Clinical response of a patient with diffuse histiocytic lymphoma to adoptive chemoimmunotherapy using cyclophosphamide and alloactivated haploidentical lymphocytes. A case report and phase I trial.
Adoptive chemoimmunotherapy has cured experimentally induced tumors in animals, but its clinical use has been limited. Six patients were treated with refractory neoplasms in a Phase I study with cyclophosphamide (CPM) and alloactivated haploidentical lymphocytes. Patients received an immunosuppressive dose of CPM (800 mg/m2) followed by haploidentical lymphocytes primed in vitro with alloantigens in mixed lymphocyte culture (MLC). One week later patients received a second infusion of alloactivated lymphocytes expanded in T-cell growth factor (TCGF). The total number of cells given to each patient progressively increased, with a single patient receiving 35.5 X 10(9) cells. Transient febrile responses and delayed-type hypersensitivity reactions at the intravenous sites were the only toxicities noted. A complete clinical response lasting 12 weeks was seen in a single patient with diffuse histiocytic lymphoma. Our experience indicates that adoptive chemoimmunotherapy can be given to patients safely and merits further clinical testing.
Kohler
P C
PC
Hank
J A
JA
Exten
R
R
Minkoff
D Z
DZ
Wilson
D G
DG
Sondel
P M
PM
D001803:Blood Transfusion; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006238:Haploidy; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007204:Indium; D007376:Interleukin-2 / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D007937:Leukapheresis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology / Q000648:ultrastructure; D016403:Lymphoma, Large B-Cell, Diffuse / Q000000981:diagnostic imaging / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011868:Radioisotopes; D011877:Radionuclide Imaging
D006680:HLA Antigens; D007376:Interleukin-2; D007519:Isoantigens; D011868:Radioisotopes; D007204:Indium; D003520:Cyclophosphamide