title: Phase I/II trial of cure-oriented high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method for refractory hematological malignancies. Nagoya CD34+ PBSCT Study Group.
abstract: A multicenter phase I/II clinical trial was conducted to evaluate the safety of a device (Isolex System; Baxter Health Corporation, Irvine, Calif., USA) using the immunomagnetic bead method to purify CD34+ stem cells from peripheral blood and to assess the efficacy and toxicity of high-dose chemoradiotherapy with peripheral blood stem-cell transplantation (PBSCT) using purified CD34+ stem cells in patients with refractory hematological malignancies. Patients eligible for the study included those who had T-cell acute lymphoblastic leukemia (T-ALL), lymphoblastic lymphoma (LBL), mantle-cell lymphoma (MCL), high-risk aggressive non-Hodgkin's lymphoma (NHL), and adult T-cell leukemia/lymphoma (ATLL) in first complete remission (CR) and those who had standard-risk aggressive NHL, indolent lymphoma, Hodgkin's disease, or acute promyelocytic leukemia (APL) in second CR or first partial remission (PR) after the completion of first-line chemotherapy and were chemosensitive to salvage chemotherapy, in whom tumor contamination of harvested peripheral blood stem cells (PBSCs) was possible due to bone marrow or peripheral blood involvement. Lack of CD34 expression by tumor cells was an important selection factor. Eight patients with hematological malignancies (six NHL patients, one ATLL patients, and one APL patient) were enrolled; their median age was 41 years (range 26-49 years). After consolidation and mobilization chemotherapy, two or three courses of apheresis were performed in each patient. After high-dose chemo(radio)therapy, in each patient a median of 1.8 x 10(6) cells/kg (range 8.2 x 10(5)-5.1 x 10(6) cells/kg) purified CD34+ PBSCs were infused; granulocyte colony-stimulating factor was given from day 1. Median times to hematopoietic recovery were as follows: WBC of > or = 1,000/microliter, day 11; platelet count of > or = 50,000/microliter, day 19; and reticulocyte count of > or = 10/1000, day 15. Two NHL patients relapsed at 23 and 9 months after PBSCT, respectively; the remaining six patients are alive and in CR. No severe toxicity was observed in any patient. Tumor contamination as measured using a polymerase chain reaction-mediated RNase protection assay at the 10-4 level was detected in the CD34(+)-purified fractions of 2 of the 5 samples analyzed; however, a reduction in contaminating lymphoma cells from the autograft of at least 1,000 to 10,000 orders of magnitude was achieved by CD34+ selection using the immunomagnetic bead method. High-dose chemoradiotherapy with transplantation of CD34+ PBSCs purified by the immunomagnetic bead method was thus shown to be an active and safe therapy for refractory hematological malignancies with bone marrow or peripheral blood involvement. However, it is too early for evaluation of the long-term survival benefit.
authors.affiliation: Division of Hematology and Chemotherapy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ogura
authors.forename: Y
authors.initials: Y
authors.lastname: Kagami
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Uehira
authors.forename: T
authors.initials: T
authors.lastname: Kurokawa
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: N
authors.initials: N
authors.lastname: Emi
authors.forename: Y
authors.initials: Y
authors.lastname: Morishima
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: R
authors.initials: R
authors.lastname: Ueda
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018189:Immunomagnetic Separation; D007564:Japan; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor