Oral Valganciclovir As Preemptive Therapy for Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5855-5855 ◽  
Author(s):  
Vildan Ozkocaman ◽  
Fahir Ozkalemkas ◽  
Ridvan Ali ◽  
Yasemin Karacan ◽  
Tuba Ersal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
Myeloid Leukemia ◽  
Preemptive Therapy ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Intravenous Ganciclovir ◽  
Hematopoietic Stem ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract Introduction: Cytomegalovirus (CMV) infection remains one of the most important complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). Preemptive therapy with oral VGC or intravenous ganciclovir has replaced universal prophylaxis. We investigated the effect of oral VGC as preemptive therapy on CMV reactivation or infection in AlloHSCT. Patient & Methods: We retrospectively studied 30 consecutive adult recipients of HLA-identical sibling allogeneic peripheral blood stem cell transplant from June 2011 through June 2014 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. Among 30 patients we studied the results of 13 patients with CMV DNA positivity. All 13 recipients and their donors were seropositive for CMV Ig G status. Their diagnosis of pretransplantation were as 8 acute myeloid leukemia (61 %) and 5 acute lymphocytic leukemia (39 %). Median age was 39 years (range 21-54). There were 9 men and 4 women (Table-1). The patients received no prophylaxis against CMV. Blood/serum samples from all patients were routinely monitored for CMV-DNA using PCR twice weekly. We iniciated pre-emptive therapy for CMV as the viral load was above and equal to 500 copies/ml in two consecutive samples. VGC was given twice daily 900 mg for 2 weeks, and maintened at a dose daily 900 mg until viral load is undetectable. Results: The PCR test was persistently negative in 17 patients (57 %) and positive at least once in 13 (43%)patients. All patients with CMV reactivations were on immunsupressive treatment. CMV infection was cleared in most patients within 2 weeks, but for those with stable or increasing CMV levels, the induction period was continued. Twelve patients were treated with oral VGC on an outpatient basis and they all became CMV negative after the first week of treatment. Only one patient received intravenous ganciclovir and he was also CMV negative after the first week of treatment. While no positivity was identified in any of the patients who received VGC on day 21, clinically unimportant low titer CMV positivity was noted in three of these patients. VGC was continued at same dose and no positivity was detected after 2-3 weeks. We were obligated interrupt VGC in only four patients for serious side effects namely neutropenia and thrombocytopenia. We did not observe CMV-related mortality. Conclusions: We concluded that VGC therapy could be safely used at outpatient clinics, with frequent monitorization to prevent severe myelotoxicity. In conclusion, based on our findings, oral VGC is effective and safe in the pre-emptive treatment of CMV disease following allo-HSCT. Therefore, preemptive strategy by oral VGC appears preferable to the prevention of CMV disease in alloHSCT with its advantage of effectiveness and usage in outpatient clinic condition. Table- 1: Management and outcome of the patient characteristics with CMV-reactivation Patients with CMV reactivation/Total number of patient 13/30 Median age, years (range) 39 (21-54) Gender Male Female 9 4 Diagnosis AML ALL 8 5 CMV serologic status Donor+/Recipient + 13 Preperative regimen Bu-Cy CY-TBI Flu/Amsc(FLAMSA) 8 4 1 GVHD propylaxis CSA+MTX CSA+MTX+MM 12 1 GVHD prior to CMV reactivation Acute chronic without GVHD 7 1 5 Prednisolone treatment at the time of starting VCG Yes No 8 5 IST at the time of starting VGC Yes No 13 0 Median duration of CMV reactivation (day) 44 (8-330) Viral load before antivial treament (copies/ml) 1153 (78-12800) Treatment VGC (900 mg, twice daily for induction) GC (5 mg/kg, twice daily for induction) VGC+GC 9 (70 %) 1 (7 %) 3 (23 %) Total treatment duration (day) 24 (10-51) CMV DNA at the end of the treatment Conversion to negative Persistently positive (low titer < 50 copies/ml) 10 (77 %) 3 (23 %) Serious side effects Interruption of therapy due to neutropenia Interruption of therapy due to thrombocytopenia Reactivation 3 (23 %) 1 (7 %) 2 (15 %) Abbreviations: AML: acute myeloid leukemia, ALL: acute lymphoblastic leukemia, CMV: cytomegalovirus,GVHD: graft-versus host disease, CSA: cylosporine, MTX: methotrexate, MMF: mycophenolate mofetil, PDN:prednizolone, IST: Immunosupressive treatment, VGC: valganciclovir, GC: ganciclovir, Bu: Busulfan, Cy: cylophosphamide, TBI: total body irradiation Disclosures No relevant conflicts of interest to declare.

scholarly journals A Step Forward Towards Cytomegalovirus Free Hematopoietic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5708-5708
Author(s):  
Alfaraj Abeer ◽  
Daniel R Reed ◽  
Gina Petroni ◽  
Sandra Monson ◽  
Paige Williams ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
Hematopoietic Stem Cell Transplantation ◽  
Median Time ◽  
Preemptive Therapy ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract Introduction: Cytomegalovirus (CMV) reactivation remains one of the most serious complications after allogeneic hematopoietic stem cell transplantation (HSCT) occurring in up to 30-50% of HSCT recipients. CMV reactivation can lead to adverse outcomes including end-organ damage and graft failure. Prevention of CMV infection may improve outcomes of HSCT recipients; however, CMV reactivation can still occur in HSCT recipients despite receiving prophylactic acyclovir. In this study, we used prophylactic ganciclovir pre-transplant to reduce the incidence of CMV reactivation and CMV disease. Methods: To reduce the incidence of CMV reactivation and disease, ganciclovir was administered before transplantation (5 mg/kg twice daily intravenously from day −8 to day −2) for all donor and recipient seropositive allogeneic HSCT. This was followed by high dose valacyclovir or acyclovir starting day 0 until one year post-transplant. Patients were monitored weekly with serum CMV PCR through Day 100 post transplantation. Preemptive therapy was started for an elevated CMV viral load. CMV reactivation was defined as a CMV viral load of more than 135 IU/ml. Over the course of the analysis period, two different PCR methods were used for CMV viral load; since 2015 Roche Cobas AmpliPrep/Cobas TaqMan CMV test was implicated. CMV disease was defined as detection of CMV by one of the following diagnostic tests including: culture, immunohistochemistry staining, or histopathology examination accompanied by documentation of disease signs and symptoms of the affected organ. Statistical analysis was performed using SAS version 9.4. Logistic regression models were explored to assess the association of age, graft source, and disease type on CMV reactivation. We performed a retrospective analysis of all recipient or donor CMV seropositive patients who received their first allogeneic HSCT at the University of Virginia between 2012 and 2017. Results: Seventy-nine consecutive patients were treated. The median age was 58 years (range 20 to 72). The most common diagnoses were acute myeloid leukemia (n=39, 49%) and acute lymphocytic leukemia (n=11, 14% ). Graft sources were matched related donor, (n=24, 30%), matched unrelated donor, (n=28, 35%), haploidentical (n=4, 5%) and cord blood (n=23, 29%). 43 patients (55%) received myeloablative (CyTBI, BuCy and FluBu) conditioning. 36 patients (45%) received reduced intensity/nonmyeloablative conditioning (Flu/Cy/TBI+/- ATG, Flu/Cy/ATG ,Flu Mel, Flu Bu and Cy ATG). All patients received calcineurin inhibitor based prophylactic immunosuppressive therapy for GVHD prevention. 24 patients (30%) had CMV reactivation with median time of reactivation of 47 days post-transplant (range 27 to 229). 22 out of the 24 (88%) patients required treatment for CMV reactivation with a median treatment duration of 37 days (range 14 to 315). Patients were treated with either ganciclovir or foscarnet, as clinically indicated. The cumulative incidence of CMV reactivation at day 100 post-transplant was 27% with a 95% CI (18%-37%). The median highest viral load was 2130 copies/ml (range 151 to 3,250,000 copies/ml). There were no patients with biopsy proven CMV disease. There were no deaths attributed to CMV reactivation or disease. The median time-to neutrophil recovery (ANC > 500 k/uL) was 18 days and the median time to platelet count greater than 20,000 k/ul unsupported was 19 days. The incidence of acute GVHD (Grades II-IV) was 25 %. The incidence of significant acute kidney injury defined by serum creatinine of more than 2.5 mg/dL was 2.4 %. 1 year overall survival estimate was 54% with 95% CI (42-65%). In multivariate analysis, patients who received cord blood transplants, were approximately 4 times more likely to have a CMV reactivation (Odds Ratio 3.9 with a 95% CI(1.4-10.9)), p= 0.01, than those who did not. Conclusions:The incidence of CMV reactivation by day 100 of 27% with pre-transplant ganciclovir may be improved compared to historical controls of 30-50%.The use of pre-transplant ganciclovir was associated with no CMV disease, in this single center study.The use of pre-transplant ganciclovir is safe, with low incidence of kidney damage. These data suggest that pre-transplant ganciclovir with Preemptive therapy for viral reactivation should be considered regardless of graft source. Future prospective randomized trials are needed to evaluate strategies for CMV prophylactic regimens. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cytomegalovirus Reactivation in Hematopoietic Stem Cell Transplant Recipients in High Endemic Population

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Muhammad Farhan ◽  
Qamar Un Nisa Chaudhry ◽  
Syed Kamran Mahmood ◽  
Tariq Ghafoor ◽  
Raheel Iftikhar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Viral Load ◽  
High Viral Load ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Endemic Population ◽  
Cmv Reactivation

Background: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). It causes end-organ disease, multi-organ dysfunction syndrome, graft failure, increased susceptibility to infections and GVHD. According to the published western data greatest risk of CMV infection is the seropositivity of the recipient, however, in a high endemic population where seropositivity is up to 100%, risk factors for CMV reactivation are different and are analyzed in this study. Methods: It is a prospective descriptive study performed at Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan from January 2017 to March 2020. Consecutive patients who underwent allogeneic HSCT during this period were enrolled. All patients were prospectively monitored for CMV reactivation by weekly or two weekly CMV DNA quantitative PCR, from engraftment till day 100 post-transplant. CMV infection was diagnosed on detection of more than 200 copies/ml on PCR. Threshold for starting preemptive antiviral therapy was kept at 2000 copies/ml. Patients with past history of CMV infection, those who expired before day 14 post-transplant or those with less than 70% of required CMV tests were not included in the study. Factors associated with CMV reactivation, outcome of antiviral therapy and effect of CMV on post-transplant survival were studied. Results: Out of 319 transplants during this period, 230 patients fulfilled the inclusion criteria. Of these, 197 were HLA matched sibling, 18 were matched family donor and 15 were haploidentical transplants. There were 163 males and 67 females. Median age at transplant was 9.5 years (0.5-53). Eighty-three transplants were done in thalassemia, 55 in aplastic anemia, 14 in Fanconi anemia, 27 in acute leukemias, 8 in CML, 9 in MDS, 12 in HLH and 22 in other hematological disorders. All the patients and donor were CMV IgG seropositive when tested before transplantation. CMV reactivation was seen in 152 out of 230 patients (66.1%). Of 152, 95 patients had CMV viral load more than 2000 copies/ml and required antiviral treatment. Median time to reactivation since transplant was 35 days (13-90). In multivariate analysis using binary regression, risk factors for high viral load CMV reactivation included steroid administration (p=0.009), recipient age less than 10 years (p=0.003) and haploidentical transplant (p=0.048). No statistically significant association was found with the use of ATG, GVHD, underlying disease, ABO blood group or gender mismatch. Survival analysis using cox regression showed significant impact of high viral load CMV reactivation on post-transplant survival. Event-free survival (EFS) with and without CMV reactivation was 70.5 % and 89.7% respectively (p=0.004) and overall survival (OS) was 80.0 % and 97.4 % with and without CMV reactivation respectively (p=0.002). Valganciclovir was given in 89 patients and 6patients were treated with ganciclovir. Mean time to clear viremia was 19.8±9 days. Myelosuppression was seen in 41% of patients treated with valganciclovir. Renal impairment was seen in 25% of patients treated with valganciclovir. One patient had resistant disease. One patient had CMV pneumonia and she recovered. One patient died of suspected CMV pneumonia Conclusion: CMV reactivation was seen in 66.1% of the transplant recipients, this is higher compared to the western world due to high CMV seropositivity is this region. Steroids administration in post-transplant period significantly increase the risk of CMV reactivation. Preemptive therapy with valganciclovir effectively treats CMV reactivation. Viral threshold for treatment should be decided considering the regional endemicity. CMV adversely effects the transplant outcome in terms of EFS and OS. Disclosures No relevant conflicts of interest to declare.

Valganciclovir Is Safe and Effective as Pre-Emptive Treatment for CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5300-5300
Author(s):  
Rocco Pastano ◽  
Federica Gigli ◽  
Giovanna Andreola ◽  
Liliana Calabrese ◽  
Fedro Peccatori ◽  
...  
Keyword(s):  
Stem Cell ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Oral Treatment ◽  
Drug Formulation ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Intravenous Ganciclovir ◽  
Hematopoietic Stem

Abstract RATIONALE OF STUDY: Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection still represents an important cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplant (HSCT). The standard pre-emptive treatment is based on intravenous administration of Ganciclovir (GCV). Valganciclovir (VGC), the pro-drug formulation of GCV is characterised by an excellent bio availability, making this drug suitable for oral administration. PATIENTS: Since March 2003 all patients treated with reduced (27 patients) or fully ablative (3 patients) conditioning regimens followed by sibling HSCT, were monitored with bi-weekly CMV/PCR and pp65/assays. Overall 15 episodes of CMV positivity were detected in seven patients. Patients resulted positive (3 cells pp65+ or 1000/100000 PCR +) started oral treatment with VGC 900 mg bid, for the first fourteen days, followed by 900 mg q.d. up to at least seven days after assays normalization. The median duration of therapy was 21 days (range 10–21 days). No significant toxicity was observed. All patients had a normalization of CMV/PCR and pp65/assays within fourteen days, with a response rate (RR) of 100%. In two patients the oral VGC therapy was changed to the intravenous administration of Foscavir, because of concomitant neutropenia and acute GvHD. CONCLUSION: Pre-emptive treatment of CMV infection with VGC is safe, feasible and effective. Furthermore, the oral administration of this drug in an outpatient setting, reduces significantly the costs compared with a therapy that needs hospitalization as intravenous Ganciclovir.

Cytomegalovirus (CMV) gB3 Genotype Is Associated with Acute Gvhd and CMV Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients (HSCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1958-1958
Author(s):  
Débora de Campos Dieamant ◽  
Sandra Helena Alves Bonon ◽  
Francisco J P Aranha ◽  
Gislaine O. Duarte ◽  
Virginio C.O. Fernandes ◽  
...  
Keyword(s):  
Viral Load ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Gastrointestinal Disease ◽  
Antiviral Treatment ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Grade Ii ◽  
Cmv Disease

Abstract Abstract 1958 Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). Objectives: The goals of this study were: identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with the CMV disease, acute GVHD and overall survival. Study design: The diagnosis of active CMV infection after allogeneic HSCT was detected by Antigenemia (AGM) and/or Nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using the N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. Results: Were evaluated 63 allogeneic HSCT recipients, 49/63 patients (78%) presented active CMV infection detected by AGM and/or N-PCR, in a median time of 38 days after the transplant. The distribution of CMV gB genotypes in these 49 patients with active CMV infection was as follow: gB1, 19/49 (38.8%); gB2, 17/49 (34.7%); gB3, 3/49 (6.1%); gB4, 7/49 (14.3%) and three patients (6.1%) had mixed infection with gB1+gB3, gB1+gB4 and gB2+gB4. Acute GVHD grade II-IV occurred in 17/49 (34.7%) patients: 8/19 (gB1-42%), 1/17 (gB2 - 5.9%), 4/4 (gB3 - 100%) and 4/9 (gB4 - 44.4%). The distribution of the frequency of acute GVHD grade II-IV between the genotypes was statistically different (p=0.008). CMV disease occurred in 3/49 (6.1%) patients, characterized for gastrointestinal disease and these three patients had infection with CMV gB3 genotype. This genotype of CMV was also associated with higher viral load during antiviral treatment and worse survival. Conclusions: This study demonstrated that the frequency of active CMV infection in HSCT population was high (78%). The most prevalent genotype in patients with active CMV infection was gB1 and gB3 genotype was associated with acute GVHD grade II-IV, CMV gastrointestinal disease, higher viral load during antiviral treatment and worse survival. Disclosures: No relevant conflicts of interest to declare.

Prevalence and Patterns of Cytomegalovirus (CMV) Reactivation In Adult Acute Lymphoblastic Leukemia Patients on Chemotherapy: Single Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2583-2583
Author(s):  
Seema Gulia ◽  
Manju Sengar ◽  
Uma Dangi ◽  
Hari Menon ◽  
Sanjay Biswas ◽  
...  
Keyword(s):  
Viral Load ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clinical Manifestations ◽  
High Dose ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Laboratory Parameters ◽  
Cmv Reactivation

Abstract Abstract 2583 Background: Management of acute lymphoblastic leukemia (ALL) requires use of immunosuppressive agents like high-dose steroids and antimetabolites for prolonged periods which can predispose these patients for CMV reactivation and disease. As opposed to hematopoietic stem cell transplant there has been a real paucity of literature regarding clinical manifestations and management of CMV reactivation in ALL. In countries like India with a background of high CMV seropositivity (>90%), reactivation is a serious concern in ALL patients while receiving chemotherapy. Timely recognition and treatment can avoid the morbidity and mortality as well as help maintaining dose intensity which is the key to achieve cure in ALL patients. Methods: This retrospective case series included adult ALL patients (>14 years) who were being treated with chemotherapy between July 2009 to July 2011 at a tertiary care centre and detected to have CMV viraemia (Real time quantitative PCR with Roche CMV DNA QuantKit). PCR was done in patients with possibility of CMV infection based on clinical suspicion. Case records were analyzed for demography, chemotherapy details, clinical features, laboratory parameters, viral load, antiviral therapy and response. Results: Among 203 adult ALL patients, 23 (males-18, females-5) were detected to have CMV viremia. Median age was 23 years (range, 16–44 years). Occurrence of CMV reactivation was most common during later part of induction or re-induction phase of therapy which includes high dose of steroids (14/23) followed by maintenance therapy with 6-mercaptopurine and methotrexate (5/23) and high dose cytarabine based treatment (4/23). Presenting features were: fever (19/23), fever alone (2/23) respiratory symptoms (9/23), anorexia (10/23), loose stools (8/23), abdominal pain (7/23) and splenomegaly (1/23). Abnormal laboratory parameters were: leukopenia or thrombocytopenia (14/23), deranged liver function tests (12/23). CT thorax was abnormal in 3 patients. Bacterial and fungal co-infection was seen in 5/23 patients. Median CMV viral load was 3.0 ×103 copy numbers (range, 708–1.38×106). Eighteen of these patients were treated with intravenous gancyclovir for a period of 14 days. In remaining 5 patients abnormal clinical and lab parameters improved either with antibiotic therapy or spontaneously. Median time to fever defervescence was 4 days (range, 2–5 days). Blood counts recovered after median period of 5 days (range 3–9 days). Gancyclovir related neutropenia and transaminitis developed in 1 patient. CMV titre became undetectable after a period of 2–4 weeks. Conclusion: Awareness of diverse clinical manifestations of CMV infection and high index of suspicion is important for timely diagnosis. Early diagnosis and treatment with gancyclovir reduces the morbidity, empirical use of other antimicrobials and avoids delays in administration of chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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 Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 21 (10) ◽  
pp. 3663
Author(s):  
Ki Hyun Park ◽  
Ji Hyeong Ryu ◽  
Hyunjoo Bae ◽  
Sojeong Yun ◽  
Joo Hee Jang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Nk Cells ◽  
Nk Cell ◽  
Disease Group ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Delayed Recovery ◽  
Cmv Disease ◽  
Cmv Reactivation

Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (n = 23), non-reactivation (n = 24) versus CMV disease (n = 11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcRγ-CD3ζ+NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFNγ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells’ maturation and cytotoxic/IFNγ production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease.

scholarly journals Cytomegalovirus reactivation following hematopoietic stem cell transplantation

2013 ◽  
Vol 7 (12) ◽  
pp. 1003-1007 ◽  
Author(s):  
Sanjeev Kumar Sharma ◽  
Suman Kumar ◽  
Narendra Agrawal ◽  
Lavleen Singh ◽  
Anjan Mukherjee ◽  
...  
Keyword(s):  
Developing Countries ◽  
Stem Cell ◽  
Gastrointestinal Tract ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Transplant ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Cmv Disease ◽  
Cmv Reactivation

Introduction: There is a high prevalence of cytomegalovirus (CMV) seropositivity in developing countries. An apparent risk of CMV reactivation increases following hematopoeitic stem cell transplantation. With effective surveillance and timely treatment using anti-viral therapy, morbidity and mortality associated with CMV reactivation can be reduced. Objectives: To evaluate the incidence and morbidity associated with CMV reactivation following hematopoeitic stem cell transplantation. Methodology: We retrospectively analysed 136 hematopoeitic stem cell transplant recipients at our centre for CMV reactivation and their complications. Quantification of CMV-DNA was done by PCR. CMV disease was confirmed histologically via CMV inclusion bodies or immunostaining of biopsy of the affected organ, mainly the gastrointestinal tract. Results: A total of 13 out of 136 patients (9.56%) had CMV reactivation. 6 out of 13 patients had CMV disease, 3 of which died (23.1% of patients with CMV reactivation). CMV reactivation occurred at a median duration of 52.5 days post transplantation (range 35-178 days). The gastrointestinal tract was the organ most commonly affected by CMV. The median follow-up was 14 months (range 6 - 64 months). Conclusion: Through a higher rate of sero-prevalance in developing countries, the incidence of CMV infection following hematopoeitic stem cell transplantation is comparable to that reported in Western literature. Oral valganciclovir was an effective pre-emptive therapy for CMV disease.

scholarly journals Late Cytomegalovirus Disease after Hematopoietic Cell Transplantation (HCT) in the Preemptive Therapy Era: Characteristics, Efficacy of PCR-Based Surveillance, and Impact on Mortality

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1135-1135
Author(s):  
Sezen Özkök ◽  
Hu Xie ◽  
Zach Stednick ◽  
Sachiko Seo ◽  
Michael Boeckh ◽  
...  
Keyword(s):  
Viral Load ◽  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Low Risk ◽  
Preemptive Therapy ◽  
Cmv Infection ◽  
Cmv Disease ◽  
Cmv Reactivation ◽  
Overall Mortality

Abstract Background: Late cytomegalovirus (CMV) disease is a well-established complication in patients undergoing HCT and extended surveillance and preemptive therapy in high-risk patients is recommended by international guidelines. The objectives of this study were to describe the incidence, clinical characteristics and outcome of, and risk factors for the development of late CMV disease in day 100 survivors of allogeneic HCT who did and did not undergo viral load-guided preemptive therapy based on a pre-defined risk algorithm. Methods: We retrospectively analyzed medical records of 1526 HCT patients (donor or recipients seropositive), who received their first allogeneic HCT at FHCRC between 2001 and 2011 and survived to day 100. PCR-based surveillance was recommended for patients who had CMV viremia or disease before day 100 or had GVHD that required systemic treatment. Preemptive therapy was recommended for CMV DNA levels of >1000 copies per mL of plasma. We evaluated all CMV disease events occurring between day 100 and 2 years. Patients were categorized by their recommended surveillance status and, among those who were in the surveillance category, adherence to the testing schedule was examined. Cox proportional hazards models were used to evaluate the risk of late CMV disease and overall mortality. Candidate variables included risk status for PCR surveillance, CMV reactivation (before day 100 and after day 100 [as time dependent variable]), steroid use (≥ 1mg/kg/day) as well as other patient/donor and transplantation related factors; for mortality late CMV disease was also analyzed as a variable. Results: Among 1526 patients there were 118 cases of late CMV disease by 2 years (cumulative incidence 8% [95% CI- 7-9%]). The first manifestation of late CMV disease was pneumonia in 57 cases (48%), gastrointestinal disease (GI) in 54 cases (46%), and retinitis in 7 cases (6%). Fifteen percent of patients with late CMV disease (1% of cohort) had a subsequent event. Among first cases of late CMV disease 97 (82%) occurred between day 100 and 1 year and 21 (18%) occurred between 1 and 2 years after HCT. The median time to first late CMV disease was 192 days for pneumonia, 196 days for GI, and 230 days for retinitis. Extended CMV surveillance after day 100 was recommended for 1246 (82%) of patients. Late CMV disease occurred in 8.7% of patients for whom continued surveillance was recommended, compared to 2.9% of patients who were considered at low risk and were not advised to continue CMV testing. The median time to first late CMV disease event was 192 days post-transplant for the high risk group and 292 days for the low risk group. Among the 8 disease cases in patients in the low risk group, 4 cases (2 pneumonia, 2 GI) occurred in the first year and 4 (1 pneumonia, 3 GI) in the second year after HCT. In a multivariable Cox model steroid treatment after day 100 (HR=6.49; 95% CI 3.4-12.3, p<0.001), CMV reactivation after day 100 (HR=3.78; 95% CI 2.5-5.7, p<0.001), and CMV reactivation before day 100 (HR=2.07; 95% CI 1.3-3.4, p=0.003) were all strongly associated with the risk of late CMV disease. The development of CMV disease and acute GVHD (grade 3-4) before day 100 were not significantly associated with late CMV disease. Late CMV disease (HR=2.2; 95% CI 1.6-3, p<0.001) and late CMV reactivation (HR=1.63; 95% CI 1.3-2, p<0.001) were associated with increased risk of death between day 100 and 2 years after HCT. An analysis of the adherence to PCR surveillance and viral load levels among breakthrough cases will be presented at the conference. Conclusions: Late CMV disease remains an important complication after HCT. Currently recommended risk stratification parameters for extended surveillance identify most patients at risk for late CMV disease, however, occasionally late CMV disease can occur in patients that were deemed at low risk at 3 months after HCT. Also, late CMV disease can occur beyond 1 year after HCT and disease recurrence is about 15%. Overall, both late CMV infection and disease continue to be independently associated with overall mortality in the preemptive therapy era. Refined strategies are needed to further reduce the late-occurring complications of CMV infection among HCT recipients. Disclosures Boeckh: Chimerix Inc.: Consultancy, Research Funding; Viropharma Inc.: Research Funding; Genentech/Roche: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Clinigen: Consultancy.

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