No Impact of Postremission Consolidation Chemotherapy Before Allogeneic Transplant in Patients with First Remission Acute Myeloid Leukemia with Intermediate or High Risk Cytogenetics.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2164-2164
Author(s):  
Lisa O. Sproat ◽  
Brian Bolwell ◽  
Lisa Rybicki ◽  
Matt Kalaycio ◽  
Robert Dean ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Allogeneic Transplantation ◽  
Intermediate Risk ◽  
Allogeneic Transplant ◽  
Consolidation Chemotherapy ◽  
P Values ◽  
First Remission ◽  
Acute Myeloid

Abstract Despite a lack of evidence that postremission consolidation chemotherapy improves outcome of allogeneic transplantation in patients with acute myeloid leukemia (AML) in first remission, high dose cytarabine and other regimens are commonly administered to these patients. We studied a consecutive cohort of 73 adult patients with AML at high risk of relapse by published criteria who underwent allogeneic transplantation in first remision to determine whether specific patient and treatment characteristics identified subgroups of patients who might benefit from consolidation therapy prior to allogeneic transplantation. Pretransplant cytogenetics were available for 56 patients. Transplantation occurred between 1988 and 2008. The primary analysis grouped patients according to cytogenetic risk (poor versus intermediate) and consolidation chemotherapy (yes versus no). Consolidation Chemotherapy No Consolidation Chemotherapy None of the measured outcomes (relapse mortality (RM), non-relapse mortality (NRM), overall survival (OS)) differed significantly between groups. Poor Risk Cytogenetics 9 13 Intermediate Risk 18 16 Cytogenetics P Values for Consolidation Versus No Consolidation by Cytogenetic Risk Poor Risk Cytogenetics Intermediate Risk Cytogenetics When cytogenetic risk was not stratified the results between consolidation and no consolidation were also not significant. RM 0.95 0.74 NRM 0.73 0.19 OS 0.77 0.21 P Values for Consolidation Versus No Consolidation RM 0.70 NRM 0.12 OS 0.14 Neither this study nor others provide evidence that consolidation chemotherapy is beneficial to all patients with AML in first remission who undergo allogeneic transplant or to cytogenetic subgroups. Delays in referral to a transplant center, in tissue typing or physician preference to administer consolidation chemotherapy are not justified and expose patients to the inconvenience, risk, and cost of unnecessary treatment. Clinicians should avoid consolidation chemotherapy and expedite allogeneic transplantion in patients with AML in first remission in whom transplantation is the preferred treatment.

Impact of FLT3ITD mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia

Blood ◽  
2014 ◽  
Vol 124 (2) ◽  
pp. 273-276 ◽  
Author(s):  
David C. Linch ◽  
Robert K. Hills ◽  
Alan K. Burnett ◽  
Asim Khwaja ◽  
Rosemary E. Gale
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutant Allele ◽  
Allogeneic Transplantation ◽  
Intermediate Risk ◽  
Relapse Risk ◽  
Key Points ◽  
First Remission ◽  
Good Risk ◽  
Acute Myeloid

Key Points In cases with intermediate-risk NPM1MUT AML, there are only minor differences in relapse risk according to FLT3ITD level. When considering allogeneic transplantation in first remission, NPM1MUT cases with low-level FLT3ITD should not be considered as good risk.

A Risk Score Combined Clinical and Molecular Profiles Identifies a High-Risk Subgroup within Intermediate-Risk Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2713-2713
Author(s):  
Xiaoxia Hu ◽  
Aijie Huang ◽  
Qi Chen ◽  
Ying Zhang ◽  
Lixia Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
High Risk ◽  
Signaling Pathway ◽  
Risk Score ◽  
Myeloid Leukemia ◽  
Intermediate Risk ◽  
Concordance Index ◽  
Scoring Model ◽  
Acute Myeloid

Introduction Acute myeloid leukemia (AML) is categorized into favorable-, intermediate- and adverse-risk groups according to European LeukemiaNet (ELN) risk stratification. The intermediate-risk AML comprises a substantial proportion of AML, and even within the intermediate-risk AML, the biology and prognosis are highly different, which suggests that more prognostic factors are needed to be identified. Method A total of 265 newly diagnosed AML patients treated between January 2010 and January 2019 who had cryopreserved DNA for mutational analyses diagnosed and treated in Changhai Hospital were included. 121 patients were aged ≤ 65y, and classified as intermediate-risk (IR)-AML. A Custom Amplicon panel targeting exons of 210 genes was used for deep sequencing at diagnosis. We used a LASSO Cox regression model to achieve shrinkage and variable selection from prognostic factors (P<0.1 in log-rank tests) to build risk score for predicting overall survival. A nomogram was constructed to display the risk of death in individuals. The discrimination of the risk score was measured by the concordance index (C-index) and areas under time-dependent receiver-operating characteristics (ROC) curves (AUCs), and the calibration of the risk score was explored graphically by calibration plots. Patients with IR-AML and aged ≤ 65y in The Cancer Genome Atlas (TCGA) data (n= 41) was used as a validation cohort. Results The median age was 44 (11-75) years, and 54% had normal karyotype. NRAS and CEBPA were the most recurrently mutated genes (both 26%), followed by KIT (24%), DNMT3A (23%), ARID1B (20%), FLT3-ITD (19%), PCLO (17%), and TET2 (17%). In univariate analyses, age ≥ 55 years, WBC ≥ 10×109/L , PLT > 40×109/L, high LDH counts at diagnosis, DNMT3A and Signaling Pathway genes mutations and the number of mutated genes ≥ 8 were significantly associated with poor OS (P < 0.05), and age ≥ 55 years, WBC≥ 10×109/L, DNMT3A and FLT3-ITD mutations were associated with worse relapse free survival(RFS, P < 0.05). Three variables were incorporated in our scoring model by LASSO, including Signaling Pathway genes mutations (including NRAS, KIT, FLT3, KRAS etc), DNMT3A mutation and WBC≥ 10×109/L. A risk scoring model was developed incorporating the weighted coefficients of these variables:0.6749 × Signaling Pathway + 1.1147 × DNMT3A + 0.7829 × WBC. The risk score grouped IR-AML patients into two subgroups: intermediate-low risk (ILR, score < 1, n= 48) and intermediate-high risk (IHR, score ≥ 1, n= 62) groups (Table1). Concordance index[OS: 0.703, 95% CI (0.643, 0.763); RFS: 0.681, 95%CI (0.620, 0.741)] demonstrated well discrimination power and calibration plots showed that the nomograms did well compared with an ideal model. The 3-year OS for ILR and IHR groups were 72.3% and 29.4% (P < 0.0001), and 3-year RFS were 63.9% and 19.4% (P < 0.0001), respectively (Figure 1A-B). The similar results were also observed in TCGA cohort (3-year OS 57.7% vs. 26.2%, P= 0.019; Figure 1C). The survival was equivalent for patients with ILR when treated with chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT, 3-year OS: 74.7% vs. 70.8%, P= 0.936, RFS: 76.4% vs. 55.0%, P= 0.225; Figure 2A-B). However, alloHSCT benefited patients with IHR. Patients who received alloHSCT had survival advantages over those who treated with chemotherapy only (3-year OS: 51.6% vs. 20.7%, P= 0.022; 3-year RFS: 38.1% vs. 7.8%, P= 0.008; Figure 2C-D). The prognosis of patients with IHR was as poor as those with adverse-risk AML (n=65 , 3-year OS: 29.5% vs. 33.3%, P= 0.794; 3-year RFS: 19.4% vs. 39.1, P= 0.294). Conclusions In this study, we developed and validated a novel scoring model that incorporated molecular and clinical profiles. According to our score model, IR-AML patients could be further stratified into two subgroups with distinct clinical outcomes. And the prognosis of patients with IHR was similar with patients with adverse-risk. Moreover, alloHSCT would override the poor outcome of patients with IHR. In summary, our scoring model might help identify patients with IR-AML who are most likely to benefit from alloHSCT. The results are needed to be validated in other independent cohorts and prospective studies before implementation into clinics. Disclosures No relevant conflicts of interest to declare.

scholarly journals FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 220-226 ◽  
Author(s):  
Mark Levis
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Allogeneic Transplantation ◽  
Current Treatment ◽  
Flt3 Mutation ◽  
Flt3 Mutations ◽  
Flt3 Inhibitors ◽  
First Remission ◽  
Acute Myeloid

Abstract Patients with acute myeloid leukemia who harbor an FMS-like tyrosine kinase 3 (FLT3) mutation present several dilemmas for the clinician. The results of an FLT3 mutation test, which can be influenced by several variables, need to be interpreted according to the clinical setting and there is a need for internationally standardized FLT3 mutation assays. Because of the lack of prospective studies, the role of allogeneic transplantation as consolidation therapy is still somewhat controversial, but the preponderance of evidence suggests that transplantation in first remission, if possible, is probably the best option. Clinically useful FLT3 inhibitors are hopefully on the near horizon and are being studied in the context of current treatment paradigms.

scholarly journals Comparison of the efficacy of chemotherapy and allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in first remission in adults

2015 ◽  
Vol 22 (3) ◽  
pp. 66-80
Author(s):  
S. N. Bondarenko ◽  
I. S. Moiseev ◽  
I. A. Samorodova ◽  
T. L. Gindina ◽  
M. A. Kucher ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
First Remission ◽  
Acute Myeloid

The aim of the study was to compare the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) and chemotherapy (CT) of acute myeloid leukemia (AML) in first remission (CR1), to identify factors influencing the results. We compare the efficacy alloHSCT in CR1 (n = 70) and CT (n = 52). Patients were stratified by age, the level of leucocytes, the origin of AML, cytogenetic risk group and response to induction CT. Five-years overall and disease-free survival (OS and DFS) were higher in the group alloHSCT (67 and 65 % vs 46 and 30 % (p = 0.02 and p = 0.001)). Benefits of DFS after alloHSCT was in standard and high-risk cytogenetic groups (78 % versus 29 % (p = 0.001), and 34 % vs 17 % (p = 0.007)). The risk of relapse (RR) was 24 % in patients after alloHSCT vs. 57 % for CT (p = 0.003). Comparing the RR after alloHSCT and CT depending on the cytogenetic risk groups: standard (HR0.2(CI95 %0.07 - 0.56) p = 0.002), and high (HR0.27(CI95 %0.08-0.86) p = 0.03). Additional factors affect the RR were the origin of AML (de novo) (HR0.47 (CI95 %0.3-0.74) p = 0.001), the hyperleukocytosis (HR1.91 (CI95 %1.09 - 3.32) p = 0.02), and no remission after the first course CT (HR3.32(CI95 %1.57-7.0) p = 0.002). The efficacy of alloHSCT compared with CT is higher both in standard and high-risk cytogenetic group.

A Novel Regimen for Consolidation Chemotherapy in Adult Acute Myeloid Leukemia in First Remission

1994 ◽  
Vol 17 (1) ◽  
pp. 62-65
Author(s):  
G. Maschmeyer ◽  
T. Büchner ◽  
W. Hiddemann ◽  
W. Gassmann ◽  
A. Heinecke ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Consolidation Chemotherapy ◽  
First Remission ◽  
Acute Myeloid

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.

Karyotypic Complexity In Acute Myeloid Leukemia In The Context Of Adverse Prognosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 489-489 ◽  
Author(s):  
Friedrich Stölzel ◽  
Brigitte Mohr ◽  
Michael Kramer ◽  
Christoph Röllig ◽  
Tilmann Bochtler ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Normal Karyotype ◽  
Control Group ◽  
Cytogenetic Aberrations ◽  
First Remission ◽  
The Uk ◽  
Acute Myeloid

Abstract Introduction Cytogenetic analysis is a mandatory component in the diagnostic evaluation of acute myeloid leukemia (AML) providing information regarding the biology of the disease including response or resistance to therapy. One of the cytogenetic markers which reflect an adverse outcome in conventional chemotherapy regimens is the complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities. In AML two definitions have been established which differ in the perception of unbalanced aberrations as well as the number of single aberrations. The ELN classification scheme adopts three unrelated abnormalities while the UK MRC recently recommended four abnormalities as the most informative cut-off of complexity in the context of an adverse prognosis. The aim of this work was to study the best cut-off defining complexity (3 vs. 4) in AML with other cytogenetic high-risk markers. Methods The databases of three clinical multicentric, randomized, and prospective SAL trials (NCT 00180115, 00180102, and 00180167) were analyzed for AML patients with multiple cytogenetic aberrations as well as normal karyotypes (control group). Unbalanced abnormalities were counted as two aberrations according to the recommendations of the MRC (i.e. a single unbalanced translocation leading to gain and loss of chromosomal material as two unique abnormalities). The following single aberrations associated with an adverse prognosis according to ELN as well as UK MRC recommendations were included: inv(3), t(3;3), abn(3q), -5, del(5q), t(5q), t(6;9), -7, add(7q)/del(7q), t(11;v)(q23;v) (except t(9;11)), and abnl(17p). Results Complete data were analyzed from 2056 patients: normal karyotype (NK) n=1590, three aberrations (K3) n=65, ≥ four aberrations (K4) n=355, t(8;21)/inv(16)/t(16;16) and at least two additional aberrations n=46. All four groups differed significantly in 5–year overall survival (OS): 35% [95% CI 32–37], 19% [95% CI 9–29], 7% [95% CI 4–10], 67% [95% CI 53–81], respectively, p≤0.001. The K4 group had a significant inferior 5–year OS as compared to the K3 group, 19% [95% CI 9–29] and 7% [95% CI 4–10], p≤0.001. HSCT was performed in first remission in 25% of patients with K3 (n=16) and 17% of patients with K4 (n=59) (p=n.s.). As demonstrated earlier, multiple aberrations additional to the good risk anomalies (t(8;21), inv(16), or t(16;16)) did not impact on the favourable prognosis of the respective group. In the K3 and K4 groups single adverse risk abnormalities were found in 55% (abnl(17p) 12%) and 83% (abnl(17p) 37%) in these patients, respectively. A hyperdiploid karyotype (HDK) with gains of whole chromosomes without any structural aberration or monosomy was present in 14% of K3 and 3% of K4-patients. Interestingly, HDK with three trisomies as well as ≥ four trisomies led to a survival similar to K4 patients without HDK. Therefore, the K3 group lost its inferior survival as compared to NK when patients with adverse risk, which induce a worse prognosis per se, as well as HDK were excluded (5y–OS: 29% [9–44] vs. 35%, [95% CI 32–37], p=n.s.). HDK patients or patients with additional single adverse risk abnormalities had a worse survival compared to NK (5y–OS: 11%, [95% CI 0–32], p=0.012; and 15%, [95% CI 3–28], p=0.004 vs. 35%, [95% CI 32–37], respectively). In contrast, when comparing the K4 group after exclusion of adverse risk and HDK patients to NK, the K4 group remained its inferior OS as compared to NK, p<0.001. Conclusions Hence, our investigation confirms and therefore favors the ≥4 cut-off of complexity in the context of an adverse prognosis as proposed by the MRC with the exception of HDK patients. HDK patients should be considered as high-risk independent of the level of complexity. Whether K3 patients without single adverse risk abnormalities and HDK should be treated as intermediate risk, as suggested by our results, needs to be investigated prospectively in clinical trials. Disclosures: Platzbecker: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

Allogeneic Transplantation Versus Chemotherapy as Postremission Therapy for Acute Myeloid Leukemia: A Prospective Matched Pairs Analysis

2014 ◽  
Vol 32 (4) ◽  
pp. 288-296 ◽  
Author(s):  
Matthias Stelljes ◽  
Utz Krug ◽  
Dietrich W. Beelen ◽  
Jan Braess ◽  
Maria C. Sauerland ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Allogeneic Transplantation ◽  
Rank Test ◽  
Control Group ◽  
Matched Pairs ◽  
Postremission Therapy ◽  
Matching Criteria ◽  
Acute Myeloid

Purpose The majority of patients with acute myeloid leukemia (AML) who achieve complete remission (CR) relapse with conventional postremission chemotherapy. Allogeneic stem-cell transplantation (alloSCT) might improve survival at the expense of increased toxicity. It remains unknown for which patients alloSCT is preferable. Patients and Methods We compared the outcome of 185 matched pairs of a large multicenter clinical trial (AMLCG99). Patients younger than 60 years who underwent alloSCT in first remission (CR1) were matched to patients who received conventional postremission therapy. The main matching criteria were AML type, cytogenetic risk group, patient age, and time in first CR. Results In the overall pairwise compared AML population, the projected 7-year overall survival (OS) rate was 58% for the alloSCT and 46% for the conventional postremission treatment group (P = .037; log-rank test). Relapse-free survival (RFS) was 52% in the alloSCT group compared with 33% in the control group (P < .001). OS was significantly better for alloSCT in patient subgroups with nonfavorable chromosomal aberrations, patients older than 45 years, and patients with secondary AML or high-risk myelodysplastic syndrome. For the entire patient cohort, postremission therapy was an independent factor for OS (hazard ratio, 0.66; 95% CI, 0.49 to 0.89 for alloSCT v conventional chemotherapy), among age, cytogenetics, and bone marrow blasts after the first induction cycle. Conclusion AlloSCT is the most potent postremission therapy for AML and is particularly active for patients 45 to 59 years of age and/or those with high-risk cytogenetics.

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