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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cord blood-derived stem cells are successfully used in the treatment of cancer and congenital disorders in children. This alternative source of stem cells is also explored for adult cancer patients with limited donor options. However, delayed engraftment, prolonged neutropenia, secondary graft loss, and graft-versus-host disease (GVHD) in recipients of cord blood transplantation (CBT) make opportunistic infections a serious concern. We evaluated the spectrum of infections in adults and children undergoing CBT at our National Cancer Institute-designated comprehensive cancer center. The infection incidence rate ratio (total infection episodes/days at risk [survival after CBT] x 100) was 2.4 times higher in 35 adult patients than in 62 children, especially in adults with neutropenia (3 x higher) and GVHD (1.9 x higher). Ninety-two percent of fungal infection episodes occurred within 100 days after transplantation; half of these infections occurred in the first 30 days after CBT. Most bacterial infections (80%) were also diagnosed in the first 100 days, whereas late (>100 d) post-CBT cytomegalovirus and varicella zoster virus infections occurred only in children with chronic GVHD. Multivariate analysis showed that resolution of lymphocytopenia (> or =1000 cells/microL) (hazard ratio [HR] 0.71; p < 0.0001) and successful engraftment (HR 0.20; p < 0.0001) were associated with a low risk of serious infection. Children (HR 0.36; p < 0.0002) with sustained engraftment (HR 0.39; p < 0.004) and those with cancer in remission (HR 0.47; p < 0.007) were less likely to die from infection. More effective measures for surveillance and prevention of late cytomegalovirus and varicella zoster virus infections in children with CBT and chronic GVHD are needed.
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PMID:Infections in 100 cord blood transplantations: spectrum of early and late posttransplant infections in adult and pediatric patients 1996-2005. 1800 77

This report describes a 56-year-old man who developed meningoencephalitis as a result of varicella-zoster virus (VZV) without dermatomal manifestations. The patient received an allogeneic bone marrow transplantation for malignant lymphoma, and during treatment for chronic graft-versus-host disease, he presented with a fever and headache. Cerebrospinal fluid analysis revealed an increased cell count with lymphocyte predominance and an extremely high amount of VZV DNA, and an MRI study showed multiple lesions of increased T2 intensity within deep white matter regions. Meningoencephalitis was diagnosed and the patient was successfully treated with aciclovir administered at a dose of 30 mg/kg/day for four weeks.
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PMID:[Varicella-zoster virus meningoencephalitis without skin manifestation in an allogeneic bone marrow transplantation patient successfully treated with aciclovir]. 1808 May 12

Human herpes virus 6 (HHV6) is known to reactivate after hematopoietic stem cell transplantation (HSCT), and has been suggested to be associated with severe clinical manifestations in adults. The clinical significance in children remains unclear. We investigated the incidence of HHV6 reactivation in relation to HSCT-associated morbidity and mortality in children. Between January 2004 and May 2006, 58 pediatric patients, median age 7.6 years (range: 0.1-18.1 years), received their first allogeneic HSCT. After HSCT, HHV6, Epstein Barr Virus (EBV), cytomegalovirus (CMV), and adenovirus (AdV)-plasma loads were weekly measured by quantitative PCR. Clinical features, engraftment, graft-versus-host disease (GVHD), and HSCT-associated mortality and morbidity were monitored. HHV6 reactivations were classified in group I (no reactivation), group II (loads <1000 cp/mL) and group III (loads >1000 cp/mL). CMV, EBV, Herpes Simpex Virus, Varicella Zoster Virus, and AdV-reactivations were treated according to local guidelines. HHV6 was treated only when there was clinical suspicion of disease. Thirty-six HLA-identical and 22 HLA nonidentical grafts were transplanted of which 43 were bone marrow or peripheral blood stem cells grafts and 15 were cord blood (CB) grafts. Median follow-up of the patients was 15.5 (1-35) months. HHV6 reactivation occurred in 39 of 58 (67%) patients with 31 of 39 (80%) occurring within the first 30 days post-HSCT. In 26 of 58 (45%) patients (group III), HHV 6 reactivation was significantly associated with higher nonrelapse mortality (P = .02), using multivariate Cox proportional hazard models and grade 2-4 acute GVHD (P = .03) and chronic GVHD (P = .05) in a multivariate logistic regression analysis. HHV6 reactivation is very common after HSCT in children and is associated with serious transplantation-related morbidity and mortality. Although the exact role of HHV6 reactivation after HSCT has to be elucidated, early detection and initiation of therapy might be of benefit.
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PMID:Human herpes virus 6 plasma DNA positivity after hematopoietic stem cell transplantation in children: an important risk factor for clinical outcome. 1854 Dec 4

Reactivation of latent varicella zoster virus is one infectious complication associated with the extensive immunosuppression necessary for hematopoietic stem cell transplant. Most cases are limited to skin and mortality is low. Isolated visceral zoster is rare, presenting with ileus/abdominal pain, hepatitis, and/or hyponatremia. We present 2 cases of visceral varicella zoster virus in adolescents with chronic graft-versus-host disease after hematopoietic stem cell transplant. Both presented with elevated liver enzymes, severe abdominal pain, and hyponatremia but lacked cutaneous involvement. Both received high-dose acyclovir and showed improvement, but eventually expired from hepatic failure. The diagnosis of visceral zoster can be difficult especially without cutaneous manifestations. Vigilance is necessary in patients with chronic graft-versus-host disease, abdominal pain, and/or hepatitis and antiviral therapy should be initiated promptly.
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PMID:Visceral varicella zoster virus (VZV) after allogeneic hematopoietic stem cell transplant (HSCT) in pediatric patients with chronic graft-versus-host disease (cGVHD). 1913 84

Two adolescents, on immunosuppressive therapy for graft-versus-host disease, developed hemophagocytic lymphohistiocytosis (HLH) after varicella zoster virus (VZV) reactivation. In the absence of dermatome restricted characteristic skin lesions, VZV reactivation was not immediately recognized and treatment with acyclovir was delayed. The first patient developed optical neuritis and died 2 months after the VZV episode due to massive intracranial hemorrhage. The second patient presented with severe abdominal pain and pancreatitis, followed by atypical skin eruptions, which prompted a faster diagnosis. Both patients recovered from their HLH, the first patient being successfully treated with immunosuppressive agents and the second with VZV treatment only. These two cases demonstrate the difficulties in recognizing VZV reactivation, and in order to start adequate and timely treatment, the need to consider VZV as a possible cause of HLH in severely immunocompromised patients.
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PMID:Atypical varicella zoster infection associated with hemophagocytic lymphohistiocytosis. 1935 24

To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.
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PMID:Incidence and risk of postherpetic neuralgia after varicella zoster virus infection in hematopoietic cell transplantation recipients: Hokkaido Hematology Study Group. 1945 Jul 57

Graft-versus-host disease and graft rejection are major complications of allogeneic HLA-mismatched stem cell transplantation or organ transplantation that are caused by alloreactive T cells. Because a range of acute viral infections have been linked to initiating these complications, we hypothesized that the cross-reactive potential of virus-specific memory T cells to allogeneic (allo) HLA molecules may be able to mediate these complications. To analyze the allo-HLA reactivity, T cells specific for Epstein-Barr virus, cytomegalovirus, varicella zoster virus, and influenza virus were tested against a panel of HLA-typed target cells, and target cells transduced with single HLA molecules. Eighty percent of T-cell lines and 45% of virus-specific T-cell clones were shown to cross-react against allo-HLA molecules. The cross-reactivity of the CD8 and CD4 T-cell clones was directed primarily against HLA class I and II, respectively. However, a restricted number of CD8 T cells exhibited cross-reactivity to HLA class II. T-cell receptor (TCR) gene transfer confirmed that allo-HLA reactivity and virus specificity were mediated via the same TCR. These results demonstrate that a substantial proportion of virus-specific T cells exert allo-HLA reactivity, which may have important clinical implications in transplantation settings as well as adoptive transfer of third-party virus-specific T cells.
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PMID:Allo-HLA reactivity of virus-specific memory T cells is common. 2016 Jan 65

Paraproteinaemia following allo-SCT is common. We analysed 91 consecutive patients undergoing allo-SCT; conditioning included alemtuzumab in 42% of the patients. Paraproteinaemia incidence at 2 years was 32%. In univariate analysis paraproteinaemia was associated with unrelated donor, age, recipient seropositivity for CMV and alemtuzumab conditioning (hazard ratio (HR) 3.93, P=0.0006). Paraproteinaemia was not associated with haematological diagnosis; disease status at transplant; varicella zoster, herpes simplex or EBV serology; reduced-intensity vs myeloablative conditioning or GVHD. CMV reactivation-more frequent in alemtuzumab recipients-was associated with paraproteinaemia (HR 7.52, P<0.0001). In multivariate analysis, only increasing age (HR 1.04 per year, P=0.048) and CMV reactivation (HR 5.74, P=0.001) were significantly associated with paraproteinaemia. Alemtuzumab without CMV reactivation, however, resulted in significantly more paraproteinaemia, suggesting an effect that is independent of CMV reactivation. OS was poorer in patients with paraproteinaemia (HR 2.54, P=0.04) and relapse increased (HR 2.38, P=0.087). Paraproteinaemia was not significantly independently associated with decreased survival on multivariate analysis. Post transplant paraproteinaemia is associated with CMV reactivation, is more frequent in alemtuzumab-conditioned transplants and is not associated with improved OS.
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PMID:Paraproteinaemia after allo-SCT, association with alemtuzumab-based conditioning and CMV reactivation. 2232 36

Although the use of nonmyeloablative (NMA) hematopoietic stem cell transplantation (HSCT) regimens has expanded in the past decade, little data exist to support antiviral prophylaxis to prevent herpes zoster (HZ) in recipients who are seropositive for varicella-zoster virus in this population. The present study examined the clinical features, incidence, and risk factors for HZ in a homogeneous cohort of NMA allogeneic HSCT recipients. We conducted a retrospective cohort study assessing all patients who underwent sibling NMA HSCT at Maisonneuve-Rosemont Hospital (Montreal) between July 2000 and December 2008. All patients received the same conditioning regimen, immunoprophylaxis, and graft-versus-host disease therapy. The diagnosis of HZ was defined clinically. Factors associated with HZ were identified using a Cox proportional hazards model. A total of 179 patients were followed for a median of 33 months (interquartile range, 21-59). HZ developed in 66 patients (37%) at a median of 8.3 months post-HSCT; the incidence rate was 175 cases/1000 person-years. The estimated cumulative HZ incidence was 27% at 1 year, 36% at 2 years, and 44% at 3 years. Thoracic dermatomes were most frequently involved (30%); dissemination occurred in 5 patients. No deaths resulted from HZ, but 23% of patients developed postherpetic neuralgia. In multivariate analysis, reactivation of cytomegalovirus and herpes simplex virus was associated with a reduced likelihood of HZ (hazard ratio, 0.54 and 0.33, respectively). Antiviral prophylaxis or treatment for cytomegalovirus and herpes simplex virus reactivations were protective against HZ. The incidence of HZ in our cohort of NMA HSCT recipients is similar to the incidence reported in HSCT recipients who received a myeloablative conditioning regimen. Given the observed high risk, we conclude that recommendations for antiviral prophylaxis should apply, at least for the first year, to the NMA HSCT population as well.
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PMID:High incidence of herpes zoster in nonmyeloablative hematopoietic stem cell transplantation. 2097 44

Patients lose protective immunity to vaccine-preventable diseases after haematopoietic stem cell transplantation (HSCT). Therefore, revaccination of HSCT recipients represents an important strategy for reducing morbidity and mortality associated with these infections. Since there is little consensus on vaccine recommendations and practices for allogeneic HSCT recipients with active chronic graft-versus-host disease (GVHD) the German-Austrian-Swiss-Consensus Conference on Clinical Practice in Chronic GVHD developed an immunization schedule with the aim to provide optimal patient care. The proposed vaccine recommendations include immunization against Haemophilus influenzae type b, pertussis, pneumococci, meningococci, tetanus, diphtheria, hepatitis A and B, measles, mumps and rubella, influenza, poliomyelitis, varicella-zoster virus, human papilloma virus, and tick-borne encephalitis with a particular focus on vaccination of patients with active chronic GVHD.
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PMID:Vaccination of allogeneic haematopoietic stem cell transplant recipients: report from the international consensus conference on clinical practice in chronic GVHD. 2134 79


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