Biology of Blood and Marrow Transplantation
Volume 13, Issue 7 , Pages 871-872, July 2007

Systemic Toxoplasmosis Post Allogeneic Stem Cell Transplantation (Allo-SCT): Lessons Learned from HIV?

St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF, United Kingdom

published online 10 May 2007.

Article Outline

 

A 51-year-old woman with Imatinib-resistant chronic myelogenous leukemia underwent a reduced-intensity allogeneic-stem cell transplant (Allo-SCT) conditioned with fludarabine 150 mg/m2, melphalan 140 mg/m2 and alemtuzumab 100 mg from an unrelated donor. The graft was unmanipulated and contained 8.3 × 106 cells/kg CD34+ cells. The patient was seropositive for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and toxoplasmosis and seronegative for HBV, HCV, and HIV. The HLA-matched donor was seropositive for CMV and EBV and seronegative for HBV, HCV, HIV, and toxoplasmosis. There was prompt engraftment (neutrophils >0.5 × 109/L and platelets >20 × 109/L on days +15 and +12, respectively) complicated by acute gastrointestinal graft-versus-host disease (GVHD) grade II responsive to high-dose prednisolone. Full donor multilineage lympho-hematopoietic chimerism was achieved by day +60 and the patient was clinically well on a steroid dose-tapering program. Antimicrobial prophylaxis included oral cotrimoxazole 480 mg once daily for 7 days immediately prior to day 0 and from day +28 onward.

The patient’s course post-Allo-SCT was complicated by 5 episodes of CMV reactivation as well as graft failure without evidence of disease recurrence from day +140 onward. In view of pancytopenia, cotrimoxazole was stopped, and she received granuloctye-colony stimulating factor (G-CSF) support. On day +270 the patient was readmitted with fever and symptoms of sepsis. Despite immediate broad-spectrum antimicrobial treatment, she deteriorated rapidly with progressive septic shock and multiorgan failure, and died despite intensive care support 3 days after readmission. Histology of samples obtained at autopsy from the lung, the heart, and the bone marrow revealed disseminated toxoplasmosis (Figure 1). Immune-reconstitution studies revealed poor reconstitution of CD4+ T cells (see Figure 2).

Disseminated toxoplasmosis is a rare complication of Allo-SCT. As the prevalence of seropositivity for toxoplasmosis is variable among countries, toxoplasmosis after Allo-SCT has been reported to occur in <1% in Britain but in 5% in France [1]. Although eliciting an antibody response, the causative intracellular parasite, Toxoplasma gondii, is controlled predominantly by the cellular immune response with a vital role for T cells and Th1 cytokines [2]. Patients who receive alemtuzumab as in vivo T cell depletion or who are seropositive recipients of seronegative cells are particularly at risk of toxoplasmosis reactivation [3]. Nonetheless, no consensus regarding screening the donor recipient pair for toxoplasmosis serostatus prior to transplantation has been reached [4] and a European Group for Blood and Marrow Transplantation survey confirmed that <50% of participating centers routinely determined toxoplasmosis serology in recipients or donors [5]. This is in contrast with practice in the setting of HIV: The Infectious Disease Society of America recommends toxoplasma screening for all HIV+ patients and prophylaxis is advised depending on CD4+ levels: if the CD4+ cells are <100/μL, all patients should receive cotrimoxazole or alternatively dapsone-pyrimethamine or atovaquone [6]. Interestingly, our patient had CD4+ levels <100/ML throughout the whole course after the transplantation (Figure 2). Also of note, when the patient’s condition worsened, she did not take any regular prophylaxis against Toxoplasma gondii. Therefore, this case illustrates the need to assess toxoplasmosis serology pretransplant and to use effective prophylaxis. The analogous situation in HIV+ patients suggests that absolute levels of lymphocyte subsets may be of value in determining the duration of prophylaxis in Allo-SCT patients.

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References 

  1. Mele A, Paterson PJ, Prentice HG, Leoni P, Kibbler CC. Toxoplasmosis in bone marrow transplantation: a report of two cases and systematic review of the literature. Bone Marrow Transplant. 2002;29:691–698
  2. Denkers EY, Gazzinelli RT. Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev. 1998;11:569–588
  3. Lim Z, Baker B, Zuckermann M, et al. Toxoplasmosis following alemtuzumab based allogeneic haematopoietic stem cell transplantation. J Infect. 2007;54:e83–e86
  4. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients (Recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation). Cytotherapy. 2001;3:41–54
  5. Martino R, Bretagne S, Rovira M, et al. Toxoplasmosis after hematopoietic stem transplantation (Report of a 5-year survey from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation). Bone Marrow Transplant. 2000;25:1111–1114
  6. Masur H, Kaplan JE, Holmes KK. Guidelines for preventing opportunistic infections among HIV-infected persons—2002 (Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America). Ann Intern Med. 2002;137(5 Pt 2):435–478

PII: S1083-8791(07)00218-2

doi:10.1016/j.bbmt.2007.03.010

Biology of Blood and Marrow Transplantation
Volume 13, Issue 7 , Pages 871-872, July 2007

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