Risk Factors For Readmission Following Allogeneic Hematopoietic Stem Cell Transplantation and Impact On Overall Survival

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 555-555
Author(s):  
Laura Spring ◽  
Shuli Li ◽  
Robert J. Soiffer ◽  
Joseph H. Antin ◽  
Edwin P. Alyea ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Significant Risk ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
The Impact

Abstract Background Recent initiatives to improve patient safety and reduce healthcare costs have focused on preventing hospital readmissions. Historically, patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of hospital readmission. The purpose of this study was to identify the incidence and associated risk factors for readmissions in allogeneic HSCT patients and to evaluate the impact of readmissions on overall survival. Methods A retrospective review of patients receiving a myeloablative (MAC) or reduced intensity conditioning (RIC) HSCT at Dana Farber/Brigham and Women’s Hospital between January 1, 2005 and December 31, 2010 was performed. At our institution, RIC transplant patients are typically discharged on day +1. The 30-day readmission rate, a standard benchmark used by the Centers for Medicare & Medicaid Services, and the day 100, a traditional assessment point in transplantation, readmission rates were examined. Reasons for readmission as well as sociodemographic, disease, and HSCT-related variables were evaluated. Risk factors for readmission and the impact of readmission on overall survival were assessed by multivariate regression analysis. Results A total of 1097 HSCT patients were reviewed. In the MAC group, 130 of 495 (26.3%) patients were readmitted within 30 days of discharge and 194 (39.2%) patients were readmitted by day 100 following transplantation. 74.2% of the MAC patients had one readmission by day 100. In the RIC group, 105 of 602 (17.4%) patients were readmitted within 30 days of discharge and 185 (30.7%) patients were readmitted by day 100 following transplantation. 69% of the RIC patients had one readmission by day 100. In both groups, the most frequent reasons for readmission were infection (27.6% in MAC group, 26% in RIC group), fever without a source (19.1% in MAC group, 19% in RIC group), and graft versus host disease (17.9% in MAC group, 15.1% in RIC group). In the MAC group, a multivariate logistic regression model of the probability of being readmitted suggested that the principal risk factors for readmission by day 100 were infection during the index transplant admission (OR 1.9, p=0.0006) and Latino ethnicity (OR 4.6, p=0.013). In the RIC group, active disease at the time of HSCT (OR 2.1, p=0.0001), infection during the index admission (OR 4.8, p<0.0001), a mismatched donor (OR 2.1, p=0.030) and non-private (32.1% Medicaid, 66.4% Medicare, 1.5% other) insurance (OR 1.6, p=0.029) were significant risk factors for readmission by day 100. In a landmark analysis of patients who survived beyond the studied time points, the 5-year overall survival (OS) for those readmitted within 30 days of discharge from the index HSCT in the MAC group was 42% compared with 56% among patients not readmitted (p=0.0026). Similarly, OS in the RIC group was 26% compared with 50% (p<0.0001). The 5-year OS for those readmitted by day 100 following HSCT in the MAC group was 52% compared with 61% among patients not readmitted (p=0.058) and in the RIC group was 26% compared with 57% (p=<0.0001). After adjusting for age, donor type, and the disease risk index (DRI), a multivariate analysis confirmed that readmission within 30 days of discharge or by day 100 was associated with decreased OS (table 1). Conclusions Infection and fever without a source were the most common causes of readmission after HSCT. In the RIC group, disease, transplant, and sociodemographic factors were associated with readmission. Being readmitted within 30 days of discharge from transplant was a significant risk factor for a lower 5-year overall survival rate in both the RIC and MAC groups. A better understanding of the risk factors for readmission in the HSCT population will allow for more transitional care and clinical resources to be focused on the highest risk patients. Strategies to decrease readmissions may improve the overall survival of patients undergoing allogeneic HSCT. More research is needed to better learn how to balance early discharge with preventable readmissions. Disclosures: No relevant conflicts of interest to declare.

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with Recurring Hodgkin’s Lymphoma: An EBMT Study on 151 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3061-3061 ◽  
Author(s):  
Alexander Claviez ◽  
Carmen Canals ◽  
Marc Boogaerts ◽  
Jerry Stein ◽  
Stephen Mackinnon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
The Impact ◽  
Time Point

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients. Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005. Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively. Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.

The Use of Imatinib with Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation Improves Survival of Philadelphia Positive Acute Lymphoblastic Leukemia in Adults

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3653-3653
Author(s):  
Josefina Perez-Nuñez ◽  
Antonio Jimenez-Velasco ◽  
Katy Hurst ◽  
Manuel Barrios-Garcia ◽  
MJ Moreno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Philadelphia positive acute lymphoblastic leukemia (Ph + ALL) accounts for approximately 20% -30% of all adult ALL. The prognosis of patients with Phi + ALL is unfavorable when treated with standard chemotherapy schemes, presenting a long-term survival of 15% -20%. Since the introduction of Imatinib (IM) to treatment regimens the survival of these patients has improved, although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. We conducted a retrospective analysis of Ph + ALL patients before and after IM became available in order to analyze the impact of IM on survival in adult Phi + ALL. Patients and methods Between April 1997 and April 2013 we diagnosed 120 over 15 year old patients with ALL (B and T lineage), 31 (25.8%) of which were Phi +, all B lineage. Of these 31 cases, 30 were treated with protocols from Spanish group PETHEMA with curative intent. 14 of them (47%) were treated with chemotherapy and Imatinib (IM cohort) and 16 (53%) with chemotherapy (pre-IM cohort). In 17 of the 30 cases allogeneic HSCT was performed, 7 in the pre-IM cohort and 10 in the IM cohort. In the post-transplant period, two patients were treated with Dasatinib due to positive minimal residual disease (BCR-ABL1 positive). The probabilities of overall survival (OS) (death) and event free survival (EFS) (no response, relapse or death) were estimated using the Kaplan-Meier product limit method. Differences between groups were tested using the X2 test. Univariate analysis was performed using Cox regression models or log-rank test. Multivariate analysis was performed using Cox proportional hazards regression model. The study was conducted in accordance with the Declaration of Helsinki. Results The median age was 38 years (range, 15-66 years), 17 patients were males and 13 females. The whole series survival was 32.4 ± 9.2%. The OS mean of the pre-IM cohort was 3.1 years (CI 95%, 0.5-5.7) and 6.9 years (CI 95%, 4.4-9.4) in the IM cohort (figure 1). The main characteristics of both groups are reflected in Table 1. When we analyzed the EFS, the variables that influenced it were being treated with IM (48% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.03), having received an allogeneic HSCT (45% versus 8%, p = 0.004) and being in first complete remission before allogeneic HSCT (51% versus 0%, p <0.001). In the analysis of OS, the only variables with prognostic significance were: treatment with IM (63% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.01) and having received an allogeneic HSCT (55 % versus 0%, p <0.001). When the 17 patients that received allogeneic HSCT were analyzed separately, OS in the pre-IM cohort was 29 ± 17% versus 79 ± 13% in the IM cohort (p = 0.057). Table 1. Patient characteristics (N=30) Characteristic Pre-IM cohort(N=16) IM cohort(N=14) P Female/Male 7/9 6/8 0.96 Age ² 40 years 12 (75%) 10 (71%) 0.82 ³ 50 x109/L WBC 8 (50%) 4 (29%) 0.23 Transcript type: e1a2 b2a2/b3a2 12 (75%) 4 (25%) 11 (79%) 3 (21) 0.83 Morphological CR after induction 13/15 (88%) 13/13 (100%) 0.17 No. of Allo-HSCT 7 (44%) 10 (71%) 0.13 CR pre Allo-HSCT: 1CR 2CR 5 (71%) 2 (29%) 10 (100%) 0 (0%) 0.07 Relapse 8/13 (61.5%) 4/13 (31%) 0.12 Exitus 14 (87.5%) 5 (36%) 0.003 Abbreviations: IM, imatinib. WBC, white blood cells. CR, complete remision. Allo-HSCT, allogenetic hematopoietic stem cell transplantation. Figure 1 Figure 1. Conclusions In our study we show how adult Phi + ALL patients who are treated with chemotherapy associated with IM and subsequently receive an allogeneic HSCT exhibit a higher overall survival rate than those treated in the pre-IM era. Although Phi + ALL is still considered of very high risk, in our series of patients treated in the IM era, with a follow-up of over 7 years, overall survival was of 63%, higher than that of historical series of adults with Phi negative ALL. This work has been financed by a grant from the Malaga Association for Research in Leukemia "AMPILE" and the FIS 11-01966 project. Disclosures No relevant conflicts of interest to declare.

Risk Factor Analysis Of Idiopathic Pneumonia Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation In Children

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5459-5459
Author(s):  
Hirozumi Sano ◽  
Ryoji Kobayashi ◽  
Akihiro Iguchi ◽  
Daisuke Suzuki ◽  
Kenji Kishimoto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Rapid Progression ◽  
Hematopoietic Stem ◽  
Idiopathic Pneumonia Syndrome ◽  
Allogeneic Hsct

Abstract Idiopathic pneumonia syndrome (IPS) is a critical complication following allogeneic hematopoietic stem cell transplantation (HSCT); however, few reports have analyzed the risk factors for IPS in children. A total of 210 consecutive pediatric patients, including 131 boys and 79 girls, with various hematologic malignancies, aplastic anemia, or solid tumors who underwent allogeneic HSCT were analyzed to clarify the incidence and risk factors for IPS. Patient and transplantation characteristics after allogeneic HSCT were compared between patients with and without IPS. Cumulative incidence rates of IPS 120 days after allogeneic HSCT were 6.7% (14/210). Of 14 patients with IPS, 11 (78.6%) died after developing IPS. The presence of prior HSCT was more frequent in patients with IPS (IPS group) than in those without (non-IPS group) (35.7 vs 12.8%, respectively, P=0.018). The IPS group contained more patients with acute GVHD (grade II-IV) than the non-IPS group (50.0 vs 18.9%, respectively, P=0.006). The association of these two factors with IPS was further confirmed by multivariate analysis. We should be aware of these risk factors in patients who have undergone allogeneic HSCT. The rapid progression to respiratory failure and high mortality rate following the onset of IPS, despite advances in supportive care, require the development of new preventive measures and treatment modalities. Further preclinical and clinical studies are required to understand the pathogenesis of IPS and improve the prognosis of HSCT recipients. 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.

Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3463-3471 ◽  
Author(s):  
André Tichelli ◽  
Christoph Bucher ◽  
Alicia Rovó ◽  
Georg Stussi ◽  
Martin Stern ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Autologous Hsct

Abstract We assessed incidence and risk factors of cardiovascular events in 265 patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) between 1980 and 2000 and who survived at least 2 years. Results were compared with a cohort of 145 patients treated during the same period with autologous HSCT. The median age of patients with allogeneic HSCT at last follow-up was 39 years, and median follow-up was 9 years. Eighteen (6.8%) patients after allogeneic and 3 (2.1%) patients after autologous HSCT experienced an arterial event. The cumulative incidence of first arterial event after allogeneic HSCT was 22.1% (95% CI, 12.0-40.9) at 25 years. The cumulative incidence 15 years after allogeneic HSCT was 7.5% as compared with 2.3% after autologous HSCT. Adjusting for age, risk of an arterial event was significantly higher after allogeneic HSCT (RR 6.92; P =.009). In multivariate analysis, allogeneic HSCT (RR: 14.5; P =.003), and at least 2 of 4 cardiovascular risk factors (hypertension, dyslipidemia, diabetes, obesity) (RR: 12.4; P =.02) were associated with a higher incidence of arterial events after HSCT. Thus, long-term survivors after allogeneic HSCT are at high risk for premature arterial vascular disease. HSCT might favor the emergence of established risk factors, such as hypertension, diabetes, and dyslipidemia.

scholarly journals Investigating the Effects of Clonal Hematopoiesis in Healthy Marrow and Blood Donors on the Outcomes of Recipients Following Hematopoietic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2180-2180
Author(s):  
Wing Hing Wong ◽  
Kevin Elliot ◽  
Iskra Pusic ◽  
John F. DiPersio ◽  
Todd E Druley
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Time Points ◽  
Clonal Hematopoiesis ◽  
The Impact

Abstract Background: Using error-corrected sequencing with a detection limit of 0.0001, Young et al. (2016) found that 95% of healthy individuals harbor somatic mutations in blood cells in genes associated with leukemia. In addition to increasing the risk of AML (Jaiswal et al. 2014), these clones have recently been associated with cardiac dysfunction (Fuster et al. 2017; Jaiswal et al. 2017). This prompted us to consider the impact of clonal hematopoiesis from healthy donors on outcomes in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Indeed, donor-derived hematological complications have been anecdotally documented where rare donor clones harboring pathogenic mutations expanded in the recipients following HSCT. As a result, hematopoietic progenitors harboring mutations conferring self-renewal or growth advantages that facilitate preferential engraftment could be unknowingly transferred from donor to recipient (Gibson et al. 2017). Several retrospective studies of secondary hematopoietic malignancies post-HSCT have shown that donor clones harboring mutations in JAK2 and DNMT3A with low variant frequency (VAF) have undergone clonal expansion in the recipients (Yasuda et al. 2014). To date, there has not been a systematic and quantitative study to assess how donor clonal hematopoiesis engrafts and potentially affects the clinical outcome of recipients. In this study, we aim to quantify the spectrum of donor clones that engraft the recipient by longitudinally tracking clonal dynamics in the recipients at three time points post-HSCT. We also aim to compare individual patient outcomes with clonal engraftment. Methods: Error-corrected sequencing (ECS) on 80 genes frequently mutated in AML was performed on 133 isolated peripheral blood leukocytes from 27 allogeneic HSCT recipients at Washington University and the Siteman Cancer Center. Five samples were obtained for each patient which include the matched donor sample from the CIBMTR (n=25) along with pre-transplant, day 30 post-HSCT (D30), day 100 post-HSCT (D100) and one year post-HSCT (D360) for all patients. Independent biological replicates were sequenced for each sample and only the somatic events found in both replicates will be considered true positives using published and validated computational pipelines and thresholds. Results and Conclusions: All D30 and D100 samples harbor clonal mutations (mean 5.67 variants in D30 samples; 5.52 variants in D100 samples) with VAFs ranging from 0.0005 - 0.11. A total of 126 variants are only observed in D30 samples while 122 variants are only observed in D100. Twelve patients have 27 filtered mutations observed in both time points with general increase in VAFs in the later time point. Interestingly, we found SRCAP to be most recurrently mutated in both D30 and D100 samples (48.1% and 33.3%, respectively). This gene has recently been implicated in therapy-related clonal hematopoiesis following cytotoxic treatment (Wong et al. 2018). SRCAP is not frequently observed in clonal hematopoiesis in individuals without preceding hematological disorders or cytotoxic treatments. Therefore, these observed SRCAP variants could either: 1) be present in donors in very low VAFs or 2) arise after transplantation. Analysis of donor sequencing data would provide insight into this. Overall, we find that ECS is a specific and sensitive method for quantitatively characterizing the dynamics of clonal engraftment and proliferation in allogeneic HSCT recipients. In addition, we have found that mutated SRCAP appears to promote clonal engraftment and expansion after conditioning therapy, similar to recent results post-chemotherapy. Future work: Computational analysis of donor and recipient pre-transplant samples along with D360 samples is underway and nearly complete. Correlating ECS results with clinical and demographic (e.g. age and gender of donor and recipient) data is also underway. 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 promotor 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 GG 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.

Mycobacterial Infections in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A Cohort Study in a High Endemic Area

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2202-2202 ◽  
Author(s):  
Liu Yao-Chung ◽  
Chi-Jung Wu ◽  
Sheng-Hsuan Chien ◽  
Nai-Wen Fan ◽  
Ming-Hung Hu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Endemic Area ◽  
Hematopoietic Stem ◽  
Mycobacterial Infections ◽  
Allogeneic Hsct ◽  
Post Transplant

Abstract Background Mycobacterial infection is an important and potentially life-threatening complication of patients receiving organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We therefore aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and nontuberculous mycobacterium (NTM). Patients and Methods We included in this study 422 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2013. A total 26 subjects who developed post-transplant mycobacterial infections were identified. Risk factors, clinical features, and survival for post-transplant mycobacterial infections in recipients of HSCT were collected and analyzed. Results Post-transplant mycobacterial infections occurred in 26 (6.2%) of 422 HSCT patients. Two-year cumulative incidences in MTB and NTM were 1.4 % and 5.4%. In the multivariate analysis, being age > 45 years (adjusted HR 2.21, 95% CI 1.01-4.83)) and extensive chronic graft-versus-host disease (cGVHD) (adjusted HR 4.95, 95% CI 2.14-11.46) were identified as independent risk factors of post-transplant mycobacterial infections. There was a trend as a risk factors in relapsed patients (P=0.088). For patients with cGVHD, there was a significant difference of post-transplant survival between mycobacterial infections and none (median: 6.82 months versus not reached, P=0.036). Pneumonia with or without other infections contributed most to mortality (n = 11, 42.3%). Conclusion The 2-year cumulative incidence is higher in NTM (5.4%) than TB (1.4%) in recipients of allogeneic HSCT. Patients with age > 45 years, and extensive cGVHD are at risk of mycobacterial infections. Poor post-transplant survival in cGVHD patients developed mycobacterial infections and 42.3% patients in our study died of pneumonia. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of infections. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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