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.

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.

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 The Economic and Health Utilization Cost of Clinically Significant Cytomegalovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3437-3437
Author(s):  
Michelle K Yong ◽  
Shio Yen Tio ◽  
Jake Valentine ◽  
Joe Sasadeusz ◽  
Lynette C.Y. Chee ◽  
...  
Keyword(s):  
Health Care ◽  
Stem Cell ◽  
Viral Load ◽  
Research Funding ◽  
Resource Utilisation ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Total Cost ◽  
Allogeneic Hsct ◽  
Clinically Significant

Introduction Understanding the economic impact of managing allogeneic hematopoietic stem cell transplant (HSCT) recipients with cytomegalovirus (CMV) is important for future planning within institutional transplant programs. CMV remains the most frequent viral infection following HSCT of which the clinical impact on transplant outcomes has been well described. However, much less is known about the impact of CMV on health resource utilisation, re-admissions and hospital costs. In addition to antiviral therapy, there are nursing, medical and pharmacy costs to consider. We therefore undertook a study to evaluate the clinical and economic burden of CMV infection following HSCT in a large Australian transplant centre operating under a universal health care system. Methods A retrospective single centre study at the Royal Melbourne Hospital, Melbourne, Australia was performed on all consecutive allogeneic HSCT recipients between January 2015 to December 2017. CMV pre-emptive monitoring using quantitative CMV plasma viral load was performed twice weekly from time of transplant to 100 days or longer in the presence of graft versus host disease. Clinically significant CMV (csCMV) was defined as patients receiving anti-CMV treatment, often with a plasma CMV viral load &gt;400 IU/ml. Throughout the study period, the first line anti-CMV therapy was ganciclovir; either as oral valganciclovir for outpatient management in asymptomatic patients or IV ganciclovir as an inpatient for patients with concerns about oral absorption. Second-line therapy was IV foscarnet. Hospital costing data for the first and subsequent re-admissions for the first 12 months were obtained from the business intelligence unit. Financial year costing was available for FY2015/2016 to FY2017/2018. Ethics was approved by the Melbourne Health Human Ethics Review Committee (HREC 2017.368). Results A total of 255 patients underwent alloHSCT with a median age of 51 years (IQR 40-59) with the most common underlying diagnoses being AML (41%), ALL (11%) and MDS (11%) (Table 1). Thirty-one percent of transplants used myeloablative conditioning, 54% had unrelated donors and 3% had an umbilical cord source. Pre-transplant recipient CMV seropositivity was 62% (n=158), of whom 139 had detectable CMV viremia and 104 (40.8%) experienced clinically significant CMV (csCMV). The median duration of CMV treatment was 33 days (IQR 21-63). Re-admission to hospital within the first 12 months of HSCT occurred in 78.4%. There was a greater number of admissions observed in csCMV patients compared to no csCMV (median 3 vs 2 admissions, p=0.001) with the duration of admitted days within the first 12 months being significantly greater in csCMV patients compared to no csCMV (median 65 vs 36 days, p&lt;0.00001). The mean total cost of treating patients with csCMV for the first 12 months compared to the total cost for patients not requiring CMV treatment was A$196,822 (US$147,616) and A$114503 (US $85,877) (p&lt;0.0001), respectively. Therefore the crude attributable mean cost of treating csCMV was A$82,319 (US$61,739) per patient for the first 12 months of HSCT. The greatest significant contributory costs were from pharmacy A$17,807 (US$13,355), nursing A$16,944 (US$12,708) and medical A$5,898 (US$4,423). Conclusions The health care cost and resource utilisation of treating CMV infection following an allogeneic HSCT is substantial and places a heavy burden on limited health resources. In this study, patients experiencing csCMV had an increased number and longer total duration of admissions days compared to patients who did not require CMV treatment. Interventions aimed at reducing the burden of CMV in alloHSCT recipients are required. Disclosures Yong: Merck Ltd: Honoraria. Bajel:AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: travel funding. Ritchie:Sanofi: Honoraria; Novartis: Honoraria; Imago: Research Funding; Beigene: Research Funding; Takeda: Research Funding; BMS: Research Funding; Pfizer: Consultancy; Amgen: Consultancy, Honoraria, Research Funding. Slavin:Merck Ltd: Honoraria, Research Funding.

Risk Factors for Developing Human Herpes Virus-6 Encephalitis and Clinical Significance of Antiviral Therapy In Early Phase After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4538-4538
Author(s):  
Ayumi Numata ◽  
Masatsugu Tanaka ◽  
Takayoshi Tachibana ◽  
Yoshiaki Ishigatsubo ◽  
Atsuo Maruta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Viral Load ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Cell Transplantation ◽  
Hematopoietic Stem ◽  
Group A ◽  
Related Donor ◽  
Group B

Abstract Abstract 4538 Background: Human herpes virus-6 (HHV-6) encephalitis is a relatively rare complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the patients who developed HHV-6 encephalitis sometimes might be serious condition and suffer the consequences such as a disturbance of memory. We studied the viral load of HHV-6 after HSCT and evaluated risk factors of encephalitis, and assessed the clinical significance of antiviral therapy in early phase after HSCT for the prevention of HHV-6 encephalitis. Patients and methods: The viral load of HHV-6 by PCR was measured at 2, 3, and 4 weeks following HSCT for acute leukemia or myelodysplastic syndromes between April 2004 and May 2010. HHV-6 encephalitis was diagnosed with neurologic symptoms, the elevation of viral load in CSF, and abnormal MR imaging findings. Patients were divided into 2 groups based on the administration of antiviral agents (ganciclovir, valganciclovir or foscarnet) within 28 days after HSCT. Patients who had no treatment with antiviral agents until the development of HHV-6 encephalitis were defined as group A (n=96). Patients who received preemptive therapy within 28 days for the elevation of viral overload of HHV-6 or cytomegalovirus antigenemia, or other reason were defined as group B (n=34). Results: A total of 130 patients included 79 with acute myeloid leukemia (AML), 34 with acute lymphoid leukemia (ALL), and 17 with myelodysplastic syndrome (MDS).The median age was 41 years (range, 17–65). There were 66 males and 64 females. A disease risk at the time of transplant indicated a standard risk in 76 patients and a high risk in 54. Myeloablative conditioning was employed for 78 patients and reduced intensity conditioning was for 52. Bone marrow transplantation (BMT) from related donor, BMT from unrelated donor, peripheral blood stem cell transplantation from related donor, and cord blood transplantation were done for 39, 53, 12 and 26 patients, respectively. The median level of viral load at 2, 3, and 4 weeks after HSCT were 0 (range, 0–41200) (n=130), 0 (0-290000) (n=125), and 0 (0-3650) (n=114) copies/ml, respectively. Eight patients developed HHV-6 encephalitis in group A. Five of the eight patients with encephalitis had undergone UBMT and 3 had received CBT. The median age was 35 years (range, 22–59), 4 were male. Two patients had received the second HSCT for leukemia relapse. The median day from HSCT to diagnosis was 17.5 days (range, 15–26). The median of viral load was 6630 (range, 1610–22100) copies/ml at diagnosis. All patients received antiviral therapy either ganciclovir or foscarnet. Three of the 8 patients died on day 97 (sepsis), 160 (viral pneumonia), and 346 (chronic GVHD), respectively. Two of the five surviving patients have been suffering from short term memory deficit. By univariate analysis in group A, risk factors for developing HHV-6 encephalitis were unrelated donor (vs related donor: 14.8 vs 0%, p<0.01), ALL (vs AML and MDS: 19.2% vs 4.2%, p=0.03), fever338°C within 6 days after HSCT (vs fever< 38°C: 29.6 vs 0%, p<0.01), use of corticosteroid within 3 weeks after HSCT (vs no use: 45.5 vs 3.5%, p<0.01), and positive for viral load at 2 weeks after HSCT (vs negative: 27.3% vs 2.7%, p<0.01). The median time of starting preemptive antiviral therapy with either ganciclovir, valganciclovir or foscarnet in group B was day 20 (range, 11–28) after HSCT. No patients developed HHV-6 encephalitis in group B, although there was no significant difference of patient characteristics between group A and B. Conclusions: HHV-6 encephalitis occurring after HSCT is becoming a curable complication, but its sequelae such as neuropsychological disorders have a marked influence on the quality of life. Preemptive antiviral therapy for patients with risk factors and the elevation of viral load on day 14 might be a potential strategy for preventing of HHV-6 encephalitis. 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.

Expression of SOCS1 and SOCS3 Genes with Human Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3038-3038
Author(s):  
Tae Hyang Lee ◽  
Ji Yoon Lee ◽  
Sohye Park ◽  
Jae-Ho Yoon ◽  
Seung Hwan Shin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Statistical Significance ◽  
Myelogenous Leukemia ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myelogenous ◽  
Cmv Reactivation

Abstract Abstract 3038 Background: After allogeneic hematopoietic stem cell transplantation (HSCT), cytomegalovirus (CMV) infection is highly prevalent in recipients. Although the suppressor of cytokine signaling (SOCS) genes are mainly regarded as pivotal negative feedback regulators for signaling of cytokines, the expression pattern of SOCS genes in CMV infections remains largely unexplored. To understand the molecular mechanism of cytokine cascades associated with CMV infection, we investigated the expression of SOCS genes from various types of hematologic malignancies after allogeneic HSCT. Methods: In the present study, we investigated SOCS1 and SOCS3 gene expressions, in order to examine the feasibility of SOCS genes as a promising therapeutic target as well as a prognostic predictor in CMV infection. A total of 99 recipients with acute myelogenous leukemia (AML; n=64), acute lymphoblastic leukemia (ALL; n=23), myelodysplastic syndrome (MDS; n=12), who received allogeneic HSCT and 55 normal donors were included. Real-time quantitative polymerase chain reaction (RQ-PCR) was used and all sample analyses were performed in triplicate. Results: The expression levels of the SOCS3 gene were clearly decreased in recipients compared to normal donors, including in the Pre-HSCT, Post-HSCT No CMV, and Post-HSCT CMV subgroups (P=0.0007, P=0.0009, and P=0.0014, respectively). Meanwhile, expressions of SOCS1 gene were significantly decreased in the Pre-HSCT, Post-HSCT No CMV, and normal donors, when compared to Post-HSCT CMV subgroup (P=0.026, P=0.0129, and P<0.0001, respectively), suggesting a correlation between expression of SOCS genes and CMV reactivation. In addition, expression of SOCS1 gene was remarkably increased in patients who received allogeneic HSCT with myeloablative conditioning (MAC), compared to reduced-intensity conditioning transplantation (RIST) and normal donors (P=0.0119, P=0.0002, respectively), while, both regimen with MAC and RIST showed a decreasing pattern with statistical significance compared to normal donors (P=0.0037, P=0.0024, respectively). Notably, SOCS1 gene expression in acute lymphoblastic leukemia and myelodysplastic syndrome recipients were higher than acute myelogenous leukemia, when compare to normal donors (P=0.0239). Furthermore, high expression of SOCS1 gene unarguably showed high mortality (P=0.0068). In AML patients, decreased SOCS3 gene was detected (P=0.0007) and overall high expression of SOCS3 gene was displayed high mortality, but there is no statistical significance. Conclusions: We firstly report that the SOCS genes are differently expressed in human CMV infection after allogeneic HSCT, suggesting a correlation between cytokines by modulation of SOCS genes associated with CMV reactivation. This result provides a new platform for studying CMV immunobiology and these genes may be a potential of diagnostic and therapeutic targets in post-allogeneic HSCT associated with CMV infection. Disclosures: No relevant conflicts of interest to declare.

CMV reactivation in allogeneic hematopoietic stem cell transplant patients receiving post-transplant cyclophosphamide.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18533-e18533
Author(s):  
Paul Markowski ◽  
Dale G. Schaar ◽  
Catherine Wei ◽  
Anne Tyno
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Published Data ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Transplant Patients ◽  
Number Of Patients ◽  
Cmv Reactivation

e18533 Background: Post transplant cyclophosphamide (PTCY) has been shown to be an effective treatment for prevention of graft versus host disease (GVHD). However, this increased immune suppression rates may increase the risk of CMV reactivation. There is limited published data addressing CMV reactivation in this patient population. Additionally there is no data on the efficacy of prophylactic letermovir in the patients who have received PTCY. In this study we analyzed the incidence of CMV reactivation in patients treated with PTCY and those not treated with PTCY, as well as the efficacy of letermovir in preventing CMV reactivation in the PTCY population. Methods: We conducted a retrospective review of MUD, MRD, and haploidentical stem cell transplant patients at our institution from 1/1/2014 until 12/10/2018. We analyzed the incidence of CMV reactivation (PCR > 137 DNA IU/ml), peak of CMV PCR titer and time to reactivation within the first 100 days post-transplant. Results: There were 150 patients with at least 60 days of follow-up that were included in this study. These patients were split into three groups: No post-transplant cyclophosphamide (NPTCY) (N = 64), received post-transplant cyclophosphamide (PTCY) (N = 70), and received PTCY and letermovir prophylaxis. (L-PTCY) (N = 15). The incidence of CMV reactivation was increased in the PTCY patients when compared to the NPTCY (44% vs 29%). In the NPTCY patients the donor (D) serostatus increased the risk of CMV reactivation (Recipient (R)+ D+ 73% vs R+D-36%) conversely in the PTCY group the donor CMV status did not influence reactivation rates (R+D+ 52% vs R+D- 81%). The CMV reactivation rate in the L-PTCY patients was lower when compared to the PTCY patients (21% vs 44%), additionally the L-PTCY patients had much lower peak CMV titers compared to PTCY group (445 vs 2112 IU/ml). Conclusions: This study demonstrates that there is an increased incidence of CMV reactivation in patients who receive PTCY. Additionally, the donor CMV serostatus does not appear to influence the incidence of CMV reactivation in patients receiving post-transplant CY. Although the number of patients in the L-PTCY group is small, it does appear to be an effective prophylactic treatment in patients receiving PTCY.

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