Late‐onset visceral varicella‐zoster virus infection presented as acute liver failure after allogeneic hematopoietic stem cell transplantation

Although much less common than localized zoster, initial presentation of varicella‐zoster virus (VZV) as visceral infection can occur especially after allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of post‐transplant visceral VZV infection presenting as fatal acute liver failure. It developed 4 years after allogeneic HSCT when a long‐term prophylactic anti‐VZV agent administration was discontinued. VZV should be listed as a causative pathogen of acute liver failure even years after allogeneic HSCT. Indication for, and duration of anti‐VZV prophylaxis should be further investigated.     

Varicella zoster virus meningoencephalitis after allogeneic hematopoietic stem cell transplantation

Although the reactivation of varicella zoster virus (VZV) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), VZV meningoencephalitis is a rare life‐threatening infectious disease after HSCT. We describe here a patient who developed VZV meningoencephalitis 2 years after human leukocyte antigen‐matched unrelated HSCT for acute myeloblastic leukemia. She developed chronic graft‐versus‐host disease, and cyclosporine (CSA) was continued until 17 months after HSCT. Low‐dose acyclovir (ACV) at 200 mg/day was administered to prevent the reactivation of VZV from day ?7 to the termination of CSA. At 22 months, she suddenly developed fever, loss of consciousness, and seizure, with generalized skin rash. A high level of VZV DNA was detected in her cerebrospinal fluid (CSF). She was diagnosed to have VZV meningoencephalitis. Intravenous ACV at 30 mg/kg/day was given for 2 months. Although loss of consciousness was quickly resolved, some neurologic symptoms persisted. She did not have any known risk factors for VZV reactivation. Therefore, we should keep in mind that any HSCT recipient may develop VZV meningoencephalitis, and examination of CSF for VZV infection with an empiric administration of ACV may be recommended for HSCT recipients with central nervous system symptoms, even in the absence of skin manifestations.     

One-year acyclovir prophylaxis for preventing varicella-zoster virus disease after hematopoietic cell transplantation: no evidence of rebound varicella-zoster virus disease after drug discontinuation

No consensus exists on whether acyclovir prophylaxis should be given for varicella-zoster virus (VZV) prophylaxis after hematopoietic cell transplantation because of the concern of "rebound" VZV disease after discontinuation of prophylaxis. To determine whether rebound VZV disease is an important clinical problem and whether prolonging prophylaxis beyond 1 year is beneficial, we examined 3 sequential cohorts receiving acyclovir from day of transplantation until engraftment for prevention of herpes simplex virus reactivation (n = 932); acyclovir or valacyclovir 1 year (n = 1117); or acyclovir/valacyclovir for at least 1 year or longer if patients remained on immunosuppressive drugs (n = 586). In multivariable statistical models, prophylaxis given for 1 year significantly reduced VZV disease (P < .001) without evidence of rebound VZV disease. Continuation of prophylaxis beyond 1 year in allogeneic recipients who remained on immunosuppressive drugs led to a further reduction in VZV disease (P = .01) but VZV disease developed in 6.1% during the second year while receiving this strategy. In conclusion, acyclovir/valacyclovir prophylaxis given for 1 year led to a persistent benefit after drug discontinuation and no evidence of a rebound effect. To effectively prevent VZV disease in long-term hematopoietic cell transplantation survivors, additional approaches such as vaccination will probably be required.     

Long-term ultra-low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation

To evaluate the efficacy of long-term prophylaxis with ultra-low-dose acyclovir against varicella-zoster virus (VZV) reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2006 at our hospital. We started long-term oral acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least 1 year after transplantation. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. Only one breakthrough reactivation occurred during long-term acyclovir, which responded well to therapeutic dose of valacyclovir. The use of long-term acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20% vs. 50%, P < 0.0001). With this prophylaxis, visceral dissemination and serious complications other than post-herpetic neuralgia was completely eliminated, and thereby need for hospitalization was significantly reduced (21% vs. 71%, P = 0.0034). Fifteen of the 57 patients who discontinued acyclovir developed VZV reactivation, with a cumulative incidence of 32.1%. VZV reactivation following discontinuation tended to occur in patients who were receiving immunosuppressive therapy at the cessation of acyclovir. These findings suggested that long-term prophylaxis of ultra-low-dose acyclovir resulted in a successful prevention of severe VZV-related symptoms and death, with a significantly decreased overall incidence of VZV reactivation. Prolongation of prophylactic acyclovir on profound immunosuppression might be important for thorough suppression of VZV reactivation.     

Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation

T. Mori, Y. Nakamura, J. Kato, K. Sugita, M. Murata, K. Kamei, S. Okamoto. Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.
Transpl Infect Dis 2011. All rights reserved Abstract: Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft‐versus‐host disease requiring high‐dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species.     

The effect of low-dose aciclovir on reactivation of varicella zoster virus after allogeneic haemopoietic stem cell transplantation

Patients undergoing haemopoietic stem cell transplants (HSCT) are at high risk of varicella zoster virus (VZV) reactivation, with a significant incidence of dissemination. This study reports a retrospective analysis of 247 allogeneic HSCT recipients receiving anti-viral prophylaxis with low-dose oral aciclovir 400 mg/day, administered until immunosuppression was discontinued and the CD4(+) cell count exceeded 200/mm(3). Viral reactivation was successfully suppressed by aciclovir prophylaxis, with only one case of breakthrough infection. The cumulative incidence of zoster infection at 1 year post transplant was 2% and at 5 years 34%. In all, 64 patients discontinued prophylaxis. Zoster developed in 26 of these, giving a cumulative incidence of infection at 1 year after stopping aciclovir of 39% and at 3 years 44%. Infection occurred in a localised dermatomal distribution in 93% of cases. This supports previous findings that aciclovir prophylaxis prevents early VZV reactivation, although the long-term incidence is not affected as infection occurs once prophylaxis is discontinued. Such infection, however, is mild and localised. This study does not support the idea that use of such low-dose aciclovir regimens reduces the zoster incidence by permitting subclinical reactivation during prophylaxis, and therefore the re-establishment of protective anti-viral immunity.     

In vivo T‐cell depletion with alemtuzumab in allogeneic hematopoietic stem cell transplantation: Combined results of two studies on aplastic anemia and HLA‐mismatched haploidentical transplantation

We evaluated the efficacy of in vivo T‐cell depletion with alemtuzumab in two prospective studies according to the International Conference on Harmonisation (ICH)—Good Clinical Practice (ICH–GCP) guidelines; one was for patients with aplastic anemia (AA study) and the other was for patients who were undergoing hematopoietic stem cell transplantation (HSCT) from a 2‐ or 3‐antigen‐mismatched haploidentical donor (MM study). The final dose of alemtuzumab in these studies was 0.16 mg/kg/day for 6 days. At this dose, all of the 12 and 11 patients in the AA and MM studies, respectively, achieved initial engraftment and the incidences of Grade II–IV acute graft‐versus‐host disease (GVHD) were 0% and 18%. While cytomegalovirus (CMV) frequently reactivated, none of the patients developed fatal CMV disease. Transplantation‐related mortality within 1 year after HSCT was observed in only two and one patients, respectively. The numbers of CD4+ and CD8+ T‐cells and T‐cell receptor rearrangement excision circles remained low within 1 year after HSCT. These findings suggest that the use of alemtuzumab at this dose in a conditioning regimen enables safe allogeneic HSCT even from a 2‐ or 3‐antigen‐mismatched donor. However, the use of a lower dose of alemtuzumab should be explored in future studies to accelerate immune recovery after HSCT. Am. J. Hematol. 88:294–300, 2013. © 2013 Wiley Periodicals, Inc.     

Predicting risk factors for varicella zoster virus infection and postherpetic neuralgia after hematopoietic cell transplantation using ordered logistic regression analysis

To identify risk factors for varicella zoster virus (VZV) infection and postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT), we conducted a retrospective chart review of 163 consecutive patients who underwent HCT between November 2004 and July 2014. Overall, the male/female (M/F) ratio was 80/83, median age at HCT was 54 (range 15–69) years, and autologous/allogeneic HCT (auto/allo-HCT) ratio was 71/92. Forty-four patients [M/F, 25/19; median age, 57 (range: 16–68) years; auto/allo-HCT, 26/18] developed VZV infection after HCT. All cases were successfully treated with acyclovir (ACV) or valacyclovir, and there was no VZV-related death. Nine (20%) of the 44 patients [M/F, 5/4; median age, 58 (range: 21–63) years; auto/allo-HCT, 7/2] developed PHN after resolution of zoster. Multivariate ordered logistic analysis identified receiving immunosuppressive therapy at the cessation of ACV [odds ratio (OR) = 74.53; 95% confidence interval (CI) = 6.99–794.32; P = 0.0004] as a risk factor for VZV infection and PHN in allo-HCT recipients. However, in auto-HCT recipients, only advanced age was identified as a risk factor (OR = 1.06, 95% CI = 1.002–1.127, P = 0.0429). Our findings indicate receiving immunosuppressive therapy at the cessation of ACV is a significant risk factor for allo-HCT recipients, while advanced age is a significant risk factor for auto-HCT recipients.     

Onset and complications of varicella zoster reactivation in the autologous hematopoietic cell transplant population

J.E. Rogers, A. Cumpston, M. Newton, M. Craig. Onset and complications of varicella zoster reactivation in the autologous hematopoietic cell transplant population.
Transpl Infect Dis 2011: 13: 480–484. All rights reserved Background. Varicella zoster virus (VZV) infections are a common complication in patients receiving autologous or allogeneic hematopoietic cell transplant (HCT). Recent guideline revisions suggest extending VZV prophylaxis to 1 year after autologous HCT. We retrospectively evaluated reactivation at our center, before implementation of extended acyclovir prophylaxis, to determine onset and outcome in the autologous HCT population. Methods. Inclusion criteria consisted of adult patients who received an autologous HCT with documentation for at least 1 year post transplant. Those excluded from review were patients who received acyclovir prophylaxis for >30 days post transplant or subsequently received an allogeneic transplant within 1 year. For patients in whom reactivation occurred, the severity of infection, the timing of onset, treatment of the reactivation, and any complications were recorded. Results. In the final analysis, 56 patients were assessed. Reactivation of zoster occurred in 16% of recipients with a median onset of 4.5 months post transplant. Complications that were observed include postherpetic neuralgia, severe pain, scarring, and motor weakness. Two patients required hospitalization for treatment, with 1 patient requiring 6 months of rehabilitation for motor weakness following the infection. Conclusions. Our study revealed a 16% incidence of VZV reactivation in our autologous HCT population. The onset of these occurrences ranged from 2 to 10 months post transplant, with significant VZV‐associated complications. We consider VZV reactivation a serious concern in the autologous transplant setting, requiring extended prophylaxis.     

Analysis of varicella zoster virus infection following allogeneic stem cell transplants

The purpose of this study was to evaluate patients who contracted the varicella zoster virus infection (VZV) following their allogeneic stem cell transplants. We retrospectively reviewed the incidence and the timing of varicella zoster virus (VZV) infections, including the clinical course, complications, and associated clinical risk factors. Between January 1998 and April 2003, a total of 71 patients received allogeneic stem cell transplants in our hospital. For prophylaxis of the herpes virus infection, all patients were given a daily oral 1000 mg dose of acyclovir from day -7 to day +35. Among the 71 patients, 28 of them (39.4%) developed VZV infection between day 77 and day 980 (median 182 days) following their allogeneic stem cell transplants. In 21 of these infected patients (75%) the occurrence was within the first 300 days after the transplant. Twenty-two patients (78.5%) were under treatment with immunosuppressive agents. Twenty-six patients developed only one episode of the VZV infection after their transplants, but two other patients developed two episodes. Twenty one patients (75%) stricken with the VZV infections had cutaneous reactivation infections of a single dermatome, and in one patient two dermatomes were affected. Five patients (17.8%) developed disseminated cutaneous zoster, and one patient (3.6%) developed a visceral infection. Treatment with acyclovir (oral or drip infusion) was successful in 25 patients. Two patients improved with vidarabine treatment, however the patient with the visceral infection died despite the use of acyclovir. The incidence of visceral infection was low, but the one case was fatal.     

Sequential systematic anti‐mold prophylaxis with micafungin and voriconazole results in very low incidence of invasive mold infections in patients undergoing allogeneic hematopoietic stem cell transplantation

Recipients of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) are at high risk for invasive mold infections (IMI). The goal of the study is to describe the incidence and outcome of IMI in patients after allo‐HSCT in a large cohort of patients receiving anti‐mold prophylaxis. We conducted a retrospective review of 988 consecutive adults who underwent allo‐HSCT in our center from 2008 through 2014. Standard prophylaxis consisted of micafungin 150 mg IV daily from admission to day +7 ± 3 followed by voriconazole until day +75 to +100. Cases meeting criteria for proven or probable IMI according to EORTC‐MSG criteria were included. Median age at HSCT was 54 years. The most common diagnoses were acute myeloid leukemia (n = 351, 36%) and lymphoid malignancies (n = 248, 25%). Matched related or unrelated donors (URD) were used in 686 (69%) patients, mismatched URD in 142 (14%) and cord blood units in 154 (16%). Twenty‐one patients were diagnosed with IMI after allo‐HSCT, 19 probable and 2 proven, and one patient was diagnosed postmortem. Microbiological diagnosis was established in 9 cases, 5 of them being Aspergillus. One‐year cumulative incidence (CI) of IMI was 1.6% (95% CI 0.9‐2.5) while 12‐week overall survival after IMI was 39% (95% CI 24‐65) Analyzed by disease, there was a trend for a higher 1‐year CI of IMI in patients with ALL (5% [95% CI 1.6‐11.4]) when compared with AML (1.4%), MDS (1.5%) and lymphoma (1.2%), P = .06. The 1‐year CI of IMI after transplantation is low in patients receiving anti‐mold prophylaxis with micafungin bridged to voriconazole, although these infections are associated with a higher risk of mortality.     

Validation of the acute leukemia‐EBMT score for prediction of mortality following allogeneic stem cell transplantation in a multi‐center GITMO cohort

Predictive models may help in determining the risk/benefit ratio of allogeneic hematopoietic stem cell transplantation (HSCT) in acute leukemia (AL). Using a machine‐learning algorithm we have previously developed the AL‐ European Society for Blood and Marrow Transplantation (EBMT) score for prediction of mortality following transplantation. We report here the first external validation of the AL‐EBMT score in a cohort of AL patients from the Italian national transplantation network. A total of 1848 patients transplanted between the years 2000‐2014 were analyzed. The median age was 45.9. Indications for HSCT were Acute Myeloid Leukemia (68.1%) and Acute Lymphoblastic Leukemia (31.9%). The majority of patients were in first complete remission (60.4%), and received myeloablative conditioning (81.3%). Median follow‐up was 2 years. The score was well‐calibrated for prediction of day 100 mortality and 2‐year overall survival (OS), leukemia free survival (LFS), and nonrelapse related mortality, with corresponding area under the receiver‐operator curves of 0.698, 0.651, 0.653, and 0.651, respectively. Increasing score intervals were associated with a decreasing probability of 2‐year OS and LFS. The highest scoring group was associated with a hazard ratio of 3.16, 2.8, and 2.27 for 2‐year OS, LFS, and NRM, respectively. In conclusion, the AL‐EBMT score identified three distinct risk groups and was predictive of OS. It is a valid tool for stratifying the risk of acute leukemia patients undergoing allogeneic HSCT.     

Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation--a randomized double-blind placebo-controlled study

Varicella-zoster virus (VZV) disease occurs in 30% of allogeneic hematopoietic cell transplant recipients who had a history of VZV infection. A safe and effective prevention strategy has not been established. In a double-blind controlled trial, 77 hematopoietic cell transplant recipients at risk for VZV reactivation were randomized to acyclovir 800 mg twice daily or placebo given from 1 to 2 months until 1 year after transplantation. VZV disease at 1 year was the primary end point; VZV disease after discontinuation of prophylaxis, VZV-specific T-cell immunity, herpes simplex virus (HSV) infection, cytomegalovirus (CMV) disease, survival, and safety were secondary end points. Acyclovir significantly reduced VZV infections at 1 year after transplantation (HR, 0.16; 95% CI, 0.035-0.74; P = .006). In the post-intervention observation period, this difference was not statistically significant (2 years: HR, 0.52; 95% CI, 0.21-1.3; 5 years: HR, 0.76; 95% CI, 0.36-1.6). There was no statistically significant difference in reconstitution of VZV-specific T-helper cell responses, HSV infections, CMV disease, chronic graft-versus-host disease, and overall survival between the groups. Acyclovir was well tolerated. Post-study VZV disease predominantly occurred in patients with continued need for systemic immunosuppression. In conclusion, acyclovir effectively and safely prevents VZV disease during the first year after hematopoietic cell transplantation. Periods of prophylaxis longer than 12 months may be beneficial for those hematopoietic cell transplant recipients on continued immune suppression.     

Viral‐specific T‐cell response in hemorrhagic cystitis after haploidentical donor stem cell transplantation

Viral hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) can be devastating. Standard treatment modalities have not been well established, but immune reconstitution may be necessary for sustained viral clearance. We studied five pediatric patients who developed viral HC after haplo‐identical HSCT. All patients developed virus‐specific CD4‐ and CD8‐positive T cells, and the emergence of these viral‐specific T cells was temporally associated with successful viral clearance.     

Chronic Graft-versus-Host Disease following Varicella-Zoster Virus Infection in Allogeneic Stem Cell Transplant Recipients

We describe 2 allogeneic stem cell transplantation patients who developed chronic graft-versus-host disease (GVHD) after dermatomal varicella-zoster virus (VZV) infection. Localized zoster did not respond to oral valaciclovir but did resolve with intravenous aciclovir. However, skin eruptions, eye/oral dryness, and liver dysfunction were observed at the healing stage of localized zoster, suggesting development of GVHD. Intensification of immunosuppressive therapy was required to control GVHD. Quantitative real-time PCR for VZV DNA was used to distinguish liver involvement by chronic GVHD from visceral dissemination of VZV in 1 patient. VZV infection may trigger chronic GVHD after allogeneic stem cell transplantation.     

Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: Real‐world experience

Cytomegalovirus (CMV) is associated with significant morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) patients. We evaluated the efficacy of letermovir as primary and secondary prophylaxis in 53 CMV‐seropositive hematopoietic stem cell transplant recipients. 70% of patients were at high risk for CMV reactivation and disease (primarily ex vivo T‐cell–depleted HCT [n = 18; 34%] or haploidentical T‐replete HCT [n = 12; 23%]). This was a retrospective, single‐center study which identified patients transplanted between January 2018 and June 2018. Patients were followed through September 2018. The primary outcome was the incidence of clinically significant CMV infection (CMV viremia requiring preemptive treatment or CMV disease). Primary letermovir prophylaxis started at a median of 7 days (range, 7‐40) after allo‐HCT. The median duration of primary letermovir prophylaxis was 116 days (range, 12‐221). With primary prophylaxis in 39 patients, the observed CMV reactivation rate was 5.1%. Twenty‐nine patients continued primary prophylaxis beyond 14 weeks with a reactivation rate of 3.4%. No recurrent reactivation was seen with secondary prophylaxis of an additional 14 patients. Our experience demonstrates the efficacy of letermovir in a real‐world setting for CMV prevention for the first 14 weeks and continued efficacy when given longer than 14 weeks after allogeneic stem cell transplantation or as secondary prophylaxis.     

Herpes zoster infection in the post-hematopoietic stem cell transplant pediatric population may be preceded by transaminitis: an institutional experience

Herpes zoster (HZ), a varicella-zoster virus reactivation, frequently complicates hematopoietic stem cell transplantation (HSCT). Its incidence, complications, and associated risk factors in 310 children undergoing HSCT were reviewed. In all, 61 of 201(32%) patients who had undergone allogeneic and 10 of 109 (9%) patients who had undergone autologous HSCT developed HZ. Of 90 VZV seropositive allogeneic patients, 50 (53%) developed HZ. Seven (17%) of 41 VZV seropositive autologous patients developed HZ. Although a substantial number of patients develop HZ in the early post-HSCT period, risk for HZ persists and HZ can occur up to 5 years post-HSCT. Risk factors for HZ included age >10 years (P<0.0001), allogeneic HSCT (P<0.001), and total body irradiation (TBI) (P<0.059) in allogeneic recipients. Of 37, 22 (59%) patients experienced an elevated alanine aminotransferase (ALT), unassociated with GVHD, in the month preceding HZ. Of the 48/64 patients (75%) hospitalized for treatment (median stay, 6 days; range, 2-39), length of stay was unaffected by donor type but increased by cutaneous dissemination and visceral involvement (P=0.023 and 0.034, respectively) in allogeneic patients. Consideration of HZ infection particularly in patients >10 years of age with elevated ALT after TBI-conditioned allogeneic HSCT may permit earlier diagnosis and therapeutic intervention.     

Epstein–Barr virus‐associated pneumonia in patients with post‐transplant lymphoproliferative disease after hematopoietic stem cell transplantation

Q.‐F. Liu, Z.‐P. Fan, X.‐D. Luo, J. Sun, Y. Zhang, Y.‐Q. Ding. Epstein–Barr virus‐associated pneumonia in patients with post‐transplant lymphoproliferative disease after hematopoietic stem cell transplantation.
Transpl Infect Dis 2010: 12: 284–291. All rights reserved. Abstract: Epstein–Barr virus (EBV) reactivation or infection after hematopoietic stem cell transplantation (HSCT) most often induces post‐transplant lymphoproliferative disease (PTLD), but it also may be associated with clinical symptoms such as pneumonia. Our aim was to investigate and describe the clinical manifestations of PTLD and PTLD accompanied by EBV‐associated pneumonia in 323 patients after HSCT. PTLD within extravisceral lymphoid tissue was identified in 7 cases (5 with CD20⁺ diffuse large B‐cell lymphoma, 1 with CD20⁺ polymorphic B‐cell hyperplasia, and 1 with CD3⁺CD45RO⁺ peripheral T‐cell lymphoma unspecified). Six of the patients with PTLD were EBV positive. Three patients had EBV‐associated pneumonia, and chest computed tomography revealed multifocal patchy and diffuse ground‐glass attenuation in both lungs. EBV‐DNA was positive in bronchoalveolar lavage (BAL) fluid, which contained mainly CD3⁺ T cells but no CD19⁺ or CD20⁺ B cells. Lung biopsy showed interstitial intra‐alveolar infiltrates of mainly CD3⁺ T cells and some CD68⁺ macrophages without CD19⁺ and CD20⁺ B cells. The patients with PTLD accompanied by EBV‐associated pneumonia developed hyperpyrexia and dyspnea, which progressed rapidly, and eventually all died within 2 weeks of the onset of PTLD. EBV‐associated PTLD accompanied by EBV‐associated pneumonia after HSCT is rare. Cytology of BAL fluid and lung biopsy may help establish the diagnosis.     

Safety of vaccinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation

Reactivation of varicella zoster virus (VZV), clinically manifested as herpes zoster (HZ) is a common complication after hematopoietic stem cell transplantation (HSCT). The optimum prophylaxis for this disease has not been defined. In this study, we examined the effects of vaccinating donors with a live-attenuated vaccine with particular reference to their immune responses and the outcome of HSCT patients. Forty prospective HLA-matched sibling donors were vaccinated before HSCT. There were humoral immune responses in both sero-positive (P<0.01) and sero-negative (P=0.058) donors. Cellular immune response was assayed in 26 donors. Significant correlation was observed between cellular immune responses as enumerated by thymidine incorporation and interferon gamma secretion (P<0.001) and the latter was used in subsequent analyses. Significant response was observed in sero-negative (6/26) and a group of sero-positive (13/26) donors while 7/26 sero-positive donors showed no response. Thirty-four HSCT were performed. These patients have a lower, albeit insignificant, risk of HZ compared with historical controls and only 3/34 patients developed single dermatomal HZ at 6, 9 and 28 months after HSCT. No patients developed VZV-related mortality. Vaccinating donors with live-attenuated VZV vaccine was safe, but whether it confers a significant protection to the patients would require further study.     

Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation

We report a retrospective analysis of VZV infection after haematopoietic stem cell transplantation (HSCT) in children. Thirty-three (30%) of the total 109 children who were transplanted during a 7 year period developed post-transplant VZV infection. Twenty-four of these 33 (73%) children had VZV infection within 1 year following HSCT. The cumulative incidences of post-transplant VZV infection at 1 and 5 years were 26% and 45%, respectively. The positive and negative predictive values of pretransplant VZV serology in recipients on the development of HZ following HSCT were 39% and 88%, respectively. Pretransplant VZV seropositivity in recipients was the only risk factor for post-transplant herpes zoster (HZ) infection on multivariate analysis. All patients responded to acyclovir. The median duration of VZV infection was 5 days. Three (11%) and one (3%) children with HZ developed visceral dissemination and post-herpetic neuralgia, respectively. No mortality was directly attributed to VZV infection. VZV infection remains a major cause of morbidity in children after HSCT. Further studies are warranted to evaluate the potential use of VZV vaccine in these children. Bone Marrow Transplantation (2000) 25, 167-172.