Successful use of non-myeloablative therapy in the treatment of severe hemoglobinopathies: Proof of principle

Lakshmanan Krishnamurti, Bruce R. Blazar, Mauro Grossi, Susan Abel, Bertram E. Lubin, Elliot Vichinsky, John E. Wagner

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Hematopoietic stem cell transplantation (HSCT) from sibling donors has been demonstrated to cure hemoglobinopathies such as sickle cell disease (SCO) and Thalassemia. Concerns about high regimen related toxicity (RRT) has prevented the use of HSCT in older patients, those with advanced organ damage or those without a HLA matched related donor. Also, potential for late sequelae such as chronic graft-versus-host disease (GVHD) and infertility have limited the acceptance of this treatment even by eligible patients. We initiated a phase I/II study evaluating the safety of a nonmyeloablative therapy for patients with hemoglobinopathy. The conditioning regimen consisted of busulfan 2mg/kg orally q!2 hours for 2 days, fludarabine 35 mg/m2 IV q.d for 5 days, antithymocyte globulin 30 mg/kg IV q.d for 5 days and total lymphoid irradiation administered as a single fraction of 500 cGy with shielding of the liver, lungs, heart, and gonads. Prophylaxis for GVHD consisted of cyclosporine A and mycophenolate moefetil. Outcomes on the first 3 patients are summarized in the table. No patient had acute or chronic GVHD. Despite severe phenotype, prior chronic transfusion, allosensitization and ABO incompatibility with the donor, sustained chimerism and disease stabilization was achieved in patient #1. This serves as "proof of principle" that such an approach can be used successfully. Newer approaches are being developed particularly for recipients of HSCT from unrelated donors. PIN, diagnosis & Donor Type & Organ toxicity ANC<500 Donor chimerism Follow up Donor Match days day 21 day 100 1. SCO d+360 Sib 6/6 None 7 89 100 2. SCO d+120 URD5/6 Mild mucositis 6 7 0 3. aThal d+30 Sib 6/6 None 5 24-35 NA.

Original languageEnglish (US)
Pages (from-to)18b
Issue number11 PART II
StatePublished - Dec 1 2000

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