scholarly journals Clinico-Haematologic association and prognostic relevance of NPM1 and FLT3-ITD mutations in acute Myeloid Leukaemia

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Rafia Mahmood ◽  
Chaudhry Altaf ◽  
Hamid Saeed Malik ◽  
Saleem Ahmad Khan
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Disease Free Survival ◽  
Npm1 Mutation ◽  
Free Survival ◽  
Positive Group ◽  
Median Disease Free Survival ◽  
Prognostic Relevance ◽  
Disease Free ◽  
Acute Myeloid

Background & Objectives: Molecular genetic abnormalities have a significant role not only in diagnosis but also in determining the clinical course and prognosis. Nucleophosmin-1 (NPM-1) is associated with good prognosis while internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) confers a poor prognosis. Knowledge of the status of these mutations in AML patients not only guides treatment decisions but also helps in predicting response to frontline induction and consolidation chemotherapy as well as the risk of relapse and overall survival. Our objectives were to determine the prevalence, clinico-haematological features and immunophenotypic characteristics of AML patients with FLT3-ITD and NPM1 mutation and to evaluate the response to induction therapy (CR) and disease free survival (DFS) in this cohort of patients. Methods: Patients diagnosed as AML from March 2015 to March 2017 at Armed Forces Institute of Pathology Rawalpindi were included in the study. Clinico-haematologic and immunophenotypic parameters were noted and molecular analysis for FLT3-ITD and NPM1 mutation was performed. Any correlation with cytogenetics or other molecular markers was also studied. Response to standard induction chemotherapy and disease-free survival were assessed. Results: A total of 108 cases of AML were analyzed. Median age was 35 years and 64.8% were males. The median age of the study group was 35 years. Of these, 70 (64.8%) were males while 38 (35.2%) were females. Twenty-nine (26.9%) patients were NPM1 positive, twelve (11.1%) were FLT3-ITD positive while eight (7.4%) were positive for both mutations. Patients with NPM1 mutations were associated with female gender, higher haemoglobin level and platelet counts while those with FLT3-ITD mutations were predominantly seen in male patients and had significantly higher WBC counts, bone marrow blasts, biopsy cellularity and LDH levels. CR rates of NPM1 positive, FLT3-ITD positive and both mutation positive groups were 72%, 60% and 71%, respectively. The median disease-free survival was significantly lower in the FLT3-ITD positive group (7.1 months) as compared to the NPM1 positive group (16.1 months). The median disease-free survival was 12 months and 11.9 months in the NPM1 positive/FLT3-ITD positive and the NPM1 negative/FLT3-ITD negative groups, respectively. Conclusion: AML patients harbouring NPM1 and FLT3-ITD mutations have distinct clinical and haematological characteristics. NPM1 mutations have a better CR and DFS as compared to FLT3-ITD group. How to cite this:Mahmood R, Altaf C, Malik HS, Khan SA. Clinico-Haematologic association and prognostic relevance of NPM1 and FLT3-ITD mutations in acute Myeloid Leukaemia. Pak J Med Sci. 2019;35(1):---------. doi: https://doi.org/10.12669/pjms.35.1.285 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Rapid Remission Induction and Improved Disease Free Survival in Acute Myeloid Leukaemia Using Daunorubicin, ARA-C, and CCNU

1990 ◽  
Vol 3 (2) ◽  
pp. 139-144 ◽  
Author(s):  
A. J. Barrett ◽  
J. G. Treleaven ◽  
D. M. Samson ◽  
M. Evans ◽  
E. Gaminara ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

Prognostic relevance of circulating matrix metalloproteinase-2 in acute myeloid leukaemia patients

2007 ◽  
Vol 25 (3) ◽  
pp. 121-126 ◽  
Author(s):  
Salah Aref ◽  
E. Osman ◽  
S. Mansy ◽  
N. Omer ◽  
E. Azmy ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Matrix Metalloproteinase 2 ◽  
Prognostic Relevance ◽  
Acute Myeloid

Autologous Bone Marrow Transplantation as an Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5121-5121
Author(s):  
Andre S. Jung ◽  
Asad Bashey ◽  
Peter R. Holman ◽  
Eva Carrier ◽  
Januario Castro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Risk Patients ◽  
Disease Free ◽  
Acute Myeloid

Abstract Introduction: Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myeloid leukemia. The optimal consolidation therapy for adults in remission without a histo-compatible donor has yet to be clearly established. Patients and Methods: This was a retrospective analysis of forty patients (23 females and 17 males) diagnosed with de novo acute myeloid leukemia, who were without a histo-compatible donor, that underwent APBSCT between the year 2000 and 2006 at a single institution. The patients’ age ranged from 18 to 73 with a median age of 50. Cytogenetic analysis was available on 37 of the patients. Complete remission (CR) was confirmed by bone marrow morphology and immunophenotype analysis by flow cytometry. Patients in remission were further consolidated with variable cycles of chemotherapy prior to stem cell transplantation. For stem cell mobilization, patients received high-dose cytarabine (2000mg/m2) and etoposide (5mg/kg) for three days followed by G-CSF at 10μg/kg, starting 10 days after the chemotherapy, before the peripheral stem cell collection. The preparative regimen prior to transplantation with unpurged stem/progenitor cells consisted of a combination of intravenous busulfan (0.8 mg/kg for 16 doses) and cyclophosphamide (60 mg/kg for two doses) (37 patients) or busulfan and melphalan (3 patients). Patients were then followed for treatment-related mortality, disease free survival, and overall survival. The analysis was stratified according to age, cytogenetic risk, and remission state. Results: There was no treatment-related mortality. Nineteen out of forty patients had relapse of their disease. The relapse rate was lowest in the low risk cytogenetic group who were under the age of 60 and highest in the high risk cytogenetic group who were over the age of 60. The overall 5 year survival for all patients was 47%. When stratified for cytogenetic risk and age, the overall survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 67%, 59%, and 75% respectively. The overall survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0% respectively. The projected rate of disease free survival at 5 years was 40%. When stratified for cytogenetic risk and age, the disease free survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 33%, 52%, and 50% respectively. Disease free survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0%. Comparing patients in CR1 versus patients in CR2, the overall survival was 47% in CR1 and 50% in CR2. The disease free survival, when grouped as above, were 41% for those in CR1 and 33% for those in CR2. Conclusion: APBSCT is a reasonable and safe intensive consolidation therapy for those patients without a compatible HLA matched donor in first or second complete remissions, notably for those under the age of 60 regardless of their cytogenetic risk. The number of standard consolidations prior to APBSCT may be an important variable predicting outcome.

Obesity Is An Adverse Prognostic Factor For Overall and Disease-Free Survival In Adult Acute Promyelocytic Leukemia But Not In Acute Myeloid Leukemia: A Pooled Analysis From Four Alliance Prospective Studies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 832-832 ◽  
Author(s):  
Jorge J. Castillo ◽  
Flora Mulkey ◽  
Susan Geyer ◽  
Jonathan E. Kolitz ◽  
William Blum ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Obese Patients ◽  
Free Survival ◽  
Race Ethnicity ◽  
Disease Free ◽  
Acute Myeloid

Abstract Introduction There are mounting data associating obesity with an increased risk of developing acute myeloid leukemia (AML) and acute promyelocytic leukemia (APML). However, the role of obesity in the outcome of patients with AML and APML has not been extensively evaluated. In this study, we assess the effect of obesity in relapse and survival rates of clinical trial patients with AML and APML. Methods Data on patients ≥18 years from 4 prospective clinical trials from the Cancer and Leukemia Group B (Alliance) were pooled for this analysis (n=2,093). This reflects exclusion of 72 patients deemed ineligible or non-evaluable, and 8 patients without height or weight data. Three studies were in de novo AML: 9621 (n=393), 10503 (n=541) and 19808 (n=714), and one study was in de novo APML: 9710 (n=445). BMI was calculated following the formula (BMI=weight/height2) and categorized according to WHO criteria as underweight/normal (BMI <25 kg/m2), overweight (BMI 25-29.9 kg/m2) and obese (BMI 30+ kg/m2). AML and APML cohorts were analyzed separately. Baseline BMI was evaluated in relation to clinical characteristics, including age, gender, ECOG performance status (PS), and race/ethnicity. Univariate and multivariable logistic regression models were used to assess relationships of these factors with obesity. Analysis of clinical outcomes included overall survival (OS) in all patients, and disease-free survival (DFS) in those patients who achieved a complete response. The impact of obesity was evaluated using Kaplan-Meier methods and log-rank tests. Multivariate Cox regression analyses were used to assess prognostic impact of obesity while adjusting for other factors such as age, gender, PS, race and ethnicity on OS and DFS. P-values <0.05 were considered statistically significant. Results In the AML cohort (n=1,648), median age was 46 years (range: 18-66 years), 53% were men, 87% had PS 0-1, 17% were non-white and 7% Hispanic. For the APML cohort (n=445), median age was 43 years (range: 18-80 years), 52% were male, 82% had PS 0-1, 18% were non-white and 11% Hispanic. The proportion of obesity at study entry for AML and APML was 38% and 50%, respectively. APML patients experienced a superior OS than AML patients (5-year OS: 81% vs. 37%). In AML, age, gender and race were all significantly related to whether or not patients were obese in univariate and multivariate settings. In APML, only age and race were significantly associated with obesity. Median follow-up time was 6.8 years for AML and 8.5 years for APML patients. In the AML cohort, 1058 of 1648 patients have died, and 813 of 1246 patients evaluable for DFS had an event. For APML, 102 of 445 patients died and 106 of 401 patients evaluable for DFS had an event. DFS and OS distributions were not significantly different in obese vs. non-obese AML patients (p=0.8 and p=0.6, respectively). However, obese APML patients had a significantly shorter OS than non-obese patients (HR=1.61, p=0.02; 5-year OS rates: 76% vs. 85%, respectively). Similarly, obese APML patients tended to have shorter DFS than non-obese patients (HR=1.49, p=0.05; 5-year DFS rates: 74% vs. 82%, respectively). Only focusing on those APML patients between 18-60 years of age, differential OS and DFS in obese patients was more pronounced with corresponding worse survival (OS: HR=2.13, p=0.003; DFS: HR=1.75, p=0.015). Conclusion Obesity did not influence OS and DFS in AML. However, in a multivariate analysis, obese APML patients had significantly inferior OS and DFS than non-obese patients. Multivariate analysis suggests that the adverse impact of obesity in APML is independent of age, sex, performance and race/ethnicity. Previous studies have suggested that obesity is a risk factor for developing APML; we now show that obesity at diagnosis also confers a worse prognosis. Reasons for our findings could include potential pharmacological issues, such as relative dose intensity, which needs further research. Moreover, it will be necessary to determine if our findings will be replicated in patients with APML treated without chemotherapy as is now becoming the standard of care for those who present with white blood cell counts <10,000/uL. Disclosures: No relevant conflicts of interest to declare.

Feasibility and potential benefit of neoadjuvant chemotherapy for colorectal liver metastasis: A single-centered retrospective study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 465-465
Author(s):  
K. Kataoka ◽  
A. Kanazawa ◽  
A. Nakajima ◽  
A. Yamaguchi ◽  
S. Tuyuki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Liver Volume ◽  
Disease Free Survival ◽  
Combination Regimen ◽  
Remnant Liver ◽  
Free Survival ◽  
Median Disease Free Survival ◽  
Disease Free

465 Background: Recently, several papers have reported the advantage of neoadjuvant chemotherapy for liver limited metastatic colorectal cancer. In these papers, most study groups used criteria for non-resectability due to size and/or number of metastases. Our criteria for resectability of colorectal liver metastases (CLM) depends on the size of remnant liver volume (>30%) and expected function after the removal of all metastases. Then, we assessed the feasibility and potential benefits of chemotherapy administered before surgery to patients with CLM retrospectively. Methods: From January 2007 to April 2010, 67 chemotherapy-naive patients were diagnosed as CLM without extra-hepatic metastases. After chemotherapy, we assessed the resectability with radiological examination.Then, each case was divided in two groups, resected group and unresected group. Overall survival, median disease-free survival and postoperative complications were analyzed. Results: 63 patients received oxaliplatin-based combination regimen and 4 patients other regimen. 30 patients (resected group) received R0 resection and 37 patients (unresected group) were considered as unresectable. No serious postoperative complications were observed. Overall survival was significantly higher in resected group than in unresected group (42.3 month and 29.1 month; P<0.001). Median disease-free survival was 18.8 months in resected group (95% CI:3.02 to 31.33). According to our retrospective review, resectable cases increased from 28 of 67 patients at baseline to 33 after chemotherapy (including 3 cases considered as CR after chemotherapy only). Conclusions: Intensive treatment with neoadjuvant chemotherapy for CLM is well tolerated. Curative surgery improved significantly overall survival in patients with CLM. Neoadjuvant chemotherapy such as mFOLFOX6 may lead to increased resectability but do not increase postoperative complications. For most patients with resectable CLM, neoadjuvant chemotherapy should be considered the standard treatment. No significant financial relationships to disclose.

Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia

1995 ◽  
Vol 90 (1) ◽  
pp. 125-130 ◽  
Author(s):  
PELLEGRINO MUSTO ◽  
CARLO BODENIZZA ◽  
ANTONIETTA FALCONE ◽  
GIOVANNI D'ARENA ◽  
POTITO SCALZULLI ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Thymidine Kinase ◽  
Myelodysplastic Syndromes ◽  
Prognostic Relevance ◽  
Acute Myeloid

High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia

Blood ◽  
2009 ◽  
Vol 114 (14) ◽  
pp. 2993-3000 ◽  
Author(s):  
Ruoping Tang ◽  
Pierre Hirsch ◽  
Fanny Fava ◽  
Simona Lapusan ◽  
Christophe Marzac ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Young Patients ◽  
Disease Free Survival ◽  
Internal Tandem Duplication ◽  
Free Survival ◽  
Downstream Target ◽  
Disease Free ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

Inhibitors of differentiation (Id) are a group of dominant inhibitors of basic helix-loop-helix transcriptional factors, which promote excessive proliferation, and also protect cells against drug-induced apoptosis in mammalians. Recently, Id1 has been identified as a common downstream target of several constitutively activated oncogenic tyrosine kinase, such as FLT3 internal tandem duplication, in leukemia cells. We analyzed Id1 expression as possible prognostic factor in 237 acute myeloid leukemia (AML) patients. High Id1 expression was associated with older age (P = .009) and with FLT3 internal tandem duplication (P = .003). However, 61% of the patients in the group of FLT3− AML were Id1+, suggesting that other tyrosine kinases are involved. In whole population, high Id1 expression independently predicted shorter disease-free survival (P = .05) and overall survival (P = .003). In young patients (age ≤ 60 years) with normal cytogenetics, Id1+ was, in multivariate analysis, associated with lower complete remission rates (P = .02), shorter disease-free survival (P = .02), and overall survival (P = .006). In conclusion, our data provide a new molecular marker for refining the risk classification of AML, especially in young patients with normal cytogenetic. Id1− patients with normal cytogenetic should be classified as favorable-risk leukemia. Id1, as a downstream target of constitutively activated tyrosine kinase, could be a suitable candidate for targeted therapy.

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