scholarly journals Performance Status and Comorbidity Predict Transplant-Related Mortality After Allogeneic Hematopoietic Cell Transplantation

2006 ◽  
Vol 12 (9) ◽  
pp. 954-964 ◽  
Author(s):  
Andrew S. Artz ◽  
Daniel A. Pollyea ◽  
Masha Kocherginsky ◽  
Wendy Stock ◽  
Elizabeth Rich ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Performance Status ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
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.

scholarly journals Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome

2016 ◽  
Vol 34 (16) ◽  
pp. 1864-1871 ◽  
Author(s):  
Brian C. Shaffer ◽  
Kwang Woo Ahn ◽  
Zhen-Huan Hu ◽  
Taiga Nishihori ◽  
Adriana K. Malone ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Weighted Score ◽  
Training Subset

Purpose To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS). Patients and Methods We examined 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT. Results Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 109/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort. Conclusion The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS.

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

scholarly journals Early transplantation-related mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seom Gim Kong ◽  
Seri Jeong ◽  
Sangjin Lee ◽  
Jee-Yeong Jeong ◽  
Da Jung Kim ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cord Blood Transplantation ◽  
Iron Chelation ◽  
Incidence Rates ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Blood Transplantation ◽  
Related Mortality

Abstract Background Transplantation-related mortality (TRM) is a major obstacle in allogeneic hematopoietic cell transplantation (allo-HCT). Approximately 60–80% of TRM occurs early, within 100 days of transplantation. Methods This was a nationwide population cohort study involving 5395 patients with acute leukemia who underwent allo-HCT between 2003 and 2015. Patient data were collected from the Korean National Health Insurance Service database. We investigated the cumulative incidence rates (CIRs) of early TRM at 50 and 100 days. Results The CIRs of early TRM at 50 and 100 days were 2.9 and 8.3%, respectively. There was no decrease in the CIRs of early TRM over time. The early mortality was significantly higher in patients with more than 9 months between the diagnosis and transplantation (CIRs of TRM at 50, 100 days; 6.0, 13.2%), previous transplantations (CIRs of TRM at 50, 100 days; 9.4, 17.2%), and cord blood transplantation (CIRs of TRM at 50, 100 days; 6.1, 8.3%). The early TRM was significantly lower in patients who received iron chelation before transplantation (CIRs of TRM at 50, 100 days; 0.3, 1.8%). Conclusions In conclusion, the overall CIR of early TRM was less than 10%. The predictable factors for early TRM included age, time from diagnosis to transplantation, the number of prior transplantations, the graft source, and previous iron chelation therapy.

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