scholarly journals Pattern of childhood acute leukemia presentation at a tertiary hospital in Nigeria: a five-year review

2018 ◽  
Vol 5 (6) ◽  
pp. 2123
Author(s):  
Adewumi B. Oyesakin ◽  
Vincent E. Nwatah ◽  
Nwankwo U. Ukpai ◽  
Ekaette I. David ◽  
Tamunomieibi T. Wakama ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Clinical Features ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Tertiary Hospital ◽  
Cross Sectional ◽  
Acute Leukemias ◽  
Lost To Follow Up

Background: Acute leukemia is the most common childhood malignancy but its occurrence in low- and middle-income countries are under-reported. Its pattern of presentation varies depending on several factors. The objective of this report is to determine the pattern of presentation of acute leukemias in children at a tertiary hospital in Nigeria.Methods: A retrospective cross-sectional study of children managed for acute leukemia at the Paediatric Department in a 5-year period. Of 31 patients, 27 had adequate records, which were reviewed. Data collected include patient’s demographics, clinical features and treatment outcome.Results: There were 16 males and 11 females, aged 8 months to 16 years (mean 7.45 years ±4.75 SD). The pattern of clinical features were fever (85.2%), pallor (92.6%) and splenomegaly (51.9%). The specific leukemia type ratio for Acute Myeloid leukemia (AML) and Acute lymphoblastic leukemia (ALL) was 1: 2.9. The parents of three patients took their children away before commencement of treatment, one patient completed treatment and 6 (22.2%) died before completing treatment. Nearly half of the patients were lost to follow up to seek alternative care while 9 (33.3%) of the patients were in remission at last follow up. Lost to follow-up was found not to be significantly associated with socioeconomic status, age and sex respectively.Conclusions: Acute lymphoblastic leukemia remains the predominant type of childhood leukemia in our setting. Majority of the patients presented with fever and pallor moreover the default to follow-up plagues treatment completion.

scholarly journals Acute leukemia of childhood: A single institution's experience

2005 ◽  
Vol 57 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Bojana Slavkovic ◽  
Marija Guc-Scekic ◽  
Gordana Bunjevacki ◽  
S. Djuricic ◽  
Aleksandra Krstic ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Rearrangements ◽  
Age Distribution ◽  
Normal Karyotype ◽  
Mediterranean Countries ◽  
B Lineage ◽  
Childhood Acute Leukemia

The aim of this study was to investigate distribution of immunophenotypic and cytogenetic features of childhood acute leukemia (AL) in the cohort of 239 newly diagnosed patients registered at the leading pediatric oncohematology center in the country during a six-year period (1996-2002). With approximately 60-70% of all childhood AL cases in Serbia and Montenegro being diagnosed and treated in this institution the used data represent a valid research sample to draw conclusions for entire country. On the basis of five phenotypic markers, the distribution of immunological subtypes was as follows: 169 (70.7%) expressed B-cell marker CD19 (137 were CD10 positive and 32 CD10 negative), 37 (15.5%) belonged to T-lineage acute lymphoblastic leukemia (T-ALL) (cyCD3 positive), and 33 (13.8%) were acute myeloblastic leukemia (AML) (CD13 positive and/or CD33 positive in the absence of lymphoid-associated antigens). The ratio of males and females was 1.5:1. Most of the cases were between the ages of 2 and 4, and were predominantly B-lineage acute lymphoblastic leukemia (B-ALL) cases. Another peak of age distribution was observed at the age of 7. The frequency of T-ALL (18% of ALL) was similar to that reported for Mediterranean countries: France (19.4%), Greece (28.1%), Southern Italy (28.3%), and Bulgaria (28.0%). Cytogenetic analyses were performed in 193 patients: 164 ALL and 29 AML. Normal karyotype was found in 57% of ALL and in 55% of AML patients, while cytogenetic abnormalities including structural, numerical, and complex chromosomal rearrangements were found in 43% of ALL and in 45% of AML patients. Our results represent a contribution to epidemiological aspects of childhood leukemia studies.

Clinical Features of DIC According to the French-american-british (FAB) Classification in Patients With Acute Leukemia and Thrombomodulin Alfa Treatment – Cross-sectional Analysis of a Post-marketing Surveillance Study Cohort –

2021 ◽  
Author(s):  
Yoshinobu Seki ◽  
Goichi Honda ◽  
Noriaki Kawano ◽  
Toshimasa Uchiyama ◽  
Kazuo Kawasugi ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Clinical Features ◽  
Lymphoblastic Leukemia ◽  
Study Cohort ◽  
Cross Sectional ◽  
Safety And Efficacy ◽  
Post Marketing Surveillance ◽  
Fab Classification ◽  
Post Marketing ◽  
French American British

Abstract Background: The aims of this study were to analyze the clinical features of a large number of cases with disseminated intravascular coagulation (DIC) associated with acute leukemia, and to clarify the safety and efficacy of thrombomodulin alfa (TM-α) using the French-American-British (FAB) classification of hematological malignancies.Methods: We retrospectively examined 644 patients with acute leukemia in post-marketing surveillance for TM-α.Results: M3, M2, M4, M1, and M5 subtypes of acute myeloid leukemia (AML), and L2 and L1 subtypes of acute lymphoblastic leukemia (ALL) have been found more frequently among patients with DIC. Bleeding symptoms at baseline were more frequent in M3 and M7 subtypes. Fibrinogen concentrations were lower and plasmin-plasmin inhibitor complex values were higher in M3 and Philadelphia-positive (Ph+) ALL. Overall DIC resolution rate was 60.2% with higher rates in L1 and Ph+ ALL, lower in M1, and generally higher in ALL than in AML. The overall survival rate was 79.8%, generally high, with higher survival rates in L3, Ph+ ALL, and M3. In M3 and M7, with high frequencies of pre-existing bleeding, TM-α improved bleeding symptoms. Post-administration DIC scores in each subtype were significantly improved compared with pre-administration scores, except in M6, M7, and MDS-overt AML.Conclusions: This study showed the clinical features of DIC associated with acute leukemia among FAB classifications and also elucidated the safety and efficacy profiles of TM-α by detailed classification based on the FAB classification in clinical practice.Trial registration: The clinical characteristics and treatment outcomes of patients with DIC treated with TM-α between May 2008 and April 2010 were retrospectively analyzed by subgroup analysis of post-marketing surveillance data.

Acute Leukemia

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.

scholarly journals Clonal Evolution of B-Cell Acute Lymphoblastic Leukemia with del(9)(p13p21) into Mixed Phenotype Acute Leukemia Presenting as an Isolated Testicular Relapse

Reports ◽  
2019 ◽  
Vol 2 (3) ◽  
pp. 18 ◽  
Author(s):  
Miller ◽  
Park ◽  
Saxe ◽  
Lew ◽  
Raikar
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Acute Leukemias ◽  
Cytogenetic Aberrations ◽  
Mixed Phenotype Acute Leukemia ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Mixed Phenotype

Lineage switch in acute leukemias is a well-reported occurrence; however, most of these cases involve a switch from either lymphoid to myeloid or myeloid to lymphoid lineage. Here, we report a case of a 14-year-old male with B-cell acute lymphoblastic leukemia (B-ALL) who initially responded well to standard chemotherapy but then later developed mixed phenotype acute leukemia (MPAL) at relapse, likely reflecting a clonal evolution of the original leukemia with a partial phenotypic shift. The patient had a del(9)(p13p21) in his leukemia blasts at diagnosis, and the deletion persisted at relapse along with multiple additional cytogenetic aberrations. Interestingly, the patient presented with an isolated testicular lesion at relapse, which on further analysis revealed both a lymphoid and myeloid component. Unfortunately, the patient did not respond well to treatment at relapse and eventually succumbed to his disease. To our knowledge, an isolated extramedullary MPAL at relapse in a patient with previously diagnosed B-ALL has not been reported in the literature before.

scholarly journals Biology of t(6;11) Fusion Proteins and Their Role in MLL-Rearranged Acute Leukemia Lineage Determination

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5033-5033
Author(s):  
Arpita Kundu ◽  
Eric Kowarz ◽  
Jennifer Reis ◽  
Rolf Marschalek
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Acute Leukemia ◽  
Fusion Proteins ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Translocation ◽  
Fusion Genes ◽  
Disease Phenotype ◽  
Acute Leukemias

Chromosomal translocations are genetic rearrangements where a chromosomal segment is transferred to a non-homologous chromosome which give rise to novel chimeras. Chromosomal rearrangements play a significant role in the development of acute leukemias (acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML)). Chromosomal translocation events occurring at 11q23 involving the KMT2A or Mixed-Lineage Leukemia (MLL) gene (n=102) can be diagnosed in about 5-10% of all acute leukemia patients (Marschalek Ann Lab Med 2016), especially prevalent in infant acute leukemias (up to 70% of cases). Different chromosomal translocation partner genes (such as AF4, AF6, AF9orENL and ELL) account for the majority of leukemia cases and have their genomic breakpoints within a major breakpoint cluster region (BCR intron 9-11; Meyer et. al. Leukemia 2018). Some rearrangements are specifically associated with particular disease phenotype e.g. the majority of ALL patients (~ 90%) are mainly caused by the following gene fusions, MLL-AF4, MLL-AF9, MLL-ENL. We are interested in a rare but yet drastic chromosomal translocation t(6;11)(q27;q23) which fuses KMT2A/MLL to Afadin (AFDN/AF6) gene. This chromosomal rearrangement has a very poor prognosis (survival-rate is ~10%) and is predominantly diagnosed in patients with high-risk AML. In this project, we investigate the molecular consequences of two different MLL-AF6 fusions and their corresponding reciprocal AF6-MLL fusions. MLL-AF6 fusions are mainly occurring within MLL intron 9 to 11 and are associated with an AML disease phenotype, while the same fusion occurring within the minor breakpoints region in MLL intron 21 until exon (ex) 24 are mainly diagnosed with T-ALL (T-cell acute lymphoblastic leukemia) disease phenotype. The molecular mechanism that determines the resulting disease phenotype is yet unknown. Therefore, we cloned all of these t(6;11) fusion proteins in order to investigate the functional consequences of the two different breakpoints (MLLex1-9::AF6ex2-30, AF6ex1::MLLex10-37; MLLex1-21::AF6ex2-30, AF6ex1::MLLex22-37). All 4 fusion genes were introduced into our inducible Sleeping Beauty system (Ivics et. al. Mobile DNA 2010; Kowarz et. al. Biotechnol J. 2015) and stably transfected reporter cell lines. Basically, these 4 fusion proteins differ only in the presence or absence of their Plant homeodomain 1-3/Bromodomain (PHD1-3/BD) domain (see Figure 1). The PHD domain regulates the epigenetic and transcriptional regulatory functions of wildtype MLL. Subsequently, we analyzed gene expression differences by the MACE-Seq (Massive Analyses of cDNA Ends). MACE data revealed fundamental differences in gene expression profiles when analyzing the two different sets of t(6;11) fusion genes. The resulting profiles have similarities to either AML or T-ALL and might give a rational explanation for the different lineages in these t(6;11) patients. Altogether, these results notably indicate that our study will provide a novel insight into this type of high-risk leukemia and subsequently will be useful for developing of novel and appropriate therapeutic strategies against acute leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Intracellular Lysozyme in Mature Neutrophils and Blast Cells in Acute Leukemia

Blood ◽  
1974 ◽  
Vol 44 (2) ◽  
pp. 247-255 ◽  
Author(s):  
Hans Karle ◽  
Niels Ebbe Hansen ◽  
Sven-Aage Killmann
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cell Mass ◽  
Leukemic Cell ◽  
High Plasma ◽  
Lysozyme Activity ◽  
Neutrophilic Granulocytes ◽  
Acute Leukemias ◽  
Myelomonocytic Leukemia

Abstract Intracellular lysozyme (muramidase) activity was measured in leukemic blasts and mature neutrophilic granulocytes from 20 patients with acute myeloblastic and myelomonocytic leukemia and in 11 patients with acute lymphoblastic leukemia after differential centrifugation of cells in Ficoll and extraction of lysozyme with n-butanol. Considerable abnormalities in cellular lysozyme activity were found both in qualitative and quantitative terms. In contrast to normal myeloblasts, leukemic blasts of the myeloid series contained lysozyme in a considerable number of cases. Although no clear-cut distinction was seen, those patients with positive blast lysozyme reactivity tended to have the highest plasma lysozyme levels, whereas no good correlation was found between morphologic differentiation along myeloblastic or monocytoblastic lines of blasts and lysozyme reactivity. Calculations of the magnitude of lysozyme production in acute leukemias with high plasma lysozyme concentration was compatible with the hypothesis that in these cases lysozyme must be secreted by intact blasts and that, consequently, plasma lysozyme activity reflects the total leukemic cell mass. In mature neutrophilic granulocytes from patients with acute myeloblastic and myelomonocytic leukemia in relapse, the mean lysozyme activity was significantly decreased, although a great deal of variation was found. In remission, neutrophil lysozyme activity seemed to increase; among several possibilities this might be a reflection of different clones being operative in relapse and remission. In acute lymphoblastic leukemia, lysozyme activity in neutrophils was constantly low in relapse and increased to normal following induction of remission, which may be the main explanation of the low plasma lysozyme activity found in this type of acute leukemia. It is unexplained and puzzling why intraneutrophil lysozyme activity is low in a leukemic type where the myeloid cells are not believed to be primarily leukemic; one possible reason might be an effect of cell-to-cell interaction with the leukemic cell population.

Evaluation of the differences between extramedullary and bone marrow relapse in adult acute lymphoblastic leukemia patients in terms of clinical features and survival outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19516-e19516
Author(s):  
Nilgun Sayınalp ◽  
Rafiye Ciftciler ◽  
Yahya Buyukasik ◽  
IC Haznedaroglu ◽  
Salih Aksu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Clinical Features ◽  
Lymphoblastic Leukemia ◽  
Care Center ◽  
Tertiary Care ◽  
Survival Outcomes ◽  
Hematopoietic Stem ◽  
Significant Difference

e19516 Background: Acute lymphoblastic leukemia (ALL) in adult patients is an uncommon and difficult-to-treat hematological malignancy that is characterized by excess lymphoblasts in the bone marrow (BM). Although many patients achieve remission with chemotherapy, relapse rates are high and survival outcomes in adults are worse than pediatric patients. With uncontrolled proliferation and accumulation of these lymphoblasts, normal hematopoiesis is suppressed and infiltrates various extramedullary (EM) regions. The aim of this study is to evaluate the difference between EM and BM relapse in adult ALL patients in terms of clinical features and survival outcomes. Methods: In this study, we retrospectively analyzed 108 patients who were diagnosed as ALL and treated in our tertiary care center between 2003 and 2019. Statistical analyses were performed using the SPSS software version 25. Results: The study included 108 patients, consisting of 64 males and 44 females with a median age of 30 (range: 17-79 years). The majority of cases were B-cell in origin; 87 (80.6%) patients had B-ALL and 21 (19.4%) had T-ALL. Median follow-up duration for all patients was 21.1 months (range: 0.49-158.7 months). In the follow-up, 28 patients (25.9%) were received allogeneic hematopoietic stem cell transplantation. A total of 27 (25%) patients relapsed during the follow-up period. In 15 (13.9%) of 27 patients, only BM relapse was observed. EM relapse was observed in 12 (11.1%) patients. EM localizations were identified: brain [n = 2, 1.8%], lung [n = 1, 0.92%], retroperitoneum region [n = 1, 0.92%], kidney [n = 2, 1.8%], breast [n = 1, 0.92%], vertebral column [n = 3, 2.7%], spleen [n = 1, 0.92%], and uvea [n = 1, 0.92%]. All of the patients relapsed with bone marrow were B-ALL. Five of the patients (41.7%) with EM relapse were T-ALL (p = 0.006). No significant difference was observed in terms of gender (p = 0.16) and age (p = 0.12) in patients with BM relapse and EM relapse. Median overall survival (OS) was 42.3 months (95% CI: 15.6-69.0) for patients with BM relapse and 32.8 months (95% CI: 20.0-45.5) for patients with EM relapse (p = 0.42). Conclusions: In conclusion, EM relapse is common in ALL patients. We observed that EM relapse is more frequent, especially in patients with T-ALL cell origin. no significant difference was observed in both groups in terms of OS. ALL patients should be carefully followed up in terms of EM relapses as well as bone marrow relapse.

Patient Stratification Based on Prednisolone-Vincristine-Asparaginase Resistance Profiles in Children With Acute Lymphoblastic Leukemia

2003 ◽  
Vol 21 (17) ◽  
pp. 3262-3268 ◽  
Author(s):  
M.L. Den Boer ◽  
D.O. Harms ◽  
R. Pieters ◽  
K.M. Kazemier ◽  
U. Göbel ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Late Relapse ◽  
Early Event ◽  
Study Group ◽  
Increased Risk

Purpose: To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol. Patients and Methods: Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol. Results: At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate ± SE was 69% ± 7.0%, 83% ± 4.4%, and 84% ± 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P ≤ .05). Resistant patients were at increased risk of an early event (nonresponse or relapse within 2.5 years of diagnosis) compared with sensitive and intermediate-sensitive patients (P = .03). The profile did not identify patients at higher risk of late relapse, which was also observed for DCLSG ALL-VII/VIII patients now analyzed at a median of 7.5 years of follow-up (range, 4.4 to 10.8 years). Despite being nondiscriminative for late relapses, the resistant profile was still the strongest prognostic factor for COALL-92 patients in a multivariate analysis including known risk factors (P = .07). Conclusion: Drug resistance profiles identify patients at higher risk of early treatment failures and may, therefore, be used to improve risk-group stratification of children with ALL.

Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia

1999 ◽  
Vol 17 (5) ◽  
pp. 1545-1545 ◽  
Author(s):  
Franco Aversa ◽  
Adelmo Terenzi ◽  
Alessandra Carotti ◽  
Rita Felicini ◽  
Roberta Jacucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Antithymocyte Globulin ◽  
Lymphoblastic Leukemia ◽  
Acute Myeloid

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell–depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell–depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

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