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Visceral leishmaniasis: a new opportunistic infection in hematopoietic stem-cell-transplanted patients

Bone Marrow Transplantation volume 33, pages 667–668 (2004)Cite this article

Visceral leishmaniasis (VL) has emerged as an opportunistic infection in HIV-infected patients in Mediterranean area; particularly in patients with CD4 lymphocyte counts ⩽200 × 106/l.1,2 It has been described after organ transplantation,3 but not after HSCT.

A 57-year-old male underwent an HLA-matched peripheral blood stem cell transplant following a dose-reduced conditioning regimen for AML (TBI 6 Gy, cyclophosphamide 60 mg/kg and ATG 10 mg/kg). At 10 weeks after transplantation, the patient developed grade IV corticosteroid-resistant acute GVHD requiring multiple immunosuppressive drugs including ATG, anti-CD25 monoclonal antibody and mycophenolate mofetil. Immunosuppressive therapy was eventually discontinued 119 weeks post transplant. Table 1 summarizes the clinical course. Fever occurred 66 weeks post transplant. Physical examination was normal. Invasive aspergillosis was suspected based upon a pulmonary nodule and the detection of Aspergillus antigen in the peripheral blood, and treated with an amphotericin B lipid complex (Abelcet 5 mg/kg/day for 1 month), followed by itraconazole. Fever recurred 94 weeks post transplantation. Despite treatment with caspofungin, fever persisted and the pulmonary nodule was surgically removed. Pathological analysis confirmed the presence of Aspergillus. The extensive investigation for unexplained persisting fever led, at week 117, to the diagnosis of VL upon detection of specific antibodies by immunofluorescence antibody test (IFAT, positive at 1/5120) and ELISA. Western blot (WB) analysis confirmed the diagnosis with antibodies directed against five antigens (14, 18, 21, 23 and 31 kDa).4 Retrospective serological analysis revealed that, during the first episode of fever, the patient had acquired the profile of an asymptomatic carrier, characterized by a negative serology by IFAT and ELISA analysis and antibodies directed against a 18-kDa protein on WB. Reactivation of latent disease occurred just before the second episode of fever. The diagnosis of VL was confirmed by the isolation of numerous Leishmania amastigotes in the bone marrow aspirate and in peripheral blood after leukocyte concentration. Culture of bone marrow yielded Leishmania promastigotes, and isoenzymatic characterization identified Leishmania infantum MON-1 (WHO Collaborative Centre, Montpellier, France). Review of bone marrow aspirates performed at weeks 71 and 87 weeks post transplantation showed rare amastigotes, previously undiagnosed. Analysis of donor and recipient pretransplant sera by WB revealed no Leishmania-specific antibodies, and detection of parasite DNA by PCR analysis in peripheral blood was negative, prior to transplantation in both individuals. Treatment consisted in a 22 mg/kg total dose of liposomal amphotericin B (4 mg/kg from day 1 to day 5 and 2 mg/kg at day 12: the last dose was reduced due to treatment-related renal failure). Fever ceased on day 3 of therapy and detection of parasite DNA by PCR analysis in peripheral blood was negative after the end of treatment. The next 14 months of follow-up were uneventful.

Table 1 Clinical course
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Authors and Affiliations

  1. Hematology Department, Centre Hospitalier, Universitaire de Nice, Hôpital l'Archet 1, 151 route de Saint-Antoine de Ginestière, BP 3079, Nice, 06202 Cedex 3, France

    A Sirvent-von Bueltzingsloewen, E Rosenthal, N Gratecos & J P Cassuto

  2. Laboratory of Parasitology-Mycology, Centre Hospitalier, Universitaire de Nice, France

    P Marty & P Delaunay

  3. Laboratory of Immunology, Centre Hospitalier, Universitaire de Nice, France

    A Allieri-Rosenthal

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Sirvent-von Bueltzingsloewen, A., Marty, P., Rosenthal, E. et al. Visceral leishmaniasis: a new opportunistic infection in hematopoietic stem-cell-transplanted patients. Bone Marrow Transplant 33, 667–668 (2004). https://doi.org/10.1038/sj.bmt.1704396

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