Collection of Ph-negative progenitor cells from interferon responsive patients with chronic myeloid leukemia: effect of granulocyte-colony-stimulating factor mobilization

• Published in: Haematologica (Roma) Vol. 85; no. 6; pp. 647 - 652
• Main Authors: Olavarria, E, Parker, S, Craddock, C, Philpott, N, Tiniakou, M, Chase, A, Kanfer, E, Apperley, JF, Goldman, JM
• Format: Journal Article
• Language: English
• Published: Pavia Haematologica 01.06.2000
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, CD34 - blood; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Count; Cytogenetics; Disease-Free Survival; Female; Graft Survival; Granulocyte Colony-Stimulating Factor - pharmacology; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Mobilization; Humans; Interferons - administration & dosage; Interferons - pharmacology; Interferons - toxicity; Leukapheresis - methods; Leukapheresis - standards; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - drug therapy; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Philadelphia Chromosome; Stem Cells - cytology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Autologous; Transplantation, Homologous; Human; Evaluation; Alpha interferon; Stem cell; Treatment efficiency; Cytokine; Hematopoietic cell; Malignant hemopathy; Transplantation; Myeloproliferative syndrome; Autograft; Chronic; Granulocyte colony stimulating factor; Surgery; Chronic myelocytic leukemia; Clonal selection; Progenitor cell
• ISSN: 0390-6078; 1592-8721

Haematology Department, Hammersmith Hospital, ICSM, Du Cane Road, London W12 0NN, UK. e.olavarria@ic.ac.uk. BACKGROUND AND OBJECTIVE: The observation that patients with chronic myeloid leukemia (CML) may relapse following stem cell transplantation because of Philadelphia positive cells contaminating the graft have led to a variety of strategies to reduce this contamination. This study investigate the feasibility of collective, Ph-re cells from patients with CML in chronic phase. DESIGN AND METHODS: A total of 18 patients with chronic myeloid leukemia in chronic phase who had responded to varying degrees to treatment with interferon-a (IFN) were subjected to mobilization with granulocyte colony-stimulating factors and peripheral blood progenitor cell collection. Nine patients were in complete cytogenetic remission (CCR) and nine were partial responders. IFN was stopped 2 to 4 weeks before the procedure. G-CSF was given by subcutaneous injection once daily at a dose of 10 microg/kg. RESULTS: Five patients underwent one collection procedure only, 10 underwent two procedures and 3 patients had three collections. The median number of nucleated cells (NC) per patient collected was 10.2 x 10(8)/kg (4.4-19.7) and the median number of CD34(+) cells was 2.5 x 10(6)/kg (0.4-9.4). Analyzable cytogenetic data were available for 26/34 (76%) leukapheresis procedures. The median percentage of Ph- negative metaphases for patients in CCR was 100% (73-100). Patients not in CCR had a higher level of Ph-positive cells in their collections (median 23%, range 0-79%, p=0.01). Of the nine patients in CCR, 8 had at least one apheresis from which progenitor cells were 100% Ph-negative; conversely, patients not in CCR had detectable Ph-positive cells in every collection. Four patients have undergone autologous stem cell transplantation. INTERPRETATION AND CONCLUSIONS: It was possible to collect sufficient Ph negative progenitor cells from patients in CCR but collections from other patients contained significant numbers of Ph-positive cells.