Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ²=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ²=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.
Humans ; Cytomegalovirus ; Retrospective Studies ; Cohort Studies ; Prospective Studies ; Cytomegalovirus Infections/prevention & control* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/prevention & control* ; Recurrence ; Antiviral Agents/therapeutic use*

Cytomegalovirus Infections/prevention & control* ; Educational Status ; Humans ; Mass Screening ; Research

BACKGROUND: The best approach to reduce congenital cytomegalovirus infection (cCMVi) is to practice behaviors that reduce cytomegalovirus (CMV) transmission during pregnancy. Expanding awareness and knowledge of CMV is expected to result in increased practice of preventative behaviors. To this end, it is necessary to understand current awareness and knowledge of CMV. METHODS: This web-based cross-sectional survey assessed the awareness and knowledge of cCMVi among pregnant women and the general public in Japan. Participants aged 20-45 years (pregnant and non-pregnant women, and men) were identified from a consumer panel. Study outcomes (all participants) included awareness of cCMVi and other congenital conditions. Among those aware of cCMVi, outcomes included knowledge of CMV transmission routes, long-term outcomes of cCMVi, and behaviors to prevent CMV transmission during pregnancy. Outcomes limited to pregnant women included the practice of preventative behaviors and opinion on how easy it is to implement these behaviors. The data of the pregnant group (pregnant at the time of the survey) were compared with those of the general group (non-pregnant women and men). RESULTS: There were 535 participants in the pregnant group and 571 in the general group. Awareness of cCMVi was generally low (pregnant, 16.1%; general, 10.2%). Pregnant participants were significantly more aware of most congenital conditions than those in the general group, including cCMVi (P = 0.004). Knowledge about CMV/cCMVi was limited; there were no significant differences between the two groups for 24 of the 26 knowledge questions. A small proportion (one third or less) of pregnant women practiced behaviors to prevent the transmission of CMV, though most (73.3-95.3%) pregnant women who were aware of cCMVi considered such behaviors easy to implement. CONCLUSIONS: Awareness and knowledge of CMV/cCMVi is low among pregnant women in Japan; the level of knowledge is similar to that among the general public. This needs to be improved. Most pregnant women considered behaviors to prevent CMV transmission easy to perform, which indicates that effectively educating pregnant women regarding the long-term outcomes of cCMVi, CMV transmission routes, and preventative behaviors will contribute to a reduced incidence of cCMVi. TRIAL REGISTRATION UMIN Clinical Trials Registry, UMIN000041260 .
Cross-Sectional Studies ; Cytomegalovirus Infections/prevention & control* ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Internet ; Japan/epidemiology* ; Male ; Pregnancy ; Pregnant Women

Breast milk is considered ideal food for premature infants, but it can also be the main source of cytomegalovirus (CMV) infection in premature infants. CMV infection may cause serious clinical symptoms, such as sepsis-like syndrome, thrombocytopenia, neutropenia, jaundice, hepatitis, and pneumonitis. This article reviews the research advances in symptoms, treatment strategies, prognosis and the prevention of breast milk-acquired CMV infection in premature infants.
Breast Feeding ; Cytomegalovirus Infections ; etiology ; prevention & control ; therapy ; Humans ; Infant, Newborn ; Infant, Premature ; Infectious Disease Transmission, Vertical ; prevention & control ; Milk, Human ; virology

PURPOSE: Extremely low birth weight infants (ELBWIs) have a high risk of acquiring cytomegalovirus (CMV) infection via breast milk and consequently developing serious symptoms. We evaluated whether freeze-thawing or pasteurization could prevent postnatal CMV infection transmitted through breast milk in ELBWIs. MATERIALS AND METHODS: Medical records of 385 ELBWIs with whole milk feeding, and freeze-thawed or pasteurized breast milk feeding were reviewed retrospectively. Postnatally acquired CMV infection was defined as an initial negative and a subsequent positive on follow-up urine CMV DNA polymerase chain reaction screening tests. The incidence, clinical characteristics, symptoms, sequelae, and long-term outcome at corrected age [(CA): 2 years of CMV infection] were analyzed. RESULTS: While no infant developed CMV infection with whole milk (0/22) or pasteurized breast milk (0/62) feeding, postnatal CMV infection was diagnosed in 8% (27/301) of ELBWIs who were fed freeze-thawed breast milk. Gestational age in the CMV group was significantly lower than the control group. In 82% (22/27) of cases, CMV infection was symptomatic and was associated with increased ventilator days and > or =moderate bronchopulmonary dysplasia (BPD). Neurodevelopmental outcome and growth status at CA 2 years were not different between the study groups. Lower gestational age and freeze-thawed breast milk feeding >60% of total oral intake during the first 8 postnatal weeks were independent risk factors for acquiring postnatal CMV infection. BPD (> or =moderate) was the only significant adverse outcome associated with this CMV infection. CONCLUSION: Pasteurization but not freeze-thawing of breast milk eradicated the postnatal acquisition of CMV infection through breast milk.
Adult ; Breast Feeding ; Bronchopulmonary Dysplasia ; Cytomegalovirus/*isolation & purification ; Cytomegalovirus Infections/epidemiology/prevention & control/*transmission ; Female ; Gestational Age ; Humans ; Incidence ; Infant ; *Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*prevention & control ; Male ; Milk, Human/chemistry/*virology ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Complications, Infectious/diagnosis ; Retrospective Studies ; Risk Factors

OBJECTIVETo observe the conditioning regimen, efficacy and side effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hemophagocytic lymphohistiocytosis (HLH).

METHODFrom 2010 to 2012, a total of 11 cases after allo-HSCT were evaluated including 8 cases with familial hemophagocytic lymphohistiocytosis (FHL) and 3 cases with Epstein-Barr virus (EBV) related HLH. Allo-HSCT from HLA haploidentical HSCT was performed for 3 cases and unrelated allo-HSCT for 8 cases; 7 cases underwent allo-HSCT with conditioning regimen of etoposide (VP16), busulphan (Bu), fludarabine (Flu) and antilymphocyte globulin (ATG) and 4 cases with Flu, melphalan (Mel) and ATG. Cyclosporine (CsA) or tacrolimus, mycophenolate (MMF) and methorexate (MTX) were used for prevention of graft versus host disease (GVHD). Four cases received anti-CD25 MoAbs, 7 cases received cord blood and 1 of them received haploidentical bone marrow to prevent GVHD.

RESULTThree cases died after allo-HSCT. The median overall survival time of the 8 cases evaluated was 585 days (154-1 115 d). All the patients were successfully engrafted. Acute GVHD (aGVHD) occurred in 8 cases, including 3 cases of gradeI/II and 5 cases of grade III/IV. Chronic GVHD (cGVHD) occurred in 4 cases. Seven cases had cytomegalovirus (CMV) reactivation.

CONCLUSIONThe allo-HSCT was successful in treating primary and refractory hemophagocytic syndrome.

Adolescent ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; Cytomegalovirus Infections ; epidemiology ; prevention & control ; Female ; Graft vs Host Disease ; epidemiology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Immunosuppressive Agents ; administration & dosage ; Lymphohistiocytosis, Hemophagocytic ; mortality ; therapy ; Male ; Survival Rate ; Tissue Donors ; Transplantation Conditioning ; methods ; Treatment Outcome

The aim of this study was to analyze the risk factors of cytomegalovirus (CMV) infection and CMV disease after nonmyeloablative allogeneic hematopoietic stem cell transplantation(NST) and develop a rational strategy for the diagnosis, monitoring and preemptive treatment of CMV infection. The Clinical data of 80 patients undergoing NST from November 2009 to November 2012 in the hospital 307 were retrospectively analyzed. The cytomegalovirus load in peripheral blood of patients was detected by using RT-PCR. The results indicated that the incidence of CMV infection was 77.5% (62/80), and the median time for the positive CMV-DNA firstly detected by RT-PCR was day 35 (17-133) after NST. The total of 100-day cumulative incidence of CMV disease was 11.3%(9/80) after early preemptive therapy. Both univariate and multivariate analysis showed thymoglobulin (ATG) used in preconditioning regimen, other herpesvirus infection and fungal infection in medical history before NST were the risk factors of CMV infection after NST.Univariate analysis revealed that CMV viremia and ATG used in preconditioning regimen were the risk factors for CMV disease, while the same result was not found in the multivariate analysis.The incidence of CMV infection in patients with II-IV grade of aGVHD was 91.3%,while the incidence of CMV infection in patients with 0-1 grade of aGVHD was 71.9% (P = 0.06), it seems that II-IV grade of aGVHD was not the risk factor of CMV infection for NST. It is concluded that the ATG used in preconditioning regimen may increase the incidence of both CMV infection and CMV disease after NST. CMV infection easily accompanies by other herpesvirus infection and fungal infection.Therefore other herpesvirus infection and fungal infection should be attentively monitored and prevented after trans-plantation.
Adolescent ; Adult ; Antilymphocyte Serum ; Cytomegalovirus Infections ; diagnosis ; prevention & control ; therapy ; Female ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; adverse effects ; Retrospective Studies ; Risk Factors ; Transplantation Conditioning ; Transplantation, Homologous ; adverse effects ; Young Adult

Cytomegalovirus ; Cytomegalovirus Infections ; prevention & control ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; T-Lymphocytes, Cytotoxic ; virology ; Transplantation, Homologous

OBJECTIVE: To explore the correlation between peripheral blood cytomegalovirus (CMV) DNA level and cyclosporine A (CsA) plasma concentration among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who received immunosuppressant treatment, and to evaluate the potential clinical value. METHODS: A total of 32 allo-HSCT patients were enrolled and their data were analyzed retrospectively. Ganciclovir was used to prevent CMV infection before the transplantation. Routine fluorescence PCR was admitted to test the blood CMV DNA level. The patients were divided into 2 groups: a CMV DNA positive group and a CMV DNA negative group. Enzyme multiplied immunoassay technique was adopted regularly to monitor the blood CsA concentration. The correlation between CMV DNA level and CsA concentration was analyzed. RESULTS: The CMV infection rate in patients who received allo-HSCT was 53.13%. The blood CsA concentration in the CMV DNA positive group was significantly higher than that in the CMV DNA negative group (P<0.05). Through the ROC curve, the area under the curve on Day 1, 7, and 14 had statistical significance compared with 0.5, and the corresponding blood CsA concentration was 203.15, 215.55, and 302.65 ng/mL, respectively. CONCLUSION Immunosuppressive drug concentration can affect the dynamic changes of CMV DNA. High blood CsA concentration may be one of the reasons for CMV infection. Monitoring the blood CsA concentration may provide guidance for clinical treatment.
Adolescent ; Adult ; Cyclosporine ; adverse effects ; blood ; therapeutic use ; Cytomegalovirus ; isolation & purification ; Cytomegalovirus Infections ; prevention & control ; DNA, Viral ; blood ; Female ; Ganciclovir ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; blood ; therapeutic use ; Leukemia ; therapy ; Male ; Retrospective Studies ; Young Adult

PURPOSE: Acute interstitial pneumonia (AIP) is a rare disease, but its prognosis is fatal because of lack of efficient treatment modality. Recently, it has been reported that there was epidemic AIP in Korea. This study aims to investigate the past and current status of AIP in Korea. METHODS: We performed a nationwide survey and a prospective study. From August 6 to 15, 2008, a questionnaire survey was conducted to identify the prevalence, local distribution, and response to current treatments. The questionnaire was answered by pediatrician working in 23 referral centers in Korea. In addition, 5 referral centers in Seoul performed a preliminary prospective observational study by obtaining clinical data and specimens from appropriate patients. The Korea Centers for Disease Control and Prevention analyzed the samples for possible pathogens. RESULTS: The survey showed 78 AIP cases had occurred and 36 patients had died. Lung biopsy was performed only on 20 patients. In 2008, 9 AIP cases developed. In a prospective study, 9 (M:F=5:4) patients developed AIP in spring and 7 (78%) died, with the mean rate of death occurring 46 days after diagnosis. Human corona virus 229 E, cytomegalovirus, influenza A virus, influenza B virus, and parainfluenza virus were isolated from the respiratory specimens. CONCLUSION: This study showed nationwide prevalence of AIP in Korea. In addition, because of the high mortality rate and rapid progress, pediatricians need to be aware of the disease. Further studies and a nationwide network are required for reducing the morbidity and mortality rates related to AIP.
Biopsy ; Centers for Disease Control and Prevention (U.S.) ; Child ; Cytomegalovirus ; Humans ; Influenza A virus ; Influenza B virus ; Korea ; Lung ; Lung Diseases, Interstitial ; Paramyxoviridae Infections ; Prevalence ; Prognosis ; Prospective Studies ; Surveys and Questionnaires ; Rare Diseases ; Referral and Consultation ; Viruses