Successful double bone marrow and renal transplantation in a patient with Fanconi anemia

In Fanconi anemia (FA), bone marrow failure (BMF) is the major cause of morbidity and mortality, whereas renal failure is less frequent with a possibly underestimated occurrence of between 25% and 30%1,2 and has a lower impact on survival. Bone marrow transplantation (BMT) provides a survival rate of greater than 80% from sibling donors2and of about 30% from unrelated donors.3,4 

We present a peculiar case of a patient with FA who, due to clinically prevalent BMF, underwent BMT that was followed by renal transplantation (RT) for end-stage renal disease.

This male patient presented at birth with renal failure caused by congenital single hypoplastic kidney. At the age of 3.5 years, because of thrombocytopenia (74 × 10⁹/L) and a positive dyepoxibutane test, he was diagnosed with FA. At the age of 4.5 years serum creatinine was 278 μM, white blood cells (WBCs) were 3.7 × 10⁹/L, neutrophils 1 × 10⁹/L, Hb 9 g/dL, and platelets 36 × 10⁹/L. At this stage the patient, without previous transfusions, underwent BMT (Table1).

Two years after the graft, a further impairment of renal function required peritoneal dialysis, and 3.5 years after BMT, the patient underwent RT from a 9-year-old, B-positive, cytomegalovirus (CMV)–positive/Epstein Barr virus (EBV)–negative cadaveric donor. Donor and recipient shared one HLA allele at locus A and one at locus DRB1. Serum creatinine normalized (53 μM) 5 days after the transplant. cyclosporin A (CyA) and steroids were given as posttransplant immunosuppression. No acute rejection occurred during the follow-up.

Currently, 6 years from BMT and 2.2 years from RT, still on steroids and CyA, the patient is well, with no evidence of tumors. WBCs are 7.4 × 10⁹/L; PMN, 4.7 × 10⁹/L; Hb, 10.1 g/dL; and platelets, 188 × 10⁹/L. The hemopoiesis (short tandem repeat polymorphism analysis on peripheral blood) is entirely of donor origin. Serum creatinine is 78 μM.

To the best of our knowledge, this is the first FA patient who underwent a double sequential BMT and RT.

Although double BMT and RT have already been performed,5-8 in the context of FA, this experience is peculiar. In fact, in FA patients who have a cancer “proneness” per se, BMT constitutes an additional risk factor for tumors because of the irradiation and alkylating agents used in the conditioning regimen, chronic graft-versus-host disease (cGVHD) occurrence, and posttransplantation immunosuppression.2,9,10 RT represents another risk factor because of the immunosuppression.

Our patient has a high risk of late cancers. In fact, apart from GVHD, he has all the other risk factors, mainly those related to the high immunosuppression load that was required by the 2 sequential transplants from 2 different donors. The choice of an EBV-negative renal donor aimed to diminish the cancer risks by reducing the chances of primary EBV infection which, in turn, is the major risk factor for posttransplant lymphoproliferative disorders.11 

No tumors have occurred thus far in our patient during his 6-year follow-up. However, since in FA patients malignancies appear at a mean of 8.2 years after BMT,10 a careful lifetime cancer monitoring looks mandatory.

This case outlines the relevance of renal malformations on the outcome of the FA patients. In addition, it shows that sequential BMT and RT in FA patients is feasible and may be successful. Even if this double procedure might imply some adjunctive risks of late tumors, it has ameliorated the duration and the quality of life of this patient.