scholarly journals Allogeneic hematopoietic stem cell transplantation can improve the prognosis of high-risk pediatric t (8;21) acute myeloid leukemia in first remission based on MRD-guided treatment

2020 ◽  
Author(s):  
Guan-hua Hu ◽  
Yi-fei Cheng ◽  
Ai-dong Lu ◽  
Yu Wang ◽  
Ying-xi Zuo ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Low Risk ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Difference ◽  
Acute Myeloid ◽  
Better Than

Abstract Background Pediatric acute myeloid leukemia (AML) with t (8;21) (q22;q22) or RUNX1-RUNX1T1 rearrangement is classified as a low-risk group. However, relapse is still the main factor affecting survival. The purpose of this study was to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t (8;21) AML based on MRD-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and define who will benefit from allo-HSCT. Methods Overall, 129 newly diagnosed pediatric patients with AML with t (8;21) were included in this study. The patients were divided into a high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after two cycles of consolidation chemotherapy. We recommended allo-HSCT for the high-risk group and chemotherapy for the low-risk group. The characteristics and outcomes of 125 patients were analyzed.Results For the high-risk patients, allo-HSCT improved event-free survival (EFS) compared to chemotherapy (87.4% [95% CI, 86%–108.7%]) vs. 61.9% [95% CI, 51.96%–80.41%]; P = 0.026). Overall survival (OS) of the high-risk HSCT group was better than that of the high-risk-chemo group but the difference was not statistically significant (82.8% [95% CI, 78.6%–101.7%]) vs. 71.4% [95% CI, 62.09%–87.6%]; P = 0.26). The EFS of the C-KIT+ high-risk-HSCT group was better than that of the C-KIT+ high-risk-chemo group but the difference was not statistically significant (82.9% [95% CI, 59.3%–84.8%]) vs. 75% [95% CI, 49.3%–85.6%]; P = 0.4). Extramedullary infiltration (EI) at diagnosis was associated with high cumulative incidence of relapse for high-risk patients (50% [95% CI, 17.2%–66.5%]) vs. 18.4% [95% CI, 3.0%–18.9%]; P = 0.004); allo-HSCT can improve survival (P = 0.009). Conclusions allo-HSCT can improve the prognosis of high-risk pediatric t (8;21) AML based on MRD-guided treatment. Patients with KIT mutation may benefit from allo-HSCT, but this result was not statistically significant. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.

Should Hematopoietic Stem Cell Transplantation in First Complete Remission Be Restricted to High-Risk Patients in Childhood Acute Myeloid Leukemia?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1094-1094
Author(s):  
Hideki Muramatsu ◽  
Nobuhiro Nishio ◽  
Asahito Hama ◽  
Hiroshi Yagasaki ◽  
Yoshiyuki Takahashi ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Low Risk ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients ◽  
Group A ◽  
Group B ◽  
First Complete Remission

Abstract Hematopoietic stem cell transplantation (HSCT) has been used as an effective consolidation therapy for children with acute myeloid leukemia (AML) in first complete remission (CR). Although it is effective in relapse prevention, often it causes severe late sequelae, such as short stature and infertility. There is a recent trend to restrict the use of HSCT in first CR for high-risk patients. However, there is no study comparing which strategy is better, risk-adapted or general recommendation for HSCT in AML children in first CR. In our institutes, all such children in first CR were recommended either allogeneic or autologous HSCT until 1997. After 1998, patients were classified into three risk-groups. Low-risk patients (t(8;21) and inv(16)) were not recommended to undergo HSCT. High-risk patients (−7, 5q-, Ph1, t(16;21) and remission failure) were recommended to undergo HSCT. Intermediate-risk (other karyotypes) patients received HSCT in first CR if a suitable donor was available. In this study, we retrospectively compared the prognosis of 66 patients who were diagnosed with de novo AML between 1991 and 1997 (group A; n=37) and between 1998 and 2003 (group B; n=29). AML with Down syndrome and AML-M3 were excluded. The median (range) age was five (0–15) years. FAB classifications were M0 (n = 1), M1 (n = 10), M2 (n = 22), M4 (n = 6), M4E (n = 5), M5 (n = 14), M6 (n = 0), and M7 (n = 8). Chromosome analysis data were t(8;21) (n = 18), inv(16) (n = 4), 11q23 (n = 10), other abnormalities (n = 14), normal karyotype (n = 14), and unknown (n = 6). Induction chemotherapy comprised VP-16, cytarabine, and mitoxantrone. Sixty-three of 66 patients (95.5%) achieved CR. HSCT in first CR was done in 24 patients (64.9%) in group A and seven patients (24.1%) in group B (p = 0.0044). Age, sex, WBC count at diagnosis, FAB classification and chromosomal abnormalities did not differ between the two groups. Fourteen (five in group A and nine in group B) patients relapsed. Six (three in group A and three in group B) of them were salvaged by HSCT. Both 5-year event-free survival (EFS) and overall survival (OS) were statistically higher in group A than in group B (5-year EFS: 83.8 ± 6.1% versus 62.1 ± 9.0%, p = 0.0404; 5-year OS: 91.6 ± 4.7% versus 71.6 ± 8.5%, p = 0.0364). Although intensified chemotherapy without HSCT for low-risk AML patients is desirable to avoid the late complications of HSCT, our analysis showed that the introduction of risk-stratified treatment strategy significantly worsened the chances of EFS and OS. Our risk stratification based on chromosomal abnormalities only may be insufficient to identify low-risk AML children. Development of more sophisticated risk classification, including molecular markers, may be required to identify true low-risk patients who should avoid HSCT in first CR.

Treatment of Acute Myeloid Leukemia with the NOPHO-AML 2004 Study in Chinese Children: A Single Center Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5270-5270
Author(s):  
Xiaoqin Feng ◽  
Chunfu Li
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Chinese Children ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Objectives: The objective of the present study was to investigate the therapeutic efficacy and feasibility of NOPHO-AML 2004 study in the treatment of acute myeloid leukemia (AML; excluding acute promyelocytic leukemia) in Chinese children. Methods: Thirty-one children with novo AML treated with the NOPHO-AML 2004 study were recruited from Jan. 2010 to Dec. 2013, and the clinical data were retrospectively analyzed. Among 31 AML children, their age were from 2-14 years old (median age 8 years old). There were 12,15 and 4 children classified in low risk group, intermediate risk group and high risk group by cytogenetic risk classification respectively. Eight children received concomitant hematopoietic stem cell transplantation. Kaplan Meier method with Log-Rank testing was employed for survival analysis. Results: Follow-up was for a median 24 months (range: 5–50 months). The complete remission rate was 83.8%. The predicted 3-year leukemia free survival (LFS) rate was 53.8%. The LFS rate of low, intermediate and high risk group were 55.6%, 52.5% and 50.0% respectively. There was no significance in risk groups. The LFS rate of chemotherapy and chemotherapy concomitant HSCT were 42.7% and 87.5%, P<0.05. There were 2 cases of treatment related mortality including one case of sepsis and one case of ARDS. Conclusions: NOPHO-AML 2004 study is clinically efficacious for the treatment of AML in Chinese children. HSCT treatment had better outcome than only chemotherapy in childhood with non low risk AML in CR1 phase. Disclosures No relevant conflicts of interest to declare.

Genetic biomarkers identify a subgroup of high-risk patients within low-risk NPM1-mutated acute myeloid leukemia

2020 ◽  
pp. 1-12
Author(s):  
Diego Carbonell ◽  
Julia Suárez-González ◽  
María Chicano ◽  
Cristina Andrés-Zayas ◽  
Miriam Díez-Díez ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
High Risk Patients ◽  
Genetic Biomarkers ◽  
Risk Patients ◽  
Acute Myeloid

Risk-Stratification Treatment Directed by Minimal Residual Disease Improves the Outcome of Acute Myeloid Leukemia with t(8;21) in First Complete Remission: Results of the AML05 Multicentre Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 139-139
Author(s):  
Honghu Zhu ◽  
Xiao-hui Zhang ◽  
Yazhen Qin ◽  
Hao Jiang ◽  
Dai-Hong Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Hazard Ratio ◽  
Low Risk ◽  
Hematopoietic Stem ◽  
Risk Patients ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 139 Background Although patients with acute myeloid leukemia (AML) and the t(8;21) translocation generally have a favorable prognosis, relapse occurs in about 40% of cases and long-term (>5years) survival less than 50%. Patients with a KIT-mutation had an even higher relapse rate up to 70% and dismal survial. Once relapse, the outcome is extremely poor, even receiving allogeneic hematopoietic stem-cell transplantation (allo-HSCT).Therefore, rapidly identifying high-risk relapse patients and preemptively treating them with more aggressive therapy, such as HSCT, may decrease the chance of relapse and improve patient survival. We sought to improve outcome in patients with t(8;21) acute myeloid leukemia(AML) in first complete remission (CR) by applying risk-directed therapy that was based on measurements of minimal residual disease (MRD) by quantitative PCR during treatment. Methods From June 1,2005, to Dec 31, 2011, 137 patients with t(8;21) AML were enrolled at three centres. MRD was detected using quantitative PCR to detect the RUNX1/RUNX1T1 transcript. High-risk was defined by not achieving major molecular remission (MMR,> 3 log reduction of RUNX1/RUNX1T1 transcript from baseline) after second consolidation therapy or loss of MMR within 6 months since achieving MMR. Low-risk was defined by achieving MMR after second consolidation therapy and maintenance of MMR within 6 months thereafter. High-risk patients were recommended to receive allogeneic hematopoietic stem-cell transplantation (allo-HSCT) and low-risk patients to high-dose cytarabine-based consolidation chemotherapy. 116 patients who achieved CR and completed second consolidation were assigned to risk-directed therapy. Finally, sixty-nine patients actually received risk-directed therapy and 47 patients received a non risk-directed treatment for patients¡ bias. Findings With a median follow-time of 36 months in patients alive, risk-directed therapy and non risk-directed therapy achieved 5 year cumulative incidence of relapse(CIR) of 15.0%±4.7% and 57.5%±8.0%(p<0.0001), disease-free survival(DFS) of 74.7%±5.8% and 37.1%±7.4%(p<0.0001) and overall survival (OS) of 82.7%±5.1% and 49.8%±8.5% (p=0.002) (Figure 1). Allo-HSCT benefited high-risk as well as KIT-mutated but impaired low-risk patients' DFS and OS (all p<0.05) (Figure 2). Multivariate analysis revealed that MRD status (high-risk vs. low-risk) and treatment (risk-directed vs. no risk-directed) were independent prognostic factor for relapse(hazard ratio 8.85, 95% CI 2.05–38.13, p=0.003; 0.26, 95% CI 0.12–0.61, p=0.002), DFS(hazard ratio 9.32, 95% CI 2.21–39.3; p=0.002; 0.36, 95% CI 0.17–0.75, p=0.007) and OS (hazard ratio10.53, 95% CI 1.41–78.83; p=0.022; 0.37, 95% CI 0.15–0.93, p=0.035).KIT-mutation was an independent prognostic factor for relapse(hazard ratio 2.12, 95% CI 1.01–4.48, p=0.049) but not for DFS and OS. Interpretation Risk-stratification treatment directed by MRD could improve the outcome of AML with t(8;21) in first complete remission. Allo-HSCT benefits high-risk as well as KIT-mutated but impairs low-risk patients¡ survival. Disclosures: No relevant conflicts of interest to declare.

The Prognostic Relevance of Comprehensive Risk Score Is Modulated By Therapy: Analysis of 292 Acute Myeloid Leukemia Patients Registered at the Genova Acute Leukemia Registry (REGAL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4885-4885
Author(s):  
Fabio Guolo ◽  
Paola Minetto ◽  
Elena Clavio ◽  
Giordana Pastori ◽  
Daniela Guardo ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Low Risk ◽  
Allogeneic Bone ◽  
Intermediate Risk ◽  
Secondary Aml ◽  
Risk Patients ◽  
Comprehensive Risk Score ◽  
Acute Myeloid

Abstract Background, methods and aims of the study. It is widely established that the prognosis of patients with acute myeloid leukemia (AML) is related to clinical (age, denovo or secondary leukemia, presence of comorbidities), cytogenetic and molecular (e.g. FLT3-ITD, NPM1 gene mutation.) factors. We have developed a Comprehensive Risk Score (CRS) identifying three prognostic subgroups with favorable (low risk karyotype or intermediate karyotype + mutations of NPM1 gene without FLT3-ITD), unfavorable (high risk cytogenetics or FLT3-ITD without NPM1 mutation or secondary AML) and intermediate (including all the other patients not belonging to previous groups) prognosis. The clinical utility of CRS was tested on a cohort of 292 AML patients included in the REGAL registry, a regional Italian registry that was established in October 2010 at the University of Genoa. Results. Analysis of age distribution confirmed the increased incidence of AML in patients older than 60 years (n. 182, 62.4%). Patients with de novo or secondary AML were 210 (71.9%) and 82, (28.1%) respectively. Patients with significant and often multiple comorbidities at diagnosis were 131 (44.8%). Seventeen patients (6%) received only supportive therapy, 217 (74.3%) intensive induction regimens (mainly FLAG-Ida and 3+7), including 96% of patients with age below 60 years and 61% of those over the age of 60 years. Therapy with hypomethylating agents (azacitidine and decitabine) was given to 31 patients (10.6%). In the whole cohort of patients 24 months projected survival (OS) was 66% among 62 patients defined as low risk according CRS (median not reached), 37,9% among 118 intermediate risk patients (median 13.8 months) and 12,7% in 112 patients included in the unfavorable risk group (median survival 4.8 months) (p =0.000, Fig. 1). In patients aged younger than 60 years, OS of favorable and intermediate risk groups were similar (77% and 72% in 39 low risk and in 44 intermediate risk patients, respectively), whereas the outcome of 27 high risk patients was worse (OS 28.2%, median survival of 10,3 months, p 0.0001). In the group of elderly patients (> 60 years) the outcome of the intermediate group was rather similar to that observed in the poor risk group (OS 16% and 7% in 74 intermediate and in 85 poor risk patients, respectively, p n.s). On the contrary OS of 23 favorable risk patients was good (49%, p = 0.0015).Twenty-nine patients have actually received an allogeneic bone marrow transplant (BMT) during first CR (66% of 44 with indication) and 14 in second or third CR. The sources of stem cells have been HLA-identical and haploidentical sibling in 45% and 50% of patients, respectively. Discussion and conclusions. Our study suggests that the predictive value of CRS is clearly affected by the therapeutic strategy. Whereas the score allows the stratification of the whole cohort of patients in three groups with different outcome, in younger fit patients a more intensive therapeutic approach, such as the FLAG-IDA regimen and a wider use of allogeneic bone marrow transplantation made possible by the use of haploidentical donors, results in the super-imposable prognosis between favorable risk and intermediate risk patients. However, the same intensive approach cannot overcome the unfavorable features of the majority of high risk patients. In the elderly group median age and comorbidities prevent patients from receiving intensive induction therapy. Therefore, intermediate and unfavorable risk patients show a similar poor outcome. In elderly patients the achievement of a good outcome is related to disease status (denovo AML), favorable cytogenetic and molecular features, good performance status and administration of intensive induction and consolidation treatment, including BMT in selected cases. Disclosures Carella: Seattle Genetics Inc.: Research Funding.

scholarly journals Evaluation of the Disease Risk Index on Outcomes Following Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2529-2529
Author(s):  
Fotios V. Michelis ◽  
Hans A. Messner ◽  
Jieun Uhm ◽  
Naheed Alam ◽  
David Loach ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Low Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myeloid

Abstract Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment option when indicated for myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The Disease Risk Index (DRI, Armand et al, 2012) has been developed to predict overall survival and progression-free survival on the basis of differences in relapse risk. The purpose of this single-center study was to retrospectively investigate the prognostic value of the DRI on the outcome of 470 patients that underwent HCT for AML and MDS between 2000 and 2013. AML patients (n=381) underwent HCT in first and second complete remission and MDS patients (n=89) underwent HCT untreated or in remission. Median age at HCT was 51 (range 18-71), 219 (47%) patients were female. Myeloablative conditioning (MAC) was used in 304 (65%) patients, reduced-intensity (RIC) in 166 (35%) patients. Donors were related for 287 (61%) patients, unrelated for 183 (39%) patients. Grafts were peripheral blood stem cells (PBSC) in 377 (80%) patients and bone marrow in 93 (20%) patients. Median follow-up of patients alive was 44 months (range 1-134). In accordance with the DRI criteria, all 470 patients were in the low risk group concerning disease stage. Concerning disease biology characterized by cytogenetic risk, 11 patients were low risk, 396 patients were intermediate risk and 63 patients high risk. Based on the DRI overall risk stratification, 11, 396 and 63 patients were low, intermediate and high risk respectively. Univariate analysis demonstrated that the DRI was significantly prognostic for overall survival (OS) with a 3-year OS of 82%, 48% and 29% for low, intermediate and high risk patients respectively (p=0.005, Figure A). For cumulative incidence of relapse (CIR), DRI was again prognostic with 3-year CIR 0%, 21% and 30% for low, intermediate and high risk patients respectively (p<0.0001, Figure B). For non-relapse mortality (NRM), DRI did not demonstrate significant prognostic relevance with 3-year NRM 18%, 32% and 43% for low, intermediate and high risk patients respectively (p=0.14). Multivariable analysis for OS confirmed the prognostic significance of the DRI with hazard ratio (HR) 3.3 and 4.9 for intermediate and high risk respectively compared to low risk (p=0.01). For CIR, DRI was highly significant (p<0.0001) while for NRM, the DRI was not predictive (p=0.22). This study confirms the prognostic relevance of the DRI for OS and CIR in our cohort of patients undergoing HCT for AML and MDS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic haematopoietic stem cell transplantation can improve the prognosis of high-risk paediatric t(8;21) acute myeloid leukaemia in first remission based on MRD-guided treatment.

2020 ◽  
Author(s):  
Guan-hua Hu ◽  
Yi-fei Cheng ◽  
Ai-dong Lu ◽  
Yu Wang ◽  
Ying-xi Zuo ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Risk Group ◽  
Kit Mutation ◽  
Chemotherapy Group ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myeloid ◽  
Better Than

Abstract Background: Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT. Methods: Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after two cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed. Results: For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009). Conclusions: allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.

scholarly journals Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic CEBPA Mutations Based on a Multi-Gene Panel and Nomogram Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Li-Xin Wu ◽  
Hao Jiang ◽  
Ying-Jun Chang ◽  
Ya-Lan Zhou ◽  
Jing Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Validation Cohort ◽  
Low Risk ◽  
Training Cohort ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myeloid

BackgroundApproximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (biCEBPA) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.MethodsIn this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (N =111) and a validation cohort (N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method.ResultsAt least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R, KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P &lt;0.001 in training cohort; 87.5% vs. 18.2%, P =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% vs. 32.6%, P &lt;0.001), survival (96.9% vs. 63.6%, P =0.001) and CIR (7.2% vs. 65.8%, P &lt;0.001) in high-risk patients but not low-risk patients (LFS, 77.4% vs. 88.9%, P =0.424; survival, 83.9% vs. 95.5%, P =0.173; CIR, 11.7% vs. 11.1%, P =0.901).ConclusionsOur study indicated that biCEBPA mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in biCEBPA mutant-positive CN-AML patients.

Prospective Evaluation of Allogeneic Hematopoietic Stem-Cell Transplantation From Matched Related and Matched Unrelated Donors in Younger Adults With High-Risk Acute Myeloid Leukemia: German-Austrian Trial AMLHD98A

2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Acute Myeloid

Purpose To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. Results Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. Conclusion Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

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