scholarly journals Invasive Mold Infections in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3434-3434
Author(s):  
Sheng-Hsuan Chien ◽  
Yao-Chung Liu ◽  
Nai-Wen Fan ◽  
Chia-Jen Liu ◽  
Tzeon-Jye Chiou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Risk Score ◽  
Cumulative Incidence ◽  
Fungal Infections ◽  
Hematopoietic Stem ◽  
Kaplan Meier

Abstract Introduction: Patients with acute leukemia exposed higher risk for developing invasive fungal infections and the invasive fungal infection is also an important cause of morbidity and mortality during allogeneic hematopoietic stem cell transplantation (allo-HSCT). In addition to candida species, the invasive mold infection (IMI) is most common in invasive fungal infections and the incidence rate is increasing in recent years. Although recent diagnostic approach and treatments for IMI are advanced, the prognosis remains poor. It is essential to understand the risk factors for developing IMI among acute leukemia patients undergoingallo-HSCT. Here, we conducted a retrospective study to demonstrate demographics, microbiology, and risk factors for the development of IMI among 245 adult acute leukemia patients undergoingallo-HSCT at our institution during a 10-year period. Method We reviewed 245 adult acute leukemia patients undergoingallo-HSCT from January 2003 to December 2014. Clinical characteristics including age, sex, underlying disease, type of allogeneic transplant, conditioning regimens, European Group for Blood and Bone marrow Transplantation (EBMT) risk score, and presence of acute graft-versus-host disease (aGVHD) or chronic GVHD (cGVHD) were collected and analyzed. Cox proportional hazard model was adopted to explore the independent risk factors for IMI development. The Kaplan-Meier method was performed to estimate the cumulative incidence and the curve was compared using the log-rank test Results Twenty out of 245 patients developed IMI during study period and the median time to onset after transplantation was 391 days (interquartile range, 220-552 days). The cumulative incidence of IMI in this cohort was 1.9 %, 5.1%, and 12.8% at 6 months, 12 months, and 24 months, respectively. Aspergillus species were the most common and presented in 55% of mold infections. The significant risk factors to predict mold infection after transplantation (Table 1) were smoking (hazard ratio [HR] 4.28, 95% confidence interval [CI] 1.40-13.12; P=0.011), EBMT risk score > 2 (HR 4.37, 95% CI 1.35-14.09; P=0.013), and extensivecGVHD(HR 3.10, 95% CI 1.20-8.00; P=0.019). The cumulative incidence of mold infection in smokers was significantly higher than non-smokers (log-rank P < 0.001) and the Kaplan-Meier curve was shown in Figure 1. Conclusion We identified three risk factors-smoking, EBMT risk score > 2 and extensivecGVHDto predict IMI among acute leukemia patients undergoingallo-HSCT. Smoking may damage respiratory tract epithelium as well as defense-microorganism mechanism and it would lead to IMI easily duringallo-HSCT. This cohort study suggests that early identification of high-risk patients and to provide better prevention strategies would reduce the incidence and severity of IMI in these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Risk Factors Analysis for Human Cytomegalovirus Viremia in Donor+/Recipient+ Hematopoietic Stem Cell Transplantation

2019 ◽  
Vol 51 (1) ◽  
pp. 74-79 ◽  
Author(s):  
Rong Yang ◽  
Runan Zhang ◽  
Yanyue Zhang ◽  
Yaping Huang ◽  
Hanying Liang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Human Cytomegalovirus ◽  
Cumulative Incidence ◽  
Hematopoietic Stem

ABSTRACT Objective To assess the rate of, and risk factors for, human cytomegalovirus viremia (HCMV) in donor+/recipient+ (HCMV serostatus matched) hematopoietic stem-cell transplantation (HSCT) recipients. Methods HCMV DNA from 144 donor+/recipient+ HSCT recipients was examined by quantitative polymerase chain reaction (qPCR). Results The cumulative incidence of HCMV viremia was 69.4% (100/144) during the 48 weeks after HSCT. In a multivariate analysis, acute graft-versus-host disease (aGVHD) was discovered to be a risk factor for the occurrence of HCMV viremia (P = .006). The cumulative incidence of HCMV viremia and increasing DNA loads were significantly associated with aGVHD occurrence (P = .001 for each). The occurrence of late-term HCMV viremia was associated with aGVHD (P = .001) and a higher DNA load during the first 12 weeks after HSCT (P = .04). Conclusions aGVHD is a risk factor for HCMV viremia. Recipients with aGVHD who have a high HCMV DNA load should be strictly monitored to prevent HCMV activation.

Risk Factors for Late Infections after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Related Donor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2848-2848
Author(s):  
Marie Robin ◽  
Raphaël Porcher ◽  
Renato De Castro Araujo ◽  
Régis Peffault de Latour ◽  
Agnès Devergie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Viral Infection ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
First Year ◽  
Hematopoietic Stem ◽  
Cmv Status

Abstract After allogeneic hematopoietic stem cell transplantation (HSCT), late infections represent a major cause of morbidity and mortality but little has been previously reported. In a retrospective cohort study, late infections incidence was determined in 196 long-term survivors after matched related HSCT. Only patients transplanted for aplastic anemia, chronic myeloid leukemia (CML) and acute myeloblastic leukemia (AML) were included in this study. Median follow-up was 8 years. Among 30 patients who died beyond the first year, 9 patients died from graft-versus-host disease (GVHD) and 10 from infections. Bacterial late severe infections occurred in 30 patients, yielding an 8-year cumulative incidence of 15%. Late invasive fungal infection occurred in 8 patients corresponding to a cumulative incidence of 3.6%. Most viral infections were hepatitis C and VZV and overall late viral infection incidence was 35%. We identified 3 risk factors for bacterial infections in multiple analysis: CMV status (positive recipient and negative donor), irradiation based conditioning regimen and extensive chronic GVHD within the first year. Extensive chronic GVHD was the only risk factor of non-HCV viral infection in patients transplanted for AML or CML. Thus, late life threatening infections may occur in nearly a fourth of late survivors even after matched related transplantation and are associated not only with chronic GVHD but also with irradiation and to CMV status prior to transplantation.

Disseminated Adenovirus Infections after Allogeneic Hematopoietic Stem Cell Transplantation: High Rate of Associated Co-Morbidity and Mortality.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2925-2925
Author(s):  
Marie Robin ◽  
Stéphanie Marque-Juillet ◽  
Catherine Scieux ◽  
Régis Peffault de Latour ◽  
Christèle Ferry ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Hematopoietic Stem ◽  
Grade Ii

Abstract Adenovirus (ADV) infection is associated with significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to determine the cumulative incidence, the evolution and the risk factors of disseminated ADV infection defined as a real time ADV PCR positive in blood and 1 or more additional sites. Between January 2000 and April 2006, 38 patients with disseminated ADV were identified. Median age at diagnosis was 15 years (4 – 48). Primary diseases were leukemia (n=16), Fanconi anemia (n=10) or others (n=2). All but one patient received an unrelated HSCT. The graft consisted in peripheral blood (n=3), bone marrow (n=10) and cord blood (n=15). Plasma ADV PCR was positive at a median of 79 days after HSCT (range: 12 – 460). Involved organs were: liver (n=12), respiratory tract (n=15), gut (n=21), cystitis (n=12) and 19 patients had fever. Twenty-one patients had grade II-IV GVHD. The majority of the patients had other concomitant infections: invasive fungal infection (n=15), 1 to 4 other virus (CMV, EBV, RSV, parainfluenzae, BK virus) (n=21) and bacteremia (n=12). Risk factors for disseminated ADV were analyzed among patients who received an unrelated HSCT, and separately in adults and in children. 265 patients received an unrelated HSCT during the same period. Cumulative incidence (with death as a competing event) of disseminated ADV was 9% (95%CI: 4–3) in adults and 18% (95%CI: 10-27) in children. In adults, grade II–IV GVHD [time dependant covariate, Hazard Ratio (HR): 3.47, 95%CI: 1.14–10.6, p = 0.029] and cord blood as source of stem cell [HR: 7.10, 95%CI: 2.41-20.9, p = 0.0038] were associated with disseminated ADV infection. In children, grade II-IV GVHD [HR: 3.94, 95%CI: 1.15–13.5, p = 0.029] and Fanconi as primary disease [HR: 5.28, 95%CI: 1.69-16.6, p = 0.0043] were associated with disseminated ADV infection. Twenty-three patients were treated by cidofovir. Four patients had complete response (CR) [negative ADV PCR], 2 patients had primary CR followed by relapse and 2 patients had stable disease 90 and 67 days after treatment initiation. Fifteen patients were refractory to treatment. Main differences between responders and non-responders were ADV DNA load at onset of treatment (1343 versus 71 674 copies/ml), median time from HSCT to ADV diagnosis (98 versus 53 days), dosage of corticosteroids at time of treatment (0.75mg/kg/d versus 1.5 mg/kg/d), neutrophil (2× 109/L versus 1.5 × 109/L) and lymphocyte count (0.135 × 109/L and 0.070 × 109/L). An increase in the plasma viral load of ≥ 4 log10 in the 30 days after the first cidofovir dose was always followed by a fatal issue (n=9). Four-month infectious-related mortality and 1-year survival after diagnosis was 72% (95% confidence interval: 55–90) and 23% (95%CI:10–51). The only survivors were among the sustained responders in whom 1-year survival was 33% (95%CI: 7–100). In spite of earlier diagnosis and cidofovir treatment, disseminated ADV disease after HSCT leads to a high mortality rate, mainly related to multiple infections for all patients, reflecting a profound underlying immune defect.

Impact of Cytogenetics on Outcome of Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for Adults with AML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 830-830 ◽  
Author(s):  
Martin Tallman ◽  
Gordon Dewald ◽  
Hillard Lazarus ◽  
Sharavi Gandham ◽  
Gene Nelson ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Kaplan Meier

Abstract Matched unrelated donor hematopoietic stem cell transplantation (MUD HSCT) is a potentially curative treatment for patients with acute myeloid leukemia (AML). The graft-versus-leukemia (GVL) effect may be potent enough to overcome the otherwise poor prognosis associated with AML though its efficacy for high risk cytogenetic subgroups is uncertain. To test this hypothesis, we analyzed outcomes by cytogenetic risk group in 324 patients in first complete remission (CR1), and 440 in CR2 undergoing NMDP-facilitated MUD HSCT between 1988–2002. Using the SWOG/ECOG classification of cytogenetic risk groups (Slovak et al. Blood, 2000) cytogenetics were classified as favorable in 14% of patients, intermediate in 71% and unfavorable in 16%. 56% of the patients were male and 42% were > 35 years at HSCT. 76% of patients and donors were matched at HLA-A, -B and -DRB1, 17% were mismatched at one or more loci and 7% were potentially matched (serologically matched at HLA-A and -B and potentially allele matched at -DR). Disease Status N Kaplan-Meier Estimate for Survival at 5 years Kaplan-Meier Estimate for Disease-Free Survival at 5 years Cumulative Incidence for 100 Day Transplant-Related Mortality Cumulative Incidence for Relapse at 5 years * p-value indeterminate; ** p=0.01 CR1 324 32 ± 6% 32 ± 5% 32 ± 5% 18 ± 4%     Intermediate 227 33 ± 7% 32 ± 7% 31 ± 6% 16 ± 5%*     Unfavorable 85 31 ± 11% 31 ± 10% 29 ± 10% 23 ± 9%* CR2 440 36 ± 5% 35 ± 5% 25 ± 4% 16 ± 3%     Favorable 93 46 ± 10% 44 ± 10% 25 ± 9% 10 ± 6%**     Intermediate 313 33 ± 6% 32 ± 5% 27 ± 5% 16 ± 4%**     Unfavorable 34 37 ± 17% 38 ± 16% 15 ± 12% 32 ± 15%** These data suggest that with the exception of the 5-year relapse rate, results of cytogenetics have little apparent influence on the outcome for patients undergoing MUD HSCT for AML in CR1. In CR2, results in patients with favorable cytogenetics appear to be better than those with intermediate or unfavorable cytogenetics, but are not statistically significantly different. Effective GVL and protection against relapse is observed, even in high risk cytogenetic subgroups. In this retrospective study, other prognostic factors may influence the outcome, but overall survival for patients with unfavorable cytogenetics appears at least as good as previously reported for matched sibling HSCT.

Evaluation for the Need of Antifungal Prophylaxis In High Risk Hematologic Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4547-4547
Author(s):  
Olga Pérez ◽  
Manuela Aguilar ◽  
Almudena Martín ◽  
Jose Falantes ◽  
Isabel Montero ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Stem

Abstract Abstract 4547 Background Fungal infections remain a vital threat to the immunocompromised patient. Due to the high mortality rate of invasive mycoses, antifungal prophylaxis and prevention appear appropriate in some settings. Patients (pts) with prolonged and severe neutropenia or recipients of allogeneic hematopoietic stem cell transplantation (HSCT) appear to be at high risk for filamentous fungal infections, which are associated with low survival rates. However, there is no consensus on the optimal prophylaxis, eligible patients or its effectiveness and clinical impact. Objective To analyze the need for antifungal prophylaxis in Acute Leukemia patients receiving chemotherapy and the effectiveness of fluconazol, followed by posaconazol if GVHD developed, in recipients of allo-HSCT as antifungal prophylaxis. Methods and patients Period: from june’07 through june’09. Acute leukemia adult patients receiving chemotherapy as induction or re-induction therapy did not received primary antifungal prophylaxis. Recipientes of Allo-HSCT received 400 mg/d of fluconazole until discharge followed by 200 mg/8h of posaconazole if graft-versus-host disease (GVHD) developed, until its resolution. Patients received secondary antifungal prophylaxis according to their IFI. There were 77 pts who presented 218 episodes of post-chemotherapy neutropenia (80 in ALL and 138 in AML), 207 received no antifungal prophylaxis. On the other hand, we analyzed 40 consecutive Allo-HSCT adult recipients with an average age of 39 years (15-65) followed as in-patient and out-patient basis during a mean period of 18 months (3-24). Standard myeloablative or reduced intensity conditioning schemes were used and donors were HLA-identical sibling (27), unrelated donor (8) and umbilical cord blood (5). Diagnoses: AML (21), ALL (10), NHL (3), MDS (2), CML (2), HL (1) and AAS (1). The GVHD prophylaxis was according to standard protocols with MTX and CsP/MMF or standard umbilical cord blood protocols. Non-normal distribution data were expressed as median values (range). Chi-square test or Fisher exact test were used to compare differences between groups of categorical data. Differences were considered statistically significant for p-values < 0.05. All statistical analyses were performed using SPSS 16.0 software (Chicago, IL). Results Acute leukemia patients: There were 8 proved or probable fungal infections (EORTC/MSG consensus), with an incidence of 3.6%. The incidence of IFI in the whole induction AML group was 2.4%, (6.9% in the consolidation AML group, 25% in the re-induction AML group) and 5.2% in induction LLA and no case (0%) in the re-induction ALL group. As etiology, Aspergillus Fumigatus (1), Aspergillus spp (4), Candida tropicalis (1) and Candida spp (2). There were 3 deaths caused by IFI (37.5% of IFI); two of them in the re-induction AML group. Allogenic hematopoietic stem cell transplantation recipients: 33 patients received fluconazole (82.5%) and 4 pts (10%) fluconazole followed by posaconazole. Other 3 received posaconazole (2) or voriconazole 200 mg/12 hours (1) as secondary prophylaxis since the conditioning. There were 7 cases of IFI (incidence of 17.5%), 3 proved IFIs and 4 probable IFIs. As etiology, Aspergillus Fumigatus (2), Aspergillus spp (4) and Candida albicans (1). Six patients had received fluconazole and one (candidiasis), fluconazole and posaconazole. The mortality attributable to IFI were 4 cases (57% of IFI). There was no IFI in the group of 9 pts without GVHD and all IFIs occurred in patients treated for GVHD. Conclusions 1) Patients in re-induction of AML may require an effective prophylaxis against fungal infections, but not AML during induction or ALL in any situation. 2) The prophylaxis regimen studied in allogenic HSCT recipients was effective in preventing IFIs in patients without GVHD but not in patients with GVHD, particularly in the case of filamentous fungi. 3) The overall incidence of IFI in allo-HSCT was similar to that reported in other series of high risk and mortality from IFI similar to that described in recent years. 4) Patients with GVHD require more effective antifungal prophylaxis regimens and are candidates for clinical trials. Disclosures: No relevant conflicts of interest to declare.

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