. There were 4 (12%) deaths. The major cause of death was fungal infection (3 had invasive fungal infection of whom 1 developed candidemia following a very late UD deferral).
Of the alternative grafts 7 (36.8%) received RD grafts and 13 (68.4%) from UD. We compared the results of RD with HLA-matched sibling (matched sibling donors [MSDs]) aSCT in 32 patients and UD in 12 patients (Table 1). One (14.3%) patient developed aGvHD (Grade 2-4). The entire RD group had sustained engraftment. Rejection incidence was 0% in the RD, 8.3% in UD and 3.4% in MSD groups, with respective thalassemia-free survival probabilities at one year of 68.6% ±18.6%, 83.3% ±15.2%, 90.0% ±5.5% (P = .549) Fig 1.
In conclusion, the present data shows that a treosulfan based reduced toxicity myeloablative regimen with a PBSC graft has the potential to allow patients to safely undergo aSCT from phenotypically identical RD.
No relevant conflicts of interest to declare.
