scholarly journals CYTOMEGALOVIRUS REACTIVATION IN ADULT RECIPIENTS OF AUTOLOGOUS STEM CELL TRANSPLANTATION: A SINGLE CENTER EXPERIENCE

2015 ◽  
Vol 7 ◽  
pp. e2015049 ◽  
Author(s):  
Omar Ziad Alrawi ◽  
Fawzi Abdel-latif Abdel-rahman ◽  
Rula Alnajjar ◽  
Husam Abujazar ◽  
Mourad Salam ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Disease Free Survival ◽  
Rank Test ◽  
Preemptive Therapy ◽  
Single Center ◽  
Cmv Infection ◽  
Cmv Reactivation ◽  
Cmv Antigenemia

Introduction: Cytomegalovirus (CMV) reactivation and infection is a well-recognized complication after allogeneic stem cell transplantation (SCT). Yet only few studies have addressed CMV reactivation after autologous SCT (ASCT).Methods: We retrospectively reviewed medical records of 210 adult patients who underwent ASCT for lymphoma or multiple myeloma (MM) at a single center from January 1, 2007 until December 31, 2012. All patients were monitored weekly with CMV antigenemia test till day 42 after transplantation, and for 2 months after last positive test in those who had any positive CMV antigenemia test before day 42.Results: thirty seven (17.6%) patients had CMV reactivation; 23 patients had lymphoma while 14 had MM as the underlying disease. There was no difference in the rate of CMV reactivation between lymphoma and MM patients (20% versus 14.7%, P = 0.32). The majority of the patients were treated with ganciclovir/valganciclovir, all patients had their reactivation resolved with therapy, and none developed symptomatic CMV infection. None of the patients who died within 100 days of transplantation had CMV reactivation. Log rank test showed that CMV reactivation had no effect on the overall survival or the disease-free survival of patients (P values, 0.29 and 0.79, respectively).Conclusion: In our cohort, CMV reactivation rate after ASCT was 17.6%. There was no difference in reactivation rates between lymphoma and MM patients. With the use of preemptive therapy, symptomatic CMV infection was not documented in any patient in our cohort. CMV reactivation had no impact on patients’ survival post ASCT. 

Prognostic Factors for CMV Reactivation/Infection after Stem Cell Transplantation and Value of Oral Valganciclovir for Preemptive Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5369-5369
Author(s):  
Thorsten Graef ◽  
Tatjana Bobrikova ◽  
Ortwin Adams ◽  
Roland Fenk ◽  
Leilani Ruf ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Response ◽  
Preemptive Therapy ◽  
Cmv Infection ◽  
Oral Valganciclovir ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract INTRODUCTION: Cytomegalovirus (CMV) infection and disease are major complications of allogeneic stem cell transplantation (SCT). Different strategies have been developed to reduce the risk for CMV-associated disease and death. Before routine use of prophylactic regimens, CMV seropositive allogeneic HCT recipients had a 70 to 80 percent risk of reactivation of this virus, and one-third of these patients developed CMV disease. Preemptive antiviral therapy has markedly reduced the incidence and severity of CMV disease, but in spite of these advances significant morbidity and mortality are associated with CMV. PATIENTS AND METHODS: In this unicenter retrospective study, we studied 197 adults who received allogeneic HSCT mostly because of myeloid leukaemia between 2000 and 2004. The median age was 46 years (range, 17-68), included were 80 female and 117 male patients. The grafts consisted mainly of PBSC (94%) and in 54% unrelated donors were used. Conditioning regimens included TBI in 42% cases. The CMV-serostatus proportions were D-/P- 34%, D-/P+ 20%, D+/P- 14% and D+/P+ 32%. All patients with ablative regimens received prophylactic i.v. acyclovir starting one day after SCT. After discharge oral CMV-prophylaxis consisted of famciclovir (52%), acyclovir (30%), valacyclovir (8%) or ganciclovir (10%). The prognostic factors for CMV reactivation in recipients were assessed by univariate analyses and Pearson correlations. RESULTS: CMV seropositive recipients (p=.00001) and donors (p=.03) were significantly associated with a higher rate of CMV reactivations, and also the use of an unrelated donor was a prognostic factor for more frequent CMV reactivations (p=.007). TBI, age and GvHD were not associated with more frequent of CMV reactivations. Famciclovir and acyclovir were associated (p=.0001) with a higher rate of CMV-reactivations in CMV+ recipients, than valacyclovir or ganciclovir. In all, we observed 60 cases (31%) of CMV reactivation/infection (D-/P- 14%, D-/P+ 30%, D+/P- 7% and D+/P+ 49%) after a median of 50 days (range, 9-403). 48 of them (80%) were CMV+ before SCT and 50 of 60 (83%) were successfully treated. In all, 30 patients (7 CMV-, 23 CMV+) were treated with valganciclovir and 30 (5 CMV-, 25 CMV+) received other agents (valacyclovir n=11, foscarnet n=4 or ganciclovir n=15) after a single dose of i.v. IG. 29 of 30 patients who received valganciclovir had a negative PCR result, confirmed by 2 consecutive CMV-PCRs, after a median of 24 days (range, 9 – 365). In the group of the CMV+ recipients, valganciclovir resulted in a statistically superior therapeutic response (p=0.024) when compared to other agents. Oral valganciclovir therapy was well tolerated and toxicity was limitted to manageable cytopenia. 11 of 12 CMV- recipients (91%) were also successfully treated after CMV-infection, with no significant difference between the different therapeutic agents. CONCLUSION: CMV seropositive recipient is the primary prognostic factors for CMV reactivation after allogeneic SCT. The prophylactic use of valacyclovir and ganciclovir were significantly better in CMV+ recipients, than famciclovir or acyclovir. Valganciclovir resulted in a better therapeutic response in comparison to other agents after CMV reactivation and should be tested as primary preemptive therapy in randomized trials.

scholarly journals Letermovir Is Effective for Prevention of Cytomegalovirus Reactivation in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2858-2858
Author(s):  
Takahide Ara ◽  
Yuta Hasegawa ◽  
Hiroyuki Ohigashi ◽  
Souichi Shiratori ◽  
Atsushi Yasumoto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Cmv Infection ◽  
Advisory Committees ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract [Introduction] Cytomegalovirus (CMV) infection is a common viral infection in recipients of allogeneic hematopoietic stem cell transplantation (allo-SCT). Early CMV reactivation after allo-SCT is associated with worse non-relapse mortality (NRM) and overall survival (OS). Recently, T-cell replete HLA-haploidentical SCT using post-transplant cyclophosphamide (PTCy-haplo SCT) has been developed and spread rapidly worldwide. Rationale of this strategy is assumed to be selective and cytotoxic depletion of alloreactive T cells which are responsible for graft-versus-host disease (GVHD), while preserving non-alloreactive T cells which can contribute to fight infections. However, recent studies showed that PTCy-haplo SCT was associated with the increased incidence of CMV infection. Letermovir (LET), a novel anti-CMV agent, which inhibits the CMV DNA terminase complex, was approved for the prevention of CMV reactivation in allo-SCT recipients in 2018 in some countries including Japan based on the result of a phase 3 trial. Our facility performs LET prophylaxis in allo-SCT recipient if either donor or recipient is seropositive CMV. Although LET is effective for the prevention of CMV reactivation in allo-SCT recipients, the clinical effectiveness of LET prophylaxis in PTCy-haplo SCT is not well elucidated. Based on these things, we retrospectively evaluated the efficacy of LET prophylaxis in PTCy-haplo SCT. [Methods] We retrospectively analyzed consecutive 99 recipients who received PTCy-haplo SCT at Hokkaido University Hospital from March 2013 to March 2021. We compared the cumulative incidence of CMV reactivation between the LET prophylaxis group (LET group, 33 patients) and LET non-prophylaxis group (non-LET group, 66 patients). LET was initiated on the day 0 at a dosage of 480mg daily. All patients were monitored for CMV reactivation by using the anti-CMV pp65 monoclonal antibody HRP-C7 assay at least once a week from the time of engraftment. CMV reactivation was defined as the detection of CMV antigen positive cells per 50000 white blood cells, whereas CMV disease was defined by organ dysfunction attributable to CMV. [Results] As baseline patient's characteristics were summarized in Table1, there were no difference between LET and non-LET group in terms of age, sex, underlying disease, disease risk at transplantation, prior transplantation, conditioning intensity, and CMV serostatus. All patients received peripheral blood stem cell transplantation. GVHD prophylaxis consisted of Cy (40-50 mg/kg on day 3 and 4), tacrolimus (from day 5), and mycophenolate mofetil (from day 5). The cumulative incidence of CMV reactivation at 150 days after transplantation in LET group was significantly lower than that in non-LET group (30.3% versus 69.7%; P <.001, Figure1A). Importantly, CMV disease were occurred in three patients without LET prophylaxis (gastritis, enteritis, and retinitis), but not in the patients with LET prophylaxis. The cumulative incidence of NRM at 1 year was similar between the patients with and without LET prophylaxis (17.6% versus 9.2%; P=0.366, Figure1B), as was OS at 1 year (71.5% versus 69.4%; P=0.801, Figure1C). Neutrophil engraftment was achieved in 32 patients (97%) at a median of 15 days in LET group and 64 patients (97%) at a median of 14.5 days in non-LET group (P=0.243). Furthermore, platelet engraftment was achieved in 26 patients (79%) at a median of 34 days in LET group and 57 patients (86%) at a median of 31 days in non-LET group (P=0.282). These findings suggest that LET does not affect engraftment. Interestingly, the length of hospitalization in the LET group was significantly shorter than that in non-LET group (the median, 59.5 days versus 71 days; P=0.0488), suggesting that LET suppresses CMV reactivation leading to early discharge. [Conclusion] To our best knowledge, this is the largest retrospective study about the efficacy of LET in PTCy-Haplo SCT. LET is effective for prevention of CMV reactivation in PTCy-haplo SCT. Further studies focused on the long term effect of LET prophylaxis in PTCy-haplo SCT, such as the incidence of relapse and chronic GVHD, is warranted. Figure 1 Figure 1. Disclosures Nakagawa: AbbVie GK: Research Funding; Takeda Pharmaceutical Company: Research Funding. Teshima: Gentium/Jazz Pharmaceuticals: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Honoraria; Nippon Shinyaku Co., Ltd.: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Fuji pharma CO.,Ltd: Research Funding; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; TEIJIN PHARMA Limited: Research Funding; Astellas Pharma Inc.: Research Funding; Bristol Myers Squibb: Honoraria; Janssen Pharmaceutical K.K.: Other; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Sanofi S.A.: Research Funding.

Risk Factors and Mortality Associated with CMV Reactivation Post Autologous Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4531-4531
Author(s):  
Claudia Bley ◽  
Fabio PS Santos ◽  
Guilherme Fleury Perini ◽  
Ricardo Helman ◽  
Andreza Alice Feitosa Ribeiro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Real Time Pcr ◽  
Cmv Infection ◽  
Cmv Reactivation

Abstract Abstract 4531 Introduction: Cytomegalovirus (CMV) is one of the most common viral pathogens post-allogeneic stem cell transplantation (SCT). However, CMV reactivation and disease are relatively uncommon events after autologous stem cell transplantation (ASCT), with a reported incidence of 2–9%. There are few studies describing risk factors for development of CMV reactivation post-ASCT. Objective: To describe the incidence and risk factors for CMV reactivation post-ASCT in our institution and its impact on survival. Methods: The charts of patients who underwent ASCT at our institution from January 2005 until July 2009 were manually reviewed. CMV reactivation was detected by antigenemia assay and/or real-time PCR. Variables associated with CMV in a univariate analysis with a p<0.15 were included into a multivariable logistic regression model to determine risk factors for developing CMV reactivation. Overall survival (OS) was defined from time of ASCT until death from any cause and was estimated by Kaplan-Meier method. Logrank test was used to compare unadjusted OS between patients with and without CMV reactivation. Results: A total of 115 ASCTs were performed at our institution during that time frame (bone marrow=8; peripheral blood stem cells=107). CMV reactivation was investigated in 50 patients (43.5%) who presented with persistent fever and 14 (12.3%) were found to be positive for CMV by either antigenemia and/or real-time PCR. Diagnosis included multiple myeloma (N=7) non-Hodgkin's lymphoma (N=6) and multiple sclerosis (N=1). Median time to CMV reactivation was 18 days (range 12–41). Seventy-two patients had information on absolute lymphocyte count at day 15. Patients with an ALC < 0.5×109/L at day 15 had a higher incidence of CMV reactivation (28.5% vs. 8%, p=0.02). Variables entered in the logistic regression multivariate analysis were age, sex, years between diagnosis and ASCT and ASCT in the last 12 months. Only age (odds ratio [OR]=1.06; p=0.05) and ASCT in the last year (OR=3.7; p=0.03) were significantly associated with CMV reactivation in the multivariate analysis. When analyzing only the 72 patients that had information on day 15 ALC, the multivariate analysis revealed ASCT in the last 12 months (OR=1.56, p=0.05) and day 15 ALC < 0.5×109/L (OR=4.71, p=0.03) as being associated with CMV reactivation. Patients who had CMV reactivation had a significantly inferior OS (2-years 61% vs. 23.4%, p=0.03). Conclusion: We detected a relatively high incidence of CMV infection post-ASCT and this was associated with a higher mortality. Patients who develop CMV infection post-ASCT may represent a subset that has a higher degree of immunesuppression, as manifested by a lower ALC at day 15 post ASCT. We believe that patients should be monitored post-ASCT for the presence of CMV reactivation, particularly if they present with persistent lymphopenia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Increased Incidence of Viral Reactivation after T Cell Replete Haploidentical Stem Cell Transplantation in Association with Delayed Immune Reconstitution

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4511-4511
Author(s):  
Ioannis Tsonis ◽  
Dimitrios Karakasis ◽  
Maria Bouzani ◽  
Chara Giatra ◽  
Zois Mellios ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Cell Transplantation ◽  
Viral Reactivation ◽  
Cmv Infection ◽  
Haploidentical Stem Cell Transplantation ◽  
Travel Grant ◽  
Cmv Reactivation

Introduction: The preferred method for haploidentical stem cell transplantation (haploSCT) is currently the use of post-transplantation cyclophosphamide (PTCY) since it obviates the need for depletion of T lymphocytes, which is associated with profound immunosuppression. Despite preservation of non-alloreactive donor T cells, reconstitution of pathogen-specific immunity may be delayed even after T cell replete haploSCT. The incidence and clinical sequelae of viral reactivation may thus compromise the outcomes of the procedure. Patients and Methods: The study included 47 patients, who underwent haploSCT with PTCY from 12/2013 until 05/2019 and achieved stable donor engraftment. Median age at transplant was 53 years (range, 19-70). The indications for transplant were acute myeloid (n=19) or lymphoblastic (n=10) leukemia, myelodysplastic syndrome (n=10), myelofibrosis (n=4), chronic myeloid (n=2) or lymphocytic (n=1) leukemia, and T-prolymphocytic leukemia (n=1). Myeloablative conditioning was mainly utilized (n=36), with the exception of certain patients who received reduced-intensity (n=10) or non-myeloablative (n=1) regimens. The graft source was peripheral blood in 29 and bone marrow in 18 cases. Tacrolimus in combination with mycophenolate mofetil was administered for prevention of graft-versus-host disease. Recipient/donor cytomegalovirus (CMV) serostatus was -/- (n=2), -/+ (n= 5), +/- (n=11), or +/+ (n=29). CMV, Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months post haploSCT. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood specimens in cases with symptoms suggestive of hemorrhagic cystitis (HC). Prophylaxis with letermovir was available in 1 patient only, and preemptive antiviral therapy was the principal modality for the management of CMV infection. Cellular immunity reconstitution was assessed by flow cytometry at 3, 6, and 12 months after transplant. Results: With a median follow-up time of 30 months (range, 2-64), the cumulative incidences (CIN) of relapse and non-relapse mortality (NRM) were 13.4% (95% confidence interval [CI], 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free (DFS) and overall survival (OS) were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. The CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34 out of 45 patients who were at risk, whereas recurrent CMV reactivation was observed in 17 patients with a median number of 1.5 episodes (range, 1-6) per patient. The median total duration of antiviral therapy for CMV infection was 27 days (range, 14-199). CMV disease (pneumonia) was documented in 2 patients. The CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 12 months. No case of EBV-related post-transplant lymphoproliferative disorder was observed, however preemptive therapy with rituximab was required in 2 patients with rapidly increasing EBV viral load. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%), but only one required therapy with foscarnet due to high viral load (>10,000 copies/ml). The CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy for bladder hemostasis was required in 5/13 and nephrostomy in 1/11 patients with HC. Reconstitution of helper T cell immunity was considerably delayed, with median absolute CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was significantly associated with the recovery of CD4+ cells at 3 months (Figure; median CD4+ count of 191/uL versus 62/uL in patients with 1 and 2 or more episodes of CMV reactivation, respectively; p=0.009). Conclusions: HaploSCT with PTCY is associated with substantial rates of viral reactivation (especially CMV and BKV) resulting in the need for prolonged antiviral therapy and considerable morbidity. Strategies to prevent viral infection are strongly warranted in haploidentical stem cell transplantation. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution following haploSCT. Figure Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Gilead: Other: Travel Grant; Aenorasis: Other: Travel Grant; Takeda: Other: Travel Grant; Pfizer: Other: Travel Grant; Innovis: Other: Travel Grant.

scholarly journals Cytomegalovirus Infections after Hematopoietic Stem Cell Transplantation: Current Status and Future Immunotherapy

2019 ◽  
Vol 20 (11) ◽  
pp. 2666 ◽  
Author(s):  
Sung-Yeon Cho ◽  
Dong-Gun Lee ◽  
Hee-Je Kim
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Infectious Complications ◽  
Current Status ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

Cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) is one of the critical infectious complications related to host immune recovery. The spectrum of CMV infection is quite extensive, from asymptomatic CMV reactivation presenting mainly as CMV DNAemia to fatal CMV diseases involving gut, liver, lungs, or brain. In addition to organ involvement, CMV reactivation can exert indirect effects such as immunosuppression or graft failure that may result in the development of concurrent infectious complications. Currently, preemptive therapy, which is based on PCR-based monitoring of CMV from blood, is a mainstay enabling improvement in CMV-related outcomes. During the past decades, new antiviral drugs, clinical trials for prophylaxis in high-risk groups, and vaccines for preventing CMV infection have been introduced. In addition, data for immunologic monitoring and adoptive immunotherapy have also been accumulated. Here, we review the current status and recent updates in this field, with future perspectives including immunotherapy in HSCT recipients.

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