Severe hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone developed as initial manifestation of human herpesvirus‐6–associated acute limbic encephalitis after unrelated bone marrow transplantation

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo‐SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus‐6–associated post‐transplantation acute limbic encephalitis (HHV‐6 PALE) after allo‐SCT. A 45‐year‐old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus‐mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV‐6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV‐6 PALE, and close monitoring of serum sodium levels in high‐risk patients for HHV‐6 PALE is necessary for immediate diagnosis and treatment initiation.     

Retrospective case analysis of antiviral therapies for HHV‐6 encephalitis after hematopoietic stem cell transplantation

Human herpesvirus 6 (HHV‐6) is one of the most common causes of encephalitis in allogeneic hematopoietic stem cell transplant (HCT) recipients and is associated with significant morbidity and mortality. There are no FDA‐approved treatments specifically for HHV‐6 encephalitis; HHV‐6 disease is typically treated with CMV antivirals. A review of antiviral medications used to treat HHV‐6 encephalitis was conducted by aggregating data from case reports found on PubMed. Articles were included if they examined at least one HCT patient diagnosed with HHV‐6 encephalitis and described their treatment course and outcome. Key data were abstracted from 123 cases described in 52 studies. The proportion of patients with encephalitis who died or developed sequelae was 63.6% among ganciclovir monotherapy recipients (n = 44), 55.3% among foscarnet monotherapy recipients (n = 47), and 37.5% among recipients of combination therapy with foscarnet and ganciclovir (n = 32). Logistic regression revealed that recipients of foscarnet (OR 4.286, 95% CI 1.235‐14.877, P = .022) and ganciclovir (OR 5.625, 95% CI 1.584‐19.975, P = .008) monotherapies were more likely to develop sequelae compared to recipients of combination therapy, respectively. In multivariate analyses, non‐cord blood transplant was identified as an independent risk factor for developing sequelae after receiving ganciclovir monotherapy (OR 5.999, 95% CI 1.274‐28.254, P = .023). There was no difference in mortality between patients who received combination therapy and those who received monotherapy. In conclusion, combination therapy with foscarnet and ganciclovir may reduce sequelae, but not mortality, secondary to HHV‐6 encephalitis.     

Antiviral prophylaxis may prevent human herpesvirus‐6 reactivation in bone marrow transplant recipients

Abstract: Human herpesvirus‐6 (HHV‐6) infects the majority of children under the age of 2 years causing roseola infantum. Following short self‐limited disease, the virus enters into a latency phase in peripheral blood lymphocytes (PBL). It has been previously reported that HHV‐6 reactivation from latency, in immunocompromised patients undergoing bone marrow transplantation (BMT), could result in febrile illness, pneumonitis, meningitis, and/or encephalitis. In our study, 14 BMT patients received two different antiviral prophylactic therapies: 8 patients received acyclovir, whereas 6 patients received ganciclovir. Clinical manifestations and virus recovery were monitored pre‐ and post‐BMT by polymerase chain reaction tests of cord blood cells cultured with the patients' PBL. No HHV‐6 recovery was shown in the 6 patients treated with ganciclovir, whereas 3 of the 8 acyclovir‐treated patients experienced virus reactivation 20–21 days post‐BMT. One of the 3 patients was asymptomatic but had late engraftment; the second patient had prolonged fever, skin rash, and hemorrhage; the third patient experienced prolonged fever, pneumonitis, marrow rejection, and fatal encephalitis. It is concluded that viral reactivation may be prevented by prophylactic treatment with ganciclovir. Our observation awaits further documentation in prospective randomized trials in high‐risk BMT recipients.     

Human herpesvirus 6‐related pure red cell aplasia,secondary graft failure,and clinical severe immune suppression after allogeneic hematopoietic cell transplantation successfully treated with foscarnet

E.D. Lagadinou, M. Marangos, M. Liga, G. Panos, E. Tzouvara, E. Dimitroulia, M. Tiniakou, A. Tsakris, N. Zoumbos, A. Spyridonidis. Human herpesvirus 6‐related pure red cell aplasia, secondary graft failure, and clinical severe immune suppression after allogeneic hematopoietic cell transplantation successfully treated with foscarnet.
Transpl Infect Dis 2010: 12: 437–440. All rights reserved. Abstract: Human herpesvirus 6 (HHV‐6) is frequently detected after allogeneic hematopoietic cell transplantation (allo‐HCT); however, the clinical interpretation of HHV‐6 viremia in a transplant patient is challenging as it may signify asymptomatic reactivation, chromosomal integration of the virus genome in the donor or recipient with no clinical significance, or severe HHV‐6 disease. Here we present a case of HHV‐6 disease after allo‐HCT presenting as pure red cell aplasia, secondary graft failure, and severe immunosuppression causing multiple severe bacterial super‐infections. Examination of pre‐transplant patient and donor samples as well as serial determination of HHV‐6 DNA copy numbers after transplantation were necessary to definitively interpret HHV‐6 viremia as active HHV‐6 infection with a causative role in pancytopenia and immune suppression. Foscarnet treatment resulted both in viral load decline and disappearance of HHV‐6‐related bone marrow suppression and predisposition to severe infections. Clinicians should be aware of the wide array of clinical manifestations and the diagnostic pitfalls of post‐transplant HHV‐6 disease. These issues are extremely challenging, as they may result either in dangerous underestimation of HHV‐6 disease or in the institution of unnecessary antiviral therapy. Late bone marrow aplasia and late severe infections after allo‐HCT without other obvious causes may be HHV‐6 related.     

No indication of increased infection rates using low‐dose alemtuzumab instead of anti‐thymocyte globulin as graft‐versus‐host disease prophylaxis before allogeneic stem cell transplantation

Background

Alemtuzumab as part of the conditioning protocol is effective in reducing graft‐versus‐host disease (GvHD), but may be associated with increased infection rates, especially when using high doses (ie, 100 mg).

Methods

We performed a retrospective, single‐center, case‐control study analyzing the rates of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein‐Barr virus (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human herpesvirus‐6 (HHV6) infection using low‐dose alemtuzumab in comparison with anti‐thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell transplantation. Forty‐four patients transplanted from unrelated donors between 2001 and 2012 were matched by age, diagnosis, and conditioning regimen and treated either with alemtuzumab 10 mg at day ?2 (respectively, 20 mg in case of mismatch transplantation) or ATG. ATG Fresenius (10 mg/kg for 3 days) or Thymoglobulin (2 mg/kg for 3 days) were used.

Results

Rates of CMV reactivation, EBV reactivation, and clinical manifest HHV6 infection or toxoplasmosis did not differ significantly between both groups until 2 years after transplantation. No case of post‐transplant lymphoproliferative disorder was observed. Also, rates of neutropenic fever during inpatient treatment after transplantation did not differ significantly in both groups.

Conclusion

We saw no indication of increased infections rates when using low‐dose alemtuzumab as GvHD prophylaxis before allogeneic stem cell transplantation in this retrospective analysis.     

Viral load and ganciclovir (GCV) concentration in cerebrospinal fluid of patients successfully treated with GCV or valGCV for human herpesvirus 6 encephalitis/myelitis following umbilical cord blood transplantation

We describe successful treatment of 3 cases of human herpesvirus 6 (HHV‐6) encephalitis/myelitis following cord blood transplantation (CBT). Ganciclovir (GCV) (10 mg/kg/day) reduced HHV‐6 load to undetectable levels in cerebrospinal fluid (CSF). Early dose reduction in the presence of HHV‐6 detectable in CSF resulted in an increased HHV‐6 load. GCV was capably shifted to valganciclovir (VGCV) with an almost equivalent concentration. GCV/VGCV may be effective for HHV‐6 encephalitis/myelitis after CBT, although HHV‐6 load in CSF should be monitored.     

Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation

The present study compared foscarnet with ganciclovir for preemptive therapy of cytomegalovirus (CMV) infection after allogeneic blood or marrow stem cell transplantation (SCT). Patients with CMV infection, as detected by weekly antigenemia or polymerase chain reaction (PCR) in blood leukocytes, were randomized to intravenous therapy for 2 weeks with either foscarnet at 60 mg/kg or ganciclovir at 5 mg/kg administered every 12 hours; if CMV infection remained detectable, patients received an additional 2 weeks of intravenous foscarnet at 90 mg/kg or ganciclovir at 6 mg/kg given once daily for 5 days per week, after which therapy was stopped. Primary efficacy endpoint was the occurrence of CMV disease or death from any cause within 180 days after SCT. A total of 213 patients were treated with either foscarnet (n = 110) or ganciclovir (n = 103). Kaplan-Meier estimates of event-free survival within 180 days after SCT were similar in the 2 treatment groups (P =.6). During study treatment, severe neutropenia (< 0.5 x 10(9)/L) occurred in 11 (11%) patients on ganciclovir versus 4 (4%) patients on foscarnet (P =.04), and impaired renal function was observed in 5 (5%) patients on foscarnet versus 2 (2%) patients on ganciclovir (P =.4). Neutropenia or thrombocytopenia required discontinuation of ganciclovir in 6 (6%) patients but in no foscarnet-treated patient (P =.03). After allogeneic SCT, preemptive therapy of CMV infection with foscarnet shows similar efficacy as with ganciclovir, but is associated with a lower proportion of patients who develop severe neutropenia and who require discontinuation of antiviral therapy due to hematotoxicity.     

Transmission of chromosomally integrated human herpesvirus 6 via cord blood transplantation

Chromosomally integrated human herpesvirus 6 (ciHHV‐6) can be transmitted via allogeneic hematopoietic cell transplantation. To date, only a few cases have been reported. Here, we report a case identified as transmission of ciHHV‐6 via cord blood transplantation. Distinguishing transmission of ciHHV‐6 from HHV‐6 reactivation in cases with high titer of HHV‐6 DNA load after transplantation is important to prevent unnecessary exposure to antiviral drugs that could be toxic.     

Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching,anti‐thymocyte globulin,and total body irradiation are additive risk factors

C. Kullberg‐Lindh, K. Mellgren, V. Friman, A. Fasth, H. Ascher, S. Nilsson, M. Lindh. Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching, anti‐thymocyte globulin, and total body irradiation are additive risk factors.
Transpl Infect Dis 2011: 13: 122–130. All rights reserved Abstract: Viral opportunistic infections remain a threat to survival after stem cell transplantation (SCT). We retrospectively investigated infections caused by cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus type 6 (HHV6), or adenovirus (AdV) during the first 6–12 months after pediatric SCT. Serum samples from 47 consecutive patients were analyzed by quantitative real‐time polymerase chain reaction assay. DNAemia at any time point occurred for CMV in 47%, for EBV in 45%, for HHV6 in 28%, and for AdV in 28%. Three patients (6.3%) died of CMV‐, EBV‐, or AdV‐related complications 4, 9, and 24 weeks after SCT, respectively, representing 21% of total mortality. These 3 cases were clearly distinguishable by DNAemia increasing to high levels. Serum positivity for CMV immunoglobulin G in either recipient or donor at the time of SCT, total body irradiation, and anti‐thymocyte globulin conditioning were independent risk factors for high CMV or EBV DNA levels. We conclude that DNAemia levels help to distinguish significant viral infections, and that surveillance and prophylactic measures should be focused on patients with risk factors in whom viral complications rapidly can become fatal.     

Fatal Fulminant Hepatitis B after Withdrawal of Prophylactic Lamivudine in Hematopoietic Stem Cell Transplantation Patients

Hepatitis B virus (HBV) reactivation can give rise to acute hepatitis and even fatal fulminant hepatitis in patients receiving immunosuppressive or cytostatic treatment. Recently, the prophylactic use of lamivudine for HBV reactivation in HBV surface antigen-positive chronic-disease patients undergoing hematopoietic stem cell transplantation (HSCT) has been reported. However, the appropriate duration for this prophylactic therapy is unclear. Here, we report 2 cases of fatal fulminant hepatitis B reactivation in HSCT patients after lamivudine withdrawal. One patient with non-Hodgkin's lymphoma completed 6 courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) and autologous peripheral blood SCT (PBSCT). Lamivudine was discontinued 3 months after transplantation. The second patient had acute myeloid leukemia. He received induction chemotherapy and postremission allogeneic PBSCT as late intensified consolidation therapy. Lamivudine treatment was discontinued 10 months after transplantation. In both patients, HBV reactivation 2 to 3 months following lamivudine cessation led to fatal fulminant hepatitis. We suggest that the duration of prophylactic use of lamivudine in chronic HBV carriers receiving HSCT be prolonged until the patient's immune system has been reconstituted.     

Human herpesvirus 6 DNA in plasma after allogeneic stem cell transplantation: incidence and clinical significance

BACKGROUND: Human herpesvirus 6 (HHV-6) is increasingly recognized as an opportunistic and potentially life-threatening pathogen in recipients of allogeneic stem cell transplants (SCTs). METHODS: To clarify the incidence and clinical relevance of active HHV-6 infection, serial titers of plasma HHV-6 DNA were determined for 50 allogeneic SCT recipients, using real-time polymerase chain reaction. RESULTS: HHV-6 DNA was detected in plasma from 24 patients (48%). HHV-6 DNA was most frequently apparent approximately 14-27 days after transplantation. An increased risk of a positive result for HHV-6 DNA was associated with transplantation from an allelic-mismatch donor (P = .02) and administration of steroids (P = .04). Steroid use was associated with high HHV-6 DNA loads (P = .02). High HHV-6 DNA loads were correlated with delayed platelet engraftment (P = .04). Among patients who had positive results for HHV-6 DNA, the HHV-6 DNA load was higher in plasma from those who developed limbic encephalitis (n = 4) (P < .0001). CONCLUSIONS: Active HHV-6 infection is not rare in SCT recipients. SCT from allelic-mismatch donors is associated with increased risk of active HHV-6 infection. Steroid therapy is associated with not only increased incidence of infection but also accelerated viral replication. Development of limbic encephalitis is associated with high HHV-6 DNA load.     

Human herpesvirus‐6 as an inducer of porphyria cutanea tarda: implications from a case

T. Weber, S. Theurich, M. Christopeit, T. Klapperstueck, G. Behre. Human herpesvirus‐6 as an inducer of porphyria cutanea tarda: implications from a case.
Transpl Infect Dis 2010: 12: 432–436. All rights reserved Abstract: Here we describe a case that might deliver a link between sporadic porphyria cutanea tarda (PCT) and human‐herpesvirus‐6 (HHV6) hepatitis. Sporadic PCT is a rare disease of the heme synthesis pathway. The pathogenesis has not been fully determined but iron overload and viral infections – e.g., hepatitis C virus – are thought to play an important role. We present the case of a patient suffering from myelo‐monocytic leukemia. He developed symptomatic sporadic PCT concomitant with HHV6‐associated subclinical hepatitis after allogeneic stem cell transplantation (SCT). Although HHV6 often reactivates after SCT and HHV6‐induced hepatitis can occur in immunocompromised patients, it has not been described that HHV6 might trigger PCT. A contribution of HHV6 to the pathogenesis of sporadic PCT could have dramatic implications on our current therapeutic approach.     

Valacyclovir for the prevention of cytomegalovirus infection after allogeneic stem cell transplantation: a single institution retrospective cohort analysis

A retrospective single center study was performed to evaluate the safety and efficacy of valacyclovir for prevention of cytomegalovirus (CMV) infection (reactivation) after allogeneic stem cell transplantation (SCT). We compared a group of 31 patients at risk for CMV reactivation (donor, recipient or both seropositive for CMV) who received valacyclovir at an oral dose of 1 g three times a day for CMV prophylaxis with a matched cohort of 31 patients who did not receive the drug or any other form of CMV prophylaxis. Valacyclovir was used as primary prophylaxis in 12 patients and as secondary prophylaxis (after a prior CMV reactivation was effectively treated with either ganciclovir or foscarnet and without CMV antigenemia at the start of valacyclovir) in the remaining 19 patients. The two treatment groups were well matched for the donor-recipient CMV serological status and other pre-transplant characteristics. CMV reactivation was detected by blood antigenemia testing using a commercially available immunofluorescence assay for CMV lower matrix protein pp65 in circulating leukocytes. For primary prophylaxis, 3/12 patients who received valacyclovir reactivated CMV compared to 24/31 patients in the control group (P < 0.001). For secondary prophylaxis, 5/19 valacyclovir patients reactivated compared to 16/24 control patients (P < 0.05). Valacyclovir was well tolerated except for infrequent and mild gastrointestinal side-effects. There was no difference in the incidence of CMV disease in the two groups. Prophylaxis with valacyclovir appears to be safe and efficacious in preventing both primary and secondary CMV reactivation in at-risk patients after allogeneic SCT. Larger prospective randomized studies will be required to confirm these observations.     

HHV‐6 in liver transplantation: A literature review

Human herpesvirus 6 (HHV‐6A and HHV‐6B) can cause primary infection or reactivate from latency in liver transplant recipients, which can result in a variety of clinical syndromes, including fever, hepatitis, encephalitis and higher rates of graft dysfunction as well as indirect effects including increased risks of mortality, CMV disease, hepatitis C progression and greater fibrosis scores. Although HHV‐6 infection is currently diagnosed by quantifying viral DNA in plasma or blood, biopsy to demonstrate histopathological effects of HHV‐6 remains the gold standard for diagnosis of end‐organ disease. HHV‐6 reactivation may be restricted to the infected organ with no evidence of active infection in the blood. HHV‐6 infections in liver transplant patients are mostly asymptomatic, but clinically significant tissue‐invasive infections have been treated successfully with ganciclovir, foscarnet or cidofovir. Inherited chromosomally integrated HHV‐6 (ciHHV‐6), in either the recipient or the donor organ, may create confusion about systemic HHV‐6 infection. Recipients with inherited ciHHV‐6 may have an increased risk of opportunistic infection and graft rejection. This article reviews the current scientific data on the clinical effects, risk factors, pathogenesis, diagnosis and treatment of HHV‐6 infections in liver transplant recipients.     

Human herpesvirus (HHV)-6 and HHV-7: two closely related viruses with different infection profiles in stem cell transplantation recipients

Human herpesvirus (HHV)-6 and HHV-7 loads were evaluated retrospectively in peripheral blood mononuclear cells (PBMC) from 78 recipients of stem cell transplantation (SCT) by real-time polymerase chain reaction. The median HHV-6 load in patients was 1357 genome equivalent copies (EqCop)/10(6) PBMC but was below the quantitation threshold in 31 immunocompetent individuals, which strongly suggests that HHV-6 reactivation occurred after SCT. The HHV-6 load was higher in patients with delayed neutrophil engraftment (P=.002) or severe graft-versus-host disease (P=.009). Moreover, the occurrence of at least 1 HHV-6-related manifestation (fever, cutaneous rash, pneumonitis, or partial myelosuppression) was statistically associated with a concomitant virus load >10(3) EqCop/10(6) PBMC (P=.007). Conversely, HHV-7 reactivation was not favored, because median HHV-7 loads were similar in patients and healthy control subjects (1053 vs. 1216 EqCop/10(6) PBMC). The kinetics of Roseolovirus loads during the posttransplantation period suggested that HHV-7 may act as a cofactor of HHV-6 reactivation.     

Transmission of chromosomally integrated human herpesvirsus 6 (HHV‐6) variant A from a parent to children leading to misdiagnosis of active HHV‐6 infection

Abstract: Only a handful of cases of chromosomally integrated human herpesvirus 6 (CI‐HHV‐6) have been reported, suggesting that this phenomenon is rare. We here present a familial case of HHV‐6 variant A (HHV‐6A) transmission through a generation, which was identified in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). A 31‐year‐old man with myelodysplastic syndrome underwent allogeneic HSCT from a human leukocyte antigen‐identical sibling, and was found to be continuously yielding high copy numbers of HHV‐6A DNA in plasma evaluated by real‐time polymerase chain reaction (PCR). Antiviral therapy with ganciclovir or foscarnet failed to decrease the copy numbers. HHV‐6A DNA was detected in the patient's buccal mucosa and hair follicles, and was also detected in the plasma, whole blood, and buccal mucosa of the patient's father and 2 siblings, but not in his mother. The sequences of HHV‐6A DNA isolated from all family members were identical. Since monitoring of HHV‐6 by PCR has been widely introduced to the field of HSCT, transplant physicians should be aware of such an alternative form of HHV‐6 transmission, particularly when HHV‐6A is detected.     

Encephalitis caused by human herpesvirus‐6B in pancreas‐after‐kidney transplantation

Human herpesvirus‐6 (HHV‐6) is a common pathogen among children, classically presenting with fever and rash that resolves without specific therapy. HHV‐6 can be reactivated in the immunosuppressed patient. After bone marrow and solid organ transplantation, HHV‐6 has been linked to various clinical syndromes, including undifferentiated febrile illness, encephalitis, myelitis, hepatitis, pneumonitis, and bone marrow suppression. However, HHV‐6 encephalitis after pancreatic transplant has rarely been reported. Early diagnosis and treatment of HHV‐6 encephalitis may be important for affected patients. We report the case of a 53‐year‐old pancreas‐after‐kidney transplant recipient who initially presented with high fever and confusion 3 weeks after operation. We managed to save the patient's life and preserve the pancreas graft function. We also review previously reported cases of HHV‐6B encephalitis in solid organ transplant recipients.     

Absence of early HHV‐6 reactivation after cord blood allograft predicts powerful graft‐versus‐tumor effect

Approximately 75% of cord blood transplant (CBT) recipients experience human herpes virus‐6 (HHV‐6) reactivation. Considering the immunomodulatory effects of HHV‐6, we hypothesized that early HHV‐6 reactivation may influence the risk of relapse of the underlying hematologic malignancy. In 152 CBT recipients with hematological malignancies, we determined the association between HHV‐6 reactivation by day +28 and 2‐year cumulative incidence of relapse. In univariate analysis, the absence of HHV‐6 reactivation (n = 32) was associated with less relapse (26 [18‐35]% vs. 7 [0‐17]% in groups with vs. without HHV‐6 reactivation, respectively; P = .03). This difference was due to a remarkably low relapse incidence among patients without HHV‐6 reactivation. In multivariable analysis, the absence of HHV‐6 reactivation was associated with less relapse (hazard ratio [95% confidence interval]: 0.2 [0.05‐0.9], P = .03). This association was independent of patient‐, disease‐, and transplant‐related characteristics known to influence the risk of relapse. Natural killer cell and T‐cell reconstitution at day +28 were similar between patients with vs. without HHV‐6 reactivation. Our results suggest that CB allografts not complicated by HHV‐6 reactivation by day +28 have a powerful graft‐versus‐tumor effect. Knowledge about early HHV‐6 reactivation may stratify patients at day +28 into low vs. high relapse risk groups.     

Human herpesvirus 6B encephalitis in a liver transplant recipient: A case report and review of the literature

Human herpesvirus 6B (HHV‐6B) encephalitis in a liver transplant recipient is rarely reported. In this report, we presented a case of HHV‐6B encephalitis in a liver transplant recipient and reviewed the relevant literature. A 56‐year‐old man was admitted to the intensive care unit (ICU) with an acute headache and intermittent convulsion 17 days after liver transplantation. Next‐generation sequencing (NGS) of the cerebrospinal fluid (CSF) revealed 30691 sequence reads of HHV‐6B and real‐time polymerase chain reaction (real‐time PCR) of the CSF detected HHV‐6B DNA at 12 000 copies/mL, so the patient was diagnosed with HHV‐6B encephalitis and received ganciclovir treatment promptly. The condition of the patient improved well and returned to the general ward with no neurologic deficits. This case indicated that adequate awareness, early diagnosis, and timely treatment are crucial to a good prognosis of HHV‐6B encephalitis after liver transplantation.     

Foscarnet – an alternative for cytomegalovirus prophylaxis after allogeneic stem cell transplantation?

 Cytomegalovirus (CMV) disease is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT) and is associated with high morbidity and mortality. Early detection of the disease by antigenemia testing and polymerase chain reaction (PCR) along with pre-emptive antiviral therapy has been shown to be very effective in decreasing the incidence of CMV. We performed an uncontrolled observational study in 21 patients after HSCT (14 related, 7 unrelated donors) to evaluate the efficacy and toxicity of foscarnet administered as prophylaxis for CMV reactivation. Ten patients received bone marrow, and eleven patients received peripheral blood stem cells. All patients received foscarnet prophylaxis to study side effects, incidence of CMV reactivation, CMV disease, and transplant-related mortality. Foscarnet (90 mg/kg) was given every 12 h, day +11 to day +16. Thereafter, foscarnet (90 mg/kg) was given once per day, three times per week until day +60. The incidence of CMV reactivation detected by antigenemia (pp65 antigen) or PCR was 23.8% (5 of 21 patients). Two patients developed CMV disease and one patient died of CMV-pneumonia. Seventeen patients (81%) reported severe side effects, such as gastrointestinal disturbance, headache, and urethritis. In eight patients (38%), the dose of foscarnet had to be reduced and, in six patients (28.5%), foscarnet application was discontinued because of side effects. Compared with other groups, we believe that the potential benefit of foscarnet administration in this early setting is outweighed by the risks of severe toxicity. Received: 24 June 1999 / Accepted: 25 February 2000