Management Of Acute Myeloid Leukemia Patients Research Articles

Minimal Residual Disease in Acute Myeloid Leukemia: Old and New Concepts.

Minimal residual disease (MRD) is of major importance in onco-hematology, particularly in acute myeloid leukemia (AML). MRD measures the amount of leukemia cells remaining in a patient after treatment, and is an essential tool for disease monitoring, relapse prognosis, and guiding treatment decisions. Patients with a negative MRD tend to have superior disease-free and overall survival rates. Considerable effort has been made to standardize MRD practices. A variety of techniques, including flow cytometry and molecular methods, are used to assess MRD, each with distinct strengths and weaknesses. MRD is recognized not only as a predictive biomarker, but also as a prognostic tool and marker of treatment efficacy. Expected advances in MRD assessment encompass molecular techniques such as NGS and digital PCR, as well as optimization strategies such as unsupervised flow cytometry analysis and leukemic stem cell monitoring. At present, there is no perfect method for measuring MRD, and significant advances are expected in the future to fully integrate MRD assessment into the management of AML patients.

Clinical features and management of germline CEBPA-mutated carriers

Familial acute myeloid leukemia (AML) pedigrees with germline CCAAT/enhancer-binding protein-α (CEBPA) mutation have been rarely reported due to insufficient knowledge of their clinical features. Here, we report two Chinese families with multiple AML cases carrying germline CEBPA mutations, one of which had 11 cases spanning four consecutive generations. Additionally, we collected clinical data of 57 AML patients from 22 families with germline CEBPA mutations, with 58.3% of them harboring double CEBPA mutations. The first mutation frequently occurred at the N-terminal of CEBP/α (78.6%), resulting in an exclusive expression of p30 of CEBPA (CEBPAp30). The second mutation was mostly found at the C-terminal of CEBP/α (CEBPAothers). Germline CEBPAp30 carriers had higher incidences of AML (80.36% vs. 42.86%) and earlier onset of AML (18 vs. 38.5 years old) compared to germline CEBPAothers carriers. Despite the high rates of relapse, most familial AML cases exhibited favorable overall survival (OS), with germline CEBPAp30 carriers having better survival outcomes (>25 years vs. 11 years for CEBPAothers carriers). Among the 27 healthy germline CEBPA-mutated carriers, we detected a pre-leukemia clone harboring a pathogenic IDH2 variant (R140Q)in one individual. These findings should aid in the genetic counseling and management of AML patients and healthy carriers with germline CEBPA mutations.

Acute Myeloid Leukemia (AML). Diagnosis, Therapy and Outcome Results from Tawam Hospital. a Retrospective Review

IntroductionAcute Myeloid leukemia (AML) is a heterogeneous group of malignant disorders of myeloid hematopoetic cells. These cells have a maturation arrest in different stages of development leading to accumulation of immature cells. This gives rise to the different symptoms and signs of disease secondary to anemia, thrombocytopenia and neutropenia.The current WHO classification broadly divides AML into 4 main groups based on morphology, immunophenotyping, genetics and clinical features. These include AML with recurrent genetic abnormalities, AML with myelodysplasia related changes; therapy related AML and AML not otherwise specified (NOS).Therapeutically AML can be divided into 2 main groups; Acute promyelocytic leukemia (APML) and non APML.MethodsTawam Tumor registry was searched for patients with diagnosis of AML from January 2010 till December 2012. Patient records were then reviewed and data was collected.ResultsWe identified 49 patients with pathologically confirmed diagnosis of AML. 19/49 patients were diagnosed with AML with recurrent cytogenetic, 5/49 with MDS related or therapy related and 25 with AML NOSCytogenetic Analysis of this cohort of 49 patients with AML showed that 15 patients (30%) had APML with 15;17 translocation, 4 patients had 8;21 translocation, 5 had complex or poor risk cytogenetic while 13 had normal karyotype. In 12/49 patients Karyotyping failed due to growth failure. Status of FLT3 and NPM1 are not known for the entire cohort.DemographicsThe median age of the cohort was 38 years (range 20 to 84 years). Older adults (age 65 years or more) make a minority of this cohort (8%). Male to female ration was 3.5:1.TreatmentIn patients with Non APML Induction therapy was a combination of Cytarabine and Idarubicin for adults < 65 years of age and with good performance status. Older adults or adults with poor performance status or co-morbidities were either given hypomehtylating agents, Clofarabine or supportive care. Patients achieving complete remission (CR) were given consolidation with High Dose Cytarabine (HIDAC) as per CALGB protocol. Only a minority of patients were able to go for allogeneic stem cell transplantation in CR1Patients with APML were treated with ATRA, Idarubicin/Mitoxantrone and Cytarabine as per PETHEMA protocol on a risk adjusted plan. This was followed by 2 year maintenance with ATRA, 6 MP and Methotrexate.Outcome of TreatmentIn non APML patients 62 % (17) achieved CR with induction therapy. Induction therapy failure was observed in 18 % (5) while there were 5 early deaths observed (during aplasia). 7 patients were treated with hypomethylating agents or best supportive care. Only 1patient was able to achieve CR (after cycle 4 of 5-azacitidine). Consolidation therapy was given to 17 patients achieving CR. With a median follow up of 15 months (range 9-24 months) 9 patients are alive and disease free while 17 patients have been lost to follow up. 8 out of these 17 patients were in remission at their last follow up.In APML patients the CR rate was 93%. There were no cases of induction failure and only 1 case of early death (7%) due to hemorrhage. With a median follow up of 17 months (range 11-41 months) 11 patients are in molecular CR while 3 have been lost to follow up.ConclusionThis is the first analysis of patients who were diagnosed with AML in a tertiary care center in UAE. The results show that the median age of patients our cohort is low as compared to international reports (approximately 38 vs. 65 years). Older adults (> 65 years of age) make only a minority of the AML cohort in Tawam Hospital. Response to induction therapy is comparable to international standards (60-80%) for AML and > 90% for APML.We also report a twofold higher incidence of APML as compared to internationally reported data (30% vs.12%). This has a very significant diagnostic and therapeutic impact on the management of AML patients at our institute leading to increase vigilance and institution of ATRA at the earliest clinical suspicion of APML. DisclosuresAlam:BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Hussain:BMS: Honoraria; Novartis: Honoraria. Lal:BMS: Honoraria; novartis: Honoraria.

Early reduction of WT1 transcripts during induction chemotherapy predicts for longer disease free and overall survival in acute myeloid leukemia

We investigated the prognostic significance of early peripheral blast clearance as assessed by WT1 transcript reduction during the first days of standard induction therapy in 57 adult patients with acute myeloid leukemia (AML). Quantification of WT1 transcript by real-time quantitative PCR in peripheral blood on days 1 and 5 of treatment was performed. WT1 ratio was defined as the ratio of copy number measured on day 1 and on day 5. The median WT1 ratio was greater in patients attaining CR as compared to non-responders (11.68 vs. 2.14, respectively; P=0.0006). Furthermore, DFS and OS were significantly longer in patients displaying a WT1 ratio greater than 5.82 (i.e. the median value of whole cohort) than in patients with WT1 ratio of 5.82 or under (P=0.024 and P<0.001, respectively). These data suggest that early decrease of WT1 copy number in peripheral blood predicts for better outcome and should be considered in the management of AML patients.