Extramedullary Disease in Adult Acute Myeloid Leukemia Is Common but Lacks Independent Significance: Analysis of Patients in ECOG-ACRIN Cancer Research Group Trials, 1980-2008

Purpose Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD. Methods Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results. Results Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7%. The sites involved were: lymph nodes (11.5%), spleen (7.3%), liver (5.3%), skin (4.5%), gingiva (4.4%), and CNS (1.1%). Most patients (65.3%) had only one site of EMD, 20.9% had two sites, 9.5% had three sites, and 3.4% had four sites. The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD ( P = .005), skin involvement ( P = .002), spleen ( P < .001), and liver ( P < .001), but not CNS ( P = .34), nodal involvement ( P = .94), and gingival hypertrophy ( P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic. Conclusion This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.

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Elderly AML: A Five-Year Retrospective Review on Prognostic Features

Blood ◽

10.1182/blood-2018-99-111418 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5187-5187

Author(s):

Akshay Amaraneni ◽

Jennifer Segar ◽

Trace Bartels ◽

Onyemaechi Okolo ◽

Andrew C Rettew ◽

...

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Acute Myeloid Leukemia ◽

Retrospective Review ◽

Myeloid Leukemia ◽

Small Sample Size ◽

Small Sample ◽

Risk Category ◽

Elderly Aml ◽

Acute Myeloid

Abstract Background: Acute Myeloid Leukemia (AML) is a disease of the elderly with a median age of diagnosis of 70 years. Prognosis in this age group is poor, with median overall survival of those undergoing treatment ranging from seven to twelve months. Treatment is difficult for a variety of reasons, including - higher incidence of co-morbid conditions (including frailty and decline in functional status), decreased ability to tolerate infections, socioeconomic considerations, and more aggressive disease phenotype. We present a single-institution retrospective review of acute myeloid leukemia outcomes with respect to these and other variables. Methods: A retrospective chart review was performed on all patients with a new diagnosis of AML from November 2013 through October 2017. Descriptive statistics were performed using excel, inferential statistics including Kaplan-Meier with comparison of survival curves by Logrank test and Cox-proportional hazard regression analysis, and correlation coefficients were performed using MEDCALC statistical software package. Results: Eighty-four AML patients in total were diagnosed with acute myeloid leukemia within the specified time frame, of these, 45 patients were age 65 or older (elderly) and were included in further analysis. Median age of elderly AML patients in this study was 70 years. Six of these patients were diagnosed with secondary AML (having arisen from MDS (N = 4), or other hematologic malignancy (N=2), and two had therapy-related AML. Eight patients had favorable risk disease, 13 intermediate risk, and 24 adverse risk according to ELN 2017 criteria. The median survival of all elderly patients was 322 days. Median survival of elderly AML according to ELN 2017 risk category criteria (Favorable, Intermediate, or Poor) was not reached (mean 880 days), 390 days, and 117 days, respectively (p = 0.0368 by cox hazard regression). Survival was not affected by type of treatment (induction vs hypomethylating agent (HMA); median 579 and 166 days (p = 0.1378) and mean 1552 and 364 days, respectively. This is likely due to small sample size, although survival does appear to favor intensive induction. Survival was not affected by number of medical co-morbidities (p = 0.66), presence of infectious complications (p=0.152), or unplanned hospitalization (p = 0.144). Overall use of clinical trials (N=3) and transplant (N=2) were low, precluding meaningful statistical analysis. However, both patients undergoing transplant exceeded the median OS (579 and 4745 days). Median OS of patients identified as White/Caucasian was greater than those identified as Hispanic/Latino (166 days vs 66 days, respectively), this did not reach statistical significance. Conclusion: Given the limitations of a retrospective review and relatively small sample size, our data shows that the 2017 ELN risk category is the strongest predictor of overall survival. Statistically, those undergoing intensive induction did not have a longer overall survival than those treated with HMAs, highlighting the need for careful selection of induction therapy candidates, and the need for clinical trials investigating other less intense treatment options for patients in this category. Interestingly, number of medical co-morbidities did not influence overall survival, nor did unplanned hospitalizations, presence/absence of significant infections during therapy, or race/ethnicity. Our data suggest an under-utilization of clinical trials and allogeneic hematopoietic stem cell transplant, both of which may serve to improve prognosis. Disclosures No relevant conflicts of interest to declare.

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Decrease in Transfusion Needs in Patients with Higher-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia Treated with 5-Azacytidine. a Retrospective Study

Blood ◽

10.1182/blood.v124.21.5608.5608 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5608-5608

Author(s):

Panagiotis Theodorou Diamantopoulos ◽

Konstantinos Zervakis ◽

Athanasios G. Galanopoulos ◽

Panagiotis Bakarakos ◽

Vasiliki Papadopoulou ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Clinical Trials ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Safety Data ◽

Supportive Treatment ◽

Efficacy And Safety ◽

Red Blood Cell Transfusions ◽

Acute Myeloid

Abstract Introduction The hypomethylating agent 5-azacytidine (AZA) has been the standard of care for higher risk Myelodysplastic Syndromes (MDS) for the last few years. Its efficacy has been proven in large clinical trials, and its safety has been shown to be superior to that of conventional treatments. We have conducted a retrospective study about the efficacy and safety of 5-azacytidine, as reported and analyzed in our center. Patients and Methods Forty four consecutive patients with MDS or Acute Myeloid Leukemia (AML) with 20-30% bone marrow blasts that were treated with AZA during the last 63 months were included in the study. The clinical and laboratory characteristics of the patients were recorded, and the efficacy and safety data were analyzed. Results The epidemiologic and hematologic characteristics of the patients are shown in Table 1. The median overall survival was 13 months (1-101) and there was no primary treatment failure (Table 2). Serious adverse events consisted mostly of neutropenic infections (blood stream and pneumonia) (Table 3). Discussion Treatment with AZA offered a favorable (complete and partial) response in 34.1% of the patients, and an overall survival of 13 months, with generally predictable toxicities, although hospitalization was frequently inevitable during the first treatment cycles, when supportive treatment was a significant part of the management. A valuable observation is that there was a considerable decrease in the patients’ transfusion needs following treatment (p<0.0001). Our results are consistent with the results of other clinical trials and point out the need for investigational 5-azacytidine combinations. Table 1. Epidemiologic and hematologic characteristics. Male: Female ratio 30:14 (2.1 : 1) Age, Median (Range) 73 (54-81) WHO classification of MDS/AML, N (%) RAEB-I RAEB-II RCMD-RS RCMD RARS CMML AML 9 (20.5) 18 (40.9) 2 (4.5) 3 (6.7) 1 (2.3) 4 (9.1) 7 (15.9) IPSS classification, N (%) Low Intermediate-1 Intermediate-2 High Not Applicable (AML) 0 (0) 3 (6.8) 29 (65.9) 5 (11.4) 7 (15.9) Complete Blood Count Parameters, Median (Range) Hemoglobin (g/dL) Absolute Neutrophil Count (x109/L) Platelet count (x109/L) 8.55 (4.5 - 12.5) 1.08 (0.0 – 16.3) 80.0 (2 – 820) Transfusion dependence, N (%) 39 (88.6) Transfusions per month, Median (Range) 3 (0 – 7) Table 2. Efficacy data AZA cycles, Median (Range) 5 (1-22) Actual AZA dose (mg/m2/cycle), Median (Range) 75 (59-75) Actual cycle duration (days), Median (Range) 28 (28-40) Dose reductions due to sustained neutropenia, N (%) 6 (13.6) Temporary AZA interruption, N (%) 26 (59.1) Reason Sustained cytopenia 10/26 (38.5) Neutropenic Infection 15/26 (57.7) Hemorrhagic Complication 1/26 (3.8) Permanent AZA discontinuation, N (%) 23/44 (52.3) Reason AML transformation 17/23 (73.9) Recurrent or severe infection 4/23 (17.4) Pyoderma gangrenosum 1/23 (4.3) Allogeneic Bone Marrow Transplantation 1/23 (4.3) AZA cycles till response (according to the IWG criteria), Median (Range) 4 (1 – 7) Response (IWG criteria), N (%) Complete response Partial response Stable disease Failure 7 (15.9) 8 (18.2) 29 (65.9) 0 (0) Overall survival (months), Median (Range) 13 (1 – 101) Post treatment transfusion dependence, N (%) 34 (77.3) Transfusions per month (post-treatment), Median (Range) 1 (0 – 5) Death rate, N (%) 29/44 (65.9) Cause of death, N (%) Infection Hemorrhage Cardiac dysrhythmia 24/29 (82.8) 3/29 (10.3) 2/29 (6.9) Table 3. Safety data Clinical adverse events, N (%) 29/44 (65.9) Neutropenic Infections 26/29 (89.7) Bloodstream Infection 9/26 (34.6) Lower respiratory infection 10/26 (38.5) Neutropenic Fever 8/26 (30.1) Septic shock 2/26 (7.7) Hemorrhagic events 2/29 (6.7) Cerebral hemorrhage (Grade 5) 1/2 (50.0) Epistaxis (Grade 3) 1/2 (50.0) Other (pyoderma gangrenosum) 1/29 (3.4) Laboratory incidents1, N (%) 44/44 (100) All grades Grades 3/4 Neutropenia 36/44 (81.8) 34/44 (77.3) Anemia 44/44 (100) 24/44 (54.5) Thrombocytopenia 31/44 (70.5) 21/44 (47.7) Supportive treatment (during AZA administration), N (%) GCSF administration 16/44 (36.4) Erythropoietin administration 7/44 (15.9) Red blood cell transfusions 39/44 (88.6) Red blood cell transfusions (units/cycle), Median (range) 3 (0-7) Pooled random donor platelet transfusions 17 (38.6) 1According to the CTCAE Version 4.0 Disclosures No relevant conflicts of interest to declare.

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Addition of Lomustine to Idarubicin and Cytarabine Improves the Outcome of Elderly Patients With De Novo Acute Myeloid Leukemia: A Report From the GOELAMS

Journal of Clinical Oncology ◽

10.1200/jco.2009.26.4648 ◽

2010 ◽

Vol 28 (18) ◽

pp. 3028-3034 ◽

Cited By ~ 24

Author(s):

Arnaud Pigneux ◽

Jean-Luc Harousseau ◽

Francis Witz ◽

Mathieu Sauvezie ◽

Marie-Christine Bene ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Elderly Patients ◽

Induction Therapy ◽

Myeloid Leukemia ◽

De Novo ◽

Group I ◽

Acute Myeloid

Purpose No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML. Patients and Methods The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m2, days 1 through 5) and cytarabine (100 mg/m2, days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m2 orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine. Results The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P < .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 ± 2.2 months v 8.7 ± 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age ≤ 69 years (P < .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P < .001). Conclusion Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.

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Number of Mutations and Type of Prior Myeloproliferative Neoplasm Are Prognostic Factors in Acute Myeloid Leukemia Post Myeloproliferative Neoplasms

Blood ◽

10.1182/blood-2018-99-114428 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2806-2806 ◽

Cited By ~ 1

Author(s):

Edmond Chiche ◽

Sarah Bonnet ◽

Sarah Bertoli ◽

Andrew T Kuykendall ◽

Lauris Gastaud ◽

...

Keyword(s):

Clinical Trials ◽

Acute Myeloid Leukemia ◽

Prognostic Factors ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Neoplasm ◽

Induction Treatment ◽

Calr Mutations ◽

Acute Myeloid

Abstract BACKGROUND Post myeloproliferative neoplasms (MPN) acute myeloid leukemia (AML) occurs respectively in 1.5%, 7.0% and 11% of patients with essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). This subgroup of AML has very poor prognosis and are often excluded from clinical trials. Therefore, only few cohorts including molecular data are available. MATERIAL AND METHODS We retrospectively collected data from 111 patients treated in four centers in France for post MPN-AML. Clinical, molecular and treatment information was available for all patients at AML and MPN stages. DNA was extracted from samples at diagnosis of MPN chronic phase, at diagnosis of AML phase and after induction treatment. JAK2-V617F mutations were identified by qPCR (Ipsogen® MutaQuant kit, Qiagen, Germany), MPL-W515L/K mutations were identified by PCR (Ipsogen® MutaScreen kit, Qiagen, Germany) and CALR mutations were identified by conventional sequencing (Applied Biosystems, 3500Genetic Analyzer). NGS on 36 genes using Ampliseq librairy and Ion Proton sequencing (Thermofisher, Waltham, MA, USA) were performed in 96/111 patients. Overall response rate (ORR) was defined by complete remission (CR), CR with incomplete hematologic recovery (CRi), partial remission (PR) and stable disease (SD). Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics). RESULTS 111 patients treated for post MPN-AML were retrospectively included in this study. Sex ratio M/F was 54%/46%. Median age at AML diagnosis was 66 years (28-89, range). Cytogenetic categories were favorable, intermediate and adverse in 2 (2%), 51 (46%) and 47 (42%) patients, respectively. 25/111 (23%) patients had a monosomal karyotype (MK). Median number of additional mutations excluding from JAK2/MPL/CALR mutations was 2 (0-6, range). The most frequent additional mutations were TP53 (23%), ASXL1 (17%), TET2 (13%), SRSF2 (10%), DNMT3A (8%), SF3B1 (8%) and RUNX1 (8%). Only 2 patients were mutated for NPM1 and 2 and 4 patients were FLT3-ITD and FLT3-TKD, respectively. Prior MPN were PV, ET and PMF in 20%, 34% and 46% of patients, respectively. First line treatment was intensive chemotherapy (IC) for 61 (55%) patients, hypomethylating agents (HMA) for 10 (9%) or other treatments including best supportive care, cytoreduction for the other ones. 24/111 (22%) underwent to ASCT. ORR was 54% (with 30/71 (42%) in CR/CRi) in patients treated by IC or HMA. We did not identify factors predicting a higher rate of CR/CRi. OS was 12 months [6-18] and was not influenced by transplant, cytogenetic categories or by the type and allele frequencies of JAK2/CALR/MPL mutations. OS was significantly longer in the group treated with HMA as compared to IC (10 versus 46 months, respectively, p=0.006); in patients with prior PV as compared to ET or MF (26 months [0-57] versus 10 months [7-13] versus 10 months [4-16] respectively, p=0.07) and in patients with presence of additional mutations other than JAK2/CALR/MPL (5 months [0-12] versus 46 months [32-60] in 38 patients without mutation versus 58 patients with presence of at least one mutation, respectively, p=0.04). By multivariate analysis, only presence of additional mutations was predictive for OS with a hazard ratio (HR) = 0.42 [0.18-0.97] (p=0.04). Finally, we followed the VAFs of JAK2 in seven patients before and after IC. We observed in 2 patients an increase of JAK2 clone correlated with CR whereas no variation of VAFs was associated with absence of CR. CONCLUSIONS In conclusion, we confirmed the poor prognosis of post MPN AML. Classical AML prognostic factors were not validated in our cohort. We identified the presence of mutations other than JAK2/MPL/CALR as the main prognostic factor whereas post-PV AML appeared to do better than post-ET and post-PMF AML. The very poor result of IC with or without ASCT highlights the need to develop specific clinical trials in this subgroup of AML. Disclosures Kuykendall: Celgene: Honoraria; Janssen: Consultancy. Sallman:Celgene: Research Funding, Speakers Bureau. Cluzeau:CELGENE: Consultancy; MENARINI: Consultancy; JAZZ PHARMA: Consultancy.

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Acute Myeloid Leukemia with High Risk Features: Routine Central Nervous System Evaluation May be Beneficial

Blood ◽

10.1182/blood-2019-125361 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3863-3863

Author(s):

Meera Yogarajah ◽

William J Hogan ◽

Naseema Gangat ◽

Dong Chen ◽

Rong He ◽

...

Keyword(s):

Central Nervous System ◽

Overall Survival ◽

Nervous System ◽

Acute Myeloid Leukemia ◽

High Risk ◽

Relapse Rate ◽

Myeloid Leukemia ◽

Cns Involvement ◽

Extramedullary Disease ◽

Acute Myeloid

Objective : Central nervous system (CNS) involvement is a known phenomenon of acute lymphoblastic leukemia. However little is known about the incidence of CNS involvement in acute myeloid leukemia (AML) as routine lumbar punctures are not done if patients are asymptomatic at diagnosis. Our practice has been to obtain lumbar puncture (LP) at or after complete remission (CR) for patients that present with any one of the following high risk features;hyperleukocytosis with WBC >10,000 or blastic crisis, extramedullary disease,monocytic differentiation. Methods: We reviewed our leukemia database at Mayo Clinic to determine the incidence of CNS involvement in patients with high risk features after due IRB approval. We also compared baseline demographic characteristics, blood counts, cytogenetic risk groups, presence of extramedullary disease, relapse rate ,transplant rate and overall survival (OS) among patients with and without CNS involvement. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Results: 298 patients with AML were identified with presence of at least 1 risk factor for CNS involvement. The results of LP were only available for 126 (42%) patients. The overall incidence of CNS involvement was 12% (15/126, figure 1). Among the patients with positive disease 3 had CSF examination at diagnosis prior to CR due to the presence of CNS myeloid sarcoma (n=2) and ambiguous lineage myeloid leukemia and were excluded from further evaluation. The incidence of CSF involvement at CR1 was 9.7% (12/123). All patient with CNS positive disease received intrathecal chemotherapy with alternating cytarabine and methotrexate until they cleared their blast and additional 2-4 treatments as per treating physician's discretion .The CNS positive and negative patients were compared and did not show any statistical difference in age, gender, presence of extramedullary disease ,cytogenetic risk group, relapse rate and transplant rate as shown in table1. Molecular data was not available in most of the patients and hence was not included for analysis. The median OS was significantly lower among patients with CNS involvement compared to absence of CNS involvement but was not statistically significant likely due to small sample size (3.9 vs12.8 years (p=0.2), figure 2). The overall CNS relapse rate in patients who did not have a LP done at CR was 5.8%(10/172). Conclusions : CNS evaluation should be done in AML patients with high risk features before declaring CR. CNS disease portends overall a poor prognosis with impaired overall survival and high relapse rate. However the sample size was small and true incidence of CNS disease will need routine diagnostic LP in all high risk patients. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

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Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

Frontiers in Oncology ◽

10.3389/fonc.2021.632094 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yin Wang ◽

Wen-Jun Weng ◽

Dun-Hua Zhou ◽

Jian-Pei Fang ◽

Srishti Mishra ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Prognostic Factors ◽

Myeloid Leukemia ◽

Wilms Tumor ◽

Event Free Survival ◽

Free Survival ◽

Wilms Tumor 1 ◽

Pediatric Aml ◽

Acute Myeloid

The prognostic impact of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile, and prognosis of AML patients with WT1 mutations in this cohort. Our results showed that 6.7% of total patients harbored WT1 mutations. These WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to the patients without WT1 mutations, patients with WT1 mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, P<0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of WT1-mutated patients. Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML.

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Early Deaths and Treatment-Related Mortality in Children Undergoing Therapy for Acute Myeloid Leukemia: Analysis of the Multicenter Clinical Trials AML-BFM 93 and AML-BFM 98

Journal of Clinical Oncology ◽

10.1200/jco.2004.01.191 ◽

2004 ◽

Vol 22 (21) ◽

pp. 4384-4393 ◽

Cited By ~ 155

Author(s):

Ursula Creutzig ◽

Martin Zimmermann ◽

Dirk Reinhardt ◽

Michael Dworzak ◽

Jan Stary ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Clinical Trials ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fungal Infections ◽

Adequate Treatment ◽

Treatment Related Mortality ◽

Related Mortality ◽

Acute Myeloid

Purpose The rates of early death (ED) and treatment-related mortality (TRM) are unacceptably high in children undergoing intensive chemotherapy for acute myeloid leukemia (AML). Better strategies of supportive care might help to improve overall survival in these children. Patients and Methods In a retrospective study, we analyzed incidence, clinical features, and risk factors for lethal complications of 901 children enrolled onto the multicenter trials Acute Myeloid Leukemia-Berlin-Frankfurt-Muenster (AML-BFM) 93 and AML-BFM 98. Results One hundred four patients (11.5%) enrolled onto the clinical trials AML-BFM 93 and AML-BFM 98 died shortly after diagnosis or as a result of treatment-related complications. Thirty-two patients (3.5%) died before (six patients) or during (26 patients) the first 14 days of treatment, mainly as a result of bleeding or leukostasis. Low performance status, hyperleukocytosis, and French-American-British type M5 were the main risk factors for a lethal event before day 15. After day 15, the predominant causes of death were complications caused by infections, particularly bacterial and fungal infections. The incidence of lethal infections was highest during induction therapy and decreased thereafter. When comparing both clinical trials, significantly fewer patients died within the first 6 weeks in AML-BFM 98 than in AML-BFM 93 (14 [3.5%] of 430 patients v 35 [7.4%] of 471 patients; P = .01). Conclusion To reduce the high incidence of ED and TRM in children with AML, early diagnosis and adequate treatment of complications are needed. Children with AML should be treated in specialized pediatric cancer centers only. Prophylactic and therapeutic regimens for better treatment management of bleeding disorders and infectious complications have to be assessed in future trials to ultimately improve overall survival in children with AML.

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Dynamic Prognostic Model to Identify Patients with Primary or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Mf) At the Highest Risk of Death and Transformation to Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v118.21.2821.2821 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2821-2821

Author(s):

Alfonso Quintás-Cardama ◽

Jenny Shan ◽

Sherry Pierce ◽

Hagop M. Kantarjian ◽

Srdan Verstovsek

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Acute Myeloid Leukemia ◽

Prognostic Factors ◽

Myeloid Leukemia ◽

Continuous Variable ◽

Risk Of Death ◽

Two Factors ◽

Acute Myeloid

Abstract Abstract 2821 BACKGROUND: While patients (pts) with primary or post-polycythemia vera (PV)/post-essential thrombocythemia (ET) myelofibrosis (MF) have a median overall survival of 5–6 years, the survival of particular subsets of pts with MF is highly variable. Pts transforming to acute myeloid leukemia (AML) represent a large proportion of those with the poorest prognosis. Prognostic tools capable of identifying pts at the highest risk of death and transformation may provide an opportunity for tailored early therapeutic intervention (e.g. allogeneic stem cell transplantation [allo-SCT]). OBJECTIVES: To identify risk factors that predict for short survival and for high risk to transformation to AML in a large cohort of pts with MF diagnosed at MD Anderson Cancer Center. PATIENTS AND METHODS: 649 pts with MF referred from Feb-1966 to Jun-2010 were assessable for survival analysis, including 177 (27%) with post-PV or post-ET MF. The median follow-up was 19 months (range, 1–180). We first evaluated an extensive list of baseline risk factors for overall survival (OS) by univariate analysis (UVA): age, sex, prior exposure to alkylating agents, hydroxyurea, immunomodulatory drugs (i.e. thalidomide derivatives), and others, MF duration, performance status, splenomegaly, hepatomegaly, hemoglobin, white blood cell count (WBC), platelets, monocytes, peripheral blood (PB) or bone marrow (BM) blast percentage (continuous variable), chromosomal abnormalities, JAK2V617F mutation (yes vs no, and as a continuous variable), total bilirubin, LDH, creatinine level. Multivariate analysis (MVA) identified age ≥60 (p=0.004;HR=1.63), baseline platelets <100×109/L (p<0.001;HR=1.62), BM blast >10% (p=0.002;HR=2.18), worst karyotype (del17p, −5, −7, complex; p<0.001;HR=2.44), transfusion dependency (≥2 red cell transfusions; p<0.001;HR=2.64), PS ≥1 (p=0.003;HR=1.47), LDH >2000 U/L (p<0.001;HR=1.62), prior hydroxyurea (p<0.001;HR=1.69), and male gender (p=0.005;HR=1.41) as independent poor prognostic factors for OS. Using the corresponding hazard ratios, a dynamic risk model for survival in MF was derived based on weighted scores of 0–1, 2–3, 4–5, ≥6. The number of pts and median OS for the 4 risk groups were: Low: 84 (13%), median OS not reached; Intermediate-1: 191 (29%), 74 months; Intermediate-2: 208 (32%), 29 months; High :166 (26%), 11 months. We then examined the same baseline variables used in the OS analysis to identify independent risk factors for AML transformation. MVA identified WBC<3×109/L (p=0.02), PB blasts ≥5% (p=0.01), BM blasts ≥5% (p=0.02), and unfavorable karyotype (p=0.04). The presence at baseline of BM blasts ≥10% and worst karyotype were identified as independent poor prognostic factors for both OS and AML-transformation. Pts with one or both of these two risk factors (n=80, 12% of the population) defined a subgroup of pts with a median OS of only 10 months. This subgroup was considered to have MF at significantly higher risk (compared to pts without any of these 2 adverse factors) for transformation to AML (1-year transformation-free survival 82% vs 98%, p<0.001). Ten of 80 (13%) of pts with any of these two factors progressed to AML within 12 months whereas only 10 of 568 (2%) pts without those two factors progressed to AML within 12 months. The yearly rates of transformation for the whole study group during the first, second, and third year of follow-up were 3%, 2%, and 3%, respectively. CONCLUSION: Analysis of a large population of pts with either primary or post-PV or post-ET MF identified risk factors that at any time during the course of MF predict for short OS and for high risk for AML transformation AML. Pts with such factors may be candidates for more aggressive therapeutic approaches such as allo-SCT. Disclosures: No relevant conflicts of interest to declare.

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Wilms Tumor 1 Mutations are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

10.21203/rs.3.rs-95114/v1 ◽

2020 ◽

Author(s):

Yin Wang ◽

Wen-Jun Weng ◽

Dun-Hua Zhou ◽

Jian-Pei Fang ◽

Li Chai ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Prognostic Factors ◽

Myeloid Leukemia ◽

Wilms Tumor ◽

Event Free Survival ◽

Free Survival ◽

Wilms Tumor 1 ◽

Pediatric Aml ◽

Acute Myeloid

Abstract Background: The role of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML) with regard to the prognostic impact. Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. Methods: The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile and prognosis of WT1 mutations in these patients. Results: WT1 mutations were founded in 6.7% of total patients. WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to patients without WT1 mutations, patients with WT1 mutations had worse 5-year event-free survival (21.7±5.5% vs 48.9±1.8%, P<0.001) and overall survival (41.4±6.6% vs 64.3±1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation had a tendency to improve prognoses of WT1-mutated patients. In multivariate analysis, WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). Conclusion: Our findings demonstrate that WT1 mutations are independent poor prognostic factors in pediatric AML.

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Improved Outcome by Addition of Lomustine (CCNU) to Idarubicin and Cytarabine in Elderly Patients with De Novo Acute Myeloid Leukemia. A Report from the GOELAMS Group

Blood ◽

10.1182/blood.v112.11.761.761 ◽

2008 ◽

Vol 112 (11) ◽

pp. 761-761

Author(s):

Arnaud Pigneux ◽

Francis Witz ◽

Mathieu Sauvezie ◽

Marie-Christine Bene ◽

Isabelle Luquet ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Retrospective Study ◽

Complete Remission ◽

Myeloid Leukemia ◽

Group I ◽

Group Ii ◽

Acute Myeloid

Abstract In elderly patients with acute myeloid leukemia (AML) treated intensively, no improvement has been shown in the last 20 years. We performed a retrospective study in 847 patients over 60 years old, prospectively enrolled in 3 trials conducted in France between 1995 and 2005, with the aim to investigate prognostic factors for complete remission (CR) achievement and survival. Induction therapy consisted in the association of Idarubicin 8mg/m2 d1-5 and Cytarabine 100mg/m2 d1-7 (Group I, 339 patients) or the same drugs with the addition of lomustine (10mg\m2 orally at day 1)(Group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course with intermediate dose cytarabine. The patients’ characteristics were similar between the two groups concerning sex, WBC count, ECOG, and cytogenetics, yet patients were older in Group II versus Group I (55% versus 45% over 69 years of age, p<0.0001).The CR rate was significantly higher for patients in Group II compared to Group I (67 % vs 57%, p= 0.002). The toxic death rate was not different between groups. In multivariate analysis, three good prognostic factors emerged for achieving complete remission: good or intermediate cytogenetics (p<0.0001), ECOG < 2 (p<0.0001), and adjunction of lomustine to induction chemotherapy (p=0.002). The median overall-survival was significantly improved for patients treated with lomustine (12.7± 2.2 months vs 8.7± 2.7 months, p=0.004). In multivariate analysis, five prognostic factors affected positively overall survival: adjunction of lomustine to induction chemotherapy (p < 0.0001), age < 69 years (p =0.001), ECOG < 2 (p =0.001), FAB other than AML0,6 or 7 (p = 0.004) and good or intermediate cytogenetics(p = 0.007). The median event-freesurvival was also improved for patients treated with lomustine (10.7± 2.2 months vs 7± 2.7 months, p=0.002). Event-free-survival was affected by the same prognostic factors as overall survival. We conclude that lomustine might be added in standard induction therapy as it allowed to obtain both better CR rate and survival in this retrospective study.

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