Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without CD52-positive malignancies.
We recently reported that the addition of in vivo alemtuzumab to the conditioning regimen enables 2- or 3-locus-mismatched hematopoietic stem cell transplantation without an excessive risk of graft rejection or graft-versus-host disease. In a later series of patients, however, one patient with refractory chronic lymphocytic leukemia with large residual tumors at transplantation developed graft rejection. While the peak alemtuzumab concentration in the previous patients without graft rejection was higher than 5 micro g/ml, the peak alemtuzumab concentration in this patient was only 1.44 micro g/ml. We considered that alemtuzumab was bound to the large residual tumors, which resulted in a low blood concentration of alemtuzumab. Therefore, it is important to debulk tumors before the conditioning regimen for patients with refractory CD52-positive hematological malignancies, or the dose of alemtuzumab should be adjusted by monitoring the blood concentration, when alemtuzumab is used for in vivo T-cell depletion in 2- or 3-locus-mismatched transplantation.
Oshima
Kumi
K
Department of Hematology, Cell Therapy & Transplantation Medicine, University of Tokyo Graduate School of Medicine and Hospital, Tokyo, Japan.
Kanda
Yoshinobu
Y
Nakahara
Fumio
F
Shoda
Eriko
E
Suzuki
Takahiro
T
Imai
Yoichi
Y
Watanabe
Takuro
T
Asai
Takashi
T
Izutsu
Koji
K
Ogawa
Seishi
S
Motokura
Toru
T
Chiba
Shigeru
S
Kurokawa
Mineo
M
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000097:blood / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000074301:CD52 Antigen; D003131:Combined Modality Therapy; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006086:Graft vs Host Disease / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000628:therapy*; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab