Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
-
Biol. Blood Marrow Transplant. · Jun 1997
Clinical Trial Controlled Clinical TrialCollection of peripheral blood stem cells following administration of paclitaxel, cyclophosphamide, and filgrastim in patients with breast and ovarian cancer.
To determine the toxicities and efficacy of paclitaxel, cyclophosphamide (Cy), and recombinant human granulocyte-colony stimulating factor (filgrastim) administered for mobilization and collection of peripheral blood stem cells (PBSC) in patients with breast and ovarian cancer. ⋯ The combination of paclitaxel, Cy, and filgrastim can be administered with acceptable toxicity, allowing collection of adequate quantities of PBSC from the majority of patients with breast and ovarian cancer. Increasing the doses of paclitaxel and Cy increased the number of CD34+ cells collected and decreased the number of apheresis procedures necessary to collect target cell doses. However, increasing drug doses did not increase the fraction of patients yielding the minimum CD34+ target dose of 2.5 x 10(6)/kg. Collection of PBSC early in the disease course is the best strategy to assure optimal CD34+ cell doses in all patients.
-
Biol. Blood Marrow Transplant. · Jun 1997
Clinical TrialHigh-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes.
To identify clinical factors predictive of treatment outcome after high-dose chemotherapy (HDC) for Hodgkin's disease and to develop a prognostic model for progression-free and overall survival. ⋯ Asymptomatic patients with Hodgkin's disease involving at most one extranodal site whose disease is controlled by conventional dose chemotherapy or radiation therapy at the time of HDC have good outcomes after this therapy. Presence of increasing numbers of risk factors are associated with poorer outcomes. Results of HDC compare favorably to those of standard dose salvage therapy. These data can be used to estimate likely outcomes in patients undergoing HDC for Hodgkin's disease, to identify potential candidates for innovative therapies, and to evaluate strategies for the optimal use of HDC in Hodgkin's disease.
-
Biol. Blood Marrow Transplant. · Apr 1997
Clinical TrialThe outcome of unrelated donor bone marrow transplantation in patients with hematologic malignancies using tacrolimus (FK506) and low dose methotrexate for graft-versus-host disease prophylaxis.
Initial studies of FK506 combined with methotrexate (MTX) in patients receiving unrelated donor BMT have demonstrated a possible-decrease in the incidence of severe GVHD but high rates of severe stomatitis and nephrotoxicity. With this background, we undertook a pilot study evaluating FK506 in combination with a lower than usual dose of MTX in an attempt to improve the tolerability of this immunoprophylaxis regimen. Between July 1993 and October 1994, 26 consecutive adults receiving unrelated donor BMT at Emory University Hospital were enrolled on this study. ⋯ All are relapse-free with a median Karnofsky performance status of 90% (range: 70-100%). The cumulative probability of 2-year disease-free survival is 50% (95% confidence interval [CI]: 0.33 to 0.77); for low risk patients 67% (95% CI: 0.47 to 0.95) and for high risk patients 23% (95% CI: 0.049 to 1.00). These preliminary data indicate that FK506-based immunosuppression following unrelated donor BMT is effective in preventing severe acute GVHD and warrants comparison to CSA-based regimens.
-
Biol. Blood Marrow Transplant. · Apr 1997
CD6+ T cell depleted allogeneic bone marrow transplantation from genotypically HLA nonidentical related donors.
The widespread use of allogeneic bone marrow transplantation (BMT) is limited by the availability of suitable donors. Recent attempts to expand the donor pool by employing HLA matched unrelated marrow have been partially successful. However, severe graft-versus-host disease (GVHD) and graft failure remain obstacles and contribute to the substantial morbidity and mortality associated with matched unrelated BMT. ⋯ Among the patients transplanted for chronic myelogenous in stable phase or acute leukemia in first remission, estimated event free survival is 69% at 2 years compared to 20% for patients with more advanced disease. Our results suggest that transplantation of mismatched related marrow using modalities designed to reduce GVHD without immune suppressive medication (CD6 depletion) is feasible and should prompt wider investigation into the extended families of patients in the search for potential marrow donors. This approach also merits investigation in recipients of matched unrelated marrow as a potential means of reducing transplant-related toxicity.
-
Biol. Blood Marrow Transplant. · Dec 1995
Perforin- and Fas-mediated cytotoxic pathways are not required for allogeneic resistance to bone marrow grafts in mice.
Failure to engraft is a major complication in allogeneic bone marrow transplantation (BMT) using T cell-depleted donor marrow. Previous work has demonstrated that radioresistant host natural killer (NK) cells, CD8+ T cells, and T cells with NK markers participate in the active rejection of donor hematopoietic stem cells in murine models of allogeneic BMT. However, the precise role of cell-mediated cytotoxic mechanisms in marrow allograft rejection remains controversial. ⋯ The findings we report here demonstrate that strong allogeneic resistance remains largely intact in perforin-deficient and Fas-ligand-defective recipient mice. Thus, perforin- and Fas-mediated cytotoxic pathways are not required for resistance to bone marrow allografts in mice. We conclude that alternative pathways of cytotoxicity and/or soluble factors can mediate resistance to allogeneic BM.