Global Leukemia Trends: Analysis and Indicators

Comparison of paired bone marrow and peripheral blood measurable residual disease in pediatric acute lymphoblastic leukemia by next-generation sequencing: A report from the dana farber ALL consortium protocol 16-001.

Leucocyte classification for leukaemia detection using image processing techniques.

Prevention of cancer is mostly attained by surveillance of the transformation zones. White blood cells (WBCs) are established in the bone marrow and intemperate growth of WBC leads to leukemia. Hematologists examine the microscopic images in manual method for predicting leukemia, but it is very complex process and without any guaranteed for accurate. In this proposed study, deep learning techniques involved to segment and classify the three types of leukemia like acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) using the BioGps dataset. The purpose of deep learning in medical science enhances the accuracy and precision of determining leukemia in early stages. In this study, introducing a sigmoid stretching (SS) in pixel enhancement for preprocessing; SegNet (St) is comfort to extract the structural features of the leukocytes and to segment the normal and blast cells for a clear classification; faster region-based convolutional neural network (faster R- CNN) carried under the process of classification and optimization done by dragon fly algorithm. The result of this work achieves best accuracy related to the existing techniques of convolutional neural network (CNN) such as support vector machine (SVM), k-nearest neighbors (kNN) and Bayesian model. This study achieves the accuracy rate of 97%, precision rate of 94% and sensitivity rate of 90% respectively with low complexity.

Background: Unlike other cell types, B cells are selected for an intermediate level of signaling strength. Critical survival and proliferation signals emanate from the B cell receptor (BCR): If B-cells fail to express a functional BCR, signaling output is too weak, resulting in “death by neglect”. If the BCR binds to ubiquitous self-antigen, BCR signals are exceedingly strong. Both attenuation below minimum (non-functional BCR; death by neglect) and hyperactivation above maximum (autoreactive BCR) thresholds of signaling strength trigger negative selection and cell death. Rationale: Unlike any other types of cancer, we recently discovered that pre-B acute lymphoblastic leukemia (ALL) cells are bound by the same rules that also govern normal B cell selection. Oncogenic tyrosine kinases in pediatric Ph-like ALL mimic active pre-BCR signaling. The Ph-like group defines the ALL subset with particularly poor clinical outcome. Current therapy approaches are largely focused on the development of more potent tyrosine kinase inhibitors (TKI) to suppress oncogenic signaling. However resistance to TKI is developed invariably. Here, we test the hypothesis that targeting hyperactivation above a maximum threshold will selectively kill Ph-like ALL cells through a mechanism that is functionally equivalent to removal of self-reactive B cells. Results: Ph-like ALL typically originates from pre-B cells that critically depend on survival signals emanating from a functional pre-BCR. Despite their pre-B cell origin, ALL cells lack expression of pre-BCR signaling chains Igα and Igβ, indicating lack of a functional pre-BCR. Reconstitution of Igα and Igβ was indeed sufficient to induce cell death in Ph-like ALL. TKI-treatment, while designed to kill leukemia cells, seemingly paradoxically rescued Ph-like ALL cells in this experimental setting. These findings suggest that Ph-like ALL cells are selectively sensitive to even incremental increases of pre-BCR signaling. Consistent with this concept, patient-derived Ph-like ALL cells express high levels of inhibitory surface receptors PECAM1, CD300A and LAIR1 that recruit and activate phosphatases SHP1 and SHIP1, which terminate pre-BCR signaling. Importantly, high expression levels of these surface receptors were strong predictors of poor outcome of patients with ALL in two clinical trials, including Ph-like ALL patients (COG; P9906). Genetic studies revealed that Pecam1, Cd300a and Lair1 were critical to calibrate pre-BCR signaling strength through recruitment of the inhibitory phosphatases SHP1 and SHIP1. Genetic deletion of Lair1, Ptpn6 or Inpp5d in BCR-ABL1 transformed ALL caused cell death in vitro and in vivo through hyperactivation of pre-BCR signaling. Testing various components of proximal pre-BCR signaling, we found that an incremental increase of SYK tyrosine kinase activity was required and sufficient to induce cell death. Hyperactive SYK was functionally equivalent to acute activation of an autoreactive BCR on ALL cells. Despite oncogenic transformation, this basic mechanism of negative selection was still functional in Ph-like ALL cells. Using chimeric PECAM1, CD300A and LAIR1 receptor decoys and a novel small molecule inhibitor of SHIP1, we demonstrated that pharmacological hyperactivation of pre-BCR signaling and engagement of negative B cell selection represents a promising new strategy to overcome drug-resistance in pediatric Ph-like ALL. Conclusion: These results indicated that inhibitory receptors and downstream phosphatases are critical regulators of pre-BCR signaling strength in Ph-like ALL, and identified targeting hyperactivation of pre-BCR signaling as a potential novel class of therapeutic strategy. This abstract is also presented as Poster B06. Citation Format: Zhengshan Chen, Huimin Geng, Clifford A. Lowell, Stephen P. Hunger, Markus Müschen. Targeted engagement of B cell autoimmunity checkpoints to overcome drug resistance in pediatric Ph-like ALL. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr PR11.

MLL Rearranged Infant Acute Lymphoblastic Leukemia Is Characterized by Silencing of the Putative Tumor Suppressor Gene FHIT.

To explore the functions of the polymorphisms in 5-methylcytosine (m5C) modification-related coding genes on the susceptibility of pediatric acute lymphoblastic leukemia (ALL). Case-control study and multinomial logistic regression analysis were performed to construct models to evaluate the susceptibility of pediatric ALL. The relationship between five functional SNPs in m5C modification-coding genes and pediatric ALL risk was analyzed. Genotyping of 808 cases and 1,340 healthy samples from South China was identified using a TaqMan assay; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the relationship between the five selected SNPs and pediatric ALL susceptibility. Among the five analyzed SNPs, NOL1 rs3764909 and NSUN4 rs10252 variants significantly increased the susceptibility of pediatric ALL, while NSUN3 rs7653521, NSUN5 rs1880948, and NSUN6 rs3740102 variants were not associated with the risk of ALL. Stratification analyses demonstrated that NOL1 rs3764909 C>A exhibited a significant association with increased pediatric ALL risk in subgroups of common B ALL, pre-B ALL, T-cell ALL, low and middle risk, other gene fusion types, non-gene fusion, hypodiploid, normal diploid, primitive lymphocytes in marrow < 5% on week 12, and minimal residual disease (MRD) <0.01% on week 12 after induced therapy; NSUN4 rs10252 G>A was related to increased risk of ALL children in subgroups of age ≥ 120 months, normal white blood cell (WBC) number, middle risk, non-gene fusion, MRD ≥ 0.01 on days 15-19, and primitive lymphocytes in marrow < 5% on day 33 after induced therapy. Compared with the reference haplotype CAGTA, children who harbored haplotypes CCGTG and ACATA were remarkably related to increased ALL susceptibility. rs3764909 and rs10252 varieties of alleles were not associated with MRD levels after the selected chemotherapeutics. In conclusion, NOL1 rs3764909 and NSUN4 rs10252 variants were enhanced by pediatric ALL risk and were suggested to be potential biomarkers for pediatric ALL.

Background: Acute lymphoblastic leukemia (ALL) is a bone marrow malignancy that is the most common cause of death in children. This study aims to determine the characteristics of ALL patients in 2016-2020 at Sanglah Hospital Denpasar, Bali.&#x0D; Methods: This study used a retrospective descriptive study with secondary data from 166 patients. Variables assessed in this study included: demographic characteristics (age, gender, place of origin), complete blood count results include of hemoglobin levels, leukocyte (white blood cell) count, absolute neutrophil count, absolute lymphocyte count, thrombocyte count, and morphology subtype of ALL based on FAB classification from bone marrow aspiration (BMA).&#x0D; Results: From demographic characteristics: most patients' age was in school-age children (&gt;6 - &lt;18 years) about 59.7%, dominated by male (60.2%), place of origin from Bali (71.7%) which is from Denpasar city (23.5%). From the laboratory results, complete blood count found that the most results are moderate anemia in children (54.7%), in adult female (70%), and in adult male (52.9%); leukocytosis in children (41%), in adult (77.8%); neutropenia in children (61.2%), in adult (59.3%); lymphocytosis in children (43.2%), in adult (81.5%); thrombocytopenia in children (97.1%), in adult (100%). From the results of the BMA examination, based on the FAB (French, American, and British) classification, the most common morphology of ALL was L2 subtype (78.9%).&#x0D; Conclusion: Characteristics of patients with ALL at Sanglah General Hospital are dominated by children, male, from Denpasar, Bali, with laboratory results showing moderate anemia, leukocytosis, neutropenia, lymphocytosis, thrombocytopenia, and the most common morphological variants are ALL-L2 subtype.

Leukemia is a group of lethal diseases characterized by hematological neoplasm with complex and abnormalities in proliferation of bone marrow stem cells, that cause sever loss of functional capacity of hematopoietic tissue. Four most common types of leukemia are included acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML). It has been reported that opium besides of pain killer effects, may have positive effects on cardiovascular disease treatments. Opium may consider as a potential treatment method in cancer. The present study aimed to assess the gene expression pattern alterations in the rat models of four types of Leukemia (ALL, AML, CLL, and CML) under taper up-off treatment method with of opium. Present study was included twelve group, referred to four type of Leukemia (ALL, AML, CLL, and CML) that each type studied in three group. Group one contented normal rats, group two rat model of each type of leukemia with no treatment and group three the rat model of that type of leukemia with 26 days period of opium taper up-off treatment. After the scarification of rats, the bone marrow tissue were extracted. Then, RNA extraction and cDNA synthesis had been conducted on bone marrow tissues. Whole genome expression profiling was conducted by using the Affymetrix GeneChip Array Platform. Microarray results were confirmed by Real time PCR. Microarray analysis detected that hundreds of genes which were involved in Ontogenesis and apoptosis, humoral immune system, tool like receptors, natural killer cells regulators and metabolic pathways and were deregulated in leukemic models, were partially reregulated in treatment groups. Results showed that opium may have positive effects on reregulation of affected gene expression patterns in all types of leukemia. It may suggest that opium taper up-off treatment could be consider as re-regulator of immune system and a novel potential treatment for leukemia with low side effects and high viability.

Risk Factors for Outcomes of Family Haploidentical Allogeneic Stem Cell Transplantation for Adults with Acute Leukemias: A Survey on Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

CITED2 Facilitates Apoptosis Induced By Histone Deacetylase Inhibitor SAHA In Human Pediatric Pre-B Acute Lymphoblastic Leukemia Cells

Introduction: Acute lymphoblastic leukemia (ALL) is a malignancy of the white blood cells and lymphoid lines of hematopoietic cells in the blood and bone marrow while lymphomas mostly involve the lymph nodes. This study showed the response rate of ALL treated with BFM (Berlin-Frankfurt-Munster) 76/79 protocol.&#x0D; Aims &amp; Objectives: To study the effects of WBC (White Blood Cells), age, and treatment protocols on the survival of ALL patients to BFM 76/79 protocol and other chemotherapy protocol.&#x0D; Place and duration of study: 6 months retrospective study on 2015-2017 indoor patient data from INMOL Hospital Lahore, Pakistan.&#x0D; Material &amp; Methods: Data of 129 patients was assessed for eligibility, and 84 patients of ALL selected. Clinical information of patients regarding Gender, Age, WBC, Fever, Hepatosplenomegaly, Lymphadenopathy, Bleeding, Bone Pain, Immunophenotype, Relapse, Death, and survival rates were recorded. Patients were grouped according to Age, WBC, Gender, and Immunophenotype. Patients were treated with BFM 76/79 Protocols and the remaining patients were treated with other protocols (CALGB, FLAG-TDA, Hyper-CVAD, EURO, COG, T-Cell ALL protocol, and ALL protocol 9111).&#x0D; Results: Out of 84 patients, 55 (65.5%) patients were treated with Berlin-Frankfurt-Munster 76/79 protocol and the remaining 20 (23.81%) patients with other protocols. After the end of induction 64 (73.8%) patients achieved complete remission and 5 (5.95%) patients did not achieve Remission.&#x0D; Conclusion: Response rate of ALL (Acute Lymphoblastic Leukemia) patients treated with BFM 76/79 protocol was better than other protocols and possibly when risk adapted for male gender, WBC &gt; 50 x 109/L and age&gt; 30 years.

Hematology-Oncology| March 01 2001 Initial Traumatic LP Adversely Affects Outcome in ALL AAP Grand Rounds (2001) 5 (3): 24. https://doi.org/10.1542/gr.5-3-24 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Initial Traumatic LP Adversely Affects Outcome in ALL. AAP Grand Rounds March 2001; 5 (3): 24. https://doi.org/10.1542/gr.5-3-24 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: blast cells, cerebrospinal fluid, leukemia, lipopolysaccharides, traumatic lumbar puncture, treatment outcome, van der woude syndrome, acute lymphocytic leukemia, atypical, central nervous system dysfunction Source: Gajjar A, Harrison PL, Sandlund JT, et al. Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia. Blood. 2000;96: 3381–3384 This retrospective study was conducted to answer an important, controversial question: does a traumatic lumbar puncture (TLP) at the time of the initial diagnostic work-up and/or induction treatment have any effect on the treatment outcome in children with acute lymphoblastic leukemia (ALL)? The authors reviewed the cerebrospinal fluid (CSF) findings of lumbar punctures (LP) performed in 546 patients enrolled on two consecutive therapeutic trials at St. Jude Children’s Research Hospital, Memphis, Tennessee between 1984 to 1991. All patients underwent 2 LPs, usually within 24–48 hrs of each other at the time of initial diagnostic evaluation and at the beginning of the induction chemotherapy. A complete blood count and examination of a centrifuged and stained CSF cell pellet were performed in all patients. The patients were divided into 5 groups depending on their central nervous system (CNS) status: LP not traumatic with <10 red blood cells (RBCs) per μL in the CNS and no leukemic blast cells (n=336), LP not traumatic with <5 white blood cells (WBCs) per μL and containing leukemic blast cells (n=80), LP not traumatic with ≥5 WBCs per μL and containing leukemic blast cells (n=16), LP traumatic with ≥10 RBCs per μL and no leukemic blast cells (TLP−, n=54), and LP traumatic with leukemic blast cells (TLP+, n=60). There were 26 patients who had 2 consecutive TLPs with blast cells (TLP++). The 5-year event-free survival (EFS± 1 SE) for the 5 groups is shown in the tableT1: The EFS was similar between patients with an atraumatic LP and no blast cells and those who were TLP− (P=.85). The EFS of patients who were TLP+ was worse than that for those who had an atraumatic LP with no blast cells (P=.026) and comparable to those who had an atraumatic LP with <5 WBCs and leukemic blast cells (P=.59). The authors conclude that a TLP during initial diagnostic evaluation and treatment of ALL leads to contamination of the CSF with circulating leukemic blast cells and will adversely affect the treatment outcome of children with ALL. Furthermore, the EFS of patients with 2 TLPs with blast cells (TLP++) was comparable to that of patients with overt CNS disease (≥5 WBCs with blast cells). The definition of CNS leukemia is controversial when the CSF contains a small number of WBCs and blasts are seen on a stained cytospin preparation. Most physicians follow the recommendation of the Rome Leukemia Workshop,1 which characterizes patients who have >5 WBCs μL with identifiable blasts as having CNS involvement. The problem is positively identifying the few “atypical” looking cells as true blasts, thus justifying more intensive CNS directed therapy. This is true even if more specific tests such as determination of surface markers by staining or flow cytometry... You do not currently have access to this content.

Background: Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer; Children with this type of leukemia have poor postural balance, which is one of the side effects of chemotherapy. Objective: Toevaluate the therapeutic effect of static and dynamic balance exercises using both sides up (BOSU) ball on balance in children with acute lymphoblastic leukemia after completing their 6 months-chemotherapy treatment. Patients and methods: Thirty children patients of both sexes (18 boys and 12 girls) were participated in this study, who were selected from Benha Children Hospital with acute lymphoblastic leukaemia and had chemotherapy treatment for 6 months participated in this study. They were randomly assigned to 2 groups of an equal number, control group, 15 child patients who were 5-8 years of age (6.53 ± 1.13) that underwent gait training therapy and study groups, 15 child patients who were 5-8 years of age (6.67 ± 1.11), that underwent the same program in addition to static and dynamic balance training program by using BOSU ball. Results: There was a significant improvement of balance performance in study group more than control group. Conclusion: Balance exercises using BOSU ball can be used effectively in treating balance defect post chemotherapy in children with acute lymphoblastic leukemia.

Background Hyperleukocytosis in childhood acute lymphoblastic leukemia (ALL) is an emergency in oncology. This condition showed high mortality and relapse rates, as well as low survival rate. The outcomes of this group of patients are not yet well studied.&#x0D; Objective To evaluate the characteristics and outcomes of childhood acute lymphoblastic leukemia (ALL) with hyperleukocytosis.&#x0D; Methods This was a retrospective cohort study. The patients were children less than 18 year of age who were diagnosed as ALL in Dr. Sardjito Hospital, Yogyakarta, from January 1st 2010 to November, 30th 2016. Event-free survival rate and overall survival rate were estimated for group of patients with the white blood cell (WBC) groups 50-200x109/L and &gt;200x109/L using the Kaplan-Meier method.&#x0D; Results There were 705 children diagnosed as ALL during the study period, 129 (18%) with hyperleukocytosis and 111 of them met the inclusion criteria, consisted of 76 children in a group of WBC 50-200 x 109/L and 35 children in a group of WBC &gt;200 x 109/L. Presentation at diagnosis: median age were 7 years (range 1 month-18 years), male was 1.5 higher than female, 92% of cases with lymphoid infiltration, 5% with CNS involvement, 40% had bleeding tendency, and 10% had clinical tumor lysis syndrome (TLS). Median WBC was 122 (range 53.4-876) x 109/L; mean Hb was 8 (SD 3) g/dL; median platelet count was 30 (range 1-221) x 109/L. Immunophenotyping was done in 23 patients, 5/23 (8%) was T cell. The patients in lower WBC group showed lower death (26% vs. 34%, P=0,389), higher two-year event-free survival (EFS) 68% vs. 45%, P=0.003, and overall survival (77% vs. 68%, P= 0.16), compared to patients in higher WBC group. Univariate and multivariate Cox regression analyses revealed that none of the variables was a significant prognostic factor for 2 years EFS or overall survival.&#x0D; Conclusion The group of children with ALL and hyperleukocytosis with lower WBC at diagnoses showed better outcomes than the higher WBC.

High Prevalence of Relapse in Australian Children with Ph-like Acute Lymphoblastic Leukemia Despite Risk Adapted Treatment