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

Summary: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 þ 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. Varicella zoster virus (VZV), a human herpesvirus, causes chicken pox as a primary infection, following which it establishes latency within the dorsal root sensory ganglia. During reactivation, the virus travels via neuronal axons to skin innervated by the relevant ganglion, resulting in the classical dermatomal vesicular rash. 1As immune surveillance is required for the maintenance of latency, immunocompromised individuals are at increased risk of reactivation, with viral escape being associated with declining numbers of VZV-specific memory T cells. 2 In addition, in the immunocompromised host, reactivation can result in disseminated infection, with a generalised vesicular rash and/or other organ involvement, the proposed mechanism for this distant spread being the tropism of VZV for circulating mononuclear cells. 3 Recipients of haemopoietic stem cell transplants (HSCT) are therefore at significantly increased risk of VZV reactivation, with an incidence of zoster ranging from 17 to 52%, 4-6 with approximately 80% episodes occurring within the first year. 5,7 This compares to an annual incidence of 0.4% among an unselected adult population. 8 The majority of reactivations occur in a localised dermatomal distribution, although with new lesion formation persisting for longer than in the immunocompetent, and with increased rates of post-herpetic neuralgia (68 vs 9%) 4 and of bacterial superinfection.In a significant minority of patients, however, viral dissemination can occur, resulting either in a generalised cutaneous rash or in hepatic, pulmonary or central nervous system (CNS) involvement. One early series reported a VZV dissemination rate of 45% ...

Section: Discussionmentioning

confidence: 99%

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

Thomson

Hart

Banerjee

et al. 2005

“…8 Neutropenic fever was managed as described by Pizzo. 9 Cytomegalovirus (CMV) pp65 antigenemia was monitored weekly with initiation of preemptive ganciclovir at positive results.…”

Section: Supportive Cares and Management Of Gvhdmentioning

confidence: 99%

Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor

Kusumi

Kami²,

Kikuchi

et al. 2004

Self Cite

Summary:To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludarabine-based (150-180 mg/m 2 , n ¼ 18) or cladribine-based (0.77 mg/kg, n ¼ 2). To enhance engraftment, antithymocyte globulin (ATG) and 4 or 8 Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclosporine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatmentrelated mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II-IV acute GVHD, and seven of 13 patients who survived 4100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P ¼ 0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients.

“…Prophylaxis of herpes virus infection using acyclovir was reported previously. 19 Broad-spectrum antibiotics were initiated at the first episode of neutropenic fever. All of the patients were monitored by CMV pp65 antigenemia once a week.…”

Section: Management Of Infectious Complicationsmentioning

confidence: 99%

High complete response rate after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens in advanced malignant lymphoma

Tanimoto¹,

Kusumi

Hamaki³

et al. 2003

Self Cite

Summary:The possible advantage of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a graft-versus-lymphoma effect. We explored the feasibility and efficacy of allo-HSCT with reduced-intensity (RI) regimens in advanced malignant lymphoma (ML). A total of 20 patients with indolent (n ¼ 9) or aggressive lymphoma (n ¼ 11) received allo-HSCT with an RI regimen (RIST). The preparative regimen consisted of a combination of purine analog and alkylating agent with or without antithymocyte globulin. A total of 11 patients had chemorefractory disease, seven had chemosensitive relapsed disease and two had residual disease. All of the patients received G-CSF-mobilized blood stem cells from HLA-matched siblings. Of the 20 patients, 19 achieved engraftment with acceptable regimen-related toxicities. Seven patients developed grade II-IV acute GVHD and 15 developed chronic GVHD. Of the 15 patients with evaluable disease, 12 achieved a complete response. One died of invasive fusariosis, four subsequently died of GVHD complicated with fungal infection and one died of progressive disease. With a median follow-up of 358 days, the Kaplan-Meier estimates for 1-year overall and progression-free survival were both 70%. The high response rate with low relapse observed in this study suggests that RIST may be an effective alternative curative treatment for patients with advanced ML. Bone Marrow Transplantation (2003) 32, 131-137. doi:10.1038/sj.bmt.1704118 Keywords: malignant lymphoma; allogeneic transplantation; reduced-intensity regimen Although clinical evidence has been reported regarding a graft-versus-lymphoma (GVL) effect following allogenic hematopoietic stem cell transplantation (allo-HSCT), 1-4 the feasibility of allo-HSCT has not been fully established in patients with malignant lymphoma (ML). There has been only one prospective study comparing allo-and auto-HSCT for ML, and this found a significantly lower recurrence rate and a trend toward improved disease-free survival after allo-HSCT. 5 Nevertheless, high regimenrelated toxicity (RRT) and treatment-related mortality (TRM) ultimately led to a survival rate equivalent to that with auto-HSCT. This has been suggested also by other studies with a nonrandomized design. [6][7][8] Recently, a new strategy for transplantation using a reduced-intensity (RIST) or nonmyeloablative preparative regimen has been developed to reduce RRT while preserving an adequate antitumor effect associated with allo-HSCT. [9][10][11][12][13] Although the preliminary data appear to be attractive, widely acceptable suitable regimens and indications for this strategy still remain to be established.RIST is recently in focus as a new promising therapeutic strategy for the treatment of ML. Nagler et al 14 reported the results of 23 patients with refractory lymphoma who were treated with fludarabine-based RIST. Observed RRT was moderate and four patients developed grade II-IV acute graft-versus-host disease (GVHD). Seven patients died of TRM, and overall and disease-free survival rates at 37 mo...