Patients who undergo bone marrow transplantation are generally immunosuppressed with a dose of cyclophosphamide (CYA) which is usually calculated based on the patient's weight. At these high doses of CYA, serious cardiotoxicity may occur, but definitive risk factors for the development of such cardiotoxicity have not been described. Since chemotherapeutic agent toxicity generally correlates with dose per body surface area, we retrospectively calculated the dose of CYA in patients transplanted at our institution to determine whether the incidence of CYA cardiotoxicity correlated with the dose per body surface area. Eighty patients who were to receive CYA 50 mg/kg/d for four days as preparation for marrow grafting underwent a total of 84 transplants for aplastic anemia, Wiskott-Aldrich syndrome, or severe combined immunodeficiency syndrome. Fourteen of 84 (17%) patients had symptoms and signs consistent with CYA cardiotoxicity within ten days of receiving 1 to 4 doses of CYA. Six of the 14 patients died with congestive heart failure. The dose of CYA per body surface area was calculated for all patients and the patients were divided into two groups based on daily CYA dose: Group 1, CYA less than or equal to 1.55 g/m2/d; Group 2, CYA greater than 1.55 g/m2/d. Cardiotoxicity that was thought to be related to CYA occurred in 1/32 (3%) of patients in Group 1 and in 13/52 (25%) patients in Group 2 (P less than 0.025). Congestive heart failure caused or contributed to death in 0/32 patients in Group 1 v 6/52 (12%) of patients in Group 2 (P less than 0.25). There was no difference in the rate of engraftment of evaluable patients in the two groups (P greater than 0.5). We conclude that the CYA cardiotoxicity correlates with CYA dosage as calculated by body surface area, and that patients with aplastic anemia and immunodeficiencies can be effectively prepared for bone marrow grafting at a CYA dose of 1.55 g/m2/d for four days with a lower incidence of cardiotoxicity than patients whose CYA dosage is calculated based on weight. This study reaffirms the principle that drug toxicity correlates with dose per body surface area.

Summary:use of intensive chemotherapy, the incidence of therapyrelated MDS is rising. [4][5][6][7] There are also recent reports of therapy-related MDS occurring after autologous transplants Therapy-related myelodysplasia (MDS) is a fatal marrow disorder distinct from primary MDS. We examined for lymphoma and breast cancer. 8-10The prognosis for patients with therapy-related MDS is the efficacy of bone marrow transplantation (BMT) as a treatment for patients with therapy-related MDS.poor. The median survival is 4 months, with deaths due to infection, bleeding, or progression to acute leukemia. 5,7,11Eighteen patients with therapy-related MDS and twenty-five patients with primary MDS received an alloThe prognosis for primary MDS is better, with a median survival of 15 months. 2 However, the outcome is variable geneic, syngeneic, or unrelated donor BMT. Graft-versus-host disease prophylaxis included methotrexate, and the prognosis depends on blast percentage, cytogenetic abnormalities, platelet count and on stage of disease as methotrexate plus cyclosporine, FK-506, or T cell depletion. Conditioning regimens consisted of described by French-American-British (FAB) classification. 12,13cyclophosphamide/total body irradiation, with and without cytosine arabinoside, busulfan/cyclophosTreatment for therapy-related MDS has included intensive induction therapy similar to the regimens used for phamide, and cyclophosphamide/etoposide/carmustine. For patients with therapy-related MDS, the median age acute myelogenous leukemia. These regimens have induced a remission in 60% of patients but the remission duration is was 32 years and the actuarial disease-free survival was 24% (95% confidence interval 6, 42%) with a median only a few months and the overall survival is poor. 14-16 Other approaches have included retinoids, 5-azacytidine, cytosine follow-up of 3 years. For patients with primary MDS, the median age was 36 years and the actuarial diseasearabinoside, growth factors, and hormonal agents, all with no improvement in survival. 17-22free survival at 3 years was 43% (95% confidence interval 22, 64%). Four of the therapy-related patients and Bone marrow transplantation (BMT) is effective therapy for selected patients with primary MDS. [23][24][25][26] The value of two of the primary patients have relapsed. Three patients experienced graft failure; all three had received BMT in patients with therapy-related MDS has been difficult to assess because the number of reported cases is small. T cell-depleted marrow and two had marrow fibrosis. Our results suggest that patients with therapy-relatedIn addition, data for therapy-related MDS have been shown together with primary MDS, making the relative utility of MDS can be successfully transplanted. Transplantation should be considered early in the disease, since longtransplantation for the two diseases difficult to determine. [26][27][28][29][30] In this study, we examine the long-term outcome term disease-free survival is achievable. Keywords: myelodysplasia; bone marrow transplan...

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Twenty-three patients with primary myelodysplasia (MDS) or secondary myelodysplasia/acute nonlymphocytic leukemia (MDS/ANLL) were treated with allogeneic or syngeneic bone marrow transplantation (BMT). Only one patient was in a chemotherapy-induced hematologic remission. Graft-versus-host disease prophylaxis included methotrexate, methotrexate plus cyclosporine, cyclosporine, or T-cell depletion using one of two anti-CD5 monoclonal antibodies. For patients with primary MDS, the median age was 19 years (range, 11 to 41 years) and the actuarial disease-free survival was 56% +/- 21% (median follow-up, 2 years; range, 0.8 to 5 years). There were three graft failures (two with autologous recovery) and two early deaths. Outcome appeared to be related to French-American-British (FAB) classification. For patients with secondary MDS/ANLL, the median age was 28 years (range, 3 to 16 years) and the actuarial disease-free survival was 27% +/- 13% (median follow-up, 5 years; range, 2.5 to 8.5 years). There were no graft failures, two relapses, and four early deaths. The presence of marrow fibrosis per se did not predict for graft failure (P = .21); however, the use of T-cell depleted marrow in patients with marrow fibrosis resulted in graft failure in three of five individuals. Our results suggest that in patients with primary MDS or secondary MDS/ANLL, BMT should be considered early in the course of the disease, and that attempts at inducing a remission prior to BMT appeared to be unnecessary. In MDS patients with marrow fibrosis, T-cell depletion should be avoided.