scholarly journals Disease Risk Index Combined with Donor T-Cell Chimerism Predicts Early Relapse Free Survival after Myeloablative Allogeneic Stem Cell Transplantation

2017 ◽  
Vol 23 (3) ◽  
pp. S307
Author(s):  
Eric Wong ◽  
Kate Mason ◽  
Jenny Collins ◽  
Barbara Hockridge ◽  
Janis Boyd ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Early Relapse

Polymorphisms of NOD2/CARD15 Are Associated with Clinical Outcome in T-Cell Depleted HLA-Identical Sibling Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1408-1408
Author(s):  
Miquel Granell ◽  
Alvaro Urbano-Ispizua ◽  
Juan Ignacio Arostegui ◽  
Francesc Fernandez-Aviles ◽  
Carmen Martinez ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
T Cell ◽  
Clinical Outcome ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Event Free Survival ◽  
Free Survival

Abstract Three single nucleotide polymorphisms (SNP) in NOD2/CARD15 have been associated with the incidence and severity of acute GVHD following allogeneic stem cell transplantation (allo-SCT). The potential clinical influence of SNP in NOD2/CARD15 in a model of allo-SCT with a low incidence of GVHD, such as T-cell depleted transplants (TCD), has not been studied. We analyzed the association of SNP in NOD2/CARD15 with the outcome of 84 patients undergoing allo-SCT with TCD by means of CD34+ selection. Results were compared with a concurrent group of 94 patients receiving an allo-SCT with unmanipulated grafts (Non-TCD). Transplants were performed in a single institution, donors were HLA identical siblings and all patients received myeloablative-conditioning regimen. Median follow-up was of 30.6 months (range, 0.2–112). SNP 8, 12 and 13 were analyzed by RT-PCR allelic discrimination method in all patients and in 137 donors. SNP in NOD2/CARD15 were detected in 13.8% of patients and in 10.7% of donors. Results of the association of patient’s NOD2/CARD15 genotype and outcome are given in the table. In TCD transplants, independent risk factors associated with event free survival in a multivariate analysis were: patient’s NOD2/CARD15 genotype (RR 2.7, p=0.02), patient’s age (RR 2.3, p=0.03) and conditioning with radiotherapy (RR 2.7, p=0.03). The only association of donor’s NOD2/CARD15 genotype with clinical outcome in the multivariate analysis was with acute GVHD (RR 3.3, p=0.03). In conclusion, polymorphisms in NOD2/CARD15 have a strong association with clinical outcome in TCD transplants, which is independent of GVHD. Overall group (n=178) SNP vs. WT P* TCD (n=84) SNP vs. WT P* Non-TCD (n=94) SNP vs. WT P* WT, wild type; N.S, non significant; * Log-rank test Acute GVHD II–IV 27 vs. 22 N.S 22 vs. 40 N.S 33 vs. 12 N.S Chronic GVHD 61 vs. 35 0.1 29 vs. 14 N.S 100 vs. 44 0.005 Event free survival 21 vs. 47 0.03 17 vs. 48 0.04 22 vs. 31 N.S Overall survival 30 vs. 59 0.01 33 vs. 56 0.04 30 vs. 48 N.S

The Revised IPSS (IPSS-R) At Transplant Predicts Overall and Relapse-Free Survival After Allogeneic Stem Cell Transplantation In MDS/sAML: A Retrospective Analysis Of The EBMT Chronic Malignancies Working Party

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 922-922 ◽  
Author(s):  
Christof Scheid ◽  
Liesbeth de Wreede ◽  
Anja van Biezen ◽  
Gudrun Göhring ◽  
Christian Koenecke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Retrospective Analysis ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
Sufficient Information ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Very High

Abstract Myelodysplastic syndromes are a heterogenous group of diseases with a very variable prognosis. Allogeneic stem cell transplantation is the only treatment modality offering the potential of cure, however its efficacy is counterbalanced by significant treatment-related morbidity and mortality. To assess the prognosis at diagnosis multiple predictive scoring systems have been developed, most recently a model based on cytogenetic features (Schanz et al. JCO 2012 30:820-829) and subsequently a revised International Prognostic Scoring System (IPSS-R) including the newly defined cytogenetic risk categories (Greenberg et al. Blood 2012 120: 2454-2465). While the prognosis at diagnosis is of primordial importance for the choice of initial treatment, the decision to transplant or not is often deferred to a later time point depending on the availability of a donor, the disease course, the response to treatment or other factors. Thus the IPSS-R calculated at transplant may differ from the score at diagnosis. To assess the usefulness of calculating the IPSS-R at transplant we performed a retrospective analysis of the EBMT database on the outcome of patients with MDS receiving an allogeneic stem cell transplantation in relation to the IPSS-R at transplant. 3276 allogeneic transplants in patients with MDS or secondary AML performed between 1982 and 2010 were found in the database. Second transplants, pediatric patients and cord blood transplants were excluded. The cytogenetic data were first scored by an independent reviewer according to Schanz et al. Blast count in the bone marrow, hemoglobin and platelet count were used as documented by the centers in the EBMT database. Absolute neutrophil count at transplant is not recorded in the database, therefore we used 50% of the leukocyte count at transplant as an estimate to calculate the IPSS-R at transplant. Statistical analysis of the outcomes overall survival (OS) and relapse-free survival (RFS) was performed by the Kaplan-Meier method with log-rank test for differences. Relapse incidence and non-relapse mortality were considered as competing risks, group impact was compared by the Gray test. 579 patients had sufficient information available to calculate IPSS-R at transplant. The median age at transplant was 52 years (range 18-72) with 55% male and 45% female patients. IPSS-R at transplant was very low in 16 (2.8%), low in 152 (26.3%), intermediate in 141 (24.4%), high in 147 (25.4%) and very high in 123 (21.2%) of the cases. Median OSfrom transplant was 17.0 mo (95% CI 11.4 – 22.6) and was significantly different according to IPSS-R: very low 23.6 mo, low 55.0 mo, intermediate 19.7 mo, high 13.5 mo, very high 7.8 mo, p<0.001). These differences remained significant when stratifying for age, era of transplantation, stem cell source, conditioning intensity or related versus unrelated donor. Median RFS was 8.8 months (95% CI 6.3 – 11.4) with significant differences according to IPSS-R: very low: 23.6 mo, low: 24.8 mo, intermediate 10.6 mo, high 7.9 mo, very high 5.5 mo, p<0.001). Cumulative incidence of non-relapse mortality was 27.5% at 24 months for the whole cohort with no significant differences related to IPSS-R at transplant. Relapse incidence at 24 months was 26.7%, 29.1%, 30.8%, 34.2% and 43.8% for very low, low, intermediate, high and very high IPSS-R respectively. These differences failed to be significant (p=0.20). We conclude that the new IPSS-R is a useful prognostic score not only at diagnosis but also at transplantation predicting OS and RFS after transplantation. While allogeneic transplantation can achieve long term disease-free survival in all IPSS-R risk groups, patients with very high IPSS-R at transplant remain a challenge and may particularly benefit from improved transplantation strategies aiming at reducing the relapse rate. Disclosures: No relevant conflicts of interest to declare.

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