We read with interest the excellent review by Sociè et al concerning nonmalignant late effects after allogeneic stem cell transplantation (SCT).1 However, we were surprised with the fact that renal side effects are not mentioned. Acute renal failure in the course of SCT is well described.2 It usually occurs in the first weeks after SCT. It results from infection and its subsequent treatment with nephrotoxic medications, graft-versus-host disease (GVHD), and veno-occlusive disease. Chronic renal failure following allogeneic SCT was recognized more than 15 years ago as related to the total body irradiation (TBI) used for conditioning.3 Indeed, many observations without TBI have been published. The initial chemotherapy including BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cyclophosphamide, ifosfamide, and the use of cyclosporine, tacrolimus, or methotrexate for the prophylaxis of GVHD may also play a role.4 Clinically, when anticalcineurins' toxicity has been ruled out as the cause of chronic renal failure, the disorder may be called bone marrow transplantation nephropathy (BMTN), a form of radiation nephropathy.5 The exact incidence of BMTN is unknown. An incidence between 0.6% and 13% has been noted in adult patients. Children appear to develop this lesion slightly more commonly, with a reported incidence as high as 45%.6 The main symptoms of BMTN are closely related to hemolytic and uremic syndrome (HUS), including constant hypertension, peripheral edema, and anemia with mild thrombopenia and the possibility of schizocytes. The anemia is out of proportion to the degree of azotemia. In a personal study of 9 patients we retrieved paradoxical low levels of erythropoietin, more pronounced than those observed for an equivalent decrease in glomerular filtration rate (GFR). The rate of decline of GFR may be chronic or acute.7 Treatments such as plasma exchange or other treatments are poorly effective in the management of the acute form, leading to mortality ranging from 50% to 100%.8 The blockade of renin-angiotensin axis is the main point in the treatment of the chronic form.6 The goal of blood pressure control is not well defined. We think that low pressure, less than 130/70 mmHg, must be obtained. We preferentially use a combination of angiotensin-converting inhibitor and angiotensin II receptor blockers. This remains to be validated. A large study concerning the prevalence of hypertension following SCT and its treatment is also needed. Despite the control of blood pressure, use of erythropoietin, and discontinuation of nephrotoxics, the evolution to chronic renal failure requiring dialysis may occur.9 Survival on dialysis therapy is often poor. Renal transplantation may be preferable.9,10 If bone marrow and kidney are from the same donor, the recipient requires little or no immunosuppression. This is of importance in view to diminish the risk of infections and malignancy.
Renal and other rare late complications following allogeneic stem cell transplantation
We read with interest the letter by Dr Vincent et al on chronic renal failure following allogeneic stem cell transplantation (SCT). Many reports and publications were not included in our review due to space constraints. We agree that chronic renal failure should have been mentioned among nonmalignant late effects. A few other effects including late cardiac failure and metabolic disorders are also worthy of mention. The X syndrome that associates hyperinsulinemia, glucose intolerance, hypertension, and hypertriglyceridemia has also been reported recently in long-term survivors following SCT.1 However, for all these complications not reviewed in our manuscript, we clearly lack well-designed analyses on a large cohort of patients to provide cumulative incidence rates and descriptions of risk factors.
Concerning late renal failure specifically, while previous reviews2 stressed the role of irradiation and of hemolytic and uremic syndrome, other risk factors including graft-versus-host disease, drug-induced toxicity, and early onset arteriosclerosis would also be worthwhile of study. As in long-term survivors of treatment in Hodgkin disease, this might expose the patients who underwent transplantation to premature cardiovascular diseases. In the case of long-term survivors of marrow transplantation, we again would like to urge physicians to conduct life-long follow-up, especially if, as in these cases, such follow-up could lead to timely therapeutic intervention and prevent the occurrence of late death.3
Members of the Late Effect Working party of the EBMT are listed in “Appendix” in the original review.4
Correspondence: Gerard Sociè, Service de greffe de moelle, University Paris VII, Hopital Saint Louis AP-HP, 1 Avenue Claude Vellefaux, Paris Cedex 10, 75475 France; e-mail: firstname.lastname@example.org