Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation

Brunstein, Claudio G.; Weisdorf, Daniel J.; DeFor, Todd E.; Barker, Juliet N.; Tolar, Jakub; Burik, Jo Anne H. Van; Wagner, John E.

doi:10.1182/blood-2006-03-011791

Cited by 260 publications

(200 citation statements)

References 62 publications

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…6 Our results showed only a significant association between HHV6 infection and CBT by multivariate analysis. For EBV and CMV, our study confirmed previous data, notably the increased risk of EBV infection in patients receiving ATG 20 and the absence of influence of the graft source on CMV infection. 21 Human herpes virus 6 was discovered in 1986 and two subtypes can be found, type A and type B. HHV6-B is extremely widespread in the population and infects almost all children within the first few years of life establishing latency after primary infection.…”

Section: Discussionsupporting

confidence: 81%

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Chevallier

Hebia-Fellah²,

Planche

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; Po0.0001), with higher viral load (Po0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR) ¼ 5.4, P ¼ 0.02 and OR ¼ 3.5, P ¼ 0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.

show abstract

Section: Discussionsupporting

confidence: 81%

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Chevallier

Hebia-Fellah²,

Planche

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…Considering the frequent development of late rejection, a high dose of MEL ( 120 mg/m 2 ) and additional modifications including ATG (Patients 3 and 4) or low-dose TBI (Patients 10-13) may be required to attain the stable chimera. ATG could provide better control of HLH activity, but may increase the risk of infection and Epstein-Barr virusassociated lymphoproliferative disease [17]. Low-dose/shielded TBI resulted in stable engraftment during unremarkable posttransplant course in our patients.…”

mentioning

confidence: 61%

Reduced‐intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis

et al. 2012

View full text Add to dashboard Cite

Familial hemophagocytic lymphohistiocytosis (FHL) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy. We studied the outcomes of 13 FHL patients who underwent the first unrelated cord blood transplantation (UCBT) after non-myeloablative conditionings. The major regimen consisted of fludarabine (FLU; n 5 12) 1 melphalan (MEL; n 5 11) ± low-dose total body irradiation (TBI 2-4 Gy; n 5 6). The median age at presentation and period to UCBT were 6 and 5 months, respectively. Central nervous system (CNS) disease developed in one infant at diagnosis, and in two others until UCBT. HLH activity was controlled in all but one at the time of UCBT. Ten patients had early engraftment on median day 21 with no grade >2 treatment-related toxicity and two controllable grade >2 acute GVHD. Two patients with early rejection successfully underwent subsequent UCBT after myeloablative conditioning. Two others had late graft failure following mixed donor chimerism. Two deaths occurred from HLH; early liver failure and late CNS disease. Of 11 FLU1MEL-conditioned patients, the frequency of disease-free complete engraftment was higher for MEL ( 120 mg/m 2 )1TBI, or high-dose MEL (180 mg/m 2 ) than for others (83% vs. 25%, p 5 0.036). The FLU1MEL-based non-myeloablative regimen was acceptable for FHL infants undergoing UCBT, although further studies will be needed for confirmation.Hemophagocytic lymphohistiocytosis (HLH) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, hyperferritinemia, and disseminated intravascular coagulopathy [1]. The lifethreatening condition arises from uncontrolled activation of proliferating lymphocytes, hemophagocytosing macrophages, and hypercytokinemia. The genetic basis of primary HLH resides in the defective cytotoxicity of Tcells and natural killer cells, although secondary HLH can occur in patients with infection, malignancy, or autoimmune disease. Familial HLH (FHL) is an autosomal recessive disease. Affected patients develop HLH mostly in childhood as the sole phenotype of the disease and require allogeneic hematopoietic stem cell transplantation (SCT) for a complete cure. The causal genes of FHL account for the structure, function, and metabolism of cytotoxic granules, such as PRF1 (FHL2), UNC13D (FHL3), STX11 (FHL4), and STXBP2 (FHL5) [2]. A potential risk of developing HLH is also a part of the clinical expressions of X-linked lymphoproliferative disease (XLP1 and XLP2), Chediak-Higashi syndrome, and Griscelli syndrome [3].Recent advances in SCT procedures have improved the survival rate of patients with FHL who undergo SCT after myeloablative conditioning, which now range from 45 to 65% [4][5][6][7][8][9][10][11]. However, there remain critical problems with SCT for FHL; early death from treatment-related events often associated with venoocclusive disease, and neurological sequelae in survivors. The early age at diagnosis also raises a clinical dilemma concerning the timing, preparative regimen, and al...

show abstract

“…Patients received low dose TBI of 2 Gy. 9 Antithymocyte globulin (ATG; Thymoglobulin; Genzyme, Lyon, France; 2.5 mg/kg per day infused over 2 days) was added in four cases who had received o2 cycles of multiagent chemotherapy within the 2 months before UCBT. Three patients (9%) received a non-TBI-based regimen, including fludarabine 150 mg/m 2 total dose, cyclophosphamide 100 mg/kg total dose and ATG 5 mg/ kg total dose.…”

Section: Conditioning Regimenmentioning

confidence: 99%

“…8 However, a marked increased risk of EBV-LPD has been observed with the use of RIC before UCBT. 9 With this background, the aim of this analysis was to investigate the incidence and potential risk factors predicting EBV reactivation following RIC UCBT and to assess its impact on clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

Perić

Cahu

Chevallier

et al. 2011

Bone Marrow Transplant

View full text Add to dashboard Cite

This single centre study assessed the incidence, kinetics and predictive factors of EBV reactivation and EBVrelated lymphoproliferative diseases (LPD) in 33 consecutive patients who received a reduced intensity conditioning (RIC) before umbilical cord blood transplantation (UCBT). During the first 6 months after UCBT, weekly all patients were DNA-PCR screened in the peripheral blood for EBV reactivation and were clinically monitored for clinical features attributable to EBV. The cumulative incidences of EBV reactivation (defined as an EBV load 41000 EBV copies per 10 5 cells measured at least once during follow-up) at 6 months and 2 years after UCBT were 9 (95% confidence interval (CI), 2-22%) and 17% (95% CI, 6-33%), respectively. In 28 patients (85%), the EBV load remained negative at all times, and none of these patients experienced any sign of LPD. Five patients (15%) experienced at least one EBV reactivation episode. EBV reactivation was observed at a median of 132 days (range, 85-438) after UCBT. Two patients developed EBV-related LPD (cumulative incidence, 6% at 3 years). With a median follow-up of 468 days (range, 92-1277) post UCBT, the OS was 62% at 3 years. Five patients died of disease progression and seven patients died of transplant-related complications, including one case of EBV-related LPD. Univariate analysis did not identify any significant risk factor associated with EBV reactivation. We conclude that patients undergoing RIC UCBT are at risk for EBV reactivation, with the need for close EBV monitoring and the use of preemptive rituximab treatment as some cases may progress to lifethreatening LPD.

show abstract

Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation

Cited by 260 publications

References 62 publications

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Reduced‐intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

Contact Info

Product

Resources

About