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Reduced-Intensity Regimens in Allogeneic Hematopoietic Stem Cell Transplantation for Hemoglobinopathies

Correspondence: Prof. Franco Locatelli, Oncoematologia Pediatrica, IRCCS Policlinico San Matteo, University of Pavia, P.le Golgi 2, I-27100 Pavia, Italy. Fax: +39-0382-501251. E-mail: f.locatelli{at}smatteo.pv.it

Abstract

The only well-established curative therapy for patients with hemoglobinopathies is allogeneic hematopoietic stem cell transplantation (HSCT), which, in the last 20 years, has been mainly performed from an HLA-matched, related donor, using bone marrow as source of hematopoietic progenitors. More recent studies indicate that HSCT from unrelated donors may offer results comparable to those obtained with HLA-identical family donors, provided that stringent criteria of compatibility are employed for selecting the donor. Cord blood transplantation was also suggested to be an equally effective, but safer, procedure than bone marrow transplantation, due to the lower incidence and severity of both acute and chronic graft-versus-host disease. In view of the early, as well as late, morbidity and mortality associated with conventional myeloablative transplantation in patients with hemoglobinopathies, it is not surprising that great interest and relevant expectations for patients with hemoglobinopathies have been raised by the introduction in the clinical practice of reduced-intensity preparative regimens. However, few reports have demonstrated the feasibility of using reduced-intensity preparative regimens for successfully treating these patients and many treatment failures, mainly due to the lack of sustained donor engraftment, have been reported. Despite these limitations, some of the concepts obtained from the use of reduced intensity regimens, such as the substitution of fludarabine for cyclophosphamide, may be important to further improve the outcome of patients with hemoglobinopathies, especially of those with poor prognostic characteristics, given HSCT.

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