scholarly journals A Study of Impact of Bacterial Blood Stream Infections (BBSI) and Antibiotic Resistance on Transplant Related Mortality (TRM) Following Allogeneic Hematopoietic Cell Transplantation (alloHCT) in Children: A Multicenter Study

2016 ◽  
Vol 22 (3) ◽  
pp. S259
Author(s):  
Prakash Satwani ◽  
Jason L. Freedman ◽  
Sonali Chaudhury ◽  
Zhezhen Jin ◽  
Marc Foca ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Cell Transplantation ◽  
Multicenter Study ◽  
Hematopoietic Cell Transplantation ◽  
Blood Stream ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Blood Stream Infections ◽  
Related Mortality

Association of HMGB1 Polymorphisms with Outcome After Allogeneic Hematopoietic Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2260-2260
Author(s):  
Brian Kornblit ◽  
Tania Nicole Masmas ◽  
Søren Lykke Petersen ◽  
Hans O Madsen ◽  
Carsten Heilmann ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Minor Allele ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Strong Linkage Disequilibrium ◽  
Myeloablative Conditioning ◽  
Allogeneic Hct ◽  
Related Mortality

Abstract Abstract 2260 Poster Board II-237 Several studies have demonstrated that genetic variation in cytokine genes can modulate the immune reactions after allogeneic hematopoietic cell transplantation (HCT). High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a proinflammatory signal, important for the activation of antigen presenting cells (APC) and propagation of inflammation. HMGB1 is implicated in the pathophysiology of a variety of inflammatory diseases, and we have recently found the variation in the HMGB1gene to be associated with mortality in patients with systemic inflammatory response syndrome (SIRS). To assess the impact of the genetic variation in HMGB1 on outcome after allogeneic HCT, we genotyped 276 and 146 patient/donor pairs treated with allogeneic HCT for hematologic malignancies following myeloablative or non-myeloablative conditioning. Associations between genotypes and outcome were only observed in the cohort treated with myeloablative conditioning. Patient homozygosity or heterozygosity for the –1377delA minor allele was associated with increased risk of relapse (hazard ratio (HR) 2.11, P=0.02) and increased relapse related mortality (RRM) (P=0.03). The –1377delA minor allele has previously been associated with mortality in patients with SIRS, and although SIRS and allogeneic HCT are different entities the confirmative association of this polymorphic locus with mortality in 2 independent studies suggests that it is of pathophysiological importance. The three polymorphisms, 3814C>G, 1177G>C and 2351insT, tended to have the same effect on transplantation outcome, due to a moderate to strong linkage disequilibrium between loci. Of these three polymorphisms, patient homozygosity for the 3814C>G minor allele showed the strongest association with increased overall survival (HR 0.13, P=0.04), progression free survival (HR 0.30, P=0.05) and decreased probability of RRM (P=0.03). Patient carriage of the 2351insT minor allele reduced the risk of grade 2 to 4 acute graft versus host disease (GVHD) (HR 0.60, P=0.01), while donor carriage of the minor allele displayed a gene dosage effect, with a successive increase in risk of developing limited or extensive chronic GVHD per minor allele carried (HR 1.54, P=0.01). That patient HMGB1 genotypes were associated with outcomes dependent on primarily patient APCs, and that donor genotypes were associated with a, in part, donor APC dependent outcome, could suggest that the polymorphisms in HMGB1 influence the transcription of HMGB1 in APCs induced by the proinflammatory milieu after myeloablative conditioning, rather than the passively released from damaged cells, although these two mechanisms are not mutually exclusive. Our findings suggest that the inherited variation in HMGB1 is associated with outcome after allogeneic HCT following myeloablative conditioning. None of the polymorphisms were associated with treatment related mortality. Disclosures: No relevant conflicts of interest to declare.

Comparable Survival and Transplant-Related Mortality Following Allogeneic Hematopoietic Cell Transplantation from HLA Allele-Matched Unrelated and HLA-Identical Sibling Donors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3146-3146 ◽  
Author(s):  
Thai M. Cao ◽  
Schickwann Tsai ◽  
Linda Kelley ◽  
Stephen C. Alder ◽  
Thomas C. Fuller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
P Value ◽  
Unrelated Donor ◽  
Related Mortality

Abstract Comprehensive analyses of unrelated donor (URD) and recipient HLA-matching for allogeneic hematopoietic cell transplantation (AHCT) have demonstrated better outcomes when allele typing is performed using high-resolution nucleotide sequence-based techniques. To evaluate survival following myeloablative AHCT using allele-level HLA-matched URD as compared with HLA-identical sibling donors, we analyzed outcomes for 430 patients treated at our center between March 1991 and April 2005. Sequence-based allele typing was retrospectively performed for HLA-A, B, C, DR and DQ when not done at time of AHCT for URD (n = 124; 29%) and non-sibling related donors (n = 19; 4%). Donors were HLA-identical siblings (n = 276; 64%), HLA allele-matched URD (n = 52; 12%), single HLA-locus mismatched donors (n = 52; 12%), or > 1 locus mismatched donors (n = 50; 12%). The median age at transplant was 23.4 years (range: 0.2 – 61). The most common diagnoses were AML (n = 107; 25%), CML (n = 90; 21%), ALL (n = 86; 20%) and MDS (n = 50; 12%). Total body irradiation-based preparative regimens were used for 283 patients (66%). Bone marrow (BM) was the graft for 388 patients (90%) and GCSF-mobilized peripheral blood stem cells (PBSC) for the remaining 42 (10%). Graft-versus-host disease (GVHD) prophylaxes were cyclosporine and methotrexate (n = 327; 76%), long methotrexate (n = 42; 10%), T-cell depletion (n = 19; 4%), or other regimens (n = 42; 10%). With a median follow-up of 4.8 years (range: 0.2 – 12.1), the 5-year estimate of overall survival (OS) for the entire group was 48.2% (95% CI: 45.7 – 50.7) and transplant-related mortality (TRM) was 31.4% (95% CI: 28.8 – 34). As shown in the Table, OS and TRM were indistinguishable between AHCT performed with HLA-identical siblings compared with HLA allele-matched URD. There was also no difference in grade III – IV acute GVHD (P = .46) between these two groups whereas there was a trend towards more extensive chronic GVHD (HR 1.8; 95% CI: 0.9 – 3.6; P = 0.12) for the URD recipients. Using a multivariate analysis to adjust for advanced disease, age (> vs ≤ 30 years), graft (BM vs PBSC) and female-to-male gender mismatch, there remained no difference in OS between HLA-identical siblings and HLA allele-matched URD (P = 0.67). These results demonstrate that key outcomes (OS, TRM, and severe acute GVHD) are equivalent in recipients of grafts from either allele-level 10/10 HLA-matched URD or HLA-identical siblings. Overall Survival TRM Number Hazard Ratio 95% CI P value Hazard Ratio95% CI P value HLA-ID Sibling 276 1 - - 1 - - HLA-ID URD 52 1.1 0.7 – 1.7 0.67 0.8 0.4 – 1.6 0.58 1 Locus MM 52 1.3 0.9 – 2.0 0.19 1.4 0.8 – 2.4 0.25 > 1 Locus MM 50 2.0 1.4 – 2.9 < 0.001 2.6 1.7 – 4.1 < 0.001

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