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.

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.

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

A Prospective Cost Analysis of Non-Myeloablative Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2239-2239
Author(s):  
Chris Skedgel ◽  
Jo-Ann Edwards ◽  
Jean Roy ◽  
Andrea McNeil ◽  
Yvonne Gulliver ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hospital Admissions ◽  
Chronic Gvhd ◽  
Direct Costs ◽  
First Year ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
The Cost

Abstract Hematopoietic stem cell transplantation (HSCT) is an intensive medical therapy used to treat both malignant and non-malignant conditions. Non-myeloablative transplantation (NMT) is an emerging transplant modality often performed on an outpatient basis. While NMT is associated with fewer acute complications compared to myeloablative HSCT, long-term complications, particularly chronic graft vs host disease (GvHD), are of concern. To our knowledge, there have been few economic evaluations of NMT and none in a Canadian healthcare environment. We prospectively developed and validated a process for capturing the costs and outcomes of NMT in order to estimate the cost per patient of NMT at a Canadian transplant centre. Ten consecutive patients undergoing NMT were followed from the first day of conditioning (Day −11) until either 1 year post-transplant or death. Donor costs were also recorded. All patient encounters, procedures and interventions during the study period were prospectively recorded. Nursing and other non-physician human resource costs were calculated based on recorded contact times and salaries. Physician costs were derived from Nova Scotia fee codes. Costs of hospital admissions were derived from Ontario Case Costing Initiative (OCCI) data and were specific to the primary diagnosis. Drug costs were based on acquisition costs at hospital and community pharmacies. Materials and equipment costs were based on costs at the QEII Health Sciences Centre, Halifax NS. The proportion of administrative costs to direct costs was derived from OCCI data and applied to local direct costs. All costs are in 2005 Canadian dollars ($CAN). Ten patients were followed for a median of 12 months (range 3.6–12) from September 2003 to April 2005. Eight patients were male and the median age of the cohort was 60 years (19–73). Five patients had AML; 3 had lymphoma and 2 had multiple myeloma.Cyclophosphamide and fludarabine were used as conditioning and tacrolimus and mycophenolate mofetil were used as GvHD prophylaxis. There were 7 hospital admissions among the 10 patients: 3 before day 100 and 4 after day 100. Eight patients survived at least one year post-transplant. No patients developed acute GvHD, while all 8 patients surviving to 1 year post-transplant developed chronic GvHD. Three patients relapsed within 1 year. The average cost per NMT was $CAN 43,377 of which $CAN 31,761 were recipient costs, $CAN 2,562 were donor costs and $CAN 8,675 were equipment and overhead costs. The key cost driver was hospital admissions for complications and/or palliative care at $CAN 9,793 per recipient. Physician fees ($CAN 6,958) and chemotherapy ($CAN 6,485) were also significant. Compared to published estimates of the cost of myeloablative HSCT, NMT appears considerably less costly in the first year post-transplant. Our analysis suggests that the lower cost of NMT was largely attributable to the limited amount of inpatient care these patients received. Further follow-up will be informative since the major complications of NMT including chronic GvHD and relapse may impact per transplant cost after the first year post-transplant. Direct comparison with myeloablative HSCT using our prospective costing method is also planned.

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.

Acute Cholecystitis Occurs More Commonly Than Expected Following Allogeneic Hematopoietic Stem Cell Transplantation and Is Ineffectively Diagnosed Using Abdominal Ultrasound

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2046-2046
Author(s):  
Stephen J. Bagley ◽  
Alison R. Sehgal ◽  
Noelle V. Frey ◽  
Saar Gill ◽  
Elizabeth Hexner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Cholecystitis ◽  
Case Control Study ◽  
Case Control ◽  
First Year ◽  
Hematopoietic Stem ◽  
Control Study

Abstract Background Having observed an unexpectedly high rate of acute cholecystitis following allogeneic hematopoietic stem cell transplantation (allo-HCT), we sought to define the risk factors for development of acute cholecystitis following allo-HCT, as well as the incidence, radiographic presentation, and outcomes of this disease in the transplant population. Methods Between January 2001 and December 2011, 644 patients underwent allo-HCT at our institution. Using ICD-9 codes, we screened this population for a diagnosis of acute cholecystitis or for cholecystectomy in the first year following HCT. Cases were confirmed through manual chart review, and were defined as having one or more imaging modalities positive for acute cholecystitis or having surgical gallbladder pathology consistent with acute cholecystitis. We then conducted a nested case-control study with controls randomly selected through incidence density sampling of the transplant cohort at a rate of 3:1, matching for age and sex. Using logistic regression, we evaluated multiple potential risk factors for the development of acute cholecystitis, including underlying hematologic malignancy, graft-versus-host-disease (GVHD), total parenteral nutrition (TPN) use, graft source, ABO incompatibility, >10% weight loss, conditioning regimen, and cytomegalovirus reactivation. Finally, we conducted a separate case-control study to evaluate the effectiveness of multiple radiographic studies in the diagnosis of acute cholecystitis in HCT recipients (n=32) compared to randomly selected non-transplant control patients who were diagnosed with acute cholecystitis at our institution (n=96). Results The incidence of acute cholecystitis in the first year of transplant was 5.0% (32/644 patients). Of the 32 patients, 21 (65.6%) were male and 11 (34.4%) were female with a median age of 52.2 years (range, 24–75 years). Median time from HCT to diagnosis of acute cholecystitis was 56.5 days (range, 6–342 days). Twenty of 32 patients (62.5%) were treated with cholecystectomy, 7 (21.9%) with percutaneous cholecystostomy drainage, and the remaining 5 (15.6%) with conservative medical management. Twenty of the 32 patients who developed acute cholecystitis died within one year of HCT (62.5%), compared with 19 of 96 control patients (19.8%), (p<0.001). Of the 20 cholecystitis patients who died, three (15%) died as a direct result of acute cholecystitis; cause of death was septic shock in all 3 cases. HCT patients who received TPN had a higher risk of developing acute cholecystitis (multivariate OR, 3.41; p=0.009), while development of GVHD was protective against developing acute cholecystitis (multivariate OR, 0.28; p=0.006). When accounting only for development of grade III-IV GVHD, a trend towards protection remained but was not statistically significant (OR, 0.24; p=0.061). Ultrasound findings were equivocal for acute cholecystitis (vs. definitively positive or negative) more frequently in allo-HCT patients than in non-HCT patients (50.0% vs. 30.6%), although this difference was not statistically significant (p=0.063). Of the 32 case patients, 30 (93.8%) had US performed, and of these only 13 (43.3%) had an US positive for acute cholecystitis. Computed tomography (CT) scan was equivocal (versus definitively positive or negative) for acute cholecystitis at similar rates in allo-HCT and non-HCT patients (54.7%, vs. 41.2%, p=0.331), and cholescintigraphy (HIDA) scan was positive for cholecystitis at similar rates in both populations (80.0% vs. 77.4%, p=0.82). Conclusions Acute cholecystitis is a common complication of allo-HCT, especially in patients who received TPN. It is associated with a high 1-year mortality rate, and abdominal US has suboptimal performance in diagnosing it. Our data suggest that a high index of suspicion and use of alternative imaging modalities are required to make a prompt diagnosis and may improve the outcomes of allo-HCT patients. Disclosures: No relevant conflicts of interest to declare.

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

2019 ◽  
Vol 37 (5) ◽  
pp. 375-385 ◽  
Author(s):  
Mareike Frick ◽  
Willy Chan ◽  
Christopher Maximilian Arends ◽  
Raphael Hablesreiter ◽  
Adriane Halik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Increased Risk

Purpose Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). Methods We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). Results A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). Conclusion Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.

Impact of White Blood Cell Count Recovery On Clinical Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4136-4136
Author(s):  
Haesook T Kim ◽  
David G Frederick ◽  
Emily Andler ◽  
Philippe Armand ◽  
Grace Kao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Blood Cell ◽  
Clinical Outcomes ◽  
Cumulative Incidence ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
One Year

Abstract Abstract 4136 Background: Studies have shown that absolute lymphocyte count (ALC) early after allogeneic hematopoietic stem cell transplantation (HSCT) affects clinical outcomes. We hypothesize that the white blood cell (WBC) count at 1 month after HSCT may also predict transplant outcomes. Methods: 1115 adult patients undergoing allogeneic HSCT from 2003 through 2009 at Dana-Farber/Brigham and Women's Hospital were analyzed. The median age was 51 yrs (range 18–74); median follow up time among survivors was 4.3 years (range 1.1–9.2); 596 patients received reduced intensity conditioning (RIC) and 519 received myeloablative conditioning (MAC). Using the restricted cubic spline estimates on the log relative hazard over WBC at 1 month post HSCT, WBC was categorized as: low (0-<2), normal (2–10), and high (>10×109 cells/L). Results: The outcomes are summarized in the table and figure below. One-year OS was 52%, 71%, 48% for low, normal, high WBC at 1 month post HSCT, respectively, (p<0.0001) and 1-year PFS was 39%, 56%, and 44% for low, normal, high WBC, respectively (p<=0.0001). One year cumulative incidence of NRM was 15%, 5.2%, 9.1% for low, normal, high WBC (p=0.008 for low vs normal, p=0.33 for high vs normal) in RIC and 23%, 15%, 28% for low, normal, high WBC (p=0.28 for low vs normal, p=0.001 for high vs normal) in MAC. One year cumulative incidence of relapse was 51%, 44%, 58% for low, normal, high WBC (p=0.49 for low vs normal, p=0.04 for high vs normal) in RIC but 27%, 22%%, 23% for low, normal, high WBC (p=n.s.) in MAC. In multivariable multinomial logistic regression analysis, age (OR=0.94, p=0.004) and sirolimus containing GVHD prophylaxis (OR=3.3, p=0.044) in MAC, and mismatched donor type (OR=3.0, p=0.03) in RIC were the risk factors for low WBC; AML/CML (OR=8.2, p=0.009), CLL (OR=13.9, p=0.0036) in RIC and high disease-relapse index (ref. Armand et al, Blood, 2012) (OR=3.26, p=0.04) were risk factors for high WBC. In multivariable Cox model adjusting for other prognostic factors, both low and high WBC at 1 month were associated with poor OS (Low WBC: HR 1.59, p=0.01; High WBC: HR 1.85, p=0.007) and PFS (low WBC: HR 1.59, p=0.008; high WBC: HR 1.68, p=0.017) in RIC and high WBC at 1 month was associated with both poor OS (HR 1.93, p<0.0001) and PFS (HR 1.7, p=0.0006) in MAC. Furthermore, low or high WBC was associated with viral or fungal infection within 100 days of HSCT (viral: 27%, 9%, 9%,p=0.019 in MAC; 9%, 4%, 15%, p=0.01 in RIC; fungal: 27%, 6%, 9%,p=0.0006 in MAC; 2%, 2%, 9%, p=0.046 in RIC). In the MAC cohort, high WBC at 1 month was associated with development of subsequent grade II-IV acute GVHD: 41%, 39%, 51% for low, normal, (p<0.001). In the RIC cohort, only 48% in low (p<0.001) and 54% in high WBC (p=0.02) achieved ≥90% donor chimerism by day 30 post HSCT compared to 76% of patients in normal WBC, suggesting that the abnormal WBC reflects poor donor engraftment or persistence of underlying disease. There was a weak correlation between WBC and ALC at 1 month (correlation coefficient = 0.46). Low ALC is associated with poor outcome, but not high ALC. Conclusion: Out data suggest that WBC at 1 month after allogeneic HSCT predicts transplant outcomes independent of ALC and chimerism. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Association of recipient and donor interleukin 6 polymorphisms 174 and 597 with outcome after allogeneic hematopoietic stem cell transplantation in children

2021 ◽  
Author(s):  
Laura Wetzel ◽  
Susan Wittig ◽  
Bernd Gruhn
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Interleukin 6 ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Significant Risk ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Purpose The success of allogeneic hematopoietic stem cell transplantation (HSCT) is compromised by complications such as infection, relapse, and graft-versus-host disease (GVHD). The investigation of non-HLA immunogenetics, particularly of cytokines, could identify predictors of an unfavorable outcome after allogeneic HSCT. In this study, we examined the impact of single nucleotide polymorphisms (SNPs) within the promoter region of interleukin 6 (IL6) on the development of GVHD after pediatric allogeneic HSCT. Methods In this retrospective analysis, we included 320 pediatric patients with a median age of 10 years who underwent an allogeneic HSCT and their respective donors. We used TaqMan real-time polymerase chain reaction to analyze the SNPs IL6-174 (G/C) and IL6-597 (G/A). The IL6-174 polymorphism was examined in 300 recipients and 295 donors. The IL6-597 polymorphism was analyzed in 299 recipients and 296 donors. We investigated the influence of the IL6-174 and IL6-597 polymorphisms on overall survival, event-free survival, relapse incidence, transplant-related mortality, and the occurrence of GVHD. Results G polymorphism at position 174 of the recipient IL6 gene was associated with a higher incidence of acute GVHD (GG vs. GC/CC; P = 0.024). Patients with IL6-597 GG genotype developed acute GVHD more frequently than individuals with an A allele (GG vs. GA vs. AA; P = 0.013). IL6-174 GG homozygous recipients had a more frequent occurrence of chronic GVHD (GG vs. GC/CC; P = 0.049). We observed a significant increased risk of chronic GVHD in recipients with IL6-597 GG genotype (GG vs. GA vs. AA; P = 0.043). Polymorphisms of donors did not affect the incidence of acute GVHD and chronic GVHD. In multivariate analysis, the IL6-174 and IL6-597 SNPs were independent significant risk factors for acute GVHD (P = 0.030; P = 0.007, respectively) as well as for chronic GVHD (P = 0.045; P = 0.015, respectively). In addition, older age at time of transplantation turned out to be a significant risk factor for chronic GVHD (P = 0.003). Conclusion Our study identified the IL6-174 and IL6-597 GG genotypes of pediatric allogeneic HSCT recipients as genetic risk factors for the development of acute GVHD and chronic GVHD. After evaluations in further studies, these findings could implicate the adjustment of prophylactic measures to reduce the occurrence of acute GVHD and chronic GVHD.

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.

Sign in / Sign up

Export Citation Format

Share Document