Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using a Novel Conditioning Regimen.

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 event-free 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.

New mathematical formula for differentiating thalassemia trait and iron deficiency anemia in thalassemia prevalent area: a study in healthy school-age children.

Iron deficiency anemia (IDA) and thalassemias are common diseases especially in the Mediterranean, Middle East and Asian regions. Both conditions show the same clinical findings of hypochromic and microcytic red blood cells. Although previous studies have devised mathematical formulae to differentiate between these two conditions, the prevalence of alpha- and beta-thalassemias among the affected populations may undermine the accuracy of these formulae. This study generated a new formula that was able to differentiate IDA and thalassemia traits and to determine the incidence rates of IDA and thalassemia traits. A total of 345 healthy Thai children with a mean age (+/- SD) of 11.3 (+/- 1.7) years were enrolled. Complete blood count, iron status, hemoglobin typing and DNA for alpha-1 thalassemia identification were investigated. Discriminant analysis was used to create a new mathematical formula containing significant variables to differentiate between IDA and thalassemia traits. The new formula of (1.5 Hb-0.05 MCV >14) had a receiver operator characteristic curve of 0.92 in differentiating thalassemia traits from IDA, with sensitivity and specificity of 84.6 and 87.5%, respectively. The incidence of IDA and thalassemia traits in the study group was 12% and 32%, respectively. This formula should be useful as a screening tool to differentiate between these two conditions.