scholarly journals PF232 PROGNOSTIC IMPACT OF THE 2017 EUROPEAN LEUKEMIANET (ELN) CLASSIFICATION OF YOUNGER ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) TREATED ON CANCER AND LEUKEMIA GROUP B (CALGB)/ALLIANCE PROTOCOLS

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 68-69
Author(s):  
M. Bill ◽  
K. Mrózek ◽  
A.-K. Eisfeld ◽  
J. Kohlschmidt ◽  
D. Nicolet ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Adult Patients ◽  
Prognostic Impact ◽  
Group B ◽  
Leukemia Group ◽  
Acute Myeloid

Prognostic Factors and Outcome of Core Binding Factor Acute Myeloid Leukemia Patients With t(8;21) Differ From Those of Patients With inv(16): A Cancer and Leukemia Group B Study

2005 ◽  
Vol 23 (24) ◽  
pp. 5705-5717 ◽  
Author(s):  
Guido Marcucci ◽  
Krzysztof Mrózek ◽  
Amy S. Ruppert ◽  
Kati Maharry ◽  
Jonathan E. Kolitz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Profiling ◽  
Prognostic Impact ◽  
Core Binding Factor ◽  
Cytogenetic Abnormalities ◽  
Binding Factor ◽  
Group B ◽  
Leukemia Group ◽  
Acute Myeloid

Purpose Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in acute myeloid leukemia (AML) and confer relatively favorable prognoses, these cytogenetic groups are often treated similarly. Recent studies, however, have shown different gene profiling for the two groups, underscoring potential biologic differences. Therefore, we sought to determine whether these two cytogenetic groups should also be considered separate entities from a clinical standpoint. Patients and Methods We analyzed 144 consecutive adults with t(8;21) and 168 with inv(16) treated on Cancer and Leukemia Group B front-line studies. We compared pretreatment features, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) between the two groups. Results With a median follow-up of 6.4 years, for CBF AML as a whole, the CR rate was 88%, 5-year OS was 50% and CIR was 53%. After adjusting for covariates, patients with t(8;21) had shorter OS (hazard ratio [HR] = 1.5; P = .045) and survival after first relapse (HR = 1.7; P = .009) than patients with inv(16). Unexpectedly, race was an important predictor for t(8;21) AML, in that nonwhites failed induction more often (odds ratio = 5.7; P = .006) and had shorter OS than whites when certain secondary cytogenetic abnormalities were present. In patients with t(8;21) younger than 60 years, type of induction also correlated with relapse risk. For inv(16) AML, secondary cytogenetic abnormalities (especially +22) and male sex predicted better outcome. Conclusion When the prognostic impact of race, secondary cytogenetic abnormalities, sex, and response to salvage treatment is considered, t(8;21) and inv(16) AMLs seem to be distinct clinical entities and should be stratified and reported separately.

High Expression Levels of theETS-Related Gene,ERG, Predict Adverse Outcome and Improve Molecular Risk-Based Classification of Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study

2007 ◽  
Vol 25 (22) ◽  
pp. 3337-3343 ◽  
Author(s):  
Guido Marcucci ◽  
Kati Maharry ◽  
Susan P. Whitman ◽  
Tamara Vukosavljevic ◽  
Peter Paschka ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Molecular Markers ◽  
Myeloid Leukemia ◽  
Free Survival ◽  
Expression Levels ◽  
N 93 ◽  
Group B ◽  
Leukemia Group ◽  
Acute Myeloid

PurposeTo validate ERG overexpression as an adverse predictor and assess its prognostic value in the context of other molecular markers in cytogenetically normal (CN) -acute myeloid leukemia (AML).Patients and MethodsSeventy-six adult patients with primary CN-AML, younger than 60 years and treated on Cancer and Leukemia Group B (CALGB) trial 19808, were evaluated for ERG expression by quantitative reverse transcriptase polymerase chain reaction. They were then combined with 72 patients enrolled onto CALGB 9621 for analyses that included other molecular markers.ResultsSimilar to patients enrolled onto CALGB 9621, high ERG expressers on CALGB 19808 had fewer complete remissions (CRs; P = .03) and worse event-free survival (EFS; P = .016) than low ERG expressers. In the combined set, high expressers (n = 55) had fewer CRs (P = .004) and shorter EFS (P < .001) than low expressers (n = 93). High ERG predicted failure to achieve CR (P = .004) after adjusting for BAALC expression (P = .04) and age (P = .008), and EFS (P = .004) after adjusting for FLT3 internal tandem duplication (ITD; P < .001). Among patients without FLT3-ITD (FLT3-ITD negative), only high ERG predicted shorter EFS (P = .001). Among NPM1-mutated (NPM1 positive) patients, high ERG predicted shorter EFS (P = .003), after adjusting for FLT3-ITD (P < .001). When all three markers were considered together, in the favorable FLT3-ITD–negative/NPM1-positive subset, high ERG was the only factor predicting shorter EFS (P = .002).ConclusionWe validated ERG overexpression as an adverse predictor in CN-AML. Moreover, by using ERG expression levels, we improved the previously proposed molecular-risk classification of CN-AML based on the presence or absence of FLT3-ITD and NPM1 mutations, given that we identified subsets with different outcome among FLT3-ITD–negative, NPM1-positive, and FLT3-ITD–negative/NPM1-positive patients.

Parallel Phase I Studies of Daunorubicin Given With Cytarabine and Etoposide With or Without the Multidrug Resistance Modulator PSC-833 in Previously Untreated Patients 60 Years of Age or Older With Acute Myeloid Leukemia: Results of Cancer and Leukemia Group B Study 9420

1999 ◽  
Vol 17 (9) ◽  
pp. 2831-2831 ◽  
Author(s):  
Edward J. Lee ◽  
Stephen L. George ◽  
Michael Caligiuri ◽  
Ted P. Szatrowski ◽  
Bayard L. Powell ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Phase I ◽  
Continuous Infusion ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Psc 833 ◽  
Group B ◽  
Leukemia Group ◽  
Acute Myeloid

PURPOSE: The Cancer and Leukemia Group B conducted parallel phase I trials of cytarabine, daunorubicin, and etoposide (ADE) with or without PSC-833 (P), a modulator of p-glycoprotein–mediated multidrug resistance.PATIENTS AND METHODS: One hundred ten newly diagnosed patients ≥ 60 years of age with de novo acute myeloid leukemia (AML) were treated. All patients received cytarabine by continuous infusion for 7 days at 100 mg/m2/d. The starting dose of daunorubicin was 30 mg/m2/d for 3 days. Etoposide was administered at a dose of 100 mg/m2/d for 3 days, except in the last cohort administered ADEP, who received 60 mg/m2. PSC-833 was given intravenously with a loading dose of 1.5 mg/kg over 2 hours and a simultaneous continuous infusion of 10 mg/kg/d continued until 24 hours after the last dose of daunorubicin or etoposide.RESULTS: There was no toxicity attributed to the PSC-833. Dose-limiting toxicity was primarily gastrointestinal (diarrhea, mucositis in the ADEP group). The estimated maximum-tolerated doses, calculated using a logistic regression model, were daunorubicin 40 mg/m2/d for 3 days with etoposide 60 mg/m2for 3 days in the ADEP group and daunorubicin 60 mg/m2/d for 3 days and etoposide 100 mg/m2/d for 3 days in the ADE group. Twenty-one (48%) of 44 patients achieved complete remission with ADE, compared with 29 (44%) of 66 patients treated with ADEP.CONCLUSION: It is necessary to decrease the doses of daunorubicin and etoposide when they are administered with PSC-833, presumably because of the effect of the modulator on the pharmacokinetics of these agents. A phase III trial comparing the regimens derived from this phase I trial has recently begun.

scholarly journals Patients With Acute Myeloid Leukemia and RAS Mutations Benefit Most From Postremission High-Dose Cytarabine: A Cancer and Leukemia Group B Study

2008 ◽  
Vol 26 (28) ◽  
pp. 4603-4609 ◽  
Author(s):  
Andreas Neubauer ◽  
Kati Maharry ◽  
Krzysztof Mrózek ◽  
Christian Thiede ◽  
Guido Marcucci ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Relapse Risk ◽  
Ras Mutations ◽  
High Dose Cytarabine ◽  
Group B ◽  
The Impact ◽  
Leukemia Group ◽  
Acute Myeloid

Purpose RAS mutations occur in 12% to 27% of patients with acute myeloid leukemia (AML) and enhance sensitivity to cytarabine in vitro. We examined whether RAS mutations impact response to cytarabine in vivo. Patients and Methods One hundred eighty-five patients with AML achieving complete remission on Cancer and Leukemia Group B study 8525 and randomly assigned to one of three doses of cytarabine postremission were screened for RAS mutations. We assessed the impact of cytarabine dose on cumulative incidence of relapse (CIR) of patients with (mutRAS) and without (wild-type; wtRAS) RAS mutations. Results Thirty-four patients (18%) had RAS mutations. With 12.9 years median follow-up, the 10-year CIR was similar for mutRAS and wtRAS patients (65% v 73%; P = .31). However, mutRAS patients receiving high-dose cytarabine consolidation (HDAC; 3 g/m2 every 12 hours on days 1, 3, and 5 or 400 mg/m2/d × 5 days) had the lowest 10-year CIR, 45%, compared with 68% for wtRAS patients receiving HDAC and 80% and 100%, respectively, for wtRAS and mutRAS patients receiving low-dose cytarabine (LDAC; 100 mg/m2/d × 5 days; overall comparison, P < .001). Multivariable analysis revealed an interaction of cytarabine dose and RAS status (P = .06). After adjusting for this interaction and cytogenetics (core binding factor [CBF] AML v non-CBF AML), wtRAS patients receiving HDAC had lower relapse risk than wtRAS patients receiving LDAC (hazard ratio [HR] = 0.67; P = .04); however, mutRAS patients receiving HDAC had greater reduction in relapse risk (HR = 0.28; P = .002) compared with mutRAS patients treated with LDAC. Conclusion AML patients carrying mutRAS benefit from higher cytarabine doses more than wtRAS patients. This seems to be the first example of an activating oncogene mutation favorably modifying response to higher drug doses in AML.

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