Journal Article

Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells

Levine, B L, June, C H, Badros, A, Nandi, A, Ratterree, B, Meisenberg, B, Natt, S, Ruehle, K, Mann, D, Rapoport, A P, Rollins, S, Westphal, S

2004

Overview

Four patients with chronic myelogenous leukemia (CML) that was refractory to interferon alpha (two patients) or imatinib mesylate (two patients), and who lacked donors for allogeneic stem cell transplantation, received autotransplants followed by infusions of ex vivo costimulated autologous T cells. At day +30 (about 14 days after T-cell infusion), the mean CD4+ cell count was 481 cells/microl (range 270-834) and the mean CD8+ count was 516 cells/microl (range 173-1261). One patient had a relative lymphocytosis at 3.5 months after T-cell infusion, with CD4 and CD8 levels of 750 and 1985 cells/microl, respectively. All the four patients had complete cytogenetic remissions early after transplantation, three of whom also became PCR negative for the bcr/abl fusion mRNA. One patient, who had experienced progressive CML while on interferon alpha therapy, became PCR- post transplant, and remained in a molecular CR at 3.0 years of follow-up. All the four patients survived at 6, 9, 40, and 44 months post transplant; the patient who remained PCR+ had a cytogenetic and hematologic relapse of CML, but entered a molecular remission on imatinib. Autotransplantation followed by costimulated autologous T cells is feasible for patients with chronic phase CML, who lack allogeneic donors and can be associated with molecular remissions.

• Publisher: Nature Publishing Group
• Subject: Adoptive transfer / Adoptive Transfer - adverse effects / Adoptive Transfer - methods / Adult / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Autografts / BCR-ABL protein / BCR-ABL1 gene / Biological and medical sciences / Bone marrow, stem cells transplantation. Graft versus host reaction / CD4 antigen / CD4-Positive T-Lymphocytes / CD8 antigen / CD8-Positive T-Lymphocytes / Chronic myeloid leukemia / Cytogenetics / Follow-Up Studies / Fusion Proteins, bcr-abl - genetics / Hematologic and hematopoietic diseases / Hematopoietic Stem Cell Transplantation - methods / Humans / Imatinib / Interferon / Leukemia / Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis / Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Lymphocyte Activation / Lymphocyte Count / Lymphocytes / Lymphocytes T / Lymphocytosis / Medical sciences / Middle Aged / mRNA / Myeloid leukemia / Patients / Polymerase Chain Reaction / Remission / Remission Induction - methods / RNA, Neoplasm - analysis / Salvage Therapy - methods / Stem cell transplantation / Stem cells / T-Lymphocytes - immunology / T-Lymphocytes - transplantation / Time Factors / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Transplantation / Transplantation, Autologous / Transplants & implants