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.