mesna and Bone-Marrow-Diseases

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bone Marrow Diseases; Breast Neoplasms; Carmustine; Cyclophosphamide; Defective Viruses; DNA, Complementary; DNA, Recombinant; Drug Resistance, Neoplasm; Ethics, Medical; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Interleukin-3; Interleukin-6; Mesna; Middle Aged; Paclitaxel; Pilot Projects; Recombinant Fusion Proteins; Retroviridae; Safety; Thiotepa

Chemotherapy induces high remission rates in high-grade lymphoma. However relapse remains a major problem. One approach to this is myeloablative chemotherapy with transplantation of autologous bone marrow or peripheral blood progenitor cells (PBPC). Immunological mechanisms have been suggested to play a role in the prevention of relapse after transplantation. We investigated the recovery of cellular immune functions after high-dose chemotherapy and PBPC transplantation in 5 patients with high grade non-Hodgkin's lymphoma. All patients showed rapid reconstitution of natural killer (NK) and inducible lymphokine-activated killer (LAK)-activity 10-14 days after transplantation. Four of 5 patients showed higher levels of LAK-generation in the post-transplant period compared with levels prior to myeloablative treatment. Absolute lymphocyte counts in peripheral blood reached 1.0 x 10(9)/l between days 10 and 13 with a predominance of CD8+ cells and an inversion of the CD4/CD8 ratio. Four of 5 patients had a transient increase in CD56+ and CD16+ cell counts post-transplant. No change in the proportion of CD25+ cells was noted. These results show that PBPC transplantation leads to a rapid recovery of cellular immune functions after myeloablative chemotherapy and provides evidence for an increased presence of LAK precursor cells early in the post-transplant period which can be activated by IL-2 to exert high levels of cytotoxicity.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Diseases; Busulfan; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Leukapheresis; Lymphocyte Count; Lymphocyte Subsets; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Mesna; Middle Aged; Podophyllotoxin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Time Factors; Treatment Outcome; Vincristine

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Child; Combined Modality Therapy; Cystitis; Drug Evaluation; Etoposide; Humans; Ifosfamide; Mesna; Neoplasm Recurrence, Local; Sarcoma