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HLA-mismatched CD34-selected stem cell transplant complicated by HHV-6 reactivation in the central nervous system

Abstract

We report here a patient who suffered from PCR- confirmed human herpesvirus type 6 (HHV-6) meningoencephalitis after allogeneic purified CD34+ cell transplantation from his HLA-mismatched sibling donor, even though he had been on intense prophylaxis with i.v. ganciclovir (GCV), acyclovir (ACV) and γ-globulin containing a specific antibody against HHV-6. Serological evaluation disclosed that both the donor and recipient had IgG antibody against HHV-6 before transplantation. His blood WBC count started to transiently increase on day 10, and all blood components had decreased by day 20. He then developed a severe headache and high blood pressure, and sporadic abnormal neurological findings including nystagmus and delirium. An analysis of cerebrospinal fluid (CSF) revealed 8 cells/μl, a glucose level of 130 mg/dl and a protein level of 201 mg/dl (normal, 50 mg/dl) on day 26. At the time, HHV-6 was detected only in CSF by a PCR-based method and he was diagnosed as having meningoencephalitis due to the local reactivation of HHV-6. Although he failed to respond to high-dose therapy with ACV (60 mg/kg/day) and γ-globulin, the DNA of this virus disappeared from the CNS upon treatment with GCV (30 mg/kg/day) combined with the intraventricular infusion of α-interferon. His clinical course was further complicated with meningoencephalitis due to staphylococcus epidermidis, and he died of tentorial herniation on day 79 without the recovery of blood components. This experience may indicate that intense prophylaxis to prevent reactivation of HHV-6 in the CNS is essential for the management of such profoundly immunosuppressed patients. Bone Marrow Transplantation (2000) 25, 787–790.

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References

  1. Walters MC, Sullivan KM, Bernaudin F et al. Neurologic complications after allogeneic marrow transplantation for sickle cell anemia Blood 1995 85: 879–884

    CAS  PubMed  Google Scholar 

  2. Gallardo D, Ferra C, Berlanga JJ et al. Neurologic complication after allogeneic bone marrow transplantation Bone Marrow Transplant 1996 18: 1135–1139

    CAS  PubMed  Google Scholar 

  3. Yoshikawa T, Suga S, Asano Y et al. Human herpes virus-6 infection in bone marrow transplantation Blood 1991 78: 1381–1384

    CAS  PubMed  Google Scholar 

  4. Carrigan DR, Drobyski WR, Russler SK et al. Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation Lancet 1991 338: 147–149

    Article  CAS  Google Scholar 

  5. Cone RW, Hackman RC, Hunag M-LW et al. Human herpesvirus 6 in lung tissue from patients with pneumonitis after bone marrow transplantation New Engl J Med 1993 329: 156–161

    Article  CAS  Google Scholar 

  6. Drobyski WR, Dunne WM, Burd EM et al. Human herpesvirus-6 (HHV-6) infection in allogeneic bone marrow transplant recipients: evidence of a marrow-suppressive role for HHV-6 in vivo J Infect Dis 1993 167: 735–739

    Article  CAS  Google Scholar 

  7. Drobyski WR, Knox KK, Majewski D et al. Brief report: fatal encephalitis due to variant B human herpesvirus-6 infection in a bone marrow transplantation recipient New Engl J Med 1994 330: 1356–1360

    Article  CAS  Google Scholar 

  8. Krueger GR, Klueppelberg U, Hoffmann A et al. Clinical correlates of infection with human herpesvirus-6 In Vivo 1994 8: 457–485

    CAS  PubMed  Google Scholar 

  9. Kawano Y, Takaue Y, Watanabe A et al. Partially mismatched pediatric transplants with allogeneic CD34+ blood cells from a related donor Blood 1998 92: 3123–3130

    CAS  PubMed  Google Scholar 

  10. Takaue Y, Kawano Y, Abe T et al. Collection and transplant of peripheral blood stem cells in very small children weighing 20kg or less Blood 1995 86: 372–380

    CAS  PubMed  Google Scholar 

  11. Krueger GRF, Koch B, Leyssens N et al. Comparison of seroprevalences of human herpesvirus-6 and -7 in healthy blood donors from nine countries Vox Sang 1998 75: 193–197

    Article  CAS  Google Scholar 

  12. Drobyski WR, Eberle M, Majewski D et al. Prevalence of human herpesvirus 6 variant A and B infections in bone marrow transplant recipients as determined by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization J Clin Microbiol 1993 31: 1515–1520

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Miyazaki M, Hashimoto T, Fujino K et al. Apparent response of subacute sclerosing panencephalitis to intrathecal interferon alpha Ann Neurol 1991 29: 97–99

    Article  CAS  Google Scholar 

  14. Aversa F, Tabilio A, Velardi A et al. Treatment of high-risk acute leukemia with T cell-depleted stem cells from related donors with one fully mismatched HLA haplotype New Engl J Med 1998 339: 1186–1193

    Article  CAS  Google Scholar 

  15. Henslee-Downey PJ, Parrish RS, Macdonald JS et al. Combined in vitro T lymphocyte depletion for the control of graft-versus-host disease following haploidentical marrow transplant Transplantation 1996 61: 738–745

    Article  CAS  Google Scholar 

  16. Quinones RR, Gutierrez RH, Dinndorf PA et al. Extend-cycle elutriation adjust T-cell content in HLA-disparate bone marrow transplantation Blood 1993 82: 307–317

    CAS  PubMed  Google Scholar 

  17. Marmont AM, Horowitz MM, Gale RP et al. T-cell depletion of HLA-identical transplantation in leukemia Blood 1991 78: 2120–2130

    CAS  PubMed  Google Scholar 

  18. Bacigalupo A, Mordini N, Pitto A et al. Transplantation of HLA-matched CD34+ selected cells in patients with advanced malignancies: severe immunodeficiency and related complications Br J Haematol 1997 98: 760–766

    Article  CAS  Google Scholar 

  19. Matsuda Y . Allogeneic peripheral blood stem cell transplantation using positively selected CD34-positive cells from mismatched donors Bone Marrow Transplant 1998 21: 355–360

    Article  CAS  Google Scholar 

  20. Yanagihara K, Tanaka T, Itagaki Y et al. Human herpes virus meningoencephalitis with sequelae Pediatr Infect Dis J 1995 14: 240–242

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the nursing staff of the pediatric ward at the University Hospital of Tokushima for their excellent care.

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Kawano, Y., Miyazaki, T., Watanabe, T. et al. HLA-mismatched CD34-selected stem cell transplant complicated by HHV-6 reactivation in the central nervous system. Bone Marrow Transplant 25, 787–790 (2000). https://doi.org/10.1038/sj.bmt.1702220

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