Prognostic Value of Genetic Alterations in Elderly Patients with Acute Myeloid Leukemia: A Single Institution Experience.
Heiblig Maël,Labussière-Wallet Hélène,Nicolini Franck Emmanuel,Michallet Mauricette,Hayette Sandrine,Sujobert Pierre,Plesa Adriana,Balsat Marie,Paubelle Etienne,Barraco Fiorenza,Tigaud Isabelle,Ducastelle Sophie,Wattel Eric,Salles Gilles,Thomas Xavier
Cancers
Although the outcome in younger adults with acute myeloid leukemia (AML) has improved, the benefit associated with standard intensive chemotherapy in older patients remains debatable. In this study, we investigated the incidence and the prognostic significance of genetic characteristics according to treatment intensity in patients aged 60 years or older. On the 495 patients of our cohort, (25.2%), (23.7%) and (16.8%) were the most frequent molecular mutations found at diagnosis. In this elderly population, intensive chemotherapy seemed to be a suitable option in terms of early death and survival, except for normal karyotype (NK) patients and those aged over 70 within the adverse cytogenetic/molecular risk group. The mutation was systematically associated with an unfavorable outcome, independently of the ratio. NK genotype tends to confer a good prognosis in patients treated intensively. Regarding minimal residual disease prognostic value, overall survival was significantly better for patients achieving a 4 log reduction (median OS: 24.4 vs. 12.8 months, = 0.013) but did not reach statistical significance for progression free survival. This retrospective study highlights that intensive chemotherapy may not be the most appropriate option for each elderly patient and that molecular markers may help treatment intensity decision-making.
10.3390/cancers11040570
[Coexisting mutations in NPM1-mutated elderly adults with acute myeloid leukemia].
Qin W,Chao H Y,Cai X H,Lu X Z,Liu J,Wu P,Chen M Y
Zhonghua yi xue za zhi
To explore the coexisting mutations in NPM1 mutated elderly patients with acute myeloid leukemia(AML). The clinical data of 152 elderly adults(aged≥60 years) and 49 young adults(aged 18-45 years) with AML between June 2013 and December 2018 in outpatient and hospitalized patients of Changzhou Second People's Hospital and Wuxi Second People's Hospital were retrospectively analyzed. A total of 51 gene mutations were detected using targeted next-generation sequencing (NGS) and sanger sequencing. The general clinical characteristics, the occurrence of coexistence gene mutations, the correlation between coexistence gene mutations and some clinical parameters, and the initial induction remission rate between elderly and young adult AML patients with NPM1 mutations were analyzed and compared. NPM1 mutations were detected in 46 of 152 elderly AML patients. Thirty eight patients (82.6%) with NPM1 mutations carried other gene mutations at the same time, among whom 8 patients (17.4%) carried NPM1 mutations alone, while 14(30.4%) carried 2, 16 (34.8%) carried 3, and 8 (17.4%) carried ≥ 4 mutations. NPM1 mutations frequently co-occurred with FLT3-ITD15 cases (32.6%) , DNMT3A10 (21.7%) , TET26 (13.4%) and FLT3-TKD5 (10.9%) . Compared with young adults with NPM1 mutations, elderly patients had higher TP53, FLT3-TKD rates, lower incidence of DNMT3A, RAS mutation (all 0.05) and lower coexistence rate of 4 gene mutations (0.002).The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than those in patients with single, double and 3 mutations coexisted in elderly adults AML patients(all 0.05). With the increase of the amount of mutations, the complete remission(CR) rate decreased gradually after the initial induction. Patients who carried 3 or more mutations showed a lower CR rate than those with single gene mutations (all 0.05) . Patients who carried>4 genes also showed a significantly lower CR rate than those with double gene mutations (0.031). Patients with FLT3-ITD mutations exhibited higher white blood level and lower CR rate than that in nonmutant type group (all 0.05). The CR rate of patients with DNMT3A mutation was also significantly lower than that with nonmutant type (0.033). However, patients with FLT3-TKD mutations showed a higher platelet level than that with nonmutant type (0.019). There was no significant difference in CR rate and peripheral blood cell level between TET2 mutated and nonmutant type. NPM1 mutated elderly patients with AML commonly show additional mutations, and the amount and type of coexisting mutations have an influence on the clinical features and CR rate of elderly patients with AML.
10.3760/cma.j.issn.0376-2491.2019.40.006
Acute Myeloid Leukemia (AML) In Elderly: Cytogenetic Characteristics of Patients Treated At Hematology and Pediatric Oncology Center in Casablanca.
Bendari Mounia,Khoubila Nisrine,Cherkaoui Siham,Hada Nezha,Lamchahab Mouna,Oukache Bouchra,Madani Abdellah,Rachid Mohamed,Qachouh Meryem,Quessar Asmaa
Open access Macedonian journal of medical sciences
AIM:The goals of this paper are: to report the incidence of AML in elderly, to describe cytogenetic characteristics of this population, to observe rare and novel cytogenetic abnormalities and lastly, to compare our finding with that previously reported in the literature. METHODS:We conducted a retrospective analysis of 283 patients with acute myeloid leukaemia (AML) treated in our unit, we will report the incidence of AML in elderly, describe cytogenetic characteristics of this population, observe rare and novel cytogenetic abnormalities and compare our finding with that previously reported in the literature. RESULTS:Among the 283 patients, 157 (54.4%) patients performed the karyotype, the cytogenetic analysis failed in 17 cases (11%). Prognostic group distribution was found to be favorable in 8 patients (6%) with 6 cases of t (8; 21) and 2 cases of inv (16), intermediate group in 94 patients (67%), including 58 cases (41,5%) with a normal karyotype, and an unfavorable group in 38 patients (27%) including complex karyotype (15%), -5 or del 5q (3%), -7 or del 7q (3.5%), t (9; 22) (2%). Some rare anomalies were observed. CONCLUSION:However, the occurrence of a complex karyotype was more frequent than younger patients. In our unit, elderly benefit from supportive care, our study shows that it is a heterogeneous group and our treatment approach have to change especially for the patient from favourable risk group who can benefit from intensive chemotherapy. We have to improve our diagnosis with including molecular genetics that provides a documented substrate for a thoughtfully considered treatment plan.
10.3889/oamjms.2018.484
Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged 75 years or older.
Prassek Victoria V,Rothenberg-Thurley Maja,Sauerland Maria C,Herold Tobias,Janke Hanna,Ksienzyk Bianka,Konstandin Nikola P,Goerlich Dennis,Krug Utz,Faldum Andreas,Berdel Wolfgang E,Wörmann Bernhard,Braess Jan,Schneider Stephanie,Subklewe Marion,Bohlander Stefan K,Hiddemann Wolfgang,Spiekermann Karsten,Metzeler Klaus H
Haematologica
A cute myeloid leukemia is a disease of the elderly (median age at diagnosis, 65-70 years). The prognosis of older acute myeloid leukemia patients is generally poor. While genetic markers have become important tools for risk stratification and treatment selection in young and middle-aged patients, their applicability in very old patients is less clear. We sought to validate existing genetic risk classification systems and identify additional factors associated with outcomes in intensively treated patients aged ≥75 years. In 151 patients who received induction chemotherapy in the AMLCG-1999 trial, we investigated recurrently mutated genes using a targeted sequencing assay covering 64 genes. The median number of mutated genes per patient was four. The most commonly mutated genes were (42%), (35%), (32%), (25%) and (21%). The complete remission rate was 44% and the 3-year survival was 21% for the entire cohort. While adverse-risk cytogenetics (MRC classification) were associated with shorter overall survival (=0.001), and -ITD mutations (present in 18%) did not have a significant impact on overall survival. Notably, none of the 13 -mutated patients (9%) reached complete remission. Consequently, the overall survival of this subgroup was significantly shorter than that of -wildtype patients (<0.001). In summary, even among very old, intensively treated, acute myeloid leukemia patients, adverse-risk cytogenetics predict inferior survival. The spectrum and relevance of driver gene mutations in elderly patients differs from that in younger patients. Our data implicate mutations as a novel marker for chemorefractory disease and inferior prognosis. (AMLCG-1999 trial: clinicaltrials.gov identifier, NCT00266136).
10.3324/haematol.2018.191536
Genetic alteration patterns and clinical outcomes of elderly and secondary acute myeloid leukemia.
Wang Shi-Yang,Cheng Wen-Yan,Mao Yuan-Fei,Zhu Yong-Mei,Liu Fu-Jia,Ma Ting-Ting,Shen Yang
Hematological oncology
To illustrate the clinical and genetic features of elderly and secondary acute myeloid leukemia (AML) patients, we compared 145 elderly AML (e-AML) and 55 secondary AML (s-AML) patients with 451 young de novo AML patients. Both e-AML and s-AML patients showed lower white blood cell (WBC) and bone marrow (BM) blasts at diagnosis. NPM1, DNMT3A, and IDH2 mutations were more common while biallelic CEBPA and IDH1 mutations were less seen in e-AML patients. s-AML patients carried a higher frequency of KMT2A-AF9. In treatment response and survival, e/s-AML conferred a lower complete remission (CR) rate and shorter duration of event-free survival (EFS) and overall survival (OS) compared with young patients. In multivariate analysis, s-AML was an independent risk factor for OS but not EFS in the whole cohort. Importantly, intensive therapy tended to improve the survival of e/s-AML patients without increasing the risk of early death, and hematopoietic stem cell transplantation (HSCT) could rescue the prognosis of s-AML, which should be recommended for the treatment of fit patients.
10.1002/hon.2656