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British Journal of Haematology Jul 2018Neonatal leukaemia is defined as occurring within the first 28 days of life and most, if not all, cases are congenital. With the exception of Down syndrome-associated... (Review)
Review
Neonatal leukaemia is defined as occurring within the first 28 days of life and most, if not all, cases are congenital. With the exception of Down syndrome-associated transient abnormal myelopoiesis, which is not considered here, neonatal leukaemias are rare. In two-thirds of patients the disease manifests as an acute myeloid leukaemia, frequently with monocytic/monoblastic characteristics. Most other cases are acute lymphoblastic leukaemia, particularly B lineage, but some are mixed phenotype or blastic plasmacytoid dendritic cell neoplasms. The most frequently observed cytogenetic/molecular abnormality is t(4;11)(q21.3;q23.3)/KMT2A-AFF1 followed by t(1;22)(p13.3;q13.1)/RBM15-MKL1 and t(8;16)(p11.2;p13.3)/KAT6A-CREBBP. Common clinical features include prominent hepatosplenomegaly and a high incidence of skin involvement, sometimes in the absence of bone marrow disease. A distinctive feature is the occurrence of spontaneous remission in some cases, particularly in association with t(8;16). In this review, we summarise current knowledge of the clinical, cytogenetic and molecular features of neonatal leukaemia and discuss clinical management of these cases.
Topics: Antineoplastic Agents; Dendritic Cells; Diagnosis, Differential; Exanthema; Gene Order; Histone-Lysine N-Methyltransferase; Humans; Infant, Newborn; Leukemia; Myeloid-Lymphoid Leukemia Protein; Remission, Spontaneous; Treatment Outcome
PubMed: 29806701
DOI: 10.1111/bjh.15246 -
Archives of Disease in Childhood Oct 2016Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all existing data on its clinical presentation and estimated the frequency of signs and symptoms presenting at or prior to diagnosis.
DESIGN
We searched MEDLINE and EMBASE for all studies describing presenting features of leukaemia in children (0-18 years) without date or language restriction, and, when appropriate, meta-analysed data from the included studies.
RESULTS
We screened 12 303 abstracts for eligibility and included 33 studies (n=3084) in the analysis. All were cohort studies without control groups. 95 presenting signs and symptoms were identified and ranked according to frequency. Five features were present in >50% of children: hepatomegaly (64%), splenomegaly (61%), pallor (54%), fever (53%) and bruising (52%). An additional eight features were present in a third to a half of children: recurrent infections (49%), fatigue (46%), limb pain (43%), hepatosplenomegaly (42%), bruising/petechiae (42%), lymphadenopathy (41%), bleeding tendency (38%) and rash (35%). 6% of children were asymptomatic on diagnosis.
CONCLUSIONS
Over 50% of children with leukaemia have palpable livers, palpable spleens, pallor, fever or bruising on diagnosis. Abdominal symptoms such as anorexia, weight loss, abdominal pain and abdominal distension are common. Musculoskeletal symptoms such as limp and joint pain also feature prominently. Children with unexplained illness require a thorough history and focused clinical examination, which should include abdominal palpation, palpation for lymphadenopathy and careful scrutiny of the skin. Occurrence of multiple symptoms and signs should alert clinicians to possible leukaemia.
Topics: Abdominal Pain; Adolescent; Child; Child, Preschool; Contusions; Early Detection of Cancer; Exanthema; Fever; Gastrointestinal Diseases; Hemorrhage; Hepatomegaly; Humans; Infant; Infant, Newborn; Infections; Leukemia; Musculoskeletal Diseases; Recurrence; Skin Diseases; Splenomegaly
PubMed: 27647842
DOI: 10.1136/archdischild-2016-311251 -
International Journal of Molecular... Mar 2024Infant acute lymphoblastic leukemia (Infant ALL) is a kind of pediatric ALL, diagnosed in children under 1 year of age and accounts for less than 5% of pediatric ALL. In... (Review)
Review
Infant acute lymphoblastic leukemia (Infant ALL) is a kind of pediatric ALL, diagnosed in children under 1 year of age and accounts for less than 5% of pediatric ALL. In the infant ALL group, two subtypes can be distinguished: -rearranged ALL, known as a more difficult to cure form and - non-rearranged ALL with better survival outcomes. As infants with ALL have lesser treatment outcomes compared to older children, it is pivotal to provide novel treatment approaches. Progress in the development of molecularly targeted therapies and immunotherapy presents exciting opportunities for potential improvement. This comprehensive review synthesizes the current literature on the epidemiology, clinical presentation, molecular genetics, and therapeutic approaches specific to ALL in the infant population.
Topics: Infant; Humans; Child; Adolescent; Immunotherapy; Molecular Targeted Therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38612531
DOI: 10.3390/ijms25073721 -
Hematology. American Society of... Dec 2017The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or... (Review)
Review
The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.
Topics: Adolescent; Child; Child, Preschool; DNA Repair; Female; Genes, Recessive; Genes, Tumor Suppressor; Genes, X-Linked; Genetic Predisposition to Disease; Genetic Testing; Humans; Infant; Infant, Newborn; Leukemia; Male; Myelodysplastic Syndromes
PubMed: 29222262
DOI: 10.1182/asheducation-2017.1.242 -
Cellular and Molecular Life Sciences :... Feb 2018B cell leukaemia is one of the most frequent malignancies in the paediatric population, but also affects a significant proportion of adults in developed countries. The... (Review)
Review
B cell leukaemia is one of the most frequent malignancies in the paediatric population, but also affects a significant proportion of adults in developed countries. The majority of infant and paediatric cases initiate the process of leukaemogenesis during foetal development (in utero) through the formation of a chromosomal translocation or the acquisition/deletion of genetic material (hyperdiploidy or hypodiploidy, respectively). This first genetic insult is the major determinant for the prognosis and therapeutic outcome of patients. B cell leukaemia in adults displays similar molecular features as its paediatric counterpart. However, since this disease is highly represented in the infant and paediatric population, this review will focus on this demographic group and summarise the biological, clinical and epidemiological knowledge on B cell acute lymphoblastic leukaemia of four well characterised subtypes: t(4;11) MLL-AF4, t(12;21) ETV6-RUNX1, t(1;19) E2A-PBX1 and t(9;22) BCR-ABL1.
Topics: Acute Disease; B-Lymphocytes; Cell Transformation, Neoplastic; Child, Preschool; Female; Gene Expression Regulation, Leukemic; Humans; Infant; Infant, Newborn; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pregnancy; Prognosis; Translocation, Genetic
PubMed: 28819864
DOI: 10.1007/s00018-017-2620-z -
Disease Models & Mechanisms Oct 2021For patients and their families, the diagnosis of infant leukaemia is devastating. This disease has not seen the improvements in outcomes experienced with other... (Review)
Review
For patients and their families, the diagnosis of infant leukaemia is devastating. This disease has not seen the improvements in outcomes experienced with other paediatric leukaemias and it is becoming ever more apparent that infant leukaemia is a distinct biological entity. Insights into some of the distinguishing features of infant leukaemia, such as a single mutation - the MLL-gene rearrangement, the biology of disease aggressiveness and lineage plasticity, and the high incidence of central nervous system involvement, are likely to be gained from understanding the interactions between leukaemic cells and their environment or niche. The origins of infant leukaemia lie in the embryonic haematopoietic system, which is characterised by shifting locations and dynamic changes in the microenvironment. Understanding this foetal or embryonic context is integral to understanding infant leukaemia development. Owing to its rarity and prenatal origins, developing accurate modelling systems for further investigation of infant leukaemia is essential. In this Review, we discuss how available in vitro, ex vivo and in vivo infant leukaemia models contribute to our current understanding of the leukaemia niche in embryonic development, established disease and specialised non-haematopoietic niches. The mechanistic insights provided by accurate models will help identify viable novel therapeutic options.
Topics: Animals; Cell Lineage; Cell Transformation, Neoplastic; Disease Models, Animal; Hematopoiesis; Humans; Infant; Leukemia; Stem Cell Niche
PubMed: 34713888
DOI: 10.1242/dmm.049189 -
The American Journal of Clinical... Mar 2019During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in...
BACKGROUND
During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations.
OBJECTIVES
The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) feeding a lower versus higher intensity of human milk to mixed-fed infants with acute childhood leukemia, generally, and acute lymphoblastic leukemia, specifically.
METHODS
The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980 to March 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence.
RESULTS
We included 24 articles from case-control or retrospective studies. Limited evidence suggests that never feeding human milk versus 1) ever feeding human milk and 2) feeding human milk for durations ≥6 mo are associated with a slightly higher risk of acute childhood leukemia, whereas evidence comparing never feeding human milk with feeding human milk for durations <6 mo is mixed. Limited evidence suggests that, among infants fed human milk, a shorter versus longer duration of human milk feeding is associated with a slightly higher risk of acute childhood leukemia. None of the included articles examined exclusive human milk feeding or the intensity of human milk fed to mixed-fed infants.
CONCLUSIONS
Feeding human milk for short durations or not at all may be associated with slightly higher acute childhood leukemia risk. The evidence could be strengthened with access to broadly generalizable prospective samples; therefore, we recommend linking surveillance systems that collect infant feeding and childhood cancer data.
Topics: Breast Feeding; Child; Child Health; Diet; Feeding Behavior; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Leukemia; Milk, Human; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 30982871
DOI: 10.1093/ajcn/nqy306 -
International Journal of Molecular... Apr 2023Although the prevalence of leukemia is increasing, the agents responsible for this increase are not definitely known. While ionizing radiation (IR) was classified as a... (Review)
Review
Although the prevalence of leukemia is increasing, the agents responsible for this increase are not definitely known. While ionizing radiation (IR) was classified as a group one carcinogen by the IARC, the IR-induced cancers, including leukemia, are indistinguishable from those that are caused by other factors, so the risk estimation relies on epidemiological data. Several epidemiological studies on atomic bomb survivors and persons undergoing IR exposure during medical investigations or radiotherapy showed an association between radiation and leukemia. IR is also known to induce chromosomal translocations. Specific chromosomal translocations resulting in preleukemic fusion genes (PFGs) are generally accepted to be the first hit in the onset of many leukemias. Several studies indicated that incidence of PFGs in healthy newborns is up to 100-times higher than childhood leukemia with the same chromosomal aberrations. Because of this fact, it has been suggested that PFGs are not able to induce leukemia alone, but secondary mutations are necessary. PFGs also have to occur in specific cell populations of hematopoetic stem cells with higher leukemogenic potential. In this review, we describe the connection between IR, PFGs, and cancer, focusing on recurrent PFGs where an association with IR has been established.
Topics: Infant, Newborn; Humans; Child; Translocation, Genetic; Neoplasms, Radiation-Induced; Leukemia; Chromosome Aberrations; Radiation, Ionizing
PubMed: 37047553
DOI: 10.3390/ijms24076580 -
Hematology. American Society of... 2013Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current... (Review)
Review
Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current therapies, and its unique biology that is increasingly pointing the way toward novel therapeutic approaches. This review highlights the key clinical, pathologic, and epidemiologic features of infant leukemia, including the high frequency of mixed lineage leukemia (MLL) gene rearrangements. The state of the art with regard to current approaches to risk stratified treatment of infant leukemia in the major international cooperative groups is discussed. Finally, exciting recent discoveries elucidating the molecular biology of infant leukemia are reviewed and novel targeted therapeutic strategies, including FLT3 inhibition and modulation of aberrant epigenetic programs, are suggested.
Topics: Epigenesis, Genetic; Female; Gene Rearrangement; Histone-Lysine N-Methyltransferase; Humans; Infant; Infant, Newborn; Leukemia; Male; Myeloid-Lymphoid Leukemia Protein; Protein Kinase Inhibitors; fms-Like Tyrosine Kinase 3
PubMed: 24319237
DOI: 10.1182/asheducation-2013.1.596 -
Cells Jan 2022Despite enormous improvements in pre-clinical and clinical research, acute leukemia still represents an open challenge for pediatric hematologists; both for a... (Review)
Review
Despite enormous improvements in pre-clinical and clinical research, acute leukemia still represents an open challenge for pediatric hematologists; both for a significant relapse rate and for long term therapy-related sequelae. In this context, the use of an innovative technology, such as induced pluripotent stem cells (iPSCs), allows to finely reproduce the primary features of the malignancy and can be exploited as a model to study the onset and development of leukemia in vitro. The aim of this review is to explore the recent literature describing iPSCs as a key tool to study different types of hematological malignancies, comprising acute myeloid leukemia, non-down syndrome acute megakaryoblastic leukemia, B cell acute lymphoblastic leukemia, and juvenile myelomonocytic leukemia. This model demonstrates a positive impact on pediatric hematological diseases, especially in those affecting infants whose onsets is found in fetal hematopoiesis. This evidence highlights the importance of achieving an in vitro representation of the human embryonic hematopoietic development and timing-specific modifications, either genetic or epigenetic. Moreover, further insights into clonal evolution studies shed light in the way of a new precision medicine era, where patient-oriented decisions and therapies could further improve the outcome of pediatric cases. Nonetheless, we will also discuss here the difficulties and limitations of this model.
Topics: Child; Hematologic Neoplasms; Hematopoiesis; Humans; Induced Pluripotent Stem Cells; Infant; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35159287
DOI: 10.3390/cells11030476