title: A Single-Center Experience Comparing Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning with Myeloablative Busulfan, Cyclophosphamide, and Antithymocyte Globulin for Chronic Granulomatous Disease.
abstract: Myeloablative conditioning (MAC) regimens are commonly used in transplantation for chronic granulomatous disease (CGD) but are associated with toxicity. Reduced-intensity conditioning (RIC) regimens have lower toxicity but may fail to achieve stable donor chimerism. We report a comparison between 4 patients who received a RIC regimen consisting of alemtuzumab (1 mg/kg), fludarabine (150 mg/m2), and melphalan (140 mg/m2) and 14 patients who received a MAC regimen consisting of busulfan (area under the curve, 1800 to 2000 µMol/min twice daily × 4 days), cyclophosphamide (50 mg/kg/day × 4), and antithymocyte globulin (15 mg/kg twice daily on days -2 and -1, then daily on days +1 and +2). Seventy-five percent (n = 3) of RIC patients developed mixed chimerism and needed either withdrawal of immune suppression (n = 1) or additional stem cell products (n = 2) to achieve stable donor chimerism. Ninety-two percent (n = 13) of patients in the MAC group maintained >95% donor chimerism. Complications included acute graft-versus-host disease (MAC 64%, RIC 0%), chronic graft-versus-host disease (MAC 28%, RIC 0%), sinusoidal obstructive syndrome (MAC 7%, RIC 0%), bacteremia (MAC 42%, RIC 0%), fungemia (MAC 14%, RIC 0%), viral disease (MAC 7%, RIC 25%), and death (MAC 21%, RIC 0%). A RIC regimen has lower toxicity but frequently requires interventions to maintain donor chimerism compared with a MAC regimen in CGD.
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Pooja.khandelwal@cchmc.org.
authors.forename: Pooja
authors.initials: P
authors.lastname: Khandelwal
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Bleesing
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan
keywords: CGD; Chronic granulomatous disease; Reduced-intensity conditioning regimen for CGD