title: A novel GVHD-prophylaxis with low-dose alemtuzumab in allogeneic sibling or unrelated donor hematopoetic cell transplantation: the feasibility of deescalation.
abstract: Prophylaxis of acute graft-versus-host disease (aGVHD), while maintaining the graft-versus-leukemia (GVL)/lymphoma effect and preventing severe infectious diseases, remains the main challenge in allogeneic hematopoetic cell transplantation (allo-HCT). To evaluate this, we examined the feasibility of deescalating the dose of alemtuzumab (MabCampath) in combination with cyclosporine (CsA) as the sole GVHD-prophylaxis in patients after fludarabine (Flu)-based reduced-intensity conditioning (RIC) in an observational cohort study. We included 127 consecutive patients (median age 63 years) with an unrelated (UD; n=69) or related donor (SIB; n=58) after their first transplantation, mostly presenting with advanced disease. The first 30 patients received 20 mg/day on day -2 and -1 (40 mg), the following 48 patients 10 mg/day on day -2 and -1 (20 mg), and the last 49 patients 10 mg on day -1 (10 mg) alemtuzumab intravenous (i.v.) prior to transplant. We observed no statistical differences comparing the 40 mg, 20 mg, or 10 mg dose groups, in terms of cumulative incidences of aGVHD grade III-IV 7% (confidence interval [CI] 95%; 1-51), 12% (1-40), 6% (1-40), extensive chronic GVHD (cGVHD) 24.4% (3.3-55.8), 17% (2.5-42), and 14.2% (1.5-41.5) and of aGVHD grade II-IV 7 % (0-51.5), 29% (11.9-49.1), 21% (15.3-43.1), respectively. The difference between the 20-mg and 40-mg groups was significant for aGVHD grade II-IV(P < .05). In conclusion, we demonstrate the feasibility of reducing the dose of alemtuzumab as GVHD-prophylaxis to 10 mg absolute in combination with CsA only for UD transplantation in particular.
authors.affiliation: Albert Ludwigs-University Medical Center Freiburg, Department of Hematology and Oncology, Freiburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Bertz
authors.forename: Alexandros
authors.initials: A
authors.lastname: Spyridonidis
authors.forename: Ralph
authors.initials: R
authors.lastname: Wäsch
authors.forename: Carsten
authors.initials: C
authors.lastname: Grüllich
authors.forename: Mathias
authors.initials: M
authors.lastname: Egger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect / Q000187:drug effects / Q000276:immunology; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D035781:Siblings; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab