Risk for CMV reactivation in children undergoing allogeneic hematopoietic stem cell transplantation

2014 ◽  
Vol 62 (2) ◽  
pp. 364-366 ◽  
Author(s):  
Muna Qayed ◽  
Monica Khurana ◽  
Joseph Hilinski ◽  
Scott Gillespie ◽  
Courtney McCracken ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

Safety and Efficacy of Cytotoxic Chemotherapy after Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed Hematologic Malignancy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5333-5333
Author(s):  
Nancy M. Hardy ◽  
Jeanne Odom ◽  
Kelly Snow ◽  
Robert Dean ◽  
Steven Pavletic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematologic Malignancy ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Therapy ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

Abstract Relapse of hematologic malignancy is a major problem after allogeneic hematopoietic stem cell transplantation (alloHSCT), with limited treatment options of proven benefit other than donor lymphocyte infusions (DLI). Additionally, toxicity from treatment with cytotoxic chemotherapy after alloHSCT may differ from conventional treatments, and could include graft-versus-host disease, allograft failure, or increased risk of infection. We retrospectively reviewed treatment outcomes of 25 patients who received cytotoxic chemotherapy as treatment for relapsed hematologic malignancies after reduced-intensity, matched-sibling donor alloHSCT. Combination therapies included: EPOCH+/− rituximab (n=12 patients); “7&3” AML induction (ida/ara-c) (n=2); FLAG (n=2); asparaginase/6-MP/vincristine (n=1); R-ICE (n=1); MIME (n=1); BVP (n=1); and bortezomib/doxorubicin/dexamethasone (n=1). Single-agent therapies included: bortezomib (n=6); gemcitabine (n=4), vinorelbine (n=3); vincristine (n=1); methotrexate (n=1); and intrathecal methotrexate and/or cytarabine (n=5). A total of 133 cycles or doses were administered, of which 20 were supported with donor stem cell boosts, and another 9 were followed by nonmobilized DLI. There were 52 Grade 3 or higher toxicity episodes recorded, most commonly: neutropenia (10 episodes); infection with neutropenia (5 episodes); thrombocytopenia (6 episodes); and anemia (3 episodes). There were 12 episodes of CMV reactivation in 8 of 15 patients at risk, including 2 cases of pneumonitis and 1 case of colitis. GVHD flares were considered definitely chemotherapy-induced (2), possibly chemotherapy-induced (7), and unlikely chemotherapy-induced (2). Unusual events after treatment included culture-negative sepsis-like illness after bortezomib (n=2), secondary (11q23) AML of donor origin after one cycle of EPOCH (n=1) and diffuse alveolar hemorrhage after EPOCH (n=1). Seven patients achieved CR with therapy for post-transplant relapse, including three durable remissions. Four patients achieved PR and seven achieved disease stabilization. Median survival after starting cytotoxic therapy was 263 days. Timing of relapse appeared to be associated with survival, with median overall survival of 95 days for patients requiring therapy before Day 100 vs. 508 days for patients after Day 100 (p=0.0008). Treatment of relapse with cytotoxic chemotherapy after alloSCT is feasible and can result in durable remissions in a minority of patients. However, administration of cytotoxic therapy after alloHSCT requires monitoring and support for hematologic toxicities, GVHD and CMV reactivation; selected patients may benefit from prophylactic stem cell boosts or immune suppression. Survival after Cytotoxic Therapy for Relapse after alloHSCT Survival after Cytotoxic Therapy for Relapse after alloHSCT

Incidence and risk factors for cytomegalovirus (CMV) reactivation following autologous hematopoietic stem cell transplantation in children

2014 ◽  
Vol 62 (6) ◽  
pp. 1099-1101 ◽  
Author(s):  
Ayad Ahmed Hussein ◽  
Eman T. Al-Antary ◽  
Rula Najjar ◽  
Dua'a S. Al-Hamdan ◽  
Abdulhadi Al-Zaben ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

scholarly journals Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 490-500 ◽  
Author(s):  
Francisco M. Marty ◽  
Julie Bryar ◽  
Sarah K. Browne ◽  
Talya Schwarzberg ◽  
Vincent T. Ho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Cmv Reactivation

AbstractSirolimus-based immunosuppressive regimens in organ transplantation have been associated with a lower than expected incidence of cytomegalovirus (CMV) disease. Whether sirolimus has a similar effect on CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) is not known. We evaluated 606 patients who underwent HSCT between April 2000 and June 2004 to identify risk factors for CMV reactivation 100 days after transplantation. The cohort included 252 patients who received sirolimus-tacrolimus for graft-versus-host disease (GVHD) prophylaxis; the rest received non–sirolimus-based regimens. An initial positive CMV DNA hybrid capture assay was observed in 225 patients (37.1%) at a median 39 days after HSCT for an incidence rate of 0.50 cases/100 patient-days (95% confidence interval [CI], 0.44-0.57). Multivariable Cox modeling adjusting for CMV donor-recipient serostatus pairs, incident acute GVHD, as well as other important covariates, confirmed a significant reduction in CMV reactivation associated with sirolimus-tacrolimus–based GVHD prophylaxis, with an adjusted HR of 0.46 (95% CI, 0.27-0.78; P = .004). The adjusted HR was 0.22 (95% CI, 0.09-0.55; P = .001) when persistent CMV viremia was modeled. Tacrolimus use without sirolimus was not significantly protective in either model (adjusted HR, 0.66; P = .14 and P = .35, respectively). The protective effect of sirolimus-containing GVHD prophylaxis regimens on CMV reactivation should be confirmed in randomized trials.

Dual Production of IL-2 and IFN-Gamma by CMV-Specific CD8+ T-Cells Is a Hallmark of Their Ability to Control CMV Reactivation in Patients After Hematopoietic Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4081-4081
Author(s):  
Tomas Kalina ◽  
Ladislav Krol ◽  
Jan Stuchly ◽  
Petra Keslova ◽  
Petr Hubacek ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cd8 T Cells ◽  
Antiviral Treatment ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

Abstract Abstract 4081 Introduction: Depletion of cellular immunity as a consequence of conditioning before allogeneic hematopoietic stem cell transplantation (HSCT) frequently results in CMV reactivation, which may in turn lead to life-threatening infections and require timely antiviral treatment. Methods: We have investigated the ex vivo response of CMV-specific CD4+ and CD8+ T-cells to CMV antigen (combined CMV total lysate, pp65 and IE-1 peptide mix) in 191 samples from 118 individuals. We included patients with either high or undetectable viral loads, and those who controlled or did not control their CMV reactivations. All patient subsets were compared to healthy donors. Polychromatic flow cytometric measurements of CD154 (CD40L), intracellular cytokines (IFNγ, IL2), and a degranulation marker (CD107a) revealed the functional status of various T-cells simultaneously. Results: We found that dual IFNγ/IL2 producing CD8+ T-cells were significantly increased in patients controlling their CMV reactivations (average 0.33%, SD=0.4%) compared to non-controllers (average=0.02%, SD=0.07%). In contrast, CD8+ T-cells that produced IFNγ only were the most abundant subtype but they were present in a substantial number of both, controllers (average 4.36%, SD=4.8%) and non-controllers (average 1.64%, SD=3.7%). Hierarchical clustering of distinct functional signatures revealed that polyfunctional CD8+ T-cells were acting in concert with other subsets, whereas the isolated production of IFNγ by CD8+ T cells heralds insufficient collaboration with others. On a subset of patients with reactivation of CMV post HSCT, we have evaluated the sensitivity and specificity of functional signature test (n=64 samples) to predict reactivation control. When dual IFNγ/IL2 producing cells above 0.1% cut-off were considered protective, sensitivity of 75% and specificity 93% was achieved, while IFNγ-only production by more 0.3% cells had sensitivity of 88% but specificity of 73% only. Conclusions: Our study revealed functional signatures that are useful readout of immune monitoring. Furthermore, our data may modify the interpretation of previous studies that assessed only IFNγ. Supported by the Czech Ministry of Health grant NS/9996-4, MZØFNM2005 and Czech Ministry of Education MSMT21620813 Disclosures: No relevant conflicts of interest to declare.

scholarly journals The association of conditioning regimen with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

2020 ◽  
Author(s):  
Masoud Mardani ◽  
Sara Abolghasemi ◽  
Shiva Shabani ◽  
Farzaneh Tavakoli ◽  
Anahita Saeedi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Viral Infections ◽  
Opportunistic Infections ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

Background and Objectives: Infections is yet one of the life-threatening complications of the hematopoietic stem cell transplantation (HSCT). The myeloablative and immunosuppressive conditioning regimens, which are administered before HSCT, dampen the defense capacity of the recipients’ immune systems. In this condition, opportunistic infections, especially viral infections such as cytomegalovirus (CMV) can be reactivated and cause morbidity and mortality in HSCT patients. Here, we aimed to find out any possible relationship between types of conditioning regimen and CMV reactivation in allo- geneic HSCT patients. Materials and Methods: We retrospectively analyzed the data of 145 CMV-seropositive cases out of total 201 allo-HSCT patients, including age, gender, underlying disease, conditioning regimen, prophylaxis regimen and occurrence of acute graft-versus-host disease (aGVHD) to evaluate their roles in CMV reactivation. Results: Our result showed that conditioning regimen containing Busulfan and Fludarabine (P=0.003) or Cyclophospha- mide (P=0.02) significantly decrease the early CMV reactivation. Patients who developed aGVHD (P=0.003) and those who received anti-thymocyte globulin (ATG) as prophylaxis regimen (P=0.002), had 1.84 and 2.63 times higher risks of CMV reactivation, respectively. Conclusion: Our findings suggest the conditioning regimen, aGVHD and ATG as influencing factors for early CMV reacti- vation post-HSCT which should be considered in the future studies.

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