A nationwide cross-sectional study using a web-based questionnaire survey of the duration of isolation of COVID-19 inpatients with cancer at Japanese cancer centers.

There is no clear consensus regarding the optimal isolation duration for immunocompromised patients with coronavirus disease 2019 (COVID-19). Therefore, we conducted a questionnaire survey at eight Japanese cancer centers to investigate the practices of infectious disease specialists regarding the duration of isolation for COVID-19 inpatients with cancer. For asymptomatic to severely ill COVID-19 inpatients without severe immunodeficiency, four centers reported at least 10 days of isolation without testing, and two reported at least 20 days. Two centers incorporated polymerase chain reaction (PCR) as a criterion for terminating the isolation of inpatients without severe immunodeficiency. For severely immunocompromised COVID-19 inpatients, at least 20 days of isolation were required in seven facilities, regardless of illness severity. Additionally, seven centers had implemented Ct or antigen quantification test values as criteria for de-isolating severely immunocompromised inpatients. No cases caused nosocomial outbreaks after isolation was terminated based on each facility's criteria for isolation termination. Thus, cancer patients required longer isolation periods than the general population in most facilities, and for those with severe immunodeficiency, the isolation periods were longer and more tightly controlled with tests.

Clinical characteristics and risk factors of pneumococcal diseases in recipients of allogeneic hematopoietic stem cell transplants in the late phase: A retrospective registry study.

Pneumococcal diseases are one of the most important infectious complications in the late period following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The importance of long-term follow-up care is increasing, as the number of long-term survivors following allo-HSCT increases, but there has been a dearth of research specifically focusing on pneumococcal diseases during the late post-transplant period (day >100). Using a transplant registry database between January 1, 2001 and December 31, 2011, we aimed to assess the clinical spectrum and risk factors for pneumococcal diseases in the late post-transplant period. Among the 22,514 recipients who received allo-HSCT over an 11-year period and could be followed for ≥100 days, 43 patients developed 49 episodes of pneumococcal diseases. Six of the 43 patients died from pneumococcal diseases, and four of these six patients died within a week, despite having undergone allo-HSCT two or more years ago. A history of chronic graft-versus-host disease (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.15-4.66; P = 0.02), viral infection (OR, 3.38; 95% CI, 1.70-6.72; P < 0.01), and complete remission of the underlying disease at the time of transplantation (OR, 2.38; 95%CI, 1.10-5.14; P = 0.03) were identified as risk factors. Given the risk of sudden death and the high mortality rate, attention should be paid to pneumococcal diseases in providing long-term follow-up care, even several years after allo-HSCT.

Prognostic implication of CTLA-4, PD-1, and PD-L1 expression in aggressive adult T-cell leukemia-lymphoma.

The prognosis of patients with aggressive adult T cell leukemia-lymphoma (ATLL) is dismal even with intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a promising option for patients with aggressive ATLL, but the posttransplant outcome remains unsatisfactory. Hence, to further improve clinical outcomes, novel therapeutic approaches are needed. The clinical significance of immune checkpoint protein expression has not been well-established in aggressive ATLL. This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. This retrospective study cohort included 65 patients with aggressive ATLL diagnosed between 2001 and 2015 at the National Cancer Center Hospital, Tokyo, Japan. Formalin-fixed paraffin-embedded tissue was used to immunohistochemically determine the expression of immune checkpoint proteins and assess the impact of expression profile on the probability of overall survival from diagnosis or HSCT. The current analysis shows that cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) expressions were adverse prognostic factors in patients with aggressive ATLL. Experiments that assess the efficacy of immune checkpoint inhibitors are warranted to alleviate the adverse impacts associated with negative immune checkpoints.

Cytomegalovirus reactivation is associated with an increased risk of late-onset invasive aspergillosis independently of grade II-IV acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: JSTCT Transplant Complications Working Group.

There is a matter of debate about the clinical impact of cytomegalovirus (CMV) reactivation on the development of late-onset invasive aspergillosis (IA), which occurs 40 days or later after allogeneic hematopoietic stem cell transplantation (HSCT). Using a Japanese transplant registry database, we analyzed the risk factors for the development of late-onset IA in 21,015 patients who underwent their first allogeneic HSCT between 2006 and 2017. CMV reactivation was defined as the initiation of preemptive anti-CMV antiviral therapy. Overall, there were 582 cases of late-onset IA, which occurred at a median of 95 days after HSCT. The 2-year cumulative incidence was 3.4% (95% confidence interval (CI), 3.0-3.9) in patients with CMV reactivation within 40 days after HSCT and 2.5% (95% CI, 2.3-2.8) in those without it (P < 0.001). In a multivariate analysis, CMV reactivation as a time-dependent covariate was significantly associated with the development of late-onset IA (hazard ratio (HR) 1.40, P < 0.001), as well as grade II-IV acute GVHD, age > 50 and HCT-CI ≥ 3 in the entire cohort. If we focus on the subgroup without grade II-IV acute GVHD, which is generally an indication for systemic corticosteroid therapy (n = 12,622), CMV reactivation was still a significant factor for the development of late-onset IA (HR 1.37, P = 0.045) as well as age > 50 years, HCT-CI ≥ 3, and cord blood transplantation. In conclusion, CMV reactivation was associated with an increased risk of late-onset IA after allogeneic HSCT independently of acute GVHD. Close monitoring for late-onset IA is necessary for patients who develop CMV reactivation even without grade II-IV acute GVHD.

Environmental Sampling for Severe Acute Respiratory Syndrome Coronavirus 2 During a COVID-19 Outbreak on the Diamond Princess Cruise Ship.

During a COVID-19 outbreak on the Diamond Princess cruise ship we sampled environmental surfaces after passengers and crew vacated cabins. SARS-CoV-2 RNA was detected in 58 of 601 samples (10%) from case cabins 1-17 days after cabins were vacated but not from noncase cabins. There was no difference in detection proportion between cabins of symptomatic (15%, 28/189; cycle quantification [Cq], 29.79-38.86) and asymptomatic cases (21%, 28/131; Cq, 26.21-38.99). No SARS-CoV-2 virus was isolated from any of the samples. Transmission risk of SARS-CoV-2 from symptomatic and asymptomatic patients may be similar and surfaces could be involved in transmission.

Comparison between IMP carbapenemase-producing Enterobacteriaceae and non-carbapenemase-producing Enterobacteriaceae: a multicentre prospective study of the clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are classified as carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE; the majority of CPE in Japan produce IMP carbapenemase. OBJECTIVES: We evaluated the clinico-epidemiological and microbiological information and effects of IMP-type carbapenemase production in CRE. METHODS: Patients with isolations of CRE (MICs of meropenem ≥2 mg/L, imipenem ≥2 mg/L or cefmetazole ≥64 mg/L) from August 2016 to March 2018 were included. Microbiological analyses and WGS were conducted and clinical parameters were compared between groups. Independent predictors for the isolation of CPE from patients were identified by logistic regression. For comparing clinical outcomes, a stabilized inverse probability weighting method was used to conduct propensity score-adjusted analysis. RESULTS: Ninety isolates (27 CPE and 63 non-CPE) were collected from 88 patients (25 CPE and 63 non-CPE). All CPE tested positive for IMP carbapenemase. Antibiotic resistance (and the presence of resistance genes) was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE isolation were residence in a nursing home or long-term care facility, longer prior length of hospital stay (LOS), use of a urinary catheter and/or nasogastric tube, dependent functional status and exposure to carbapenem. Although in-hospital and 30 day mortality rates were similar between the two groups, LOS after CRE isolation was longer in the CPE group. CONCLUSIONS: IMP-CPE were associated with prolonged hospital stays and had different clinical and microbiological characteristics compared with non-CPE. Tailored approaches are necessary for the investigational and public health reporting, and clinical and infection prevention perspectives for IMP-CPE and non-CPE.

Echinocandins versus non-echinocandins for empirical antifungal therapy in patients with hematological disease with febrile neutropenia: A systematic review and meta-analysis.

Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on high-quality evidence, most guidelines recommend caspofungin. The aim of this study was to clarify whether echinocandins, including micafungin, are associated with improved clinical outcomes in patients with persistent FN. We conducted a meta-analysis of randomized controlled trials (RCTs) of empirical therapy with echinocandins and non-echinocandins for FN in patients with hematological disease. The primary outcome was all-cause mortality within 7 days after completion of therapy. Secondary outcomes included treatment success, and discontinuation of therapy because of adverse events. For subgroup analysis, we compared RCTs of echinocandins with liposomal amphotericin B. Six RCTs (four that evaluated caspofungin and two that evaluated micafungin) were included in the meta-analysis. Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with non-echinocandins [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.49-0.99; RR 0.48, 95% CI 0.33-0.71, respectively]. There was no significant difference in treatment success (RR 1.09, 95% CI 0.87-1.36). Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with liposomal amphotericin B (RR 0.68, 95% CI 0.46-0.99; RR 0.53, 95% CI 0.37-0.74, respectively). In conclusion, patients with persistent FN treated with echinocandins had decreased risk of death and adverse events. Both caspofungin and micafungin may be recommended as first-line empirical antifungal therapy in these patients. However, the small number of enrolled patients and the lack of RCTs involving pediatric patients should be considered when using micafungin.

Novel Sequence Type in Bacillus cereus Strains Associated with Nosocomial Infections and Bacteremia, Japan.

Bacillus cereus is associated with foodborne illnesses characterized by vomiting and diarrhea. Although some B. cereus strains that cause severe extraintestinal infections and nosocomial infections are recognized as serious public health threats in healthcare settings, the genetic backgrounds of B. cereus strains causing such infections remain unknown. By conducting pulsed-field gel electrophoresis and multilocus sequence typing, we found that a novel sequence type (ST), newly registered as ST1420, was the dominant ST isolated from the cases of nosocomial infections that occurred in 3 locations in Japan in 2006, 2013, and 2016. Phylogenetic analysis showed that ST1420 strains belonged to the Cereus III lineage, which is much closer to the Anthracis lineage than to other Cereus lineages. Our results suggest that ST1420 is a prevalent ST in B. cereus strains that have caused recent nosocomial infections in Japan.

Characterization of Late Acute and Chronic Graft-Versus-Host Disease according to the 2014 National Institutes of Health Consensus Criteria in Japanese Patients.

To characterize the incidences and outcomes of late acute (LA) and chronic graft-versus-host disease (GVHD) in East Asians according to the 2014 National Institutes of Health criteria, we retrospectively analyzed 506 consecutive Japanese patients who had a first allogeneic hematopoietic cell transplantation (HCT) at our center between 2006 and 2013. According to manifestations at onset 91 patients (60%) had LA GVHD and 60 (40%) had chronic GVHD. The cumulative incidences of LA and chronic GVHD were 20% and 17%, respectively, at 48 months after HCT. The involved sites at the onset of LA GVHD included the skin (71%), gut (13%), and liver (8%). The cumulative incidences of relapse, nonrelapse mortality (NRM), transition to chronic GVHD, and discontinued systemic treatment were 11%, 6%, 22%, and 46%, respectively, at 48 months after onset of LA GVHD. Cox models showed that prior acute GVHD was associated with NRM, and HCT from a female donor to a male patient, myeloablative conditioning, and low Karnofsky performance status were associated with a longer duration of systemic treatment after LA GVHD. The most frequently involved sites at the onset of chronic GVHD included the mouth (83%), liver (75%), skin (69%), and eyes (62%). Cox models showed that use of antithymocyte globulin in conditioning regimens was associated with a higher risk of discontinued systemic treatment after the onset of chronic GVHD. The cumulative incidences of relapse, NRM, and discontinued systemic treatment were 16%, 11%, and 41%, respectively, at 48 months after the onset of chronic GVHD. Our results suggested several potential differences between Japanese patients and those of other ethnicities. A direct comparison is needed to formally investigate ethnic differences.

Clinical and Molecular Characteristics of Klebsiella pneumoniae Isolates Causing Bloodstream Infections in Japan: Occurrence of Hypervirulent Infections in Health Care.

Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. Clinical characteristics of K. pneumoniae bloodstream infections from hospitals across Japan were analyzed by a review of the medical records. Whole-genome sequencing of the causative isolates was performed. Bacterial species were confirmed and hvKp were identified using whole-genome sequencing data. Clinical characteristics of hvKp infections were compared with those of non-hvKp infections by bivariate analyses. Of 140 cases of K. pneumoniae bloodstream infections, 26 cases (18.6%) were caused by various clones of hvKp defined by the carriage of cardinal virulence genes. Molecular identification revealed that 24 (17.1%) and 14 (10%) cases were caused by Klebsiella variicola and Klebsiella quasipneumoniae, respectively. Patients with hvKp infections had higher proportions of diabetes mellitus (risk ratio [RR], 1.75; 95% confidence interval [CI], 1.05 to 2.94), and their infections had significantly higher propensity to involve pneumonia (RR, 5.85; 95% CI, 1.39 to 24.6), liver abscess (RR, 5.85; 95% CI, 1.39 to 24.6), and disseminated infections (RR, 6.58; 95% CI, 1.16 to 37.4) than infections by other isolates. More than one-half of hvKp infections were health care associated or hospital acquired, and a probable event of health care-associated transmission of hvKp was documented. hvKp isolates, which are significantly associated with severe and disseminated infections, are frequently involved in health care-associated and hospital-acquired infections in Japan.

Association of CD204+ macrophages with poor outcomes of malignant lymphomas not in remission treated by allogeneic HCT.

OBJECTIVE: CD204+ tumor-associated macrophages are associated with adverse outcomes of various malignancies. We performed a study to elucidate the role of CD204+ macrophages in allogeneic hematopoietic cell transplantation (allogeneic HCT). METHODS: In a total of 81 patients who received allogeneic HCT for non-remission malignant lymphoma, immunohistochemical staining of CD204 using specimens preserved before allogeneic HCT was performed. According to the average number of CD204+ macrophages in a high-power field, patients were categorized into three groups: low (<25th percentile), intermediate (≥25th percentile and <50th percentile), and high (≥50th percentile). RESULTS: The B-cell lymphoma proportion was higher in the low group, while T-cell lymphoma and adult T-cell leukemia proportions were higher in the high group. The 3-year overall survival (OS) was poorest in the high group; low vs intermediate vs high = 83.3% vs 43.7% vs 20.2% (P < .01). The 3-year cumulative incidences of relapse were significantly higher in the high group than the intermediate and low groups: 67.0% vs 38.1% vs 18.2% (P < .01). In multivariate analyses, the numbers of CD204+ macrophages were independent risk factors of poorer OS and cumulative incidences of relapse. CONCLUSIONS: CD204+ macrophages might be associated with poorer prognosis in allogeneic HCT for malignant lymphomas.

Clinical Utility of Wilms' Tumor 1 Monitoring in Patients with Myeloid Malignancy and Prior Allogeneic Hematopoietic Stem Cell Transplantation.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is 1 of the standard treatments for myeloid malignancy, relapse remains a major obstacle to cure. Early detection of relapse by monitoring of minimal residual disease (MRD) may enable us to intervene pre-emptively and potentially prevent overt relapse. Wilms' tumor 1 (WT1) is well known as a pan-leukemic marker. We retrospectively examined serially monitored WT1 levels of peripheral blood in 98 patients (84 with acute myeloid leukemia and 14 with myelodysplastic syndrome). At the time of allo-HSCT, 49 patients (50%) were in complete remission. Patients were divided into 3 groups according to WT1 levels (<50 copies/µg RNA, 50 to 500 copies/µg RNA and >500 copies/µg RNA). The cumulative incidence of relapse (CIR) and overall survival (OS) differed statistically according to the WT1 levels before allo-HSCT and at days 30 and 60 after allo-HSCT. In multivariate analysis, WT1 >500 copies/µg RNA before and at day 60 after allo-HSCT and WT1 ≥50 copies/µg RNA at day 30 were correlated with CIR. Moreover, WT1 >500 copies/µg RNA at day 60 after allo-HSCT was only correlated with worse OS. Our data suggest that serial monitoring of WT1 levels in peripheral blood may be useful for MRD monitoring and as a predictor of hematological relapse in allo-HSCT.

Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation.

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic cell transplantation (HCT). Eltrombopag is an oral thrombopoietin receptor agonist whose efficacy against persistent thrombocytopenia after allogeneic HCT has not been well characterized. This retrospective study evaluated the safety and efficacy of eltrombopag in 12 consecutive patients with persistent thrombocytopenia after allogeneic HCT. Eltrombopag was started at 12.5 mg once daily and the dose was increased by 12.5 mg daily every week until platelet counts exceeded 50,000/µL. Five patients had prolonged isolated thrombocytopenia (PIT) and 7 patients had secondary failure of platelet recovery (SFPR). The cumulative incidence rate of successful platelet recovery to ≥50,000/µL without transfusion support was 60% in PIT patients and 71% in SFPR patients. No patients discontinued the drug because of adverse events or intolerability. Notably, the rate of platelet recovery was higher (100% versus 58%; P = .0017) and recovery was faster (median, 33 days versus 137 days; P = .0078) in patients with normal numbers of bone marrow megakaryocytes before starting eltrombopag than in those with decreased numbers of megakaryocytes. Eltrombopag is a promising treatment for both PIT and SFPR after allogeneic HCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may predict the response to eltrombopag.

Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease.

This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses ≥ 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses ≥ 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses.

Positive impact of chronic graft-versus-host disease on the outcome of patients with de novo myelodysplastic syndrome after allogeneic hematopoietic cell transplantation: a single-center analysis of 115 patients.

To evaluate the impact of graft-versus-host disease (GVHD) and prognostic factors for patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation (allo-HCT), we retrospectively reviewed 115 patients with MDS or acute myeloid leukemia with multilineage dysplasia (AML-MLD) after allo-HCT at our center. Eighty one patients received reduced-intensity conditioning (RIC) regimens, whereas 34 received myeloablative conditioning regimens. Although the RIC group was significantly older and included more patients with poor cytogenetic risk, no difference in 4-yr overall survival (OS) was seen between the two groups. In a multivariate analysis, covariates associated with a worse OS were the French-American-British stage of refractory anemia excess blasts in transformation/AML-MLD at peak, poor cytogenetic risk, bone marrow blasts of 20% or higher at HCT and the absence of chronic GVHD (cGVHD). By using semi-landmark analyses, we found that the presence of cGVHD significantly improved OS in high-risk patients or the RIC group. However, there was no difference in OS between those with and without cGVHD among low-risk MDS patients. These findings suggest that the graft-versus-leukemia effect may be more beneficial in high-risk patients who do not receive intensive preparative regimens.

Campylobacter showae bacteremia with cholangitis.

We report a case of Campylobacter showae bacteremia associated with cholangitis. A 71-year-old man with advanced bile duct cancer was admitted to our hospital because of cholangitis with shock, hypoglycemia, and impaired renal function. After replacement of the biliary drainage tube, pus was drained from the tube. Specimens for blood and bile cultures were obtained, and fluid resuscitation and antimicrobial treatment were then begun. Although anaerobic blood culture yielded small curved gram-negative rods, the isolate could not be identified by conventional identification methods. The isolate was identified as C. showae by 16S rRNA gene sequencing analysis. We consider here the pathogenicity of C. showae and the association of C. showae with cholangitis.

Immunogenicity of three versus four doses of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in allogeneic haematopoietic stem cell transplantation recipients: a multicentre, randomized controlled trial.

OBJECTIVE: This multicentre, phase 2, randomized, controlled study of allogeneic haematopoietic stem cell transplantation (allo-HSCT) recipients compared the immunogenicity of two anti-pneumococcal vaccine regimens: four doses of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) (3+1+1 experimental group), and three doses of PCV13 followed by PPSV23 (3+0+1 group). METHODS: Allo-HSCT recipients without active graft-versus-host disease at enrolment were eligible. The primary endpoint was the IgG response rate (≥0.20 mg/mL) for all eight measured serotypes at 5 months after the PPSV23 booster. RESULTS: Seventy-two recipients were randomized, and seventy recipients who received over one PCV13 dose were analysed. The mean ages were 47.2 years (standard deviation, 14.4) in the 3+1+1 group (n = 35) and 49.0 years (standard deviation, 14.3) in the 3+0+1 group (n = 35). There was no significant difference in the overall IgG response rate at 5 months after the PPSV23 booster between the 3+1+1 and 3+0+1 groups (100% (26/26) vs. 93% (27/29), respectively, relative risk (RR): 1.07; 95% confidence interval (CI): 0.97-1.19). This rate was high immediately before the PPSV23 booster in the 3+1+1 group (100% (26/26) compared with 81% (21/26), respectively, RR: 1.24; 95% CI: 1.03-1.49), but this difference disappeared 1 month after the PPSV23 booster (100% (26/26) vs. 97% (28/29), respectively, RR: 1.04; 95% CI; 0.97-1.11). No serious adverse events leading to study dropout occurred. DISCUSSION: We were not able to determine the efficacy of the experimental arm based on the IgG response rate at 5 months after the PPSV23 booster in allo-HSCT recipients.

Association Between Candidemia and Noninfectious Interstitial Pneumonia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group.

Background: α-mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in mouse models. This study aimed to evaluate the association between candidemia and noninfectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients. Methods: Using a Japanese transplant registry database, we analyzed 9143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7531) or second (n = 1612) allogeneic HCT between 2009 and 2019. Results: Noninfectious IP was observed in 694 patients at a median (range) of 63 (0-1292) days after HCT. Candidemia occurred in 358 patients at a median (range) of 31 (0-903) days after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of noninfectious IP (hazard ratio [HR], 2.51; 95% CI, 1.48-4.25), along with total body irradiation (>8 Gy; HR, 1.57; 95% CI, 1.18-2.10) and malignant lymphoma (vs acute myeloid leukemia; HR, 1.30; 95% CI, 1.004-1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95% CI, 0.45-0.75) and acute lymphoblastic leukemia (vs acute myeloid leukemia; HR, 0.68; 95% CI, 0.49-0.94) were associated with reduced incidence of noninfectious IP. The median survival after the development of noninfectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs 59 days; P < .001). Conclusions: Candidemia was associated with an increased incidence of noninfectious IP. The prognosis of noninfectious IP after candidemia was extremely poor.

Risk and Predictive Factors for Candidemia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group.

Although antifungal prophylaxis that covers Candida species is a standard of care in allogeneic hematopoietic cell transplantation (HCT), candidemia mainly caused by non-albicans Candida species still occurs and is associated with a high mortality rate. This study aimed to evaluate the risk factors for candidemia after allogeneic HCT. Particularly, we evaluated the impact of patient factors such as hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and performance status (PS) in addition to well-recognized risk factors including donor type, delayed engraftment, and graft-versus-host disease (GVHD). By using data from a Japanese transplant registry database, we analyzed 26,236 pediatric and adult patients with hematological malignancies who underwent their first allogeneic HCT. The posttransplant period was divided into early (days 0-40), late (days 41-100) and very late (days 101-365) phases. The 1-year cumulative incidence of candidemia was 1.8%. When we analyzed pretransplantation factors, age ≥40 years (hazard ratio [HR] 1.85), male (HR 1.34), HCT-CI (HCT-CI 1-2, HR 1.56; HCT-CI ≥ 3, HR 2.21), PS ≥ 2 (HR 2.01), high-risk disease (HR 1.78) and donor type including HLA-mismatched related donor (MMRD) (HR 1.96), HLA-mismatched unrelated donor (HR 2.05), and cord blood (CB) (HR 2.85) were significantly associated with an increased incidence of candidemia. Focusing on the early phase (days 0-40), HCT-CI, PS, high-risk disease and CB transplantation together with engraftment and severe acute GVHD significantly affected the development of candidemia. In the late phase (days 41-100), higher HCT-CI, male, and donor type including MMRD, and CB were associated with the occurrence of candidemia together with acute GVHD and disease relapse. In the very late phase (days 101-365), HCT-CI ≥ 3 and high-risk disease significantly affected the occurrence of candidemia together with acute and chronic GVHD, and disease relapse. In addition to well-recognized risk factors including donor type, engraftment and GVHD, patient factors such as HCT-CI and PS were associated with the development of candidemia, which suggests that severely ill patients with transplantation-associated complications are more likely to develop candidemia.