Low Exposure Busulfan Conditioning to Achieve Sufficient Multilineage Chimerism in Patients with Severe Combined Immunodeficiency.

Abstract

After allogeneic hematopoietic cell transplantation (HCT), the minimal myeloid chimerism required for full T and B cell reconstitution in patients with severe combined immunodeficiency (SCID) is unknown. We retrospectively reviewed our experience with low-exposure busulfan (cumulative area under the curve, 30 mg·hr/L) in 10 SCID patients undergoing either first or repeat HCT from unrelated or haploidentical donors. The median busulfan dose required to achieve this exposure was 5.9 mg/kg (range, 4.8 to 9.1). With a median follow-up of 4.5 years all patients survived, with 1 requiring an additional HCT. Donor myeloid chimerism was generally >90% at 1 month post-HCT, but in most patients it fell during the next 3 months, such that 1-year median myeloid chimerism was 14% (range, 2% to 100%). Six of 10 patients had full T and B cell reconstitution, despite myeloid chimerism as low as 3%. Three patients have not recovered B cell function at over 2 years post-HCT, 2 of them in the setting of treatment with rituximab for post-HCT autoimmunity. Low-exposure busulfan was well tolerated and achieved sufficient myeloid chimerism for full immune reconstitution in over 50% of patients. However, other factors beyond busulfan exposure may also play critical roles in determining long-term myeloid chimerism and full T and B cell reconstitution.

• Authors: Christopher C Dvorak, Janel Long-Boyle, Jasmeen Dara, Alexis Melton, Kristin A Shimano, James N Huang, Jennifer M Puck, Morna J Dorsey, Janelle Facchino, Catherine K Chang, Morton J Cowan
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 25 Issue 7 Pg. 1355-1362 (07 2019) ISSN: 1523-6536 [Electronic] United States
• PMID: 30876930 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Busulfan

Topics

• B-Lymphocytes (immunology, metabolism)
• Busulfan (administration & dosage)
• Child
• Female
• Follow-Up Studies
• Humans
• Infant
• Male
• Retrospective Studies
• Severe Combined Immunodeficiency (blood, immunology, therapy)
• T-Lymphocytes (immunology, metabolism)
• Transplantation Chimera (blood, immunology)
• Transplantation Conditioning