Abstract

Post-transplant lymphoproliferative disorders (PTLD) are a well-recognized complication of solid organ transplantation. Their incidence increases with the intensity of immunosuppression. Most of the PTLD are of B phenotype. HCL is a rare chronic B-cell malignancy, characterized by a cellular infiltration of spleen and bone marrow by large differentiated B cells, often exhibiting hair-like protrusions. To our knowledge, HCL has only been described once in a solid organ transplant recipient (kidney transplantation). We report here the first case of HCL in a cardiac transplant recipient. A 51-year old heart transplant recipient was referred to our department for investigation of a mild leuconeutropenia and thrombopenia that gradually worsened over a year. Medical history of this patient included gout crises and a heart transplantation 7 years earlier for a valvular cardiopathy following a streptococcal endocarditis and a Bjork valvular replacement. Immunosuppression consisted of cyclosporine and prednisone. Several episodes of acute rejection required corticosteroid boluses. At admission, patient presented with normal physical examination and no recent infectious complication. Blood cell count was as follows: WBC 1.4 x 109/L, neutrophils 0.78 x 109/L, lymphocytes 0.56x109/L, presence of rare hairy cells, hemoglobin 12.3 g/dL, platelets 140 x 109/L. CD4+ lymphocyte count was low (0.140 x 109/L). Bone marrow cytology and histopathology confirmed the diagnosis of HCL with a decreased cellularity, an infiltration by 28% hairy cells and no fibrosis. Serum levels of soluble IL-2 receptors were markedly increased at 1827 pmol/L for a upper limit of normal value of 115 pmol/L. Renal function was mildly impaired (serum creatinine: 139 μmol/L). Liver function tests were within normal range. Pentostatin therapy was initiated at a dose of 4mg/m². Six cycles were administered, every two weeks for the three first and every three weeks for the three latest. First cycle was complicated by a grade 3 febrile neutropenia. Digestive tract tolerance was poor with grade 2 nausea and vomiting after each of the 6 cycles in spite of ondansetron prophylaxis. Patient also presented a gout crisis after each of the cycle despite allopurinol and oral hydration. Post-transplant immunosuppressive regimen was not modified during the chemotherapy. No episode of rejection occurred during and after chemotherapy. No antimicrobial prophylaxis was administered. Neutrophil and platelet counts normalized after the 2nd cycle. Lymphocyte count decreased below 0.1 x 109/L after first cycle and subsequently increased slowly to return to pretreatment value only 12 months after end of therapy without occurrence of any opportunistic infection. Serum level of soluble IL-2 receptors returned to normal value after cycle 3. A bone marrow biopsy performed after 6 courses of pentostatin confirmed complete remission and chemotherapy was discontinuated. With a follow-up of 32 months after diagnosis, patient is alive, in hematological remission and has a good graft function. We can conclude from this case report that pentostatin therapy given for 6 cycles did not lead to major infectious complications in our heart-transplant patient and provided a sustained complete response.

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