Reduced-intensity conditioning hematopoietic cell transplantation is an effective treatment for patients with SLAM-associated protein deficiency/X-linked lymphoproliferative disease type 1.

Abstract

X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune deficiency caused by mutations in SH2D1A. Allogeneic hematopoietic cell transplantation (HCT) is often performed because of the morbidity and mortality associated with XLP1. There is limited experience using reduced-intensity conditioning (RIC) regimens for these patients. Here we report our 8-year single-center experience. Sixteen consecutive patients diagnosed with XLP1 underwent allogeneic HCT between 2006 and 2013 after a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan. Patient phenotypes included hemophagocytic lymphohistiocytosis (HLH) after Epstein-Barr virus (n = 5) or human herpesvirus 6 (n = 1), macrophage activation syndrome (n = 1), interstitial pneumonitis and encephalitis (n = 1), B cell lymphoma (n = 8), and hypogammaglobulinemia (n = 2). One patient was asymptomatic. Fourteen of 16 patients received 8/8 HLA-matched unrelated or related bone marrow grafts, whereas 2 patients received mismatched unrelated grafts. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methylprednisolone and cyclosporine in all but 1 patient, who additionally received methotrexate. All patients had hematopoietic recovery. There were no cases of hepatic veno-occlusive disease or pulmonary hemorrhage. One patient (6%) developed acute GVHD and later also developed chronic GVHD (6%). Five patients (31%) developed mixed chimerism. Only 1 patient with mixed chimerism (6%) experienced a decline of donor chimerism to less than 50% but returned to full donor chimerism after infusion of donor lymphocytes and a CD34(+) selected stem cell boost. Infectious complications were frequent, particularly viral reactivation. One-year survival estimated by Kaplan-Meier analysis was 80%, with long-term survival estimated at 71%. Survival was similar for patients with or without a history of HLH (86% versus 75%, respectively, P = .70). There were no occurrences of lymphoma or HLH after HCT. RIC HCT with alemtuzumab, fludarabine, and melphalan is an effective treatment for patients with XLP1, offering good survival rates regardless of prior disease manifestations, including HLH.

• Authors: Rebecca A Marsh, Jack J Bleesing, Shanmuganathan Chandrakasan, Michael B Jordan, Stella M Davies, Alexandra H Filipovich
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 20 Issue 10 Pg. 1641-5 (Oct 2014) ISSN: 1523-6536 [Electronic] United States
• PMID: 24923536 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Immunosuppressive Agents
• Intracellular Signaling Peptides and Proteins
• Myeloablative Agonists
• SH2D1A protein, human
• Signaling Lymphocytic Activation Molecule Associated Protein
• Alemtuzumab
• Vidarabine
• fludarabine
• Melphalan

Topics

• Alemtuzumab
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Child
• Child, Preschool
• Female
• Graft vs Host Disease (immunology, prevention & control)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility Testing
• Humans
• Immunosuppressive Agents (therapeutic use)
• Infant
• Intracellular Signaling Peptides and Proteins (genetics, immunology)
• Lymphoproliferative Disorders (drug therapy, genetics, mortality, pathology)
• Male
• Melphalan (therapeutic use)
• Mutation
• Myeloablative Agonists (therapeutic use)
• Prognosis
• Retrospective Studies
• Signaling Lymphocytic Activation Molecule Associated Protein
• Survival Analysis
• Transplantation Chimera (genetics, immunology)
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Unrelated Donors
• Vidarabine (analogs & derivatives, therapeutic use)