title: A study of a reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation for patients with hematologic malignancies using Campath-1H as part of a graft-versus-host disease strategy.
abstract: Nonmyeloablative transplantation (NMT) is intended to be less toxic than traditional allografts, but such regimens as fludarabine/melphalan still pose a significant risk of graft-versus-host disease (GVHD). We used Campath-1H in an attempt to reduce the risk of GVHD in NMT. Patients with hematologic malignancies suitable for allogeneic transplantation underwent transplantation using a regimen of fludarabine 30 mg/m(2) on days -5 to -2 (total, 120 mg/m(2)), total body irradiation of 200 cGy on day -1, and Campath-1H 20 mg/day on days -7 to -3 (total dose, 100 mg). After loss of graft in 5 of the first 6 patients, the protocol was amended by decreasing the Campath-1H dose to 20 mg on days -4 and -3 and 10 mg on day -2 (total dose, 50 mg) for all subsequent patients. GVHD prophylaxis consisted of only cyclosporine, due to the immunosuppressive effect of Campath-1H. Patients received prophylactic acyclovir, fluconazole, and a quinolone. Other requirements included creatinine clearance > or = 25 mL/min, diffusing capacity > or = 45% of predicted, and cardiac ejection fraction > or = 40%. Twenty-five patients with hematologic malignancies entered the study. The median age was 40 years (range, 26-71 years). Median time to engraftment (defined as a neutrophil count of 500 mm(3) and a platelet count of 20,000 mm(3) without platelet support on at least 2 days) was 19 days (range, 9-32 days). All patients who were treated after the amendment engrafted with 90%-100% donor cells by day 100 except for 2 early deaths. Acute GVHD developed in 40% of the patients. Patients who underwent related transplants developed GVHD after donor lymphocyte infusions for poor engraftment or relapse whereas those undergoing unrelated transplants developed GVHD de novo. Two patients (8%) developed chronic GVHD, and 48% had cytomegalovirus reactivation, which was easily managed medically. Nonrelapse mortality within the first 12 months was 12%; 32% of the patients survived at a median of 269 days. We conclude that Campath-1H, fludarabine, and melphalan is a reasonable preparative regimen for reduced-intensity transplantation with a low nonrelapse mortality, but that issues of GVHD remain problematic, due to either the use of donor lymphocyte infusions or the use of volunteer unrelated donors.
authors.affiliation: Weill Medical College of Cornell University-New York Presbyterian Hospital, New York, New York 10021, USA. tbs2001@med.cornell.edu
authors.forename: Tsiporah
authors.initials: T
authors.lastname: Shore
authors.forename: John
authors.initials: J
authors.lastname: Harpel
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schuster
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects / Q000528:radiation effects; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D006801:Humans; D019520:Living Donors; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects; D033581:Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan