scholarly journals Infant Acute Myeloid Leukemia: A Unique Clinical and Biological Entity

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 777
Author(s):  
Charlotte Calvo ◽  
Odile Fenneteau ◽  
Guy Leverger ◽  
Arnaud Petit ◽  
André Baruchel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Study Groups ◽  
Biological Entity ◽  
Age Group ◽  
Older Children ◽  
Megakaryoblastic Leukemia ◽  
Acute Myeloid

Infant acute myeloid leukemia (AML) is a rare subgroup of AML of children <2 years of age. It is as frequent as infant acute lymphoblastic leukemia (ALL) but not clearly distinguished by study groups. However, infant AML demonstrates peculiar clinical and biological characteristics, and its prognosis differs from AML in older children. Acute megakaryoblastic leukemia (AMKL) is very frequent in this age group and has raised growing interest. Thus, AMKL is a dominant topic in this review. Recent genomic sequencing has contributed to our understanding of infant AML. These data demonstrated striking features of infant AML: fusion genes are able to induce AML transformation without additional cooperation, and unlike AML in older age groups there is a paucity of associated mutations. Mice modeling of these fusions showed the essential role of ontogeny in the infant leukemia phenotype compared to older children and adults. Understanding leukemogenesis may help in developing new targeted treatments to improve outcomes that are often very poor in this age group. A specific diagnostic and therapeutic approach for this age group should be investigated.

Differences in Cyto- and Molecular Genetic Abnormalities between Children <2 Years and Older Children with Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1830-1830
Author(s):  
Brian V. Balgobind ◽  
Iris H. Hollink ◽  
Dirk Reinhardt ◽  
Jutta Bradtke ◽  
Andrea Teigler-Schlegel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Young Children ◽  
Myeloid Leukemia ◽  
Molecular Genetic ◽  
Age Groups ◽  
Normal Karyotype ◽  
Older Children ◽  
Ras Mutations ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Young children (defined as &lt;2 years old) with acute myeloid leukemia (AML) do not differ in outcome when compared with older children with AML. Previously, distinct cytogenetic aberrations specific for AML in young children have been reported, such as t(7;12), and t(1;22), which is found exclusively in FAB M7. Moreover, young children with AML are characterized by a high frequency of 11q23-rearrangements. However, so far, no information is available on differences in the molecular genetic background of these two age groups. We therefore retrospectively investigated the distribution of different cytogenetic and molecular aberrations in a large cohort (n=435) of pediatric AML cases, of which 75 (17%) were young children. The predominant cytogenetic aberration in infant AML consisted of 11q23-rearrangements, which occurred in 44% of young children versus 17% in older children (p=&lt;0.005), without differences in the distribution of 11q23-translocation partners. We also found significant differences in other cytogenetic subgroups of AML between young and older children, i.e. normal karyotype, 5% vs. 18%, respectively (p=0.008) and complex karyotype, 12% vs. 5% (p=0.03). t(7;12) (n=3) and t(8;16) (n=3) were only detected in young children, in contrast to t(15;17) (n=16) and t(8;21) (n=44), which were only seen in older children. Patients were also screened for molecular abnormalities, including the mutational hotspots of c-KIT (n=229), FLT3 (n=230), N-RAS (n=187), K-RAS (n=187), PTPN11 (n=216), MLL-partial tandem duplications (MLL-PTD) (n=240) and NPM1 (n=291). In the overall cohort, a significantly different age distribution was found for NPM1 mutations (0% young vs. 9% in older children; p=0.05) and FLT3-ITD (0% vs. 21%, respectively; p=0.005). Mutations in the other genes showed no clear correlation with age. Several non-random associations between molecular and cytogenetic abnormalities were detected. 89% of c-KIT mutations were associated with core-binding factor AML in children ≥2 years old. In young children, 2/4 c-KIT-mutated cases were associated with an MLL-rearrangement. NPM1 and FLT3-ITD mutations in older children were significantly correlated with normal karyotype AML (57% of NPM1 mutations, and 75% of FLT3/ITD; p=&lt;0.005). In young children, 71% of RAS mutations were associated with an 11q23-rearrangement vs. 28% in older children (p=0.08). In older children however, 41% of the RAS mutations were associated with a normal karyotype. These data suggest that young children with AML are characterized by differences in the type and frequency of cytogenetic and molecular genetic abnormalities when compared with older children with AML, possibly reflecting differences in underlying biology between these age-groups. These differences may become clinically relevant in the era of molecularly targeted therapy.

Cytogenetics of Childhood Acute Myeloid Leukemia: United Kingdom Medical Research Council Treatment Trials AML 10 and 12

2010 ◽  
Vol 28 (16) ◽  
pp. 2674-2681 ◽  
Author(s):  
Christine J. Harrison ◽  
Robert K. Hills ◽  
Anthony V. Moorman ◽  
David J. Grimwade ◽  
Ian Hann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Adverse Outcome ◽  
Cytogenetic Study ◽  
Prognostic Significance ◽  
Age Groups ◽  
Older Children ◽  
Monosomy 7 ◽  
Acute Myeloid

Purpose Karyotype is an independent indicator of prognosis in acute myeloid leukemia (AML) that is widely applied to risk-adapted therapy. Because AML is rare in children, the true prognostic significance of individual chromosomal abnormalities in this age group remains unclear. Patients and Methods This cytogenetic study of 729 childhood patients classified them into 22 subgroups and evaluated their incidence and risk. Results Rearrangements of 11q23 were the most frequent abnormality found in approximately 16% of patients, with 50% of these in infants. The outcome for all patients with 11q23 abnormalities was intermediate; no difference was observed for those with t(9;11)(p21-22;q23). The core binding factor leukemias with the translocations t(8;21)(q22;q22) and inv(16)(p13q22) occurred at incidences of 14% and 7%, respectively, predominantly in older children, and their prognosis was favorable. An adverse outcome was observed in patients with monosomy 7, abnormalities of 5q, and t(6;9)(p23;q34). Abnormalities of 3q and complex karyotypes, in the absence of favorable-risk features, have been associated with an adverse outcome in adults, but the results were not significant in this childhood series. However, the presence of 12p abnormalities predicted a poor outcome. Conclusion Because the spectrum of chromosomal changes and their risk association seem to differ between children and adults with AML, biologic differences are emerging, which will contribute to the redefinition of risk stratification for different age groups in the future.

Temporal Trends in the Proportion Cured Among Patients Diagnosed with Acute Myeloid Leukemia in Sweden 1973-2001, a Population-Based Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1378-1378
Author(s):  
Åsa Rangert Derolf ◽  
Therese M-L Andersson ◽  
Paul C Lambert ◽  
Sigurdur Y Kristinsson ◽  
Sandra Eloranta ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Patient Survival ◽  
Age Groups ◽  
Population Based ◽  
Age Group ◽  
Survival Times ◽  
Population Based Study ◽  
Cure Fraction ◽  
Acute Myeloid

Abstract Abstract 1378 Poster Board I-400 Background: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is rapidly fatal without specific therapy. In a recently published population-based study we showed large differences in 1- and 5-year relative survival in AML patients in Sweden depending on age at diagnosis and year of diagnosis[1]. Here we use an alternative approach to study patient survival that simultaneously estimates the proportion of patients cured from AML and the survival time of those patients that are not cured. The cure proportion provides a better estimate of long-term survival than 5-year survival and is therefore of direct interest to patients and health care professions. Methods: We conducted a population-based cohort study including 6,439 patients aged 19-79 diagnosed with AML in Sweden 1973 to 2001. Patients are considered statistically cured when, as a group, their mortality returns the level of a comparable general population. We estimated mixture cure fraction models that provide estimates of both the cure proportion and the distribution of survival times of the “uncured”. Age at diagnosis was classified into four categories 19-40, 41-60, 61-70 and 71-80 and year of diagnosis was modeled using restricted cubic splines. Results: During the first years of the study period the cure fraction was less than 5% for all age groups and the median survival time for “uncured” approximately 0.5 years or less. In 2000 the estimated cure proportion was 68% (95% CI 56%-77%) for the youngest age group, 32% (25-39%) for those aged 41-60, 8.4% (3.1-21%) for those aged 61-70 at diagnosis and 4.3% (2.3-8.1%) for the oldest age group. The estimated median survival times for “uncured” were 0.74 (0.43-1.26), 0.71 (0.53-0.97), 0.69 (0.51-0.95) and 0.37 (0.31-0.44) years respectively (Table 1). The improvement in survival manifested as longer survival among the uncured during the early calendar years but increases in the cure proportion were observed during later years. Conclusion: There are large differences in the proportion cured between the age groups. In younger patients the cure proportion has increased dramatically, while survival of the “uncured” actually decreased in the last time period. In the older age groups improvement is merely seen within the survival of the “uncured”. [1] Derolf AR, Kristinsson SY, Andersson TM-L, Landgren O, Dickman PW, Björkholm M. Improved patient survival for acute myeloid leukemia: A population-based study of 9,729 patients diagnosed in Sweden 1973-2005. Blood. 2009 Apr 16;113(16):3666-72. Disclosures: No relevant conflicts of interest to declare.

A national study of allogeneic stem cell transplantation for adults with acute myeloid leukemia: Do gender and age above 70 years matter?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19020-e19020
Author(s):  
Josephine Emole ◽  
Leyla Shune ◽  
Oleksandra Lupak ◽  
Ajoy Lawrence Dias
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hospital Mortality ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Age Groups ◽  
Age Group ◽  
Acute Myeloid

e19020 Background: Allogeneic stem cell transplantation (alloSCT) is increasingly being offered to older patients with acute myeloid leukemia (AML) due to availability of reduced-intensity conditioning regimens and better supportive care. Though studies have shown improving alloSCT survival outcomes in older age groups, it is still not known if older age confers higher mortality and morbidity during transplant hospitalization. We queried a national inpatient database to evaluate in-hospital mortality and resource utilization during alloSCT for AML in patients >70 years compared to a younger age group. Methods: We conducted a retrospective study of alloSCT for AML patients ≥ 18 years using the 2018 National Inpatient Sample database. Hospitalizations were selected using International Classification of Disease, tenth revision (ICD-10) codes. Demographics, comorbidities, transplant, and outcome variables were compared between a reference age group (18-70 years) and a comparator group (> 70 years). Study outcomes were in-hospital mortality, length of stay (LOS) and transplant complications. Regression models were fit to assess the association between predictors and outcomes. Results: During the study period, 2610 alloSCT met the inclusion criteria. This cohort consisted of 50% males and 77% Caucasians. Only 7% of these alloSCT were performed for patients > 70 years. Patients >70 yrs had a lower proportion of females compared to the reference age group (32% versus 52%, p<0.01). There were no significant differences in racial distribution, Charlson comorbidity index or median income between the 2 age groups. In-hospital mortality rates for the reference age group versus >70 years were 3% and 5% respectively (p=0.35). In a multivariable model, we found no association between age >70 years and in-hospital transplant mortality. Acute graft versus host disease was more frequent among the reference age group (14% versus 2%, p=0.04), but there were no differences in LOS or rates of graft failure, respiratory failure, sepsis, and acute renal failure between the 2 groups. Conclusions: Despite similar in-hospital transplant outcomes as their younger counterparts, patients >70 years comprised only a small proportion of alloSCT performed for AML in our study. Females were more disproportionately affected by this age disparity. More studies are necessary to identify barriers to alloSCT for older AML patients, more so for older females.

Defining the Genomic Make up of Acute Myeloid Leukemia in Adolescents and Young Adults (AYA): Report from COG AAML03P1, AAML531 and SWOG S0106

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2576-2576
Author(s):  
Fabiana Ostronoff ◽  
Todd A. Alonzo ◽  
Megan Othus ◽  
Matthew A. Kutny ◽  
Robert B. Gerbing ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Somatic Mutations ◽  
Disease Risk ◽  
Age Groups ◽  
Therapeutic Strategies ◽  
Age Group ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a genetically heterogeneous and highly resistant hematopoietic malignancy. Despite survival gains over the past several decades, adolescent and young adult (AYA) with AML demonstrate a consistent survival disadvantage as compared to younger patients (age < 15 years). This discrepancy in outcome is likely due to distinct aspects of disease biology in this patient population. In recent years several somatic mutations with biological, prognostic and therapeutic significance have been identified in patients with AML. Nonetheless, these studies have been conducted in pediatric and older adult patients only. Therefore, the prevalence of these somatic mutations remains largely unknown in AYA patients. Herein, we investigate the prevalence of common AML-associated mutations in AYA, here defined as age 15 to 39 years, aiming to characterize the disease and identify mutations that are relevant for therapeutic strategy in this age group. We compare the distribution of these mutations in the 3 age groups: children (age< 15 years), AYA (age 15 to 39 years) and older adults (age> 39 years). Patients enrolled in the COG trials AAML03P1 and AAML0531 and in the SWOG trial S0106 were eligible for this study. Acute promyelocytic leukemia patients were excluded. AAML03P1 enrolled patients 0 to 21 years, AAML0531 enrolled patients 0 to 30 years and S0106 enrolled patients 18 to 60 years of age. We analyzed 1722 patients (age range 0 to 60 years) with newly diagnosed AML. Pre-treatment samples were obtained from AAML03P1 and AAML531 (N=1361) and S0106 (N=361). Mutation analyses were performed by a combination of targeted capture and fragment length analysis. Chi-square test was used to compare variables. The prevalence of each mutation according to age groups is shown on Table 1. Similarly to what is observed in children and older adults, NPM1 and FLT3- ITD are the two most common mutations in AYA patients with a prevalence of 19% and 14%, respectively. When compared to the other age groups, we observe a significant increase in prevalence of both FLT3- ITD and NPM1 with aging, with a significant higher prevalence of these mutations in older adults as compared to AYA and children. Previous studies have shown that mutations in epigenetic modifier genes are enriched in adults with AML as compared to pediatric patients. We evaluated the prevalence of mutations in these genes in the 3 age groups. We observed a significant increase in prevalence in mutations in all epigenetic modifiers genes with aging (Table 1). The combined prevalence of mutation in these genes (IDH1, IDH2, DNMT3A, ASXL1 and IDH1/2) in children, AYA and older adults were 9%, 19% and 39% (P< 0.0001), respectively, highlighting the clinical and biological importance of this class of genes in older patients. In this large collaborative study, we define for the first time the prevalence of common mutations in AYA with AML. Our study shows that the genomic make up of patients with AYA are different from children and older adults, suggesting unique biology of the disease in this age group. Our data raise questions about future therapeutic strategies, which should take into account the age distribution of these genetic lesions. Finally, clinical correlations to determine the prognostic significance of these mutations in AYA are underway and should provide a framework for future disease risk stratification in this age group. In summary, our data shows the distinct genomic profiling of common mutations in AYA, arguing for age specific disease risk stratification as well as therapeutic strategies in this age group. Table 1. Prevalence of common mutations in children, adolescents and young adults (AYA) and older adults with AML Children (<15 years) AYA (15-39 years) Older adults (>40 years) P value FLT3-ITD 13% 19% 23% 0.0006 NPM1 6% 14% 32% < 0.00001 CEBPA 5% 8% 3% 0.02 WT1 6% 9% 5% 0.154 IDH1/2 3% 7% 17% < 0.00001 DNMT3A 0% 2% 16% < 0.00001 ASXL1 2% 4% 7% 0.007 TET2 4% 7% 11% 0.002 Disclosures Radich: Novartis: Consultancy, Research Funding; Incyte: Consultancy; Gilliad: Consultancy; Ariad: Consultancy. Erba:GlycoMimetics; Janssen: Other: Data Safety & Monitoring Committees; Sunesis; Pfizer; Daiichi Sankyo; Ariad: Consultancy; Millennium/Takeda; Celator; Astellas: Research Funding; Seattle Genetics; Amgen: Consultancy, Research Funding; Novartis; Incyte; Celgene: Consultancy, Patents & Royalties.

An Unusual Case Of Disseminated Histiocytic Sarcoma Preceded By Myeloid Sarcoma With Concomitant Acute Myeloid Leukemia

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S107-S108
Author(s):  
A C Reddy ◽  
K S Reddy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Neck Mass ◽  
Histiocytic Sarcoma ◽  
Myeloid Sarcoma ◽  
Monocytic Differentiation ◽  
Tissue Samples ◽  
Disseminated Disease ◽  
Acute Myeloid

Abstract Introduction/Objective Histiocytic sarcoma (HS) is rare (&lt;1% of hematolymphoid neoplasms), and can present extranodally as disseminated disease. Immunophenotypically, the cells express CD163, CD68, lysozyme and CD45. HS often occurs as a secondary event following B-cell lymphomas, acute lymphoblastic leukemia or acute myeloid leukemia (AML) typically with monocytic differentiation retaining the same molecular/cytogenetic abnormalities as the primary tumor. Results Our patient, a 47 year old male was diagnosed with myeloid sarcoma (MS) following FNA of a new neck mass. A bone marrow biopsy revealed AML without monocytic differentiation. Flow cytometric findings of both marrow and neck mass were similar (positive for CD34, CD117, CD33, CD11b, CD13, CD15, CD64, CD7; negative for CD4, CD14, CD56). Karyotypic and FLT3 ITD mutation analysis were normal. CNS involvement was diagnosed 2 months later, while a marrow biopsy (status post therapy) confirmed resolution of AML. A hypermetabolic left perinephric mass noted by PET CT, when biopsied, showed large epithelioid polygonal cells with amphophilic cytoplasm and atypical vesicular nuclei (positive for CD68, PU.1; negative for LCA, CD163, CD34, CD4, pankeratin). A diagnosis of atypical epithelioid neoplasm suggestive of HS was rendered, although negativity for LCA and CD163 was unusual. No treatment was given for HS. A month later, the patient presented with a cheek mass diagnosed again as being suggestive of HS. His AML also relapsed. Next-generation sequencing (37 genes including BRAF) from both marrow and tissue samples detected the presence of a nonsense mutation in exon 7 of WT1 (p.Ser169). Conclusion Our case appears to be the first reported one of disseminated HS preceded by MS and concomitant AML, lacking monocytic differentiation. The findings overall support the hypothesis of origin as being from a common progenitor cell differentiating along both myeloid and histiocytic/other cell lineages at different time points.

scholarly journals The specific distribution pattern of IKZF1 mutation in acute myeloid leukemia

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiang Zhang ◽  
Xuewu Zhang ◽  
Xia Li ◽  
Yunfei Lv ◽  
Yanan Zhu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Genetic Alteration ◽  
Missense Mutations ◽  
Nonsense Mutations ◽  
Specific Distribution ◽  
Aggressive Clinical Course ◽  
Acute Myeloid

Abstract IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-alleleCEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.

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