Human Herpesvirus 6 Viremia in Bone Marrow Transplant Recipients: Clinical Features and Risk Factors

Yoshikawa, Tetsushi; Asano, Yoshizo; Ihira, Masaru; Suzuki, Kyoko; Ohashi, Masahiro; Suga, S.; Kudo, Kazuko; Horibe, Keizo; Kojima, Seiji; Kato, Koji; Matsuyama, Takaharu; Nishiyama, Yukihiro

doi:10.1086/339411

Cited by 161 publications

(139 citation statements)

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“…Active HHV-6B infection generally occurs only once throughout life (at the time of the primary infection) in immunocompetent individuals, but it may occur several times in transplant recipients (8) or DIHS patients (17). Frequent HHV-6B reactivation, as evidenced by the repeated isolation of the virus during an active viral infection, was observed in hematopoietic stem cell transplant (HSCT) recipients (8,18).…”

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Copy Numbers of Telomeric Repeat Sequences of Human Herpesvirus 6B in Clinical Isolates: Possibility of Mixed Infections

et al. 2014

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In order to determine whether mixed infections of human herpesvirus 6B (HHV-6B) occur in immunocompetent and immunocompromised individuals, we examined the copy numbers of telomeric repeat sequences (TRS) of clinical isolates. In clinical isolates obtained from patients with exanthem subitum caused by primary HHV-6B infection, PCR products with HHV-6B TRS ranging between 400 and 800 bp were amplified. PCR products of various sizes were amplified in four clinical isolates from druginduced hypersensitivity syndrome (DIHS) patients and 15 isolates from hematopoietic stem cell transplant (HSCT) recipients with HHV-6B reactivation. Based on the sequence analysis of the PCR products, the copy numbers of TRS in DIHS and HSCT patients were between 42 and 82 and 22 and >90, respectively. For two of the HSCT recipients, HHV-6B TRS PCR products of different sizes were detected in several isolates from each patient, which suggests mixed HHV-6B infections. In two of the posttransplant HHV-6B encephalitis patients, the sizes of the TRS nested PCR products amplified from the reactivated virus detected in the central nervous system differed from those of the virus detected in initial isolates from peripheral blood mononuclear cells. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for the discrimination of HHV-6B clinical isolates. Additionally, mixed HHV-6B infections occurred in HSCT recipients, and in some cases, compartmentalization of the HHV-6B strains to the central nervous system versus the blood compartment occurred in posttransplant HHV-6B encephalitis patients. Primary human herpesvirus 6B (HHV-6B) infection presenting as exanthem subitum (ES) (1, 2) is considered a benign febrile illness and rarely causes neurological complications, such as febrile convulsion and encephalitis (3, 4). In addition to the primary infection, HHV-6 reactivation may be associated with acute graftversus-host disease (5-8), graft rejection (9), and encephalitis (10-13) in transplant recipients. Moreover, the virus can be reactivated in patients with drug-induced hypersensitivity syndrome (DIHS), which is a severe form of drug allergy that is characterized by fever, skin rash, lymphadenopathy, hepatitis, and leukocytosis (14-16). Active HHV-6B infection generally occurs only once throughout life (at the time of the primary infection) in immunocompetent individuals, but it may occur several times in transplant recipients (8) or DIHS patients (17). Frequent HHV-6B reactivation, as evidenced by the repeated isolation of the virus during an active viral infection, was observed in hematopoietic stem cell transplant (HSCT) recipients (8, 18).Previous reports detected mixed infections with multiple cytomegalovirus (CMV) strains in the same human herpesvirus subfamily (Betaherpesvirinae subfamily) as HHV-6B in a variety of patient populations, including immunocompetent and immunocompromised patients (19)(20)(21)(22). Furthermore, other studies have suggested that the genotype of the virus may be associate...

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Copy Numbers of Telomeric Repeat Sequences of Human Herpesvirus 6B in Clinical Isolates: Possibility of Mixed Infections

et al. 2014

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“…[4][5][6][7] Infantile HSCT recipients may suffer from a primary HHV-6 infection and develop severe skin lesions similar to acute GVHD, as in our patient. Regular surveillance for HHV-6 after HSCT should be mandatory in infant patients who receive CBSCT.…”

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Primary infection of human herpesvirus-6 in an infant who received cord blood SCT

Muramatsu

Watanabe²,

Matsumoto³

et al. 2008

Bone Marrow Transplant

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“…HHV-6 reactivation is more common after allogeneic stem cell transplant (SCT) than ASCT, with reactivation usually occurring 2-3 weeks posttransplant. This is usually asymptomatic or associated with a fever and rash [6,7]. Two HHV-6 variants are recognized (HHV-6A and HHV-6B) with HHV-6B typically found in transplant patients, likely because of its differing pathogenicity [5,6].…”

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confidence: 99%

Thrombotic microangiopathy (TMA) and stroke due to human herpesvirus‐6 (HHV‐6) reactivation in an adult receiving high‐dose melphalan with autologous peripheral stem cell transplantation

et al. 2004

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We report an adult autologous stem cell transplant (ASCT) patient who developed transplant-associated thrombotic microangiopathy (TMA) due to human herpesvirus-6 (HHV-6) reactivation. A 58-year-old female with Stage IIIA IgGk multiple myeloma received a melphalan (200 mg/m 2 ) ASCT with discharge home after resolution of ASCT-related toxicities. She presented on D+20 with dyspnea, rash, and fever to 105°F, followed by worsening dyspnea, hypotension, and capillary leak. Mental status (MS) changes were noted on D+23, but head CT and EEG were unremarkable. On D+29, a generalized seizure occurred with decline in platelet count and haptoglobin. TMA was noted on peripheral blood smear and therapeutic plasma exchange (TPE) was initiated on D+31. Lumbar puncture (LP) revealed CSF protein 74 mg/dL and white blood count 7,000/mm 3 with 74% lymphocytosis. TPE was continued without improvement in her MS or thrombocytopenia despite improvement in microangiopathy. An MRI of the brain showed a left hippocampus abnormality, and an EEG was consistent with encephalopathy. Serum polymerase chain regimen (PCR) was negative for CMV, HSV1, and HSV2 but was strongly positive for HHV-6. Repeat LP protein was 597 mg/dL. Foscarnet was initiated, and cerebrospinal fluid (CSF) PCR for HHV-6 revealed 1,400 DNA copies/mL. Her MS greatly improved within 48 hr of antiviral therapy, serum HHV-6 became negative, and TPE was tapered without recurrence of her TMA. TMA with HHV-6 reactivation is likely an underdiagnosed entity. Given its fulminant course and favorable response to therapy, HHV-6 reactivation should be considered a potential etiology in patients with TMA after ASCT. Am.

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Human Herpesvirus 6 Viremia in Bone Marrow Transplant Recipients: Clinical Features and Risk Factors

Cited by 161 publications

References 35 publications

Copy Numbers of Telomeric Repeat Sequences of Human Herpesvirus 6B in Clinical Isolates: Possibility of Mixed Infections

Copy Numbers of Telomeric Repeat Sequences of Human Herpesvirus 6B in Clinical Isolates: Possibility of Mixed Infections

Primary infection of human herpesvirus-6 in an infant who received cord blood SCT

Thrombotic microangiopathy (TMA) and stroke due to human herpesvirus‐6 (HHV‐6) reactivation in an adult receiving high‐dose melphalan with autologous peripheral stem cell transplantation

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