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Nephrol Dial Transplant (2002) 17: 1931-1935
© 2002 European Renal Association-European Dialysis and Transplant Association

Cumulative prior dose of cisplatin as a cause of the nephrotoxicity of high-dose chemotherapy followed by autologous stem-cell transplantation

Kayser Caglar1,, Can Kinalp2, Fikret Arpaci3, Mustafa Turan2, Kenan Saglam2, Bekir Ozturk3, Seref Komurcu3, Izzet Yavuz1, Müjdat Yenicesu1, Ahmet Ozet3 and Abdülgaffar Vural1

1 Division of Nephrology, 2 Department of Medicine and 3 Division of Medical Oncology, Gülhane Medical School, Etlik, Ankara, Turkey

Background. Nephrotoxicity is one of the most frequent dose-limiting factors of high-dose chemotherapy to create tolerance of autologous peripheral blood stem-cell transplantation (PBSCT) for the treatment of malignant diseases. The relative importance of factors that may be responsible for the development of nephrotoxicity varied in different trials.

Methods. The factors affecting nephrotoxicity in the early period of high-dose ifosfamide, carboplatin and etoposide treatment (ICE) followed by autologous PBSCT was investigated in 47 patients. ICE was given as a conditioning regimen for 6 days. Nephrotoxicity was defined as an increase in the serum creatinine concentration of 0.5 mg/dl or more over individual baseline levels.

Results. Eleven patients developed nephrotoxicity (23.4%). There was no significant difference in baseline renal function between patients with nephrotoxicity and those without. No differences were found between the two groups in terms of average total doses of ICE, infections and antibiotic use. The age of patients was higher in those with nephrotoxicity (37±3.7 vs 26±1.7 years, P=0.019). The cumulative cisplatin dose administered prior to this regimen was higher in the group that developed nephrotoxicity (470 vs 227 mg/m2, P=0.02). The overall mortality rate was 17%, but the transplant-related deaths were higher in the presence of nephrotoxicity (54.5 vs 5.5%, P=0.001).

Conclusions. The cumulative dose of cisplatin is a strong risk factor for the development of nephrotoxicity in patients who receive high doses of ICE followed by PBSCT. Nephrotoxicity may occur with much lower doses than the currently recommended maximum doses.

Keywords: antineoplastic agent toxicity; autologous bone-marrow transplantation; high-dose chemotherapy; nephrotoxicity

Correspondence and offprint requests to: Kayser Caglar, MD, GATA Nefroloji Bilim Dali, 06010, Etlik, Ankara, Turkey. Email: kaysercaglar{at}hotmail.com


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