Chronic Lymphocytic Leukemia in Kidney Recipients

Abstract

To the Editor: In France, a recent epidemiologic report (1) stated that among the 31 436 patients with end-stage renal disease (ESRD) 18 848 were ≥ 65 years old. At present the incidence after 65 years of age of chronic lymphocytic leukemia (CLL) is estimated to be around 20 cases/100 000 persons per year (2), implying that roughly four new cases of CLL should be diagnosed every year in the population of French ESRD patients. CLL is incurable, but also very heterogeneous: some patients live for decades with no therapeutic needs, whereas others have a rapidly aggressive clinical course (3). All CLL patients taken together, the 5-year survival rate exceeds 80% (2), which is probably why some transplantation centers have circumvented a theoretical contra-indication to solid organ transplantation and allowed some of these patients to become potential kidney recipients. In 2008 we had reported in this journal the evolution (up to four years post-transplantation) of four ESRD patients with CLL who had been engrafted with a deceased donor kidney, and treated with conventional immunosuppressive drugs (4). Our aim was to warn the scientific community of this high-risk situation: all four patients had developed severe infectious episodes, and two had developed tumoral complications (namely, the rapid progression of CLL and a Kaposi sarcoma). In addition, two patients had a prominent infiltration of the graft by monoclonal B cells, along with renal failure. The aim of the present letter is, first, to report the extended follow-up on these patients, and second, to discuss the measures that could improve the outcome of future patients, both prior and post-transplantation. At present, three patients out of four are dead. One (formerly patient [fp]#4) died 46 months post-tx from CLL progression and numerous septic complications, as previously reported (4). Another one (fp #1) died 47 months post-tx, with generalized lymph node enlargement and a metastatic cancer of a native kidney. A third one (fp #2) died 53 months post-tx from refractory CLL (of note, his graft had ceased to function 1 month earlier, due to a massive B-cell graft infiltration). Eventually, only one patient (fp #3) is still alive 75 months post-tx, but she has lost her graft 54 months post-tx. The last graft biopsy (indicated by chronic graft dysfunction) revealed a diffuse lymphocytic infiltration with severe interstitial fibrosis. All these patients experienced a high morbidity, and frequent hospital admissions. Although the long-term survival rate of ESRD patients with CLL is unknown, it is not immediately obvious that dialysis increases the morbidity or the mortality consecutive to CLL. To us, the contrasting observation that both the quality and the quantity of life of the four reported patients were dramatically reduced after a kidney transplantation should lead to consider the exclusion of these patients from the waiting list. At the very least, a discussion on a case-by-case basis should be undertaken between transplant physicians and hematologists/oncologists, taking into account the new molecular prognostic markers available for CLL such as the expression of CD38, cytogenetic abnormalities and ideally the mutational status of genes coding for immunoglobulin heavy chain variable region (5). In addition, since some of the drugs used to prevent rejection potentially increase the risk of an exacerbation of CLL by reducing the immunosurveillance against tumoral cells, it might be sound to favor drugs that target the cell cycle (such as mammalian target of rapamycin inhibitors). We urge physicians to report additional cases, both with good and poor outcome, to the transplant society. Of interest, a recent case of early CLL, diagnosed post-transplant, with good prognostic markers, was reported to be uncomplicated with a 3-year follow-up, after mycophenolate mofetil discontinuation (6). A year and a half later, under a ‘weak’ immunosuppression (low dose tacrolimus and steroids), this patient has a normal performance status, a preserved graft function, and no recent history of septic or tumoral complication. Although his graft is also infiltrated by specific B cells, this infiltration is not destructive and his CLL remains remarkably stable. Prognostic markers could therefore help to sort out some ESRD patients with early-stage CLL in whom a kidney transplant is eventually a reasonable option. Regardless, these patients should come under very close scrutiny. The authors of this manuscript have no conflicts to disclosed as described by the American Journal of Transplantation.