Cytogenetic Diagnostics and Outcome in a Series of Thirty Three Greek Pediatric Acute Myeloid Leukemia Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4889-4889
Author(s):  
Kalliopi N Manola ◽  
Agapi Parcharidou ◽  
Vassilios Papadakis ◽  
Maria Kalntremtziou ◽  
Chryssa Stavropoulou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Bone Marrow Cells ◽  
Normal Karyotype ◽  
Acute Leukemias ◽  
Early Treatment Response ◽  
Pediatric Aml ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) accounting for approximately 17% of all childhood acute leukemias, arises either de novo or from a backround of myelodysplasia or previous chemotherapy. Cytogenetics is considered one of the most valuable prognostic determinants in AML while current risk–group classification in the limited cases of pediatric AML, is mainly based on cytogenetics and early treatment response. We reviewed the clinical and cytogenetic characteristics and the outcomes of 33 cases of childhood AML between 1997 and 2007 in order to investigate the incidence of the main FAB subtypes, the incidence of primary AML compared to secondary AML (s-AML) and the correlation between specific chromosome abnormalities and outcome in greek pediatric AML patients. Chromosome studies were performed on unstimulated bone marrow cells, derived from 33 pediatric AML patients, who were <18 years of age at the time of diagnosis. Eighteen patients were male and 15 were female. According to FAB classification one patient was classified as M0 (3%), 13 patients as M2 (39.4%), 4 as M3 (12.12%), 4 as M5 (12.12%), 2 as M6 (6.1%) and 4 as M7 (12.12%). No patient was classified as M4 while 5 patients with s-AML (15.15%) could not be classified. The median follow-up of all patients was 57.95 months (0.03–132.47). Overal survival and event free survival were 66,7% and 75,8% respectively. Eight patients with s-AML and 25 patients with primary AML were identified. The median age of patients with s-AML at diagnosis was 9.15 years while the median age of patients with primary AML was 7.2 years. Six out of 8 patients with s-AML died at a median follow up of 11.03 months. Nineteen out of 25 patients with primary AML are alive in complete remission (CR). Cytogenetic analysis was performed at diagnosis in 32 patients and results were obtained in 30 of them. The karyotype was abnormal in 21 out of 30 patients (70%). Normal karyotype was found in 9 patients, t(8;21)(q22;q22) in 5, t(15;17)(q22;q21) in 3, t(9;11)(p22;q23) in 3, −7/del(7q) in 5, del(9q) in 3, and complex karyotype in 4 patients. Three out of 4 patients with M3 are alive in CR with a median follow-up of 98.6 months while one with s-AML-M3 died 13 days post diagnosis. Three out of five patients with M2 and t(8;21), including 1 patient with s-AML, died at a median follow-up of 4.35 months. Three out of 5 patients with −7/del(7q) had s-AML and died in less than 4 years, while the two others are alive for more than 5 years, in CR. Although all patients with M7 had complex karyotypes, they are alive after a median follow-up of 96.73 months, 3 of them in CR and 1 in relapse. These results indicate that in greek patients, the main FAB subtypes show a distribution similar to that reported in the literature with the exception of M4 which is absent in our study but with a reported incidence of 20%. Pediatric patients with s-AML are older and their outcome is poor and is related to a higher probability of poor cytogenetic features compared to primary AML patients. Interestingly all patients with M7 had a good clinical course although they exhibited complex karyotypes.

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Abstract Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

scholarly journals Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: correlation with clinicobiologic findings [see comments]

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3688-3694 ◽  
Author(s):  
A Cuneo ◽  
A Ferrant ◽  
JL Michaux ◽  
M Boogaerts ◽  
H Demuynck ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Normal Karyotype ◽  
Clinical Findings ◽  
Trisomy 13 ◽  
Professional Exposure ◽  
Cytogenetic Profile ◽  
Acute Myeloid ◽  
Clonal Abnormalities

Cytogenetic data were studied in 26 patients with de novo acute myeloid leukemia (AML) with minimal myeloid differentiation, corresponding to the M0 subtype of the French-American-British classification, in correlation with cytoimmunologic and clinical findings. Clonal abnormalities were detected in 21 cases (80.7%), 12 of which had a complex karyotype. Partial or total monosomy 5q and/or 7q was found, either as the sole aberration or in all abnormal metaphases, in 11 patients; in 8 cases, additional chromosome changes were present, including rearrangements involving 12p12–13 and 2p12–15 seen in 3 cases each. Five patients had trisomy 13 as a possible primary chromosome change; in 5 cases, nonrecurrent chromsome abnormalities were observed. Comparison of these findings with chromosome data from 42 patients with AML-M1 shows that abnormal karyotypes, complex karyotypes, unbalanced chromosome changes (-5/5q- and/or -7/7q- and +13) were observed much more frequently in AML-M0 than in AML-M1. Patients with abnormalities of chromosome 5 and/or 7 frequently showed trilineage myelodysplasia and low white blood cell count. Despite their relatively young age, complete remission was achieved in 4 of 11 patients only. Patients with +13 were elderly males with frequent professional exposure to myelotoxic agents. Unlike patients with clonal abnormalities, most AML-M0 patients with normal karyotype showed 1% to 2% peroxidase-positive blast cells at light microscopy and frequently achieved CR. It is concluded that (1) AML-M0 shows a distinct cytogenetic profile, partially recalling that of therapy-related AML, (2) different cytogenetic groups of AML-M0 can be identified showing characteristic clinicobiologic features, and (3) chromosome rearrangements may partially account for the unfavorable outcome frequently observed in these patients.

Coagulopathy in HLA-DR Antigen-Negative Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4457-4457
Author(s):  
Hideki Uchiumi ◽  
Takafumi Matsushima ◽  
Arito Yamane ◽  
Hiroshi Handa ◽  
Hiroyuki Irisawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Myeloid Cell ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Hla Dr ◽  
Risk Of Mortality ◽  
Acute Myeloid

Abstract Background: HLA-DR antigen is present on hematopoietic progenitors and granulocyte/monocyte, erythrocyte and megakaryocytic precursors but absent at the promyelocytic stage during myeloid cell maturation. In accordance with this, majority of promyelocytic leukemia (APL) cells were negative for HLA-DR. Meanwhile, some of non-APL acute myeloid leukemia (AML) cells is found to express HLA-DR. However, the clinical significance of HLA-DR antigen on AML cells is currently unclear. Purpose: We sought to determine the prevalence and clinical characteristics of negativity in HLA-DR expression by retrospectively analyzing 181 consecutive patients with de novo adult AML. Patients and Methods: AML patients examined in the current study (aged 15–86 years) had been diagnosed between August 1995 and July 2004, and categorized to M0 (8 patients), M1 (35), M2 (74), M3 (20), M4 (25), M5 (15), and M6 (4), based on the FAB classification. Median follow-up time was 19.3 months. Phenotypic analyses of leukemic cells were performed using CD45 gating methods. HLA-DR-negative AML was defined as HLA-DR expression less than 20% of cells in the CD45 leukemic cell gate. Results: Among 181 patients, HLA-DR antigens were not detected on AML cells from 46 patients; 20 with APL and 26 with non-APL (non-APL/DR(−)), the latter of which included M0 (2 patients), M1 (15), M2 (7), M4 (2). Leukemic cells from other non-APL patients were HLA-DR-positive (non-APL/DR(+)). None of non-APL/DR(−) patients had t(15;17) nor PML/RARa rearrangement on cytogenetic analysis. Twenty out of 26 patients with non-APL/DR(−) had normal chromosome, and 6 had abnormal karyotypes. In the non-APL/DR(−) group, various degrees of nuclear folding, convolution, or lobulation were observed in 9 patients. Although treatment response and overall survival rate were similar in the three groups (APL, non-APL/DR(−), and non-APL/DR(+)), both FDP levels at diagnosis (57.3 vs 13.2, p&lt;0.05) and maximal FDP levels (232.6 vs 43.8, p&lt;0.01) were significantly higher in non-APL/DR(−) compared with non-APL/DR(+). The maximal FDP levels in the non-APL/DR(−) patients were comparable to those in the APL patients. FDP levels greater than 40 mg/ml were significantly more prevalent in the non-APL/DR(−) than in the the non-APL/DR(−) group. Logistic regression analysis demonstrated that low HLA-DR expression was an independent risk factor for FDP &gt; 40 mg/ml. Conclusion: Our study suggests that AML with negative HLA-DR antigen tend to be associated with abnormality in coagulation and fibrinolysis even if they are genetically non-APL. We propose that more attention should be paied for HLA-DR expression to avoid a devastating coagulopathy which carries a high risk of mortality unless specifically addressed.

The Detection of Multilineage Dysplasia (MLD) Has No Influence on Prognosis in NPM1 Mutated Acute Myeloid Leukemia (AML) with Normal Karyotype

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2518-2518
Author(s):  
Ulrike Bacher ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
Tamara Weiss ◽  
Claudia Haferlach ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Biological Entity ◽  
Prognostic Impact ◽  
Npm1 Mutation ◽  
Cox Regression Analysis ◽  
Multilineage Dysplasia ◽  
Acute Myeloid

Abstract Acute myeloid leukemia with mutated nucleophosmin (AML NPM1mut) represents about one-third of all adult AML and shows distinctive biological and clinical features. For this reason, AML NPM1mut is planned to be included as a separate category in the revised WHO classification. A yet controversial issue, however, is whether AML NPM1mut with or without multilineage dysplasia (MLD) may differ biologically and clinically, as the presence of MLD might confer a negative prognostic impact. A further feature that was suggested to be typical for NPM1 mutated AML is “cup-like” morphology of blasts. We here analyzed 128 pts with AML NPM1mut and normal karyotype at first manifestation (59 females, 69 males; median age 60.5 years; 23.5–79.3 y). We investigated in parallel cytomorphology from bone marrow and/or peripheral blood, chromosome banding analysis, and molecular analyses. Presence of dysplasia was defined by dysplastic features in ≥50% of cells in the respective hematopoietic lineage as defined by the WHO. A 5% cut-off was taken for the presence of “cup-like” morphology of blasts. All cases were additionally analyzed for the FLT3-ITD, and in 122 pts for the FLT3-TKD. Statistical analysis was performed for overall survival (OS), and event-free survival (EFS) according to Kaplan-Meier using the 2-sided log-rank test. Cox regression analysis related OS and EFS with the analyzed parameters. We found a predominance of the FAB M1 (21.3% of all cases), M2 (33.9%), and M4 subtypes (28.3%). Cup-like morphology in ≥5% of all blasts was observed in 39 of 127 evaluable cases (31.3%) confirming previous observations of an association of the NPM1mut and this specific blast appearance. Molecular characterization detected NPM1 mutation subtype A (n=90/122; 73.8%), B (15/122; 12.3%), and D (7/122; 5.7%), which was in accordance to previous studies. In 56 cases (43.8%) there was a coincidence with an FLT3-ITD. Dysplasia of granulopoiesis was detected in 28/126 (22.2%), of erythropoiesis in 28/104 (26.9%), and of megakaryopoiesis in 57/87 (44.5%) cases in which the respective cell lineage could be analyzed. MLD (≥2 dysplastic hematopoietic lineages) was detected in 28 of 105 evaluable cases (21.9%). Clinical follow-up was available in 104 pts. (median follow-up 12,7 months). CR rate was 83.1% in 77 evaluable pts., and median EFS was 42.1 months in 104 evaluable pts (median OS not reached). An additional FLT3-ITD had a significantly inferior OS (p=0.003) and EFS (p=0.007), confirming the present series being representative. However, the presence of MLD was not significantly related to any endpoint such as CR rate, EFS, or OS. There was no association between MLD and the NPM1-subtype. Also, there was no significant correlation of MLD and the presence of a FLT3-ITD. In conclusion, the presence of MLD in AML NPM1mut with normal karyotype had no impact on CR rate and outcome, whereas coincidence of FLT3-ITD significantly worsened prognosis. These results give further evidence that AML with NPM1mut AML is a unique biological entity with clinical course mainly influenced by FLT3-ITD coincidence. These data do not support any additional prognostic influence of MLD in this AML subtype.

Rapid Detection of Nucleophosmin (NPM1) Mutations to Determine Prognostic Implications in Acute Myeloid Leukemia Patients with a Normal Karyotype.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4676-4676
Author(s):  
Seo-Jin Park ◽  
Hyun-Sook Chi ◽  
Kyung Ran Jun ◽  
Sook Kyoung Min ◽  
Seongsoo Jang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Direct Sequencing ◽  
Screening Method ◽  
Normal Karyotype ◽  
Npm1 Mutation ◽  
Prognostic Groups ◽  
Acute Myeloid

Abstract Abstract 4676 INTRODUCTION Mutations of the nucleophosmin gene (NPM1) occur in up to 40-50% of adult acute myeloid leukemia (AML) with a normal karyotype and are associated with a higher frequency of fms-like tyrosine kinase-3 internal tandem duplications (FLT3-ITD) and responsiveness to induction chemotherapy. The incidence of NPM1 mutations in Caucasians have been previously reported in several studies whereas there have been few reports from Asian countries including Japan, China, and Taiwan. The objectives of our study was to determine the prevalence of NPM1 mutations and distribution of AML subtypes in the normal karyotype AML Korean population in addition to establishing an easily applicable yet reliable method to indentify these mutations. We also examined treatment outcomes and survival (relapse-free survival (RFS) and overall survival (OS)) by stratifying them into groups according to NPM1 and FLT3-ITD mutation status. METHODS We retrospectively analyzed the prevalence of NPM1 mutations in 185 patients with normal karyotype AML diagnosed between 2002 and 2009. Genomic DNA extracted from bone marrow aspirate specimens obtained at diagnosis was amplified by PCR, followed by analysis on an ABI 3130 Genetic Analyzer (Applied Biosystems) by capillary electrophoresis. Cases found to have mutation peaks at 174bp by Gene Mapper ID v3.2 software (Applied Biosystems) were further analyzed by direct sequencing of exon 12 of NPM1 gene. Follow-up data was reviewed by retrospective chart review for treatment outcome and survival analyses. Among the 185 AML patients, 18 with less than a 1-month follow-up period were excluded since they could not be sufficiently evaluated. RESULTS Mutations in exon 12 of NPM1 were found in 37 of 185 (20.0%) normal karyotype AML patients and were composed of TCTG duplications (Type A, 32/37, 86.5%), 3 previously reported variants, and 2 new variants previously not reported. Mutations were most frequently seen in AML M1 patients (12/37, 32.4%) and other subtypes such as M2, and M4 were often observed. NPM1 mutations were particularly associated with CD34-negativity (<0.0001) and higher bone marrow blast (%) at diagnosis (p=0.0067). There was a mild trend towards frequent FLT3-ITD mutations in NPM1+ patients in comparison to the NPM1- group (35.1% and 19.6%, p=0.0787). After exclusion of the 18 patients lost during follow-up, no significant differences in RFS (8.5 and 10.8 months, p=0.7922) and OS (11.5 and 13.6 months, p=0.6147) were observed between the NPM1+ and NPM1- groups. Stratification into good (NPM1+/FLT3-ITD-), intermediate (NPM1-/FLT3-ITD- & NPM1+/FLT3-ITD+), and poor (NPM1-/FLT3-ITD+) prognostic groups did not reveal significant differences in median values of RFS and OS (in months; RFS, 16.0 and 13.8 and 7.3, p=0.1872; OS, 16.0 and 10.8 and 7.3, p=0.3661). However, the Kaplan-Meier survival analysis of these stratified prognostic groups showed a trend toward a difference in RFS (p=0.084) and a significantly longer OS in the NPM1+/FLT3-ITD- (good prognostic) group (p=0.031). CONCLUSIONS The prevalence of NPM1 mutations in normal karyotype AML patients in Koreans was lower than those reported in Western studies. In areas with low prevalence, a screening method to detect mutations enables rapid reporting with only selective cases requiring the labor-intensive direct sequencing step. In accordance with previous studies, a significantly longer OS in the NPM1+/FLT3-ITD- group suggests that NPM1+ may be associated with a favorable outcome. However, discordant parameters such as prevalence and RFS may signify that elucidation of the prognostic significance of NPM1 mutations in different ethnic groups may be necessary. Thus, NPM1 mutation studies should be considered in the diagnostic work-up of all AML patients with a normal karyotype given its role as a prognostic marker. Disclosures: No relevant conflicts of interest to declare.

The Prognostic Impact and Stability of IDH2 Mutation and the Insufficiency of the Mutation Alone for Leukemogenesis In Adult Patients with Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2697-2697
Author(s):  
Weng-Chi Lei ◽  
Wen-Chien Chou ◽  
Bor-Shen Ko ◽  
Hsin-An Hou ◽  
Hwei-Fang Tien
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Normal Karyotype ◽  
Idh1 Mutation ◽  
Group 12 ◽  
Worse Prognosis ◽  
Idh2 Mutation ◽  
Acute Myeloid

Abstract Abstract 2697 Purpose: Although the clinical and biological features of Isocitrate dehydrogenase (IDH) mutations in acute myeloid leukemia (AML) have been characterized, its stability and in vivo sufficiency of the mutation alone for leukemogenesis remain uninvestigated. Patients and Methods: Mutations of IDH and other clinically relevant genes were analyzed in the bone marrow from 446 adult patients with de novo non-M3 AML. IDH2 mutations were examined serially in 140 patients at diagnosis and after chemotherapy. Results: Among the 446 adults with de novo non-M3 AML, IDH2 R172, R140, and IDH1 R132 mutations occurred at a frequency of 2.9%, 9.2%, and 6.1%, respectively. IDH2 mutation was associated with higher platelet counts (p=0.046), intermediate-risk (p=0.002) or normal karyotype (p=0.023), and isolated +8 (p=0.014), but was inversely correlated with expression of HLA-DR (p=0.002), CD34 (p=0.039), CD15 (p=0.003), CD7 (p=0.010), and CD56 (p=0.048), and was mutually exclusive with WT1 mutation (p=0.037) and core-binding factor translocations (p=0.001). All these correlations became stronger when IDH1 and IDH2 mutations were considered together, suggesting similarity of biological roles between these 2 mutations. However, IDH2 but not IDH1 mutation conferred a better prognosis (Fig 1), especially in those with normal karyotype or intermediate cytogenetics (median overall survival: not reached vs. 58 months, p=0.044 and not reached vs. 19 months, p=0.027 for normal and intermediate karyotype group, respectively). Importantly, IDH2 but not IDH1 mutation was an independent favorable prognostic factor (HR: 0.332, 95% CI: 0.159–0.694; p=0.003). Patients with IDH2−/FLT3-ITD+ genotype had especially worse prognosis (median OS of IDH2−/FLT3-ITD+ vs. IDH2+/FLT3-ITD− group: 12 months vs. not reached; p=0.003; median OS of IDH2−/FLT3-ITD+ vs. IDH2+/FLT3-ITD+ or IDH2−/FLT3-ITD− group : 12 months vs. 35 months; p<.0001) (Fig 2A). The worse prognosis was also seen in patients with IDH−/FLT3-ITD+ genotype (Fig 2B). Serial analyses of IDH2 mutations during the clinical course of 140 patients confirmed the stability of this mutation; all the patients with IDH2 mutations at diagnosis harbored the same mutation at relapse with the exception of one patient who had extramedullary but not bone marrow relapse, while none of the IDH2-wild patients acquired this mutation at relapse. Importantly, sequential samples from two patients in long-term remission retained the original R140Q mutation while other accompanied mutations, FLT3-ITD in the first patient and NPM1 in the second, respectively, disappeared. In the first patient, the skin tissue was absent of the mutation and in the second, the mutation was restricted in myeloid cells but spared in lymphocytes indicating the mutation was acquired in these two patients. Conclusion: IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis. FLT3-ITD combined with wild type IDH2 exerted synergistic negative impact on survival. IDH2 mutation alone is insufficient for leukemogenesis. Disclosures: No relevant conflicts of interest to declare.

Interim results of protracted low doses of temozolomide in high-risk acute myeloid leukemia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7052-7052
Author(s):  
B. C. Medeiros ◽  
J. R. Gotlib ◽  
S. E. Coutre ◽  
C. Jones ◽  
S. A. Khan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Elderly Patients ◽  
Promoter Methylation ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Normal Karyotype ◽  
Low Doses ◽  
Npm1 Mutation ◽  
Acute Myeloid

7052 Background: High treatment-related mortality and low response rates often discourage elderly patients with acute myeloid leukemia from receiving treatment. Previous data demonstrate that only patients lacking expression of O6-alkylguanine-DNA alkyltransferase (AGAT) in leukemic blasts are sensitive to temozolomide. Protracted exposure to low doses of temozolomide can significantly inhibit AGAT enzymatic activity. Methods: Phase II clinical trial of tailored temozolomide therapy to high-risk AML patients according to AGAT methylation promoter status. Patients demonstrating evidence of AGAT promoter methylation were stratified to conventional doses of temozolomide at 200 mg/m2 orally x 7 days. Patients demonstrating lack of AGAT promoter methylation (unmethylated) received protracted doses of temozolomide (100 mg/m2 orally x 14 days) followed by conventional doses of temozolomide. Patients who achieved CR were given up to 5 consolidation treatments. Results: Fifteen patients have completed treatment to date. The median age was 78 (68–83) and nine were male. De novo AML was diagnosed in eight patients and five patients had s-AML. Nine patients had a normal karyotype and three patients had a complex karyotype. Two patients had only a NPM1 mutation and one had NPM1mut/FLT3-ITD. In 13 patients, the AGAT promoter was found to be unmethylated. AGAT protein was present in 5/11 patients. All patients had an intact mismatch repair pathway. Thirteen patients had HCT-CI scores of 0–2. Six patients (6/13) achieved a complete remission (CR) after 1 cycle of therapy (1/2 for patients with methylated and 5/11 for patients with unmethylated AGAT promoter). Nonhematologic toxicities were minimal. Drug-related hematologic toxicities were difficult to distinguish from disease-related cytopenias. Three patients remain in CR with a median duration of 22 weeks (14–36 weeks). Seven patients have died from disease progression, while two patients died of neutropenic sepsis (early deaths). With a median follow-up of 38 weeks (10–48), the median overall survival for the entire population is 12 weeks (3.5 - 38) weeks (responders 26.5 weeks). Conclusions: These preliminary results suggest that temozolomide therapy may be individually tailored to elderly patients with AML according to AGAT promoter status. [Table: see text]

scholarly journals Orbital myeloid sarcoma misdiagnosed for subperiostal hematoma: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Bahaa Razem ◽  
Mohamed Raiteb ◽  
Sanaa El Mrini ◽  
Faiçal Slimani
Keyword(s):  
Acute Myeloid Leukemia ◽  
Case Report ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Myeloid Sarcoma ◽  
Orbital Mass ◽  
Genetic Features ◽  
Immature Myeloid Cells ◽  
Acute Myeloid

Abstract Background Myeloid sarcoma is a solid tumor that consists of immature myeloid cells occurring at an extramedullary site. It can present before, concurrent with, or after the diagnosis of acute myeloid leukemia or other myeloproliferative diseases, and a proportion of patients never develop bone marrow infiltration. Only a few isolated cases of pediatric orbital myeloid sarcoma have been reported, and they are often associated with a high misdiagnosis rate. Case report We report a rare case of pediatric orbital myeloid sarcoma associated with blunt trauma in a 3-year-old Caucasian male patient, which was clinically and radiologically misdiagnosed for orbital subperiostal hematoma. The patient underwent a surgical intervention to drain the hematoma when an orbital mass was found. The microscopic, immunologic, and genetic features of the tumor and the myelogram were in favor of LAM2, and the patient was started with chemotherapy with a favorable evolution within 18 months follow-up. Conclusion Orbital myeloid sarcoma usually exhibits clinical and radiological features that can be easily misleading, especially if it happens de novo or as the first manifestation of acute myeloid leukemia. Only a few isolated cases have reported and proposed trauma as a trigger event of the onset of this type of tumor proliferation, but further investigations and evidence are needed to support this hypothesis.

scholarly journals Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

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