Transplantation From 8/8-Matched or 7/8-Matched Unrelated Donors Compared with HLA-Matched Siblings in Acute Myeloid Leukemia in First Complete Remission

Abstract Abstract 2040 Comparable survival after 8/8-matched unrelated donor (URD) transplantation with HLA-matched siblings (MSD) has been reported in AML from a few multicenter studies. However, the role of 8/8-matched URD in acute myeloid leukemia (AML) with first complete remission (CR1) is uncertain because they applied various methods for HLA typing, such as low or intermediate resolution or partly high resolution (HR) typing, and/or included various disease status at transplantation. Additionally, there have been few studies comparing the clinical outcomes of 7/8-matched URD with current standard donors, such as MSD or 8/8-matched URD, particularly in AML, as a single disease. According to the risk-adapted treatment strategy, AML CR1 with intermediate or adverse cytogenetics received allogenetic transplantation as a post-remission treatment, if MSD or 8/8-matched URD was available. Patients with no available donor received 7/8-matched URD or autologous transplantation (only intermediate cytogenetics). Among 567 consecutive adult patients with AML who underwent transplantation between January 2002 and December 2009, in order to investigate the role of URD type in AML CR1, we assessed the transplantation outcomes of 8/8-matched URD (n=59) or 7/8-matched URD (n=36) classified by HR HLA typing, compared to MSD (n=165). Only intermediate or adverse cytogenetics was included, and we defined high-risk group as having one of the poor risk features, including adverse cytogenetics, hyperleukocytosis at diagnosis (over 100×109/L), older age over 60 years, or AML with myelodysplasia-related changes. In all, multivariate analyses showed that 8/8-matched URD had comparable 5-year disease-free survival (DFS; HR, 0.94; P=0.803), relapse (HR, 1.03; P=0.935), and non-relapse mortality (NRM; HR, 0.62; P=0.294) to MSD, while 7/8-matched URD had higher relapse (HR, 1.95; P=0.034) and a lower trend for DFS (HR, 1.47; P=0.154) than MSD without the difference in NRM (HR, 0.61; P=0.390). The equivalent outcomes of 8/8-matched URD were consistent irrespective of risk groups (high or standard). Particularly, only in standard-risk group, 7/8-matched URD (n=18) failed to show any benefit compared to concurrently performed autologous transplantation (n=67), contrasting to the superior survival of 8/8-matched URD (n=32) as well as MSD (n=108). In conclusion, the equivalent outcomes between MSD and 8/8-matched URD, irrespective of risk-group in AML CR1, suggest that 8/8-matched URD is useful for standard-risk as well as high-risk group of AML CR1, when lacking of MSD. On the other hand, the inferior outcome of 7/8-matched URD raise the necessity of trials comparing with other alternative graft sources, such as umbilical cord bloods or haploidentical family donors, particularly in AML with high-risk group. Disclosures: No relevant conflicts of interest to declare.

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Significance of Modified Risk Stratification Msmart 3.0 and Autologous Stem Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood-2019-130092 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5593-5593

Author(s):

Andrey Garifullin ◽

Sergei Voloshin ◽

Vasily Shuvaev ◽

Irina Martynkevich ◽

Elizaveta Kleina ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Risk Stratification ◽

Risk Group ◽

High Risk Group ◽

Prognostic Impact ◽

Newly Diagnosed ◽

Genetic Abnormalities ◽

Standard Risk

Background The risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies and other factors. The most extensive and modern system in this time is mSMART risk stratification involving many parameters such as genetic anomalies, albumin, beta-2-microglobulin, LDH, Plasma Cell S-phase and GEP levels. It is possible to use risk-adapted treatment programs with or without ASCT. Nevertheless, the role of complex karyotype, combination of genetic abnormalities and ASCT remains unclear. Aims To estimate the genetic abnormalities in patients with newly diagnosed multiple myeloma and define the role of risk-stratification and ASCT in prognosis of disease. Methods The study included 159 patients (median age 63 years, range 28 - 83; male: female ratio - 1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). ASCT was performed at 42% patients. Results The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) - 16.3% (26/159), t(4;14) - 5.0% (8/159); TP53/del17p - 5.6% (9/159); 1p32/1q21 amp/del - 12% (19/159); hypodiploidy - 3.1% (5/159); hyperdiploidy - 1.25% (2/159); del5q - 0,6% (1/159); other - not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (>3 aberrations) - in 4.4% (7/159) patients. The median OS in "two aberration" and "complex abnormalities" groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 26 months and was not reached, respectively (p=.00015). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p=.011). Differences between "two aberration" and "complex abnormalities" groups were not find (p> .05). We modified high-risk (gain 1q, p53 mutation, del 17p deletion, t(4;14), t(14;16), t(14;20), R-ISS stage III, double and triple hit myeloma) mSMART 3.0 by adding "two aberration" and "complex abnormalities" groups on based the OS and PFS results. The final analysis was based on the results of the complex examination of 87 patients: 53 patients in standard-risk group and 34 patients in high-risk group. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0mod - 48 months; 5-years OS was 62% and 38%, respectively (p=0.0073). The median PFS was 43 and 29 months, respectively (p=.09). The best results of OS and PFS were reach in both groups of patient who performed ASCT. The median OS in standard-risk mSMART 3.0 with ASCT (n=37) was not reached, in high-risk mSMART 3.0mod with ASCT - 48 months (n=20); standard-risk mSMART 3.0 without ASCT - 40 months (n=16); in high-risk mSMART 3.0mod without ASCT - 22 months (n=14); 5-years OS was 81%, 60%, 33% and 28%, respectively (p=0.0015). The median PFS was not reached, 46, 22 and 19 months, respectively (p=.017). Conclusions The combination of two aberrations and complex abnormalities is unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk group according mSMART 3.0mod. The ASCT can improve treatment's outcomes and life expectancy especially in patients with high-risk. It can be useful for update risk stratification in a future. Disclosures Shuvaev: Novartis: Consultancy; Pfize: Honoraria; Fusion Pharma: Consultancy; BMS: Consultancy.

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Pretreatment Cytogenetic Abnormalities Are Predictive of Induction Success, Cumulative Incidence of Relapse and Overall Survival in Patients >60 Years of Age with Newly Diagnosed Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v106.11.3293.3293 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3293-3293

Author(s):

Richard F. Schlenk ◽

Sabine Kayser ◽

Martina Morhardt ◽

Konstanze Döhner ◽

Hartmut Döhner ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Myeloid Leukemia ◽

Risk Group ◽

Normal Karyotype ◽

Risk Groups ◽

High Risk Group ◽

Newly Diagnosed ◽

Balanced Translocations ◽

Acute Myeloid

Abstract Purpose: Karyotype at diagnosis provides the most important prognostic information in younger adults with acute myeloid leukemia (AML). However, there are few data available looking in particular at patients (pts.) above 60 years of age. We prospectively analyzed 361 elderly pts. with newly diagnosed AML. All pts. were treated within the AMLHD98B treatment trial and received intensive induction and consolidation therapy. Pts. exhibiting a t(15;17) received an age-adjusted AIDA-regimen. Median follow-up time was 48 months. The median age was 67 years (range 60–85 years). Results: 160 pts. had a normal karyotype (44%); 48 pts. (13%) exhibited the balanced translocations t(8;21) (n=12), inv(16) (n=14), t(15;17) (n=11), or t(11q23) (n=11); in the absence of these balanced translocations, 73 pts. exhibited a single aberration, 179 pts. two aberrations, and 61 pts. a complex karyotype (≥3 aberrations; including 44 pts. with 5 or more aberrations). Analyses were normalized to the complete remission (CR) rate (52%), cumulative incidence of relapse (CIR) (77%) and overall survival (OS) (13%) after 4 years of pts. with normal karyotype. Pts. exhibiting a t(15;17) showed a significantly better CIR (29%) and OS (55%), whereas pts. with the other balanced translocations [t(8;21), inv(16)/t(16;16) and t(11q23)] did not differ from pts. with normal karyotype. The limited backward selected Cox-model for OS [t(15;17) excluded] revealed two risk groups: standard-risk [normal karyotype, t(8;21), inv(16), t(11q23), +8 and +11 in absence of a complex karyoytpe] and high-risk [all other aberrations]. The CR rates were 56% and 18%, and the OS-rates after 4 years for the standard- (n=223) and the high-risk group (n=127) were 15% and 0%, respectively. The MRC risk classification system for patients >55 years applied to our patients revealed CR- and OS-rates after 4 years of 73% and 19%, 47% and 12%, as well as 7% and 0% for the low (n=26), intermediate (n=282) and high risk groups (n=44), respectively [t(15;17) excluded]. In conclusion, our risk classification system identified a large high-risk group (36%) of elderly patients with AML who did not benefit from intensive chemotherapy.

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Efficacy and Safety of Decitabine Combined with IA Regimen in the Treatment of Newly Diagnosed Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2021-145027 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2341-2341

Author(s):

Lifen Kuang ◽

Juan Li

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

High Risk ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

Risk Group ◽

High Risk Group ◽

Newly Diagnosed ◽

Efficacy And Safety ◽

Acute Myeloid

Abstract Objective: To evaluate the efficacy and safety of decitabine combined with IA regimen in the treatment of newly diagnosed acute myeloid leukemia. Methods: From September 1, 2013 to October 18, 2019, 164 newly diagnosed acute myeloid leukemia patients who received IA or decitabine combined with IA induction chemotherapy who were hospitalized in the Department of Hematology of the First Affiliated Hospital of Sun Yat-sen University were enrolled. The efficacy and side effects of treatment were analyzed. Results: The complete remission rate of decitabine combined with IA regimen chemotherapy group (n=88) and IA regimen chemotherapy group (n=76) was 83.0% vs. 68.4% (P=0.029, Fig 1). Subgroup analysis (table 1) showed that age ≥40 years old, WBC＜10*10^9/L, Hb＞85g/L, PLT≥50*10^9/L, MCV≥98fL, ratio of bone marrow immature cells ≤45%, NCCN intermediate-risk or high-risk group, patients with FLT3ITD mutation had a higher CR rate in the decitabine combined with IA regimen group. Multivariate analysis showed that combined decitabine was an independent favorable factor affecting the CR rate (OR 3.559, 95% CI: 1.554-8.151, P=0.003). Compared with the IA group, patients in the decitabine combined with IA group took longer to rebuild the granule system (20 days vs 19 days, P=0.026), and the incidence of infection was higher (93.2% vs 78.8%, P=0.028) (table 2). Conclusion: Compared with the IA regimen, the decitabine combined with the IA regimen significantly improves the induction chemotherapy response rate of newly diagnosed non-M3 AML patients, especially for patients with the following characteristics: age ≥ 40 years old, WBC <10*10^ 9/L, Hb＞85g/L, PLT≥50*10^9/L, MCV≥98fL, bone marrow immature cell proportion ≤45%, NCCN risk stratification medium-risk or high-risk group, FLT3ITD mutation. After combining with decitabine, the patient's granular bone marrow suppression increased. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Study AML-BFM 2004: Improved Survival In Childhood Acute Myeloid Leukemia without Increased Toxicity

Blood ◽

10.1182/blood.v116.21.181.181 ◽

2010 ◽

Vol 116 (21) ◽

pp. 181-181 ◽

Cited By ~ 9

Author(s):

Ursula Creutzig ◽

Martin Zimmermann ◽

Michael Dworzak ◽

Jean-Pierre Bourquin ◽

Christine Neuhoff ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Myeloid Leukemia ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Therapeutic Window ◽

Liposomal Daunorubicin ◽

Off Label ◽

Acute Myeloid

Abstract Abstract 181 Acute Myeloid Leukemia - Therapy, excluding Transplantation: Pediatric and Adult AML Therapy Study AML-BFM 2004 was designed to improve outcome of children and adolescents with AML without increasing toxicity. Patients were stratified into a standard- (SR)* or high-risk (HR)** group according to morphology, cyto-/molecular genetics including FLT3-ITD, and therapy response on day 15. Notably, reclassification of SR patients to the HR group in case of FLT3-ITD positivity was newly established in this study. Improvement of prognosis was attempted by intensification of chemotherapy: (1) Randomized introduction of liposomal daunorubicin (L-DNR) in a higher equivalent dose than idarubicin during induction in both risk groups (L-DNR 80mg/m2/day/3x) in comparison to standard induction using idarubicin 12mg/m2/day/3x, each combined with cytarabine and etoposide (L-DNR may offer an increased therapeutic window due to lower cardiotoxicity) and (2) randomised introduction of 2-chloro-2-deoxyadenosine (2-CDA, 2×6mg/m2) as intensification during the cytarabine/idarubicin (AI) consolidation in HR patients only. Overall results improved compared to the previous study AML-BFM 98: Survival estimates at 5 year (pOS) in patients (excluding Myeloid leukemia in Down syndrome) were 72% + 3% vs. 64% + 2% (AML-BFM 04 n=566 vs. AML-BFM 98 n=472), plogrank=0.02; the 5-year event-free survival (pEFS): was 54% + 3% vs. 50% + 2%, plogrank=.40. Results in the 197 SR patients were excellent: pOS 88% + 3% vs. 78% + 3% (n=182), plogrank=.01, EFS 69%, + 4% vs. 64% + 4%, plogrank=.40. Results in the 368 HR patients also improved: pOS 63% + 4% vs. 56% + 3% (n=290), plogrank=.07, EFS 46%, + 3% vs. 41% + 3%, plogrank=.43. OS improvement was partly due to better results after treatment of relapse or nonresponse (3-year pOS after nonresponse/relapse in 171 patients of study 2004 40% + 5% vs. 32% + 4% in 198 patients in AML-BFM 98, plogrank=.017). Results for the 1st randomization L-DNR vs. idarubicin during induction were similar (pOS 78% + 4% vs. 70% + 4%, plogrank=.15, pEFS 60% + 4% vs. 54% + 4%, plogrank=.17). There were less early deaths (4 vs. 8 patients) and less treatment related deaths in remission in the L-DNR group (2 vs. 5 patients). The rate of severe infection was slightly lower with L-DNR (pFisher 0.15). Two L-DNR vs. 6 idarubicin patients showed grade III/IV cardiotoxicity after induction. Results of the 2nd randomization in HR patients (AI/2-CDA vs. AI) were also similar: p=OS 75% + 5% vs. 65% + 5%, plogrank=.18, pEFS 51% + 5% vs. 51% + 5%, plogrank=.98. Toxicity rates of the intensification with 2-CDA were tolerable. In conclusion, compared to the previous study AML-BFM 98, results of study AML-BFM 2004 show significant improvement in both risk groups. This appears attributable to a combination of factors including therapy intensification, better supportive care and improved treatment of patients with relapse or nonresponse. Given the reduced toxicity of L-DNR and a trend towards better survival rates by adding L-DNR during induction and 2-CDA during HR consolidation, these agents will be further used in the forthcoming AML-BFM study. *Standard risk group definition: FAB M1/M2 with Auer rods, FAB M4eo or favorable cytogenetics [t(8;21) or inv(16)] and blasts in the bone marrow on day 15 <5%, and FAB M3 (all patients) **High-risk group definition: all others. Disclosures: Off Label Use: liposomal daunorubicin is used, which is off label for pediatric AML. It was used because it offers a possibility to increase cumulative dosages of anthracyclines with lower cardiotoxicity.

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

Blood ◽

10.1182/blood.v124.21.5270.5270 ◽

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.

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Rapid Donor Identification Improves Survival in High-Risk First-Remission Patients With Acute Myeloid Leukemia

JCO Oncology Practice ◽

10.1200/jop.19.00133 ◽

2020 ◽

Vol 16 (6) ◽

pp. e464-e475

Author(s):

John M. Pagel ◽

Megan Othus ◽

Guillermo Garcia-Manero ◽

Min Fang ◽

Jerald P. Radich ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

High Risk Group ◽

Hla Typing ◽

Allogeneic Hct ◽

Donor Identification ◽

Risk Patients ◽

Acute Myeloid

PURPOSE: Patients with acute myeloid leukemia with high-risk cytogenetics in first complete remission (CR1) achieve better outcomes if they undergo allogeneic hematopoietic cell transplantation (HCT) compared with consolidation chemotherapy alone. However, only approximately 40% of such patients typically proceed to HCT. METHODS: We used a prospective organized approach to rapidly identify donors to improve the allogeneic HCT rate in adults with high-risk acute myeloid leukemia in CR1. Newly diagnosed patients had cytogenetics obtained at enrollment, and those with high-risk cytogenetics underwent expedited HLA typing and were encouraged to be referred for consultation with a transplantation team with the goal of conducting an allogeneic HCT in CR1. RESULTS: Of 738 eligible patients (median age, 49 years; range, 18-60 years of age), 159 (22%) had high-risk cytogenetics and 107 of these patients (67%) achieved CR1. Seventy (65%) of the high-risk patients underwent transplantation in CR1 ( P < .001 compared with the historical rate of 40%). Median time to HCT from CR1 was 77 days (range, 20-356 days). In landmark analysis, overall survival (OS) among patients who underwent transplantation was significantly better compared with that of patients who did not undergo transplantation (2-year OS, 48% v 35%, respectively [ P = .031]). Median relapse-free survival after transplantation in the high-risk cohort who underwent transplantation in CR1 (n = 70) was 11.5 months (range, 4-47 months), and median OS after transplantation was 14 months (range, 4-44 months). CONCLUSION: Early cytogenetic testing with an organized effort to identify a suitable allogeneic HCT donor led to a CR1 transplantation rate of 65% in the high-risk group, which, in turn, led to an improvement in OS when compared with the OS of patients who did not undergo transplantation.

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Risk Stratification Using a New Prognostic Model for Patients with Secondary Acute Myeloid Leukemia - Results of the DSIL-AML96 Trial.

Blood ◽

10.1182/blood.v114.22.2652.2652 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2652-2652

Author(s):

Friedrich Stölzel ◽

Walter E. Aulitzky ◽

Heinrich Bodenstein ◽

Martin Bornhäuser ◽

Michael Kramer ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Myeloid Leukemia ◽

Prognostic Model ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Allogeneic Hsct ◽

Secondary Acute Myeloid Leukemia ◽

Acute Myeloid

Abstract Abstract 2652 Poster Board II-628 Background: Secondary acute myeloid leukemia (sAML) following a myelodysplastic syndrome (mdsAML) or deriving as therapy-related AML (tAML) is regarded as an entity with a poor prognosis and patients are normally treated as high risk AML. However due to progress in elucidating the impact of molecular and cytogenetic markers and therefore combining biological and clinical data for prognosis and treatment outcome the aim of this analysis was to provide a prognostic scoring system for this entity by including clinical and laboratory data from patients being treated in the prospective AML96 trial of the DSIL study group. Patients and methods: A total of 318 patients with sAML (mdsAML = 239 and tAML = 79) were treated within the AML96 trial with a median follow-up for patients alive of 5.66 years (95% CI 4.426 – 6.895). All patients received double induction chemotherapy. Consolidation therapy contained high-dose cytosine arabinoside and for patients ' 60 years of age the option of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) according to donor availability. Prognostic factors for survival were analyzed in the whole group of sAML patients in a multivariate Cox regression model for overall survival (OS) stratified by treatment groups (chemo-consolidation vs. allogeneic HSCT). Model selection was performed by backward selection applying the Likelihood-Ratio-Test. Results: Complete remission (CR) rate for all patients was 30.8% (n = 96). CR rate was lower in patients with mdsAML compared to patients with tAML (25.9% vs. 44.3%, p=.003). Patients with mdsAML were older and had a higher percentage of CD34+ blasts at diagnosis but to a lower extend aberrant karyotypes than patients with tAML. OS and disease free survival (DFS) at three years for all patients was 15.8% and 20.6%, respectively. While disease status (mdsAML vs. tAML) had no independent influence on survival, the dichotomized prognostic factors platelet count in the peripheral blood at diagnosis [HR = 0.535 (95% CI .415 – .689), p=<.000] as well as the NPM1 mutational status in the bone marrow at diagnosis [HR = 0.572 (95% CI .351 – .933), p=.025] were detected as independent predictors for overall survival. By combining these two variables, a prognostic model for OS with two risk groups for patients with sAML could be established with the low risk group being NPM1 positive or having platelets of >50 Gpt/l at diagnosis and the high risk group being NPM1 negative and having platelets of '50 Gpt/l at diagnosis. Three year OS for patients who received chemo-consolidation in the low risk group was 19.9% [95% CI = .128 - .270] and for patients in the high risk group 5.1% [95% CI = .014 - .088], p<.001. For patients who underwent allogeneic HSCT in first CR belonging to the low risk group the three year OS was 53.8% [95% CI = .346 - .730] and for patients in the high risk group 15.4% [95% CI = .000 - .35], p<.001. Conclusions: For patients with sAML we provide a new prognostic model for risk stratification: 1) NPM1+ or Platelets >50 Gpt/l defining a low risk group and 2) NPM1- and Platelets ' 50 Gpt/l defining a high risk group. Disclosures: No relevant conflicts of interest to declare.

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10-Year Real-World Data on Acute Myeloid Leukemia: The Paradigm of a Public Health Center in Brazil

Blood ◽

10.1182/blood-2020-140858 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Camilla C. Campos ◽

Lorena M. Caldas ◽

Lais T. Silva ◽

Monica Botura ◽

Alessandro de M. Almeida ◽

...

Keyword(s):

Public Health ◽

High Risk ◽

Myeloid Leukemia ◽

Risk Group ◽

Developed Countries ◽

High Risk Group ◽

Intermediate Risk ◽

Molecular Tests ◽

Unknown Risk ◽

Acute Myeloid

Introduction Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults and originates from hematopoietic precursor cells that suffers genetics and epigenetics alterations leading to a clone able to proliferate with survival advantages. The last years have been of great advances in AML because of more profound knowledge of its pathogenic mechanisms. This lead to a better stratification of the patients based on cytogenetics and molecular criteria and development of targeted therapy that changed its natural course. Unfortunately, the tests and new drugs are expensive and not easily available worldwide, especially in low and middle-income countries (LMIC) with distinct realities between private and public care. Methods To determine the profile and outcomes of patients in a public health center in Brazil, we did a retrospective analysis of all the cases of non-promyelocytic AML diagnosed between 2007 and 2017 in the University Hospital Professor Edgar Santos of Federal University of Bahia. 62 patients were included and we used a modified model of European LeukemiaNet 2017 classification to risk stratification, with cases of secondary AML (sAML) included in the high risk group. Results A total of 62 patients were analyzed, 1 died prior treatment and was excluded. Median age at diagnosis was 44 years (range, 16-83 years) with 58% females. 68% werede novoAML. 11% of patients were classified as favorable risk, 8% as intermediate and 42% as high risk. 39% had unknown risk because of absence of cytogenetic and/or molecular tests. The chemotherapy protocol in patients eligible to intensive treatment was 7+3 in 87%. 20% of the patients died during induction and 65% achieved response (53% complete + 12% partial remission). Analyzing only sAML, 35% were considered fit for intensive treatment and most of less intensive regimens were based in low-dose cytarabine (64%). The overall response rate of sAML after induction was 20%. During the treatment, 31% relapsed with a median time to relapse of 8 months. 43% of the relapses happened in patients classified as unknown risk. 37% of patients that survived induction were submitted to allogeneic bone marrow transplant (alloBMT) and had survival advantage (hazard ratio, HR: 2,52, 95% CI: 1.103 - 5,795;P= 0.028; Figure 1), with superior median overall survival (mOS) (49 months) when compared with the chemotherapy group (11 months) (P= 0.021). During the follow-up, 77% of the patients died and most of the deaths (61%) occurred in the first year of diagnosis. The primary cause of death was infection (52%) followed by leukemia progression (31%). The mOS was 7 months and 5-year OS was 27%. Stratifying by the risk, the mOS was shorter in patients with unknown and high risk (5 and 4 months, respectively) than in low and intermediate risk (not reached,P= 0.01; Figure 2). The median relapse free survival (RFS) was 15 months, reached only in the high risk group (14 months;P= 0.31; Figure 3). The patients with sAML had mOS of 3 months versus 11 months ofde novoAML(P =0.024; Figure 4). Discussion In summary, we found statistical difference in better OS among patients that received BMT, AMLde novoand favorable/intermediate risk. Our findings were similar to those reported by other groups of university hospitals in Brazil. An alarming data is the high proportion of patients who were not adequately stratified. Our data are from real life and this subgroup still exists because cytogenetic and molecular tests are not universally available in the brazilian public health system. Those patients had similar outcomes to high risk ones suggesting that a proportion of them were undertreated. It is important for every center to be aware of their survival curves to better individualize their approaches. We suggest that patients with inadequate risk assessment should undergo alloBMT as this remains the primary curative intervention and the main outcome changer in real-world setting of LMIC. Our high mortality rate, in comparison with data from developed countries, reflects the absence of more effective therapies, especially for high risk cases, and an inferior hospital infrastructure contributing to a higher incidence of infections. Considering the discovery of new powerful drugs, the tendency of discrepant outcomes between centers from LMIC and developed countries is considerably high. Therefore, the improvement of access to diagnostic techniques and treatment is still an unmet need in AML scenario. Disclosures No relevant conflicts of interest to declare.

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Construction of Immune-Related Prognostic Signatures in Acute Myeloid Leukemia

10.21203/rs.3.rs-51235/v1 ◽

2020 ◽

Author(s):

Ruyi Xu ◽

Yi Li ◽

Yang Liu ◽

Jianwei Qu ◽

Wen Cao ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Myeloid Leukemia ◽

Cox Regression ◽

Risk Group ◽

Early Stage ◽

Chemotherapy Resistance ◽

High Risk Group ◽

Cox Regression Analysis ◽

Acute Myeloid

Abstract Background: Acute Myeloid Leukemia (AML) is characterized as a type of hematological malignancy with poor survival. Accumulated evidence showed that dysregulated immune activities contribute to the pathogenesis of AML and accelerate the development of chemotherapy resistance. Thus, we aimed to construct prognostic signatures based on patients’ immune features to sort out the high-risk group and to identify survival-related checkpoint molecules as potential therapeutic targets.Methods: In the current study, we developed two prognostic signatures based on immune genes and infiltrated fraction of immune cells, respectively, using a least absolute shrinkage and selection operator model, and Cox regression analysis on 415 samples obtained from TCGA and GEO databases. Results: We found the optimum strategy for predicting patients’ survival is combined using these two prognostic immune-related signatures. Through our established signatures, we classified patients into Favorable Risk group and Poor Risk group, who showed significantly different OS and DFS. We further demonstrated the checkpoint molecules’ profile in different risk groups. Conclusions: we constructed a powerful prognostic tool here to help classify high-risk patients in early-stage, who may benefit from additional immune therapies by targeting identified checkpoint molecules.

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Abstract 19763: Role of HAS-BLED Score on Major Bleeding in Atrial Fibrillation Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents

Circulation ◽

10.1161/circ.132.suppl_3.19763 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Yoshitaka Ito ◽

Kazuhiro Naito ◽

Katsuhisa Waseda ◽

Hiroaki Takashima ◽

Akiyoshi Kurita ◽

...

Keyword(s):

Atrial Fibrillation ◽

High Risk ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Stent Implantation ◽

Risk Group ◽

High Risk Group ◽

Low Risk

Background: While anticoagulant therapy is standard management for atrial fibrillation (Af), dual antiplatelet therapy (DAPT) is needed after stent implantation for coronary artery disease. HAS-BLED score estimates risk of major bleeding for patients on anticoagulation to assess risk-benefit in Af care. However, it is little known about usefulness of HAS-BLED score in Af patient treated with coronary stents requiring DAPT or DAPT plus warfarin (triple therapy: TT). The aim of this study was to evaluate the role of HAS-BLED score on major bleeding in Af patients undergoing DAPT or TT. Methods: A total of 837 consecutive patients were received PCI in our hospital from Jan. 2007 to Dec. 2010, and 66 patients had Af or paroxysmal Af at the time of PCI. Clinical events including major bleeding (cerebral or gastrointestinal bleeding) were investigated up to 3 years. Patients were divided into 2 groups based on HAS-BLED score (High-risk group: HAS-BLED score≥4, n=19 and Low-risk group: HAS-BLED score<4, n=47). DAPT therapy was required for a minimum 12 months after stent implantation and warfarin was prescribed based on physicians’ discretion. Management/change of antiplatelet and anticoagulant therapy during follow-up periods were also up to physicians’ discretion. Results: Baseline characteristics were not different between High-risk and Low-risk group except for age. Overall incidence of major bleeding was observed in 8 cases (12.1%) at 3 years follow-up. Major bleeding event was significantly higher in High-risk group compared with Low-risk group (31.6% vs. 4.3%, p=0.002). However, management of DAPT and TT was not different between the 2 groups. Among component of HAS-BLED score, renal dysfunction and bleeding contributed with increased number of the score. Conclusion: High-risk group was more frequently observed major bleeding events compared with Low-risk group in patients with Af following DES implantation regardless of antiplatelet/anticoagulant therapy.

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