Summary:We report a patient with pre-existing end-stage renal disease (ESRD) who underwent successful matched related donor allogeneic bone marrow transplantation for AML in second complete remission (CR2) using conditioning with high-dose cyclophosphamide (CY, 60 mg/kg/day ؋ 2) and TBI (165 cGy twice daily ؋ 4 days). The timing of hemodialysis after high-dose CY was extrapolated from available data on the pharmacokinetics of high-dose CY and hemodialysis clearance of conventional dose CY and its metabolites. Pharmacokinetic analyses indicated that the elimination of highdose CY and its alkylating metabolites is impaired in ESRD but is cleared with hemodialysis. The patient's early post-transplant course was uncomplicated, and WBC and platelet engraftment occurred by day ؉22. Bone marrow examination on day ؉25 showed trilineage engraftment with no AML; cytogenetics showed 100% donor karyotype. The patient remains in remission with 100% donor karyotype at 3 years post transplant. Clinical results indicate that the administration of high-dose CY is feasible with hemodialysis support for patients with ESRD. Keywords: allogeneic BMT; renal disease; cyclophosphamide; AML; pharmacokinetics; hemodialysis High-dose chemotherapy with BMT is considered to be contraindicated in patients with severe renal dysfunction since it is often assumed that the pharmacokinetics and/or pharmacodynamics of high-dose chemotherapy are significantly altered. High-dose cyclophosphamide (CY) is a common component of preparative regimens. The effect of renal dysfunction on the pharmacokinetics of high-dose CY is not known although pharmacokinetic models suggest that Correspondence: Dr JJ Perry, Section of Hematology/Oncology, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA 27157 Received 9 July 1998; accepted 12 November 1998 clearance of two important CY metabolites, 4-OH CY and aldophosphamide, may be reduced if severe renal impairment is present.1 The pharmacokinetics of conventionaldose CY and its alkylating metabolites are altered in patients with renal insufficiency.2,3 However, the toxicity profile has not been reported to be different from patients with normal renal function 4 leading some authors to suggest that conventional doses of CY do not require modification in patients with renal dysfunction. 5 In this report, we describe the clinical BMT course of a patient with endstage renal disease (ESRD) (on chronic hemodialysis) and AML in CR2 who received high-dose CY. The pharmacokinetics of high-dose CY and CY-alkylating metabolites are also presented. Case reportA 42-year-old male was diagnosed with AML (subtype FAB-M2) in January 1994. He achieved CR after treatment with daunorubicin 45 mg/m 2 i.v. × 3 days and cytarabine 100 mg/m 2 /day by continuous i.v. infusion (CIVI) ϫ 7 days. He was given four courses of post-remission therapy using daunorubicin 45 mg/m 2 i.v. ϫ 2 days and cytarabine 100 mg/m 2 /day CIVI ϫ 5 days, completed in July 1994. ...
Summary:We report long-term results of high-dose cyclophosphamide, etoposide and carboplatin with ABMT in 20 patients with metastatic breast cancer. Median age of the group was 41 years, ECOG performance status = 0 in 18 patients and 1 in two patients. Twelve patients had received adjuvant chemotherapy. Predominant sites of metastases were lung (eight), chest wall (four), liver (four), bone (three) and lymph nodes (three). Response to pretransplant chemotherapy was complete (CR) in four patients, partial (PR) in 10 patients and stable (SD) in five patients. After high-dose chemotherapy eight patients were in CR, six PR, four SD and one progressive disease. Two patients died of regimen-related toxicities (candidal sepsis and alveolar hemorrhage). With a median follow-up period of 55 months (minimum 48 months), 12 patients have died of recurrent breast cancer, one died of toxicity of salvage chemotherapy, two are alive with disease, two are alive and free of progressive disease. One patient with relapsed disease was lost to follow-up. Median event-free survival is 6 months and median overall survival is 17 months. All three of the long-term disease-free survivors had predominantly nodal disease. Two of these three patients presented with metastatic disease and received high-dose chemotherapy with ABMT as part of initial therapy for breast cancer; two of three attained CR to standard-dose cytoreductive therapy; none received doxorubicin-containing adjuvant chemotherapy. Keywords: high-dose chemotherapy; metastatic breast cancer; autologous bone marrow transplantation High-dose chemotherapy with autologous stem cell support is commonly used to treat metastatic adenocarcinoma of the breast. Such therapy is considered by many to be effective therapy for metastatic breast cancer despite the attendant risks, expense, and minimal evidence of long-term benefit.From 1990 to 1993 we treated 20 women with metastatic breast cancer with a unique high-dose combination of cyclophosphamide, etoposide and carboplatin supported by autologous bone marrow infusion. In general, ours was a poor risk group of patients, five of whom had no response to pretransplant cytoreductive therapy. With a minimum follow-up time of 4 years, we now present mature results of this high-dose regimen. Materials and methodsPatients with metastatic breast cancer who had at least a stable disease response to most recent standard-dose (cytoreductive) chemotherapy were eligible for this study. All patients had either progressed on hormonal therapy or had estrogen receptor-negative tumors. All patients were required to have an ECOG performance status of 0-2 and have adequate end-organ function including serum creatinine р2.0 mg/dl, total bilirubin р2.0 mg/dl, FEV 1 , FVC and DLCO Ͼ 60% of predicted values, left ventricular ejection fraction Ͼ45% by MUGA or echocardiography and WBC Ͼ 4.0 × 10 9 /l and platelets Ͼ 100 × 10 9 /l. Patients with central nervous system metastases or metastases confined to bone only were excluded. Other pertinent patient characterist...
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