scholarly journals Predictors of Transplant-Related Mortality at One Year in Pediatric and Adolescent Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Malignant and Non-Malignant Diseases

2016 ◽  
Vol 22 (3) ◽  
pp. S250-S251
Author(s):  
Justine Kahn ◽  
Naima Al Mulla ◽  
Mahvish Qureshi ◽  
Grace Kim ◽  
Zhezhen Jin ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Malignant Diseases ◽  
Adolescent Patients ◽  
One Year ◽  
Related Mortality

Treosulfan-Based Myeloablative Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation Is Associated with Reduced Toxicity without Increased Risk of Relapse.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1152-1152
Author(s):  
Sebastian Giebel ◽  
Jerzy Wojnar ◽  
Malgorzata Krawczyk-Kulis ◽  
Iwona Wylezol ◽  
Miroslaw Markiewicz ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Platelet Recovery ◽  
Grade Ii ◽  
One Year ◽  
Reduced Toxicity ◽  
Risk Of Relapse

Abstract The goal of this study was to evaluate toxicity and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) with Treosulfan (alkylyting agent, soluble Busulfan-derivative)-based conditioning as a preparative regimen. The outcome of 27 patients (CML-15, AML-9, ALL-1, SAA-2) given Treosulfan 3x14 g/m2 + Fludarabine 5x30 mg/m2 (n=15) or cyclofosfamide (CTX) 120 mg/kg (n=12) was compared with that of 146 patients treated with Busulfan 16 mg/kg + CTX 120 mg/kg between 2000–2004. In case of unrelated donor (URD)-HCT patients were additionally given anti-thymocyte globulin. GVHD prophylaxis consisted of cyclosporin A and short-course Methotrexate. The indications for alloHSCT were comparable for both subgroups. The patients age was 35(14–56)y and 30(14–55)y, the proportion of URD-HCT was 55% and 45%, peripheral blood was used as a source of stem cells in 33% and 11% of cases, and the proportion of patients with advanced disease (AML and ALL >CR1; CML > CP1) equaled 26% and 19%, respectively. The cumulative incidence of non-relapse mortality at one year was 8% for the Treosulfan (EBV-LPD n=1, cerebral hemorrhage n=1) and 32% for the Busulfan group (p=0.11). Grade II-IV neutropenic infections occurred in 5% and 13% (p=NS) and grade II-IV mucositis in 9% and 61% of patients (p<0.001), respectively. Other serious adverse events were infrequent. Both subgroups did not differ in terms of time to neutrophil and platelet recovery, as well as for need of RBC and platelet transfusions. Median hospital stay since the date of alloHCT was shorter after Treosulfan- compared to Busulfan-based conditioning (31 (21–55) d. vs. 40.5 (21–153) d., p<0.001). The overall survival and disease-free survival at one year equaled 92% vs. 67% (p=0.11), and 92% vs. 66% (p=0.09) for the Treosulfan group and the Busulfan group, respectively. None of the patients experienced hematologic relapse among Treosulfan- compared to 3% among Busulfan-treated alloHCT recipients. However, in two CML patients given Treosulfan-based regimen, the immunosuppression taper and interferon or imatinib therapy was neccessary to establish complete chimera. We conclude that Treosulfan + Fludarabine (or CTX) +/− ATG conditioning regimen is characterized by reduced toxicity resulting in shorter hospital stay and low transplat-related mortality. The pattern of hematopoietic recovery is similar to that of Busulfan + CTX indicating myeloablative character of the Treosulfan-based regimen. The risk of relapse is low and comparable for both kinds of treatment.

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.

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