Evaluation of seasonal changes in the diagnosis of acute leukemia in Turkey

Objective: The etiology of acute leukemia (AL) has been under investigation for decades but the exact cause is still unknown. There are studies suggesting that infection plays a critical role in the development of AL in conjunction with other risk factors. In some studies, it has been shown that the incidence of AL increases after influenza endemics. This shows that viruses may play a role in the etiology. The theory that viruses might have a role in the etiopathogenesis created the idea that AL frequency may peak during some specific months; therefore, in this study, we aimed to research the relationship between AL diagnosis frequency and seasons in Turkey. Method: 186 patients who were diagnosed with de novo acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) diagnosis at our center were included in the study. Results: The frequency of ALL diagnoses were as follows: 25 (34.3%) in winter, 19 (26%) in spring, 15 (20.5%) in autumn, and 14 (19.2%) in summer. The frequency of AML diagnose was as follows: 24 (21.2%) in winter, 30 (26.6%) in spring, 27 (23.8%) in autumn and 32 (28.4%) in summer. In our study, we did not find a statistically significant relationship between AL diagnosis frequency and seasons. Conclusion: According to our literature review, there are two studies including our study, searching for a relationship between AL diagnosis frequency and seasons in Turkey. Neither of the studies found a relationship between AL and seasons. According to our analysis the numbers of the patient in studies are limited; therefore the studies with high number of patients are needed to find out a relation between seasons and diagnosis time of AL.

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Spinal Cord Compression in Patients with Acute Myeloid and Lymphoid Leukemia

Blood ◽

10.1182/blood-2020-137446 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 26-27

Author(s):

Shehab Fareed Mohamed ◽

Elabbass Abdelmahmuod ◽

Elrazi Awadelkarim A Ali ◽

Abdulqadir Jeprel Nashwan ◽

Dina Sameh Soliman ◽

...

Keyword(s):

Spinal Cord ◽

Acute Myeloid Leukemia ◽

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Spinal Cord Compression ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Cord Compression ◽

Myeloid Sarcoma ◽

Acute Myeloid

Introduction Acute leukemias can be divided into acute myeloid leukemia and acute lymphoblastic leukemia. Common presentations of acute leukemia include fever, symptoms of anemia, bleeding, bone pain palpable Lymph nodes or spleen and symptoms due inflation or leukocystasis. Extramedullary mass is rare and can be of myeloid tissue and known as Chloroma or myeloid (granulocytic) sarcoma which one of the WHO classifications for acute myeloid leukemia. Common sites of occurrence are skin, sinuses, bone and other. It's rarely involve central nervous system. Spinal cord involvement usually manifest as epidural mass causing cord compression. Spinal epidural tumor with acute leukemia and myeloid sarcoma is rare and can be found in 3-9% in patients with leukemia. In this review we decide to review the cases of spinal cord compression caused by acute myeloid leukemia (including Chloroma) and acute lymphoblastic leukemia due to the significance of such presentation in addition to reports that Myeloid sarcoma of the spine has very poor prognosis Methodology: We have reviewed the literature using: PubMed, google scholar, Scopus for patient with spinal cord compression and acute leukemia. We used the search term and synonyms : : acute myeloid leukemia , acute myelocytic leukemia , acute monocytic leukemia , acute lymphoblastic leukemia , acute lymphoid leukemia, chloroma , myeloid sarcoma ,granulocytic sarcoma, spinal cord compression .We included adult patients above 18 years old only cases we exclude pediatrics cases and cases of chronic leukemia's and other myeloproliferative disorders as well as cases of central nervous system involvement other than spinal cord Results We gathered the information from 98 cases with general demographics, presentation, image modality, cytogenetics and molecular in addition to management and outcome. We have found mean age for the patients is 38 years old with male predominance with 70% of the cases. The most presenting symptom was back pain in around 75% of the cases. Neurological findings showed sensory loss and parapreresis in most of the documented cases. MRI was most performed modality of imaging 63% followed by Computed tomography(CT) 15 % and then myelogram 13 %, which is least used due to invasive nature and before the era of MRI. The most common affected site on spinal cord were thoracic followed by lumbar. Cytogenetics and molecular data was not reported in most of the cases. Patients were treated with either steroids or surgery or radiotherapy and or chemotherapy while few underwent bone marrow transplant, but the most common approach was surgery+ radiotherapy + chemotherapy combination. Steroids used in most of the cases especially in the cases of acute lymphoblastic leukemia and dexamethasone was the steroids of the choice mainly. The outcome of the patients were variable, 30 % were alive at the time of the reports 30 % died and 30 % between relapse and complete remission. Conclusions Acute leukemia can be presented as mass causing spinal cord compression which is very serious. There are is no standardized management of patients with acute leukemia who presented with spinal cord compression nether guidelines or steps to follow. Some reports speculated also specific morphology and cytogenetics association with predisposition to have Extramedullary mass, however there lack of reporting of such a valuable information. Large studies including all adjusted variables required to determine if spinal cord compression presentation can be an independent risk facto or not Effective diagnosis and prompt action should take place. Figure Disclosures No relevant conflicts of interest to declare.

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De novo acute myeloid leukemia risk factors

Cancer ◽

10.1002/cncr.27442 ◽

2012 ◽

Vol 118 (18) ◽

pp. 4589-4596 ◽

Cited By ~ 26

Author(s):

Sara S. Strom ◽

Robert Oum ◽

Kplola Y. Elhor Gbito ◽

Guillermo Garcia-Manero ◽

Yuko Yamamura

Keyword(s):

Risk Factors ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Acute Myeloid

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Acute Leukemia

10.2310/im.1247 ◽

2016 ◽

Author(s):

Richard A. Larson ◽

Roland B Walter

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Myeloid Leukemia ◽

Who Classification ◽

Lymphoblastic Leukemia ◽

World Health ◽

Acute Leukemias ◽

Acute Myeloid

The acute leukemias are malignant clonal disorders characterized by aberrant differentiation and proliferation of transformed hematopoietic progenitor cells. These cells accumulate within the bone marrow and lead to suppression of the production of normal blood cells, with resulting symptoms from varying degrees of anemia, neutropenia, and thrombocytopenia or from infiltration into tissues. They are currently classified by their presumed cell of origin, although the field is moving rapidly to genetic subclassification. This review covers epidemiology; etiology; classiﬁcation of leukemia by morphology, immunophenotyping, and cytogenetic/molecular abnormalities; cytogenetics of acute leukemia; general principles of therapy; acute myeloid leukemia; acute lymphoblastic leukemia; and future possibilities. The figure shows the incidence of acute leukemias in the United States. Tables list World Health Organization (WHO) classification of acute myeloid leukemia and related neoplasms, expression of cell surface and cytoplasmic markers for the diagnosis of acute myeloid leukemia and mixed-phenotype acute leukemia, WHO classification of acute lymphoblastic leukemia, WHO classification of acute leukemias of ambiguous lineage, WHO classification of myelodysplastic syndromes, European LeukemiaNet cytogenetic and molecular genetic subsets in acute myeloid leukemia with prognostic importance, cytogenetic and molecular subtypes of acute lymphoblastic leukemia, terminology used in leukemia treatment, and treatment outcome for adults with acute leukemia. This review contains 1 highly rendered figure, 9 tables, and 117 references.

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Uncommon CD markers in acute myeloid leukemia

Bangabandhu Sheikh Mujib Medical University Journal ◽

10.3329/bsmmuj.v11i4.37281 ◽

2018 ◽

Vol 11 (4) ◽

pp. 267-269

Author(s):

Azad Abul Kalam ◽

Md. Rafiquzzaman Khan ◽

A. B. M. Hassan Habib ◽

Masuda Begum

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Leukemia ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Color Flow ◽

Mixed Phenotype Acute Leukemia ◽

International Data ◽

Mixed Phenotype ◽

Cd Markers ◽

Acute Myeloid

This study was done to assess the unusual CD expression in 100 cases of acute myeloid leukemia from October 2016 to April 2018. The age limit was from 3 to 50 years. Four color flow cytometry was used to diagnose the fresh aspirated bone marrow or peripheral blood sample of acute leukemia. The unusual lymphoid CD expression on myeloblasts was analyzed. Among the cases, 44% were acute myeloid leukemia, 52% of patients were of acute lymphoblastic leukemia and mixed phenotype acute leukemia was 4%. Aberrant CD expression was observed in 58% acute myeloid leukemia patients. Both aberrant CD5 and CD7 lymphoid markers expressed in acute myeloid leukemia patients were 4.2%. Aberrant CD7, CD5, cCD79a and cCD3 were in 45.8%, 33.3%, 8.3%, 8.3% of acute myeloid leukemia patients respectively. In acute myeloid leukemia, the frequency of aberrant CD expression was compared with recent international data.

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HRX involvement in de novo and secondary leukemias with diverse chromosome 11q23 abnormalities [see comments]

Blood ◽

10.1182/blood.v81.12.3197.3197 ◽

1993 ◽

Vol 81 (12) ◽

pp. 3197-3203 ◽

Cited By ~ 113

Author(s):

SP Hunger ◽

DC Tkachuk ◽

MD Amylon ◽

MP Link ◽

AJ Carroll ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Topoisomerase Ii ◽

De Novo ◽

Lymphoblastic Leukemia ◽

Myelogenous Leukemia ◽

Chromosome Band ◽

11Q23 Abnormalities ◽

Acute Myeloid ◽

Secondary Leukemias

Abstract Chromosome band 11q23 is a site of recurrent translocations and interstitial deletions in human leukemias. Recent studies have shown that the 11q23 gene HRX is fused to heterologous genes from chromosomes 4 or 19 after t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations to create fusion genes encoding proteins with structural features of chimeric transcription factors. In this report, we show structural alterations of HRX by conventional Southern blot analyses in 26 of 27 de novo leukemias with cytogenetically diverse 11q23 abnormalities. The sole case that lacked HRX rearrangements was a t(11;17)-acute myeloid leukemia with French-American-British M3-like morphology. We also analyzed 10 secondary leukemias that arose after therapy with topoisomerase II inhibitors and found HRX rearrangements in 7 of 7 with 11q23 translocations, and in 2 of 2 with unsuccessful karyotypes. In total, we observed HRX rearrangements in 35 leukemias involving at least nine distinct donor loci (1q32, 4q21, 6q27, 7p15, 9p21–24, 15q15, 16p13, and two 19p13 sites). All breakpoints localized to an 8-kb region that encompassed exons 5–11 of HRX, suggesting that fusion proteins containing similar portions of HRX may be consistently created in leukemias with 11q23 abnormalities. We conclude that alteration of HRX is a recurrent pathogenetic event in leukemias with 11q23 aberrations involving many potential partners in a variety of settings including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia in blast crisis, and topoisomerase II inhibitor- induced secondary leukemias of both the myeloid and lymphoid lineages.

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Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43

Cancers ◽

10.3390/cancers11091253 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1253 ◽

Cited By ~ 4

Author(s):

Caroline Spertini ◽

Bénédicte Baïsse ◽

Marta Bellone ◽

Milica Gikic ◽

Tatiana Smirnova ◽

...

Keyword(s):

Acute Leukemia ◽

Vascular Endothelium ◽

Lymphoblastic Leukemia ◽

Critical Role ◽

Leukemia Cell ◽

Hematologic Malignancies ◽

Selectin Ligands ◽

Blast Cells ◽

Acute Myeloid

Acute myeloid and lymphoblastic leukemia are poor prognosis hematologic malignancies, which disseminate from the bone marrow into the blood. Blast interactions with selectins expressed by vascular endothelium promote the development of drug resistance and leukostasis. While the role of selectins in initiating leukemia blast adhesion is established, our knowledge of the involved selectin ligands is incomplete. Using various primary acute leukemia cells and U937 monoblasts, we identified here functional selectin ligands expressed by myeloblasts and lymphoblasts by performing biochemical studies, expression inhibition by RNA interference and flow adhesion assays on recombinant selectins or selectin ligands immunoadsorbed from primary blast cells. Results demonstrate that P-selectin glycoprotein ligand-1 (PSGL-1) is the major P-selectin ligand on myeloblasts, while it is much less frequently expressed and used by lymphoblasts to interact with endothelial selectins. To roll on E-selectin, myeloblasts use PSGL-1, CD44, and CD43 to various extents and the contribution of these ligands varies strongly among patients. In contrast, the interactions of PSGL-1-deficient lymphoblasts with E-selectin are mainly supported by CD43 and/or CD44. By identifying key selectin ligands expressed by acute leukemia blasts, this study offers novel insight into their involvement in mediating acute leukemia cell adhesion with vascular endothelium and may identify novel therapeutic targets.

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Assessment of Serum IL-15 in Adult Acute Leukemia Patients

QJM ◽

10.1093/qjmed/hcaa052.065 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

M M Moussa ◽

E A Abdelhady ◽

M A Shazly ◽

N H Abdallah ◽

M S Sheeba

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Leukemia ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

High Serum ◽

Newly Diagnosed ◽

Control Subjects ◽

Interleukin 15 ◽

Average Serum ◽

Acute Myeloid

Abstract Background Interleukin 15 (IL-15), a proinflammatory cytokine, regulates the functions of the immune system and controls the differentiation of hematopoietic cells. However, it may also promote the development of leukemia through its role in enhancing the survival, proliferation and differentiation of leukemic precursors. Aim of the work To assess expression of IL-15 level in adult Egyptian acute leukemia patients, its correlation with disease free survival, overall survival and relapse rate, as well as its possible correlation with other prognostic parameters. Patients and methods Serum IL-15 level was measured using enzyme-linked immunosorbent assay in 30 newly diagnosed acute lymphoblastic leukemia (ALL) patients, 30 newly diagnosed acute myeloid leukemia (AML) patients and 30 age and sex-matched healthy control subjects. The patients were recruited from clinical hematology department at Ain shams university hospital over the period from April 2017 to October 2018. Results In ALL patients: The serum IL-15 level was higher in ALL patients compared to control subjects (P = 0.015). Patients with ALL with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P = 0.005). In AML patients: The serum IL-15 level was higher in AML patients compared to control subjects (P = 0.010). Patients with AML with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P < 0.001). Serum IL15 level has negative correlation with the date of death in patients with AML (P = 0.001). Conclusion Interleukin 15 (IL-15) is a useful poor prognostic marker in patients with newly diagnosed acute leukemia, also it can be used as a predictor for survival. Abbreviations AML (acute myeloid leukemia), ALL (acute lymphoblastic leukemia), IL-15 (Interleukin 15).

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The Reliability and Specificity of c-kit for the Diagnosis of Acute Myeloid Leukemias and Undifferentiated Leukemias

Blood ◽

10.1182/blood.v92.2.596 ◽

1998 ◽

Vol 92 (2) ◽

pp. 596-599 ◽

Cited By ~ 134

Author(s):

M.C. Bene ◽

M. Bernier ◽

R.O. Casasnovas ◽

G. Castoldi ◽

W. Knapp ◽

...

Keyword(s):

Acute Leukemia ◽

De Novo ◽

Lymphoblastic Leukemia ◽

Cell Lineage ◽

Specific Marker ◽

Acute Leukemias ◽

Routine Basis ◽

Immunological Classification ◽

B Lineage ◽

Acute Myeloid

Abstract We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819 acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4 undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of the French-American-British (FAB) subtype, one third of BAL, all four AUL, but only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified as: T-cell lineage (two thirds), mainly pro-T–ALL or T-I, and B lineage (one third); cells from 62% of these ALL cases coexpressed other myeloid markers (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML or ALL cases according to age being similar in the adult and pediatric groups. Our findings demonstrate that c-kit is a reliable and specific marker to detect leukemia cells committed to the myeloid lineage, and therefore should be included in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid commitment of the blasts. c-kit expression should score higher, at least one point, in the system currently applied to the diagnosis of BAL, as its myeloid specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c-kit identifies a subgroup of cases, which may correspond to leukemias either arising from early prothymocytes and/or early hematopoietic cells, both able to differentiate to the lymphoid and myeloid pathways.

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Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA)

Blood ◽

10.1182/blood-2002-03-0990 ◽

2002 ◽

Vol 100 (8) ◽

pp. 2717-2723 ◽

Cited By ~ 370

Author(s):

Claude Preudhomme ◽

Christophe Sagot ◽

Nicolas Boissel ◽

Jean-Michel Cayuela ◽

Isabelle Tigaud ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Prognostic Significance ◽

Prognosis Factor ◽

Cebpa Mutations ◽

Factor C ◽

French Association ◽

Acute Myeloid

The transcription factor C/EBPα is crucial for differentiation of mature granulocytes. Recently, differentCEBPA gene mutations likely to induce differentiation arrest have been described in nearly 10% of patients with acute myeloid leukemia (AML). In the present study, we retrospectively analyzed the prognostic significance of CEBPA mutations in 135 AML patients (French-American-British [FAB]-M3 excluded). All patients were prospectively enrolled between 1990 and 1996 in a multicenter trial of the ALFA (Acute Leukemia French Association) Group (median age 45 years, median follow-up 5.7 years). Mutations were assessed using direct sequencing of the CEBPA gene. Twenty-two mutations were found in 15 (11%) of 135 patients tested. Twelve patients had at least one mutation located in the N-terminal part of the protein leading to the lack of expression of the full-length C/EBPα protein. CEBPA mutations were present only in patients belonging to the intermediate cytogenetic risk subgroup and associated with the FAB-M1 subtype (P = .02). FLT3 internal tandem duplication (ITD) was found in 5 of 15 CEBPA-mutated as compared with 30 of 119 CEBPA-nonmutated cases tested (P = .54). Presence of CEBPA mutations was identified as an independent good prognosis factor for outcome even after adjustment on cytogenetics and FLT3 status (estimated 5-year overall survival 53% vs 25%, P = .04).FLT3-ITD appeared to act as a major bad prognosis factor in patients with CEBPA-mutated AML. We thus propose a risk classification that includes in the favorable subgroup all patients from the intermediate subgroup displaying CEBPA mutations when not associated with FLT3-ITD.

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Acute Myeloid Leukemia with Coexpression of Lymphoid-Associated Antigens: Clinicobiological Associations and Prognostic Implications,

Blood ◽

10.1182/blood.v118.21.3596.3596 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3596-3596

Author(s):

Georgia Voutiadou ◽

Konstantina Kotta ◽

Barbara Tachynopoulou ◽

Apostolia Papalexandri ◽

Chryssanthi Vadikolia ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Critical Role ◽

Flow Cytometric Analysis ◽

Prognostic Impact ◽

Prognostic Implications ◽

Cytogenetic Profile ◽

De Novo Aml ◽

Acute Myeloid

Abstract Abstract 3596 Immune phenotyping plays a critical role in the diagnosis and classification of acute leukemia. Several studies have reported a variable proportion of patients with acute myeloid leukemia (AML) expressing lymphoid-associated antigens (LAA). The exact frequency and true clinical significance of this phenomenon remains undefined due to inconsistencies between series, likely related to methodological aspects or potential case selection biases. We retrospectively evaluated the expression of LAA in blast cells from 278 consecutive and unselected patients with AML diagnosed in our Department between 2002 and 2010. The patient cohort included 168 males and 110 females with a median age of 61 years (range, 10–88); 146/278 cases were above the age of 60. Within this cohort, 190 cases (68%) had de novo AML, whereas the remaining 88 cases (32%) concerned secondary AML (sAML) to either MDS (n=80) or other non-hematologic malignancies (n=8). Patients were treated uniformly according to age with Aracytin/Idarubicin induction regimens (“3+7” or “2+5” for ages \q60 or ≥60, respectively). The immunophenotype was determined by flow cytometric analysis of (mainly) bone marrow aspirate and/or peripheral blood samples utilizing a primary CD45/side scatter (SSC) gating procedure with antibodies against CD7, CD13, CD19, CD33, CD4, CD10, CD34, CD117, CD64, HLA-DR, CD20, CD2, CD15, CD56, CD14, CD8, MPO, CD3, CD79a, CD22, TdT and lysozyme; a cut-off value for positivity of 20% was adopted. Overall, we identified 153/278 cases (55%) expressing at least one LAA. The most commonly expressed LAAs were CD4 (outside AML with monocytic differentiation), CD56, CD7, CD2, CD10 and CD79a (in 39%, 33%, 29%, 14%, 10% and 8% of LAA+ AML cases, respectively); interestingly, all CD79a-positive cases co-expressed at least one more LAA. A significant association was identified between LAA expression and cytogenetic profile: in particular, at least one LAA was detected in 37/50 cases (74%) with adverse cytogenetics (SWOG unfavorable and/or monosomal karyotype), compared to 24/41 (58%) cytogenetically favorable cases and 68/134 (51%) cytogenetically intermediate risk cases (p=0.01). No other statistically significant associations were found for LAA expression (positive vs. negative) in respect to age and complete remission (CR) rate. Furthermore, the frequency of LAA-positive cases was identical (55%) in both de novo AML (105/190 cases) and sAML (48/88 cases). Monoparametric statistical analysis was also performed individually for each of the six more frequent LAAs. Significant associations (p<0.05) were identified between: (i) CD7 expression and adverse cytogenetics; (ii) CD10 expression and adverse cytogenetics as well as failure to achieve CR, at both cohort level as well as patients \q60 years with de novo AML; and (iii) CD2 expression and shorter overall and disease-free survival (DFS and OS, respectively). Cox-multivariate analysis identified CD2 expression in addition to advanced age, sAML and adverse cytogenetic profile as negative prognostic indicators (p=0.05) for both DFS and OS. In conclusion, expression of LAAs is frequent in AML, among both de novo AML and sAML cases, and significantly associated with adverse cytogenetics. Although the negative prognostic impact of CD2 expression is noteworthy, however, the precise prognostic implications of the expression of individual LAAs are hard to define on single institution retrospective series and will require evaluation in large prospective and well-controlled studies. Disclosures: No relevant conflicts of interest to declare.

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