Summary:Long-term outcome was analyzed in 28 patients transplanted between 1989 and 1992 following busulfan and cyclophosphamide and who had busulfan levels studied. While there was no significant correlation of busulfan levels with diagnosis, patients who had received extensive prior chemotherapy had a significantly higher area under the curve (AUC; P = 0.02) and maximum busulfan levels (Cmax; P = 0.03). High AUC was associated with the development of hepatic veno-occlusive disease (P = 0.03) and with early transplant-related mortality (P = 0.06). No significant correlation of busulfan levels with relapse, late non-relapse death, late complications, nor event-free survival was detected. Bone Marrow Transplantation (2001) 27, 1121-1124.
Etoposide plus G-CSF is an effective and safe method for mobilization of PBPCs. Etoposide is an effective agent in tumor reduction in NHL and HD and is less effective in breast cancer. The substantially lower incidence of prior exposure to this agent compared with cyclophosphamide favors its use.
Summary:Results in 164 patients who underwent allogeneic marrow transplantation following busulfan and cyclophosphamide over a 15 year period were analyzed. Age (median 37, range 14-66 years) did not significantly affect the incidence of graft-versus-host disease (GVHD), but patients who received methotrexate with cyclosporine had a significantly lower incidence (P = 0.002) of chronic GVHD compared to those who received methylprednisolone with cyclosporine. Hepatic veno-occlusive disease (VOD) occurred less frequently in chronic phase patients (P = 0.002) and in those transplanted shortly after diagnosis (P = 0.001). Five year leukemia-free survival (LFS) for the entire group was 49% (95% CI 41-57%). For 102 patients who underwent transplantation in chronic phase, results were significantly improved by transplantation at a short interval following diagnosis, particularly within 3 months (P = 0.01), by the use of methotrexate and not corticosteroids for GVHD prevention (P = 0.03), and by use of HLA-identical sibling donors (P = 0.01). Age was not a significant adverse prognostic factor and transplantation was successfully performed in individuals up to age 66. Allogeneic transplantation in CML, including older patients and those with unrelated donors, can be most safely and effectively performed shortly after diagnosis. Bone Marrow Transplantation (2000) 26, 1037-1043. Keywords: allogeneic transplantation; CML; BuCy Allogeneic marrow transplantation is the preferred treatment for 'young' patients with CML who have human leukocyte antigen (HLA)-identical sibling donors. However, because most individuals with CML are older than the 40 or 50 year threshold below which early transplantation is generally recommended 1-3 or lack histocompatible sibling donors, only a small proportion undergoes allogeneic mar-
Summary:The use of VP-16 for stem cell mobilization has been cited as a significant risk factor for the development of therapy-related myelodysplasia/leukemia (tMDS/tAML) following autologous transplantation. The present study analyzed a large cohort of patients who underwent autotransplantation following stem cell mobilization with VP-16 and radiation-free preparation in order to determine the risk of tMDS/tAML. The estimated incidence of 9.9% at 7 years suggests that in the absence of TBI, VP-16 priming is not associated with an increased incidence of tMDS/tAML. Therapy-related myelodysplasia (tMDS) and acute leukemia (tAML) occur in up to 15% of patients following autotransplantation. 1-7 Risk factors include older age, prior fludarabine, mechlorethamine, or chlorambucil therapy, prior radiotherapy, and lower doses of infused progenitor cells. [1][2][3][4][5][6][7][8] The inclusion of total body irradiation (TBI), particularly 413.2 Gy, in the transplant preparative regimen has also been identified as a risk factor. [4][5][6][7][8] Krishnan et al 9 reported that stem cell mobilization with VP-16 is a significant risk factor for the development of tMDS/tAML following transplantation for Hodgkin's disease and non-Hodgkin's lymphoma, dampening enthusiasm for this priming method. Most of the patients in that study received transplantation conditioning with TBI. In order to determine the risk following VP-16 priming and radiation-free preparative therapy, we analyzed the largest reported cohort of such patients.
Patients and methodsFrom January 1992 through May 2001, 480 consecutive patients with non-Hodgkin's lymphoma (NHL) (n ¼ 153), Hodgkin's disease (n ¼ 71), or breast cancer (n ¼ 256) underwent mobilization of peripheral blood progenitor cells with 2 g/m 2 of VP-16 and 5 mg/kg daily of G-CSF as previously described. 10 Survivors were followed for a minimum of 18 months after transplantation. All NHL and Hodgkin's patients underwent preparation for transplantation with busulfan (14 or 16 mg/kg, respectively) and cyclophosphamide (120 mg/kg) with (n ¼ 209) or without VP-16 (n ¼ 15), 11 and breast cancer patients with thiotepa, carboplatin, and cyclophosphamide (STAMP V, n ¼ 256). Marrow examination with cytogenetic analysis was routinely performed prior to transplantation.
ResultsThe median age was 46 years (range 14-72 years). There were no patients with abnormal cytogenetic analysis prior to BMT identified. The median follow up for surviving patients exceeds 36 months (range 18-124 months) and 63 patients were surviving for more than 5 years at the time of analysis. Data was analyzed as of December 1, 2002. In this cohort, five of 480 of patients who received priming with VP-16 developed tMDS or tAML. Two patients developed myelodysplastic syndrome (MDS) 5.5 and 7.5 years following autotransplantation for Hodgkin's disease and one patient developed MDS 6.5 years following transplantation for breast cancer. The fourth and fifth developed AML 1 year following transplantation for non-Hodgkin's lymphoma and 3.5 y...
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