Subject(s)
Antibodies, Monoclonal/therapeutic use , Graft vs Leukemia Effect , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adolescent , Adult , Antilymphocyte Serum , Disease-Free Survival , Female , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Myelodysplastic Syndromes/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapyABSTRACT
We investigated whether a novel chemotherapy-alone conditioning regimen would permit durable engraftment of standard doses of CD34+ purified stem cell grafts from full-haplotype mismatched related donors. We also examined the role of infusing limited doses of donor leukocytes for prevention of leukemia relapse. Our conditioning regimen consisted of thiotepa, fludarabine, rabbit antithymocyte globulin, melphalan, cyclosporin, and prednisolone. Since October 1998, 14 patients with high-risk leukemia were treated; 13 donor-patient pairs shared 3 of 6 HLA antigens, and 1 pair shared 5 of 6 HLA antigens. A median of 5.4 x 10(6) CD34+ cells per kilogram, 1.62 x 10(4) CD3+ cells per kilogram, and 9.32 x 10(4) CD19+ cells per kilogram were infused. T-cell depletion was the only graft-versus-host disease (GVHD) prophylaxis. All patients had prompt engraftment, and no late graft rejections were observed. All surviving patients received at least 1 infusion of donor whole blood containing 5, 7, 10, 25, or 50 x 10(3) CD3+ cells per kilogram between days 25 and 95 after transplantation, after which 8 developed acute GVHD (3 grade I, 2 grade II, 2 grade III, and 1 grade IV) and 2 developed a bronchiolitis obliterans-like syndrome. After attaining complete remission, 5 patients relapsed and died with active leukemia. The estimated relapse-related mortality at 4 years is 38.1%. As of June 15, 2003, 6 of 14 patients have survived a median of 43.5 months after transplantation with 100% donor cells. All 6 surviving patients developed acute GVHD and had a natural killer cell mismatch with their donors in the direction of graft versus host. The estimated overall survival and event-free survival for the 14 patients at 4 years is 41.7% +/- 13.5%.
Subject(s)
Antigens, CD34 , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Haplotypes , Hematopoietic Stem Cell Transplantation/methods , Histocompatibility , Transplantation Conditioning/methods , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/toxicity , Female , Graft Survival , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Leukemia/complications , Leukemia/mortality , Leukemia/therapy , Lymphocyte Depletion , Lymphocyte Transfusion , Male , Middle Aged , Survival Analysis , Transplantation Conditioning/adverse effects , Transplantation, Homologous , Treatment OutcomeSubject(s)
Antiemetics/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Granisetron/therapeutic use , Hematopoietic Stem Cell Transplantation , Immunosuppression Therapy/adverse effects , Indoles/therapeutic use , Nausea/prevention & control , Ondansetron/therapeutic use , Vomiting/prevention & control , Adult , Combined Modality Therapy , Female , Humans , Leukemia/therapy , Male , Multiple Myeloma/therapy , Myelodysplastic Syndromes/therapy , Nausea/chemically induced , Transplantation, Autologous , Transplantation, Homologous , Tropisetron , Vomiting/chemically inducedABSTRACT
For Autologous Bone Marrow Transplantation (ABMT) the patient's own marrow is harvested before myelotoxic high-dose radio-chemotherapy and later returned to promote hemopoietic reconstitution. Between harvest and return the bone marrow must be preserved. The time elapsed between harvest and return depends on the intended therapy. Although--bone marrow may keep its hematopoietic potential for a few days without freezing, preservation for longer periods imposes the need for cryopreservation. Some of the current methods for marrow preservation are reviewed, with special emphasis given to cryopreservation. Hospital de Santa Maria Bone Marrow Transplant Unit cryopreservation method is described.
