NDT Advance Access originally published online on February 17, 2007
Nephrology Dialysis Transplantation 2007 22(6):1791-1792; doi:10.1093/ndt/gfm052
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Long-term molecular efficacy and safety of imatinib in a patient with chronic myeloid leukaemia after renal transplantation
Email: f.bridoux{at}chu-poitiers.frSir,
Chronic myeloid leukaemia (CML) is a rare malignant complication in solid organ recipients [1]. Imatinib mesylate, a potent inhibitor of the Bcr-Abl protein tyrosine kinase encoded by the Philadelphia chromosome, has proven to be effective and is currently approved for first-line treatment of CML. The goal of imatinib treatment is to achieve not only cytogenetic remission, but also complete molecular remission, as defined by undetectable blood levels of BCR-ABL transcripts using quantitative polymerase chain reaction (PCR). Although cytogenetic remission of de novo CML with imatinib therapy has been recently reported in a renal transplant patient [2], the efficiency and tolerance of the strategy in this particular population remains to be confirmed.
In July 2000, a 53- year-old Caribbean woman received a cadaveric kidney transplant for end-stage renal failure secondary to diabetic nephropathy. Immunosuppressive treatment consisted of anti-thymocyte globulin, ciclosporin A (CsA), mycophenolate mofetil (MMF) and steroids. In August 2002, she developed CML (leukocytosis 28.6 x 109/l, Table 1) confirmed by cytogenetic analysis of bone marrow smears. Imatinib was started at conventional dose of 400 mg daily, while CsA and MMF were maintained. Seven weeks later, imatinib was transiently discontinued because of neutropenia, and resumed at 300 mg daily with a 25% reduction in CsA dose. Worsening of glycaemic control required combined oral antidiabetic and insulin therapy. In April 2003, MMF was switched to azathioprine because of chronic diarrhoea. At this time, the patient had achieved complete cytogenetic and molecular response, with bcr-abl/abl ratio <0.01% by PCR, which was maintained at last follow-up (Table 1). In January 2004, a breast cancer was diagnosed. A complete remission was obtained with mastectomy, radiotherapy and hormonal treatment. An allograft biopsy, performed because of progressive degradation of renal function (creatininaemia 203 µmol/l, without proteinuria), revealed border-line cellular rejection and grade I chronic allograft nephropathy without peritubular capillaries C4d deposits, but diffuse staining of glomerular and tubular basement membranes with anti-gamma, anti-kappa, anti-lambda and anti-albumin conjugates, as expected because of diabetes. Arterial and arteriolar sections appeared nearly normal without fibrous endarteritis, nor subendothelial hyalinosis (Figure 1).
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In conclusion, we report the first case of sustained molecular remission of CML with first line prolonged imatinib therapy in a renal allograft recipient. With slight reduction of CsA and imatimib doses, both substrates of CYP3A4, tolerance of imatimib therapy was good. That our patient required intensification in antidiabetic therapy does not support recent data suggesting beneficial effects of imatinib on glycaemic and lipid control [3,4]. Imatinib is also a selective PDGF-R tyrosine kinase inhibitor with vascular antiproliferative properties, including prevention of chronic allograft nephropathy [5], or reduction of heart allograft arteriosclerosis [6] in animals. Although a beneficial role of imatimib in the prevention of chronic renal allograft vasculopathy remains unproven, imatimib was a safe therapy in our patient, with almost normal vascular sections despite grade I chronic allograft nephropathy on a late kidney biopsy.
Conflict of interest statement. None declared.
Departments of Nephrology
(AT, FB, RAA, GT), Hematology
(BD, FG) and Pathology (SM)
CHU de Poitiers
2, rue de la Milétrie
86021 Poitiers
France
References
- Adler KR, Lempert N, Scharfman WB. Chronic granulocytic leukemia following successful renal transplantation. Cancer (1978) 41:2206–2208.[CrossRef][ISI][Medline]
- Koca E, Cetiner D, Goker H, et al. Complete cytogenetic remission with imatinib mesylate treatment in chronic myelogenous leukemia (CML) developed after renal transplantation. Clin Nephrol (2005) 64:324–325.[ISI][Medline]
- Veneri D, Franchini M, Bonora E. Imatinib and regression of type 2 diabetes. N Engl J Med (2005) 352:1049–1050.
[Free Full Text] - Gottari M, Manzato E, Gherlinzoni F. Imatinib and hyperlipemia. N Engl J Med (2005) 353:2722–2723.
[Free Full Text] - Savikko J, Taskinen E, Von Willebrand E. Chronic allograft nephropathy is prevented by inhibition of platelet-derived growth factor receptor: tyrosine kinase inhibitors as a potential therapy. Transplantation (2003) 75:1147–1153.[CrossRef][ISI][Medline]
- Sihvola R, Tikkanen J, Krebs R, et al. Platelet-derivated growth factor receptor inhibition reduces allograft arteriosclerosis of heart and aorta in cholesterol-fed rabbits. Transplantation (2003) 75:334–339.[CrossRef][ISI][Medline]
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