Thalassemia free survival after allogeneic stem cell transplantation (SCT) is about 80–90% with either matched related or unrelated donors. However, the probability of finding a HLA-compatible donor is less than 50%. We explored the use of a mismatched related (“Haplo-”) donor. All patients received two courses of pre-transplant immunosuppression therapy (PTIS) with fludarabine (Flu) and dexamethasone (Dxm) to facilitate engraftment. After two courses of PTIS, a reduced-toxicity conditioning regimen of rabbit anti-thymocyte globulin (ATG), Flu, and IV Busulfan (Bu) was given followed by T-cell replete peripheral blood progenitor cells (PBPC). GVHD prophylaxis consisted of cyclophosphamide (Cy) on days SCT +3 and +4 (Post-Cy), and on day SCT +5 tacrolimus or sirolimus was started together with a short course of mycophenolate mofetil. Thirty-one patients underwent haplo-SCT. Their median age was ten years (range, 2 to 20 years). Twenty-nine patients engrafted with 100% donor chimerism. Two of three patients with high titers of donor-specific anti-HLA antibodies suffered primary graft failure. Median time to neutrophil engraftment was 14 days (range, 11 to 18 days). Five patients developed mild to moderate, reversible veno-occlusive disease, while nine patients developed acute GVHD grade II, that quickly responded to steroid therapy. Only five patients developed limited chronic GVHD. Projected overall and event-free survival rates at two years are 95% and 94%, respectively. The median follow up time is 12 months (range; 7 to 33 months). This haplo-SCT protocol may yield excellent outcomes for thalassemia patients, and provide a treatment option for patients lacking a HLA-matched donor.

rFVIIa appears to be a useful adjunctive treatment to blood component transfusion for controlling active bleeding in children with DHF especially when platelet concentrate is not readily available.

Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haploidentical related donors, we introduced a program consisting of a pharmacologic pretransplant immune suppression phase (PTIS) and 2 courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-i.v. busulfan and post-transplant graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil. We transplanted 83 consecutive transfusion-dependent patients with thalassemia (median age, 12 years; range, 1 to 28 years) with a minimum follow-up of 6 months (median, 15 months; range, 7 to 53 months); the 3-year projected overall and eventfree survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients, we had 2 graft failures, both of them occurring in patients with extremely high titers of anti-donor-specific HLA antibodies (anti-DSAs), but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti-DSAs and using pharmacologic dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia, yielding results comparable to those available for patients with fully matched donors.

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