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

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 181-181 ◽  
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.

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 ◽  
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 &gt;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.

Integrative prognostic risk score in acute myeloid leukemia with normal karyotype

Blood ◽  
2011 ◽  
Vol 117 (17) ◽  
pp. 4561-4568 ◽  
Author(s):  
Frederik Damm ◽  
Michael Heuser ◽  
Michael Morgan ◽  
Katharina Wagner ◽  
Kerstin Görlich ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Risk Score ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Normal Karyotype ◽  
Risk Groups ◽  
Risk Of Death ◽  
Risk Patients ◽  
Acute Myeloid

Abstract To integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external controls were evaluated for mutations/polymorphisms in NPM1, FLT3, CEBPA, MLL, NRAS, IDH1/2, and WT1. Transcript levels were quantified for BAALC, ERG, EVI1, ID1, MN1, PRAME, and WT1. Integrative prognostic risk score (IPRS) was modeled in 181 patients based on age, white blood cell count, mutation status of NPM1, FLT3-ITD, CEBPA, single nucleotide polymorphism rs16754, and expression levels of BAALC, ERG, MN1, and WT1 to represent low, intermediate, and high risk of death. Complete remission (P = .005), relapse-free survival (RFS, P < .001), and overall survival (OS, P < .001) were significantly different for the 3 risk groups. In 2 independent validation cohorts of 94 and 131 patients, the IPRS predicted different OS (P < .001) and RFS (P < .001). High-risk patients with related donors had longer OS (P = .016) and RFS (P = .026) compared with patients without related donors. In contrast, intermediate-risk group patients with related donors had shorter OS (P = .003) and RFS (P = .05). Donor availability had no impact on outcome of patients in the low-risk group. Thus, the IPRS may improve consolidation treatment stratification in CN-AML patients. Study registered at www.clinicaltrials.gov as #NCT00209833.

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

Blood ◽  
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 &lt;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.

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.

scholarly journals Construction of Immune-Related Prognostic Signatures in Acute Myeloid Leukemia

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.

scholarly journals A three-gene signature might predict prognosis in patients with acute myeloid leukemia

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xin Zhu ◽  
Qian Zhao ◽  
Xiaoyu Su ◽  
Jinming Ke ◽  
Yunyun Yi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Transcription Factor ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Risk Group ◽  
White Blood Cells ◽  
Gene Signature ◽  
Low Risk ◽  
Acute Myeloid

Abstract The identification of effective signatures is crucial to predict the prognosis of acute myeloid leukemia (AML). The investigation aimed to identify a new signature for AML prognostic prediction by using the three-gene expression (octamer-binding transcription factor 4 (OCT4), POU domain type 5 transcription factor 1B (POU5F1B) and B-cell-specific Moloney murine leukemia virus integration site-1 pseudogene 1 (BMI1P1). The expressions of genes were obtained from our previous study. Only the specimens in which three genes were all expressed were included in this research. A three-gene signature was constructed by the multivariate Cox regression analyses to divide patients into high-risk and low-risk groups. Receiver operating characteristic (ROC) analysis of the three-gene signature (area under ROC curve (AUC) = 0.901, 95% CI: 0.821–0.981, P&lt;0.001) indicated that it was a more valuable signature for distinguishing between patients and controls than any of the three genes. Moreover, white blood cells (WBCs, P=0.004), platelets (PLTs, P=0.017), percentage of blasts in bone marrow (BM) (P=0.011) and complete remission (CR, P=0.027) had significant differences between two groups. Furthermore, high-risk group had shorter leukemia-free survival (LFS) and overall survival (OS) than low-risk group (P=0.026; P=0.006), and the three-gene signature was a prognostic factor. Our three-gene signature for prognosis prediction in AML may serve as a prognostic biomarker.

Impact of allogeneic hematopoietic stem cell transplantation on pediatric acute myeloid leukemia of FAB subtypes M4 and M5

2020 ◽  
Author(s):  
Yu-juan Xue ◽  
Pan Suo ◽  
Yi-fei Cheng ◽  
Ai-dong Lu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Pediatric Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Background: FAB-M4 and M5 are unique subgroups of pediatric acute myeloid leukemia. However, for these patients, few studies have demonstrated the clinical and biological characteristics and efficacy of hematopoietic stem cell transplantation (HSCT), and especially haplo-HSCT. Procedure: We retrospectively evaluated the outcomes of 70 children with FAB-M4/M5 enrolled in our center from January 2013 to December 2017. Results: Of the patients, 32, 23, and 15 were in low-risk, intermediate-risk, and high-risk groups, respectively. T(16;16), inv16/CBFB-MYH11 was the most frequent cytogenetic abnormality. Among detected genetic alterations, WT1 was mutated at the highest frequency, followed by FLT3-ITD, NPM1, and CEBPA. Thirty-three patients received HSCT (haplo-HSCT = 30), of which four, 18, and 11 were in low-risk, intermediate-risk, and high-risk groups, respectively. For all patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 85.3 ± 4.3%, 69.0 ± 5.7%, and 27.9 ± 5.2%, respectively. By multivariate analysis, low-risk stratification predicted superior OS, EFS, and PLT ≤ 50 × 109/L at diagnosis, with FLT3-ITD mutations predicting higher CIR and poorer EFS. In intermediate- and high-risk groups, HSCT was independently associated with higher EFS and lower CIR. With a median post-transplant observation time of 30.0 months, the 3-year OS, EFS, CIR, and non-relapse mortality in the haplo-HSCT group were 74.2 ± 8.6%, 68.3 ± 8.9, 24.6 ± 7.6%, and 6.6 ± 4.1%, respectively. Conclusions: Risk-oriented treatment is important for pediatric FAB-M4/M5. For intermediate- and high-risk groups, HSCT significantly improved survival and haplo-HSCT might be a viable alternative approach.

Clinicopathologic Characterization of Acute Myeloid Leukemia and Myelodysplastic Syndrome with Inv(3)(q21q26.2)/t(3;3)(q21;q26.2) Reveals That Complex Karyotype but Not Blast Percentage Is Associated with Poor Survival; A Bone Marrow Pathology Group Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3847-3847
Author(s):  
Heesun J. Rogers ◽  
James W. Vardiman ◽  
John Anastasi ◽  
Gordana Raca ◽  
Natasha M Savage ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Risk Group ◽  
Risk Groups ◽  
Complex Karyotype ◽  
Genetic Abnormalities ◽  
Very High ◽  
Acute Myeloid

Abstract Abstract 3847 Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2); RPN1-EVI1 [inv3/t3] is a distinct type of AML with recurrent genetic abnormalities (RGA) in the 2008 WHO classification, with poor response to therapy and poor prognosis. The resulting dysregulation of EVI1 plays an important role in stem cell self-renewal and leukemogenesis. Although myelodysplastic syndrome (MDS) with inv3/t3 has a high risk of progression to AML, inv3/t3 is not among the genetic abnormalities sufficient for diagnosis of AML, irrespective of blast percentage (%) in the WHO classification. The revised International Prognostic Scoring System (IPSS-R) includes comprehensive cytogenetic subgrouping to better define prognosis in MDS patients. In this system, inv3/t3 is included in a poor risk karyotype group. The objective of this multicenter study was to evaluate a series of patients with MDS/AML and inv3/t3 in order to characterize their clinicopathologic features and outcome, and to apply the IPSS-R to inv3/t3 MDS patients. 111 patients (40 MDS and 71 AML with inv3/t3) were gathered from 8 medical centers. The median age at diagnosis was 56.5 years and was significantly older in MDS than AML with inv3/t3 patients (65 vs 54.5, p=0.03). Patients typically presented with normocytic anemia, thrombocytopenia and mild leukopenia (median Hb 9.1 g/dL, platelet 91 x109/L, WBC 3.6 x109/L). MDS with inv3/t3 patients had lower WBC than AML with inv3/t3 (median 3.1 vs 5.5, p<0.001). 19% of patients had hepatosplenomegaly. The median bone marrow (BM) blast% was 4% in MDS and 50% in AML with inv3/t3 and BM cellularity was higher in AML (70%) than MDS (40%) with inv3/t3 (both p<0.001). 88% of patients showed dysmegakaryopoiesis with characteristic small uni/bilobated forms. Dysgranulopoiesis (46%) and dyserythropoiesis (56%) were common and 59% of patients displayed multilineage dysplasia. The cytogenetics showed isolated inv3/t3 in 41% of patients, one additional abnormality in 33% and complex karyotype in 26%. −7/del7q (37%) was a frequent additional abnormality. Philadelphia chromosome (Ph) was noted in 10% of AML with inv3/t3. Overall 83% of patients (75% of MDS and 87% of AML with inv3/t3) expired (median follow up of 7.9 months (mo)). Most patients received therapy including 54% with chemotherapy (CTX; topoisomerase II inhibitors and/or antimetabolites) alone, 27% with CTX and allogeneic stem cell transplant (SCT) and 19% with supportive care. 16% of patients (10 MDS and 8 AML with inv3/t3) were associated with prior therapy for solid tumors and lymphomas. 57% of MDS with inv3/t3 patients subsequently evolved to AML. There was no significant difference in overall survival (OS) between MDS and AML with inv3/t3 (12.9 vs 8.0 mo, Cox PH p=0.11, Figure 1). There was no OS difference between MDS and AML after excluding Ph+ cases (Cox PH p=0.17) nor between de novo and therapy related MDS/AML with inv3/t3 (Cox PH p=0.89). Patients with isolated inv3/t3, one additional cytogenetic abnormality, and a complex karyotype showed progressively shorter OS (12.9, 10.0 and 4.3 mo, Cox PH p<0.001, Figure 2). The patients who received CTX and SCT showed superior OS to patients receiving CTX alone or supportive care only (15, 7 and 5 mo, respectively, Cox PH p=0.02). In multivariate analysis, choice of therapy and complex karyotype retained independent prognostic significance (Cox PH p= 0.02 and p<0.001, respectively). MDS with inv3/t3 patients were classified into IPSS Intermediate (Int)-1 (21), Int-2 (13), and high (6) risk groups. IPSS-R categorized MDS patients into low (3), Int (6), high (14) and very high (17) risk groups. 57% of IPSS Int-1 risk group patients (expected OS 3.5 year) were reclassified to high or very high risk group in IPSS-R (expected OS <1.6 year). Thus, the IPSS-R scores were higher relative to IPSS score (signed rank test, P<0.001). However, 72.5% and 77.5% of MDS with inv3/t3 patients had shorter OS than expected OS by IPSS-R and IPSS scores. The IPSS-R better reflects the OS of inv3/t3 than IPSS but may not fully reflect the generally dismal prognosis. Patients with MDS and AML with inv3/t3 follow a similarly aggressive clinical course, supporting classification of MDS with inv3/t3 as an AML with RGA irrespective of blast%. Additional cytogenetic abnormalities are associated with shorter OS in AML/MDS with inv3/t3 and our data suggest that aggressive therapy with SCT should be considered in these patients. Disclosures: Vardiman: Celgene Corporation: review of slides for clinical trials not relevant to this abstract Other. Foucar:e. Honoraria–Scientific Symposium Pathology Education: ASCP Press; ARP, Amirsys, ASCP Press; ARP, Amirsys Patents & Royalties, Honoraria, Not relevant to this abstract Other.

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

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2040-2040
Author(s):  
Byung-Sik Cho ◽  
Jae-Ho Yoon ◽  
Seung-Hwan Shin ◽  
Seung-Ah Yahng ◽  
Sung-Eun Lee ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Autologous Transplantation ◽  
High Risk Group ◽  
Hla Typing ◽  
Standard Risk ◽  
First Complete Remission ◽  
Acute Myeloid

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.

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

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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