Background: Diamond Blackfan anemia (DBA) is a rare disorder characterized by red cell aplasia, congenital anomalies and a predisposition to cancer. Corticosteroids and red cell transfusions are the mainstays of therapy. Hematopoietic stem cell transplantation is curative in DBA, however its role in these patients is controversial.

Purpose: The purpose of this report is to review the outcome and treatment-related morbidity for HLA matched sibling versus alternative donor SCT for DBA patients enrolled in the Diamond Blackfan Anemia Registry (DBAR).

Methods: The DBAR is a comprehensive database of patients with DBA who are enrolled after informed consent is obtained. The patients, their families, and their physicians complete a detailed questionnaire. A review of medical records and telephone interviews are performed to complete and clarify the information provided.

Results: As of May 1, 2005, 420 patients have been enrolled in the DBAR, 36 of which have met the criteria for the diagnosis of DBA and have undergone an allogeneic HLA-matched sibling or alternative donor SCT. The median age at SCT for all patients was 7 years 10 months; 7 years 4 months versus 9 years 8 months for the 21 HLA-matched sibling and 15 alternative donor SCT, respectively. The major indication for SCT was transfusion dependence. In addition, two patients developed severe aplastic anemia and one significant thrombocytopenia. The majority of HLA-matched sibling transplants were done using a non-irradiation-containing conditioning regimen. One patient undergoing an HLA-matched umbilical cord SCT using a non-myeloablative conditioning regimen is engrafted but too early to evaluate. The majority of alternative donor transplants were performed using total body irradiation. One unrelated bone marrow transplant recipient also underwent non-myeloablative conditioning and is fully engrafted one year post-transplant. Sixteen of the 21 HLA-matched sibling donor transplants are alive and well, 4 of the failures occurring in patients older than 10 years of age (11, 12, 12 and 22 years) from interstitial pneumonia of unknown etiology, uncharacterized infection, veno-occlusive disease (VOD) of the liver and, in a heavily iron-overloaded patient with hepatitis C, adenovirus pneumonia, respectively. A 21 month old died from VOD. Of the 15 alternative donor SCT, one patient received bone marrow from a 3/6-mismatched sibling; another patient received a 5/6-mismatched parental bone marrow; 8 received unrelated bone marrow; 4 unrelated cord blood; and 1 unrelated peripheral blood stem cells. Three of these 15 patients are alive. The survival for allogeneic sibling versus alternative donor SCT is 72.7% ± 10.7% versus 19.1% ± 11.9% at greater than 5 years from SCT (p=0.01) (excluding a patient with osteogenic sarcoma diagnosed after SCT) or 17.1% ± 10.8% (including the osteogenic sarcoma patient, p=0.012). For patients under 10 years of age, the survival for allogeneic sibling versus alternative donor SCT is 92.3% ± 7.4% and 16.7% ± 14.8%, respectively, at greater than 4 years from SCT (p=0.01).

Conclusions: The best outcomes for stem cell transplantation in DBA patients occur when performed prior to the age of 10 years, using HLA-matched sibling donors. Given the poor survival with alternative donor SCT, these transplants should be reserved only for those DBA patients with other complications requiring transplantation, i.e. aplastic anemia, red cell allosensitization or leukemia.

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