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Cardiac tamponade potentially related to sirolimus following cord blood transplantation

Bone Marrow Transplantation volume 47, pages 294–295 (2012)Cite this article

We present the case of a 28-year-old female patient with advanced myelodysplastic syndrome. Her BM examination at diagnosis showed the presence of 16% blasts and multi-lineage dysplasia, findings consistent with refractory anemia with excess blasts-2 (RAEB-2). Cytogenetic analysis revealed a deletion 5q and the rare translocation t(3;12)(q26;p13) with rearrangement of the ecotropic viral integration-1 gene (EVI1) by FISH. An allogeneic hematopoietic SCT (HSCT) was considered to be urgent due to the high-risk nature of her disease. Unfortunately, neither a family nor a matched unrelated donor was available. We therefore decided to proceed with a cord blood transplantation from a 6/6 HLA-matched donor. The unit contained a total nucleated cell dose of 3.87 × 107/kg; both donor and recipient were seronegative for CMV. The preparative regimen included fractioned TBI (12 Gy), CY (120 mg/kg) given over two days and fludarabine (75 mg/m2) in three doses. GVHD prophylaxis consisted of tacrolimus (beginning on day −3) and mycophenolate mofetil (as of day +1).

The patient developed acute headache and systolic hypertension during graft infusion. She seized 2 h later and was subsequently transferred to the intensive care unit for further investigation and monitoring. Magnetic resonance imaging of the brain showed multiple white matter lesions, compatible with posterior reversible encephalopathy syndrome. GVHD prophylaxis with tacrolimus was stopped as this drug was suspected to contribute to the formation of the lesions.1 Sirolimus was used as replacement (loading dose of 12 mg, followed by daily oral intake aiming at blood trough levels of 8–12 ng/L). On day +19, a chest CT scan performed for investigation of neutropenic fever showed a small pericardial effusion. In the subsequent days, the patient developed signs of rapidly progressive cardiac tamponade, necessitating pericardiocentesis, which was performed on day +28. A volume of 350 mL of straw-colored clear fluid was drained. Analysis of pericardial fluid was compatible with a transudate (pericardial fluid LDH/serum LDH ratio <0.6). The differential cell count showed 70% mesothelial cells, 26% monocytes, 1% lymphocytes and 3% polymorphonuclear cells. Cytology was negative for malignant cells, as well as gram stain and cultures. On day +35, symptoms of tamponade recurred. A second urgent pericardiocentesis was repeated and 600 mL of fluid was drained. Once again, analysis of the cardiac effusion specimen was consistent with a transudate. Methylprednisolone was introduced at a dose of 50 mg/day because of the possibility of immune-mediated capillary leak syndrome. Sirolimus was discontinued simultaneously because of suspected contribution to the pericardial effusion. Because of persistent cytopenias and fever, peripheral blood PCR for human herpesvirus 6 (HHV-6) was performed and found to be positive at a level of 1.3 × 104 copies/mL, whereas pericardial fluid PCR results for HHV-6 were found to be positive at 2.43 × 105 copies/mL. Antiviral therapy with foscarnet (45 mg/kg i.v. every 8 h for 12 days) was introduced three days after discontinuation of sirolimus for treatment of HHV-6 infection. This was done in an effort to treat all possible causes of recurrent pericardial effusion in the face of clinical deterioration of the patient's condition. The patient improved dramatically; there was no further pericardial fluid re-accumulation as demonstrated by serial cardiac echographies.

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References

  1. Wong R, Beguelin GZ, de Lima M, Giralt SA, Hosing C, Ippoliti C et al. Tacrolimus-associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation. Br J Haematol 2003; 122: 128–134.

    Article  CAS  PubMed  Google Scholar 

  2. Hoit BD . Pericardial disease and pericardial tamponade. Crit Care Med 2007; 35 (8 Suppl): 355–364.

    Article  Google Scholar 

  3. Norkin M, Ratanatharathorn V, Ayash L, Abidi MH, Al-Kadhimi Z, Lum LG et al. Large pericardial effusion as a complication in adults undergoing SCT. Bone Marrow Transplant 2011; 46: 1391–1392.

    Article  Google Scholar 

  4. Seber A, Khan SP, Kersey JH . Unexplained effusions: association with allogeneic bone marrow transplantation and acute or chronic graft-versus-host disease. Bone Marrow Transplant 1996; 17: 207–211.

    CAS  PubMed  Google Scholar 

  5. Chevallier P, Hebia-Fellah I, Planche L, Guillaume T, Bressolette-Bodin C, Coste-Burel M et al. Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source. Bone Marrow Transplant 2010; 45: 1204–1211.

    Article  CAS  PubMed  Google Scholar 

  6. Sashihara J, Tanaka-Taya K, Tanaka S, Amo K, Miyagawa H, Hosoi G et al. High incidence of human herpesvirus 6 infection with a high viral load in cord blood stem cell transplant recipients. Blood 2002; 100: 2005–2011.

    CAS  Google Scholar 

  7. Steele GH, Adamkovic AB, Demopoulos LA, Rothrock LC, Caulfield ME, Blum MD et al. Pericardial effusion coincident with sirolimus therapy: a review of Wyeth's safety database. Transplantation 2008; 85: 645–647.

    Article  CAS  PubMed  Google Scholar 

  8. Montalbano M, Neff GW, Yamashiki N, Meyer D, Bettiol M, Slapak-Green G et al. A retrospective review of liver transplant patients treated with sirolimus from a single center: an analysis of sirolimus-related complications. Transplantation 2004; 78: 264–268.

    Article  CAS  PubMed  Google Scholar 

  9. Cutler C, Stevenson K, Kim HT, Brown J, McDonough S, Herrera M et al. Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis. Bone Marrow Transplant 2011; 46: 659–667.

    Article  CAS  PubMed  Google Scholar 

  10. Cutler C, Antin JH . Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: an update. Curr Opin Hematol 2010; 17: 500–504.

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Hemato-Oncology, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada

    A Holbro, I Ahmad, L Busque, S Cohen, S Lachance, D C Roy, J Roy, G Sauvageau & T Kiss

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  1. A Holbro
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Correspondence to T Kiss.

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Holbro, A., Ahmad, I., Busque, L. et al. Cardiac tamponade potentially related to sirolimus following cord blood transplantation. Bone Marrow Transplant 47, 294–295 (2012). https://doi.org/10.1038/bmt.2011.44

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