High-dose cyclophosphamide with autologous lymphocyte–depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia

• Published in: Blood Vol. 101; no. 1; pp. 71 - 77
• Main Authors: Huhn, Richard D., Fogarty, Patrick F., Nakamura, Ryotaro, Read, Elizabeth J., Leitman, Susan F., Rick, Margaret E., Kimball, Janice, Greene, Adeira, Hansmann, Kristin, Gratwohl, Alois, Young, Neal, Barrett, A. John, Dunbar, Cynthia E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.01.2003; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Chronic Disease; Cyclophosphamide - administration & dosage; Cyclophosphamide - toxicity; Female; Graft Survival; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematologic and hematopoietic diseases; Humans; Leukapheresis - methods; Lymphocyte Depletion; Male; Medical sciences; Middle Aged; Peripheral Blood Stem Cell Transplantation - adverse effects; Peripheral Blood Stem Cell Transplantation - methods; Pilot Projects; Platelet Count; Platelet diseases and coagulopathies; Platelet Transfusion; Purpura, Thrombocytopenic, Idiopathic - complications; Purpura, Thrombocytopenic, Idiopathic - therapy; Salvage Therapy; Time Factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Autologous - adverse effects; Antineoplastic agent; Autoimmunity; Human; Immunopathology; Stem cell; Hematopoietic cell; Hemopathy; Autograft; Blood cell; Chemotherapy; Chronic; Cyclophosphamide; Oxazaphosphinane derivatives; Platelet; Depletion; Treatment; Nitrogen mustard; Graft; Myelosuppression; Therapeutic protocol; Immune thrombocytopenic purpura; High dose; Lymphocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2001-12-0171

Patients with refractory chronic autoimmune thrombocytopenia (AITP) have a significant risk of morbidity and mortality related to hemorrhage. High-dose (HD) cytotoxic therapy may produce remissions but entails risks related to myelosuppression. Hematopoietic stem cell support with lymphocyte-depleted grafts may accelerate hematologic recovery and concomitantly reduce repopulation by autoreactive immunocytes. Fourteen patients with chronic AITP, in whom multiple prior therapies including corticosteroids, splenectomy, intravenous immunoglobulin, and various cytotoxic or immunomodulatory regimens had failed, were treated with HD cyclophosphamide (50 mg/kg/d) and autologous granulocyte colony-stimulating factor (G-CSF)–mobilized leukocytes depleted of lymphocytes by immunomagnetic CD34+selection. There were no significant adverse events related to G-CSF, intravenous device insertion, or leukapheresis. Treatment-related complications included transient hemorrhagic cystitis (1 patient), vaginal bleeding (2 patients), gastrointestinal bleeding (1 patient), epistaxis (1 patient), and antibiotic-responsive febrile neutropenia (all patients). The mean time to absolute neutrophil count (ANC) more than 500/mm3was 9 ± 0.6 days. Eight patients experienced antibiotic-responsive gram-positive bacteremia. A median of 2 platelet transfusions was required for stem cell mobilization, intravenous catheter insertion, and apheresis and a median of 9 platelet transfusions was required during hematopoietic recovery. Six patients obtained durable complete responses (platelet counts > 100 000/mm3without other therapy) with maximum follow-up of 42 months. Two additional patients obtained durable partial responses (platelet counts significantly increased over baseline with reduced medication requirements and cessation of bleeding complications). This therapeutic approach is feasible for patients with severe chronic AITP, a substantial proportion of whom may obtain durable remissions. Larger controlled trials are recommended.