Low-dose alemtuzumab (Campath) in myeloablative allogeneic stem cell transplantation for CD52-positive malignancies: decreased incidence of acute graft-versus-host-disease with unique pharmacokinetics.
Alemtuzumab is effective in reducing the risk of acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (ASCT). Alemtuzumab may also delay immune reconstitution and reduce graft-versus-leukemia effects. The optimal dose has not been established. We investigated engraftment, acute GVHD incidence and severity, and pharmacokinetics of alemtuzumab associated with the use of low-dose alemtuzumab/cyclophosphamide/total body irradiation and ASCT for patients with aggressive CD52-positive hematologic malignancies. In all, 12 patients were treated. Alemtuzumab 10 mg daily on days -7 to -3 was given intravenously. Tacrolimus and methotrexate were used for GVHD prophylaxis. Alemtuzemab was not detected in any of the 36 sequential serum samples tested between days -1 and +21 of transplant. All patients engrafted rapidly; the median time to an absolute neutrophil count >0.5 x 10(9)/l was 14 days (range 11-17 days), and the median time to a platelet count >20 x 10(9)/l was 16 days (range 6-30 days). By 1 month after transplant, nine patients had 100% donor chimerism, while three had mixed donor chimerism. At 3 months, 11 had achieved 100% donor chimerism. No cases of grade III/IV acute GVHD occurred. At a median follow-up interval of 14.7 months (range 4-24), seven patients remained alive, and five remained free of disease.
Khouri
I F
IF
Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ikhouri@mdanderson.org
Albitar
M
M
Saliba
R M
RM
Ippoliti
C
C
Ma
Y C
YC
Keating
M J
MJ
Champlin
R E
RE
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000276:immunology / Q000628:therapy; D000074301:CD52 Antigen; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab