Phenotypic transformation of CD52(pos) to CD52(neg) leukemic T cells as a mechanism for resistance to CAMPATH-1H.
Immunotherapy utilizing CAMPATH-1H for patients with chemotherapy-refractory chronic lymphocytic leukemia has yielded encouraging results with many reports of complete remission. Here we report the outcome of two patients with CD4-positive T cell prolymphocytic leukemia treated with CAMPATH-1H. Both patients responded rapidly to treatment and subsequently developed CD4 lymphopenia. One patient remained in complete remission after 14 weeks of treatment. Serial peripheral blood flow cytometry revealed that the CD52 antigen was present throughout treatment. The other patient who was initially CD52-positive, became CD52-negative after 6 weeks of treatment, and developed progressive symptoms of T cell prolymphocytic leukemia. Immunotherapy was stopped, chemotherapy proved futile, and the patient died. This change in phenotype from CD52-positive to -negative during CAMPATH-1H therapy points out a need to develop strategies for maintaining antigenic expression during monoclonal antibody therapy.
Birhiray
R E
RE
Department of Hematology/Oncology, Marshfield Clinic, Marshfield, WI, USA.
Shaw
G
G
Guldan
S
S
Rudolf
D
D
Delmastro
D
D
Santabarbara
P
P
Brettman
L
L
D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000494:pharmacology*; D015703:Antigens, CD / Q000032:analysis* / Q000187:drug effects; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D000074301:CD52 Antigen; D019008:Drug Resistance, Neoplasm; D017809:Fatal Outcome; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D015461:Leukemia, Prolymphocytic, T-Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012074:Remission Induction
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