Total body irradiation and cyclophosphamide is a conditioning regimen for unrelated bone marrow transplantation in a patient with chronic myelogenous leukemia and renal failure on hemodialysis

Abstract

Summary:Five years after the diagnosis of Ph chromosome-positive chronic myeloid leukemia (CML) a 31-year-old patient developed malignant nephrosclerosis with renal failure. He then underwent an allogeneic unrelated BMT in first chronic phase CML. The preparative regimen consisted of fractionated total body irradiation (TBI) and cyclophosphamide (CY). We studied the pharmacokinetics of cyclophosphamide on hemodialysis and compared clinical parameters including time to engraftment and toxicity with parameters of a patient with normal renal function who also received an unrelated marrow as treatment for CML in first chronic phase. Our results suggest that TBI/CY is a suitable conditioning regimen for allogeneic transplantation in patients with hematological malignancy and renal failure on hemodialysis. Keywords: bone marrow transplantation; renal failure; cyclophosphamide; total body irradiation; pharmacokinetics; hemodialysis Matched unrelated donor (MUD) transplantation is the best available treatment for young patients with CML in chronic or accelerated phase without a matched sibling donor. 1-3However, a serious therapeutic problem for BMT is hemodialysis-dependent renal insufficiency. An important question in this clinical setting relates to the optimal conditioning regimen to ensure an adequate myelosuppression in patients with disturbed renal function on hemodialysis. There is concern with regard to the tolerance of intensive chemotherapy in hematological patients with severe renal failure. 4 The aim of our report is to show that a conditioning regimen with TBI and CY can be used successfully in a patient with CML and severe renal insufficiency requiring hemodialysis. Patients and methodsA 31-year-old patient with Ph+ CML (patient A) was treated with a combination of alpha-interferon and hydroxyurea for 5 years and with hydroxyurea alone for the last 6 months before admission to our department. A MUD transplantation was offered to the patient according to the recommendations of the Consensus Panel chaired by EC Gordon Smith stating that for patients with CML in chronic phase or accelerated phase, unrelated donor BMT should be considered as the best available treatment at present for patients without a matched sibling donor.2 The patient developed malignant nephrosclerosis and was hemodialysis-dependent on admission. The data were compared to the data in a matched pair patient (patient B) with similar clinical characteristics conditioned with the same regimen ( Table 1). The conditioning regimen for BMT consisted of TBI with a total dose of 13.5 Gy from days Ϫ6 to Ϫ4 and CY 60 mg/kg once daily i.v. on days Ϫ3 and Ϫ2 (total dose 120 mg/kg).CY concentration was determined in serum and dialysate of patient A, and in serum and urine of patient B. Hemodialysis was performed in patient A 6 h after each CY infusion over a period of 6 h on days Ϫ3 and Ϫ2. The patient received, in addition, a bladder irrigation, 5 and a continuous i.v. infusion of mesna 60 mg/kg body weight/24 h on days Ϫ3 and Ϫ2. Patient B received...

How I treat acute myeloid leukemia presenting with preexisting comorbidities

“…Allogeneic transplantation in patients on chronic dialysis has been reported. 47,48 Ordinarily, we do not consider it except in rare cases of a young highly motivated individual who has a very poor-prognosis genotype.…”

Management of hematological malignancies in patients affected by renal failure

“…Therefore, documented experiences in this setting remain extremely limited. Indeed, to the best of our knowledge, only four case reports have been published, demonstrating the feasibility of allogenic HSCT in carefully selected patients [114][115][116][117]. Reduced-intensity conditioning allogeneic HSCT has been proposed as an alternative transplantation option to reduce HSCT-related toxicity.…”

Altered cyclophosphamide and thiotepa pharmacokinetics in a patient with moderate renal insufficiency

“…However, data are controversial. Minimal eVects of renal dysfunction upon cyclophosphamide AUC have been reported [8,11,12], while others have shown an elevated AUC in those with impaired renal function [9,10,13]. A report in an anephric child indicated that oV haemodialysis clearance of cyclophosphamide was similar to cyclophosphamide clearance in children with normal renal function [14].…”

“…Scarce information is available about the pharmacokinetics of (high dose) cyclophosphamide and thiotepa in patients with renal insuYciency. Earlier studies have described the pharmacokinetics of cyclophosphamide in adults with renal dysfunction receiving either standard dose [7][8][9][10][11] or myeloablative doses of cyclophosphamide [12,13]. However, data are controversial.…”