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Clinics in Perinatology Mar 2021Neonates are at risk for 3 major forms of leukemia in the first year of life: acute leukemia, juvenile myelomonocytic leukemia, and transient abnormal myelopoiesis... (Review)
Review
Neonates are at risk for 3 major forms of leukemia in the first year of life: acute leukemia, juvenile myelomonocytic leukemia, and transient abnormal myelopoiesis associated with Down syndrome. These disorders are rare but generate interest due to aggressive clinical presentation, suboptimal response to current therapies, and fascinating biology. Each can arise as a result of unique constitutional and acquired genetic events. Genetic insights are pointing the way toward novel therapeutic approaches. This article reviews key epidemiologic, clinical, and molecular features of neonatal leukemias, focusing on risk stratification, treatment, and strategies for developing novel molecularly targeted approaches to improve future outcomes.
Topics: Down Syndrome; Humans; Infant, Newborn; Infant, Newborn, Diseases; Leukemia; Leukemia, Myelomonocytic, Juvenile; Leukemoid Reaction
PubMed: 33583502
DOI: 10.1016/j.clp.2020.11.002 -
Archives de Pediatrie : Organe Officiel... Jan 2020Feeding problems and gastrointestinal disorders are the most common anomalies in people with Down syndrome (DS) and have a significant impact on their daily life. This... (Review)
Review
BACKGROUND AND METHOD
Feeding problems and gastrointestinal disorders are the most common anomalies in people with Down syndrome (DS) and have a significant impact on their daily life. This study lists the various anomalies on the basis of 504 references selected from a PubMed search in October 2018.
RESULTS
The anomalies are grouped into three categories: anatomical anomalies: duodenal atresia and stenosis (3.9%), duodenal web and annular pancreas; aberrant right subclavian artery (12% of children with DS with cardiac anomaly); Hirschsprung's disease (2.76%); anorectal malformation (1.16%); congenital vascular malformations of the liver; orofacial cleft, bifid uvula (4.63%), and submucous orofacial cleft; esophageal atresia (0.5-0.9%); pyloric stenosis (0.3%); diaphragmatic hernia; malrotation of small intestine or duodenum inversum; omphalocele, gastroschisis or anomalies of the median line, anomalies of the umbilical vein; biological, immunological, and infectious anomalies: neonatal cholestasis (3.9%); neonatal hepatic fibrosis; Helicobacter pylori infection (75.8% in institutionalized children with DS, between 29.2 and 19.5% in non-institutionalized); non-alcoholic fatty liver disease (NAFLD; 82% in obese and 45% in non-obese); biliary lithiasis (6.9% under 3 years); celiac disease (6.,6%); geographical tongue (4%); hepatitis B virus sensitivity; autoimmune hepatitis and cholangitis; Crohn's disease, inflammatory bowel disease (IBD); pancreatitis; vitamin D deficiency (45.2% in Italy); functional disorders: suction, swallowing and chewing disorders (13 of 19 children with DS under 4 years); gastroesophageal reflux (47% in children with sleep apnea); achalasia (0,5% in adults); obesity (51.6% of males and 40.0% of females in Ireland) and overweight (32.0% and 14.8%); constipation (19.0%). Based on their practice, the authors insist on the following points: malformations are sometimes detected late (chronic vomiting after the introduction of food pieces, resistant constipation despite appropriate measures); prescription of preventive doses of vitamin D is advised; jaundice in a baby with DS may be retentional; in the event of transient leukemoid reaction it is vital to monitor liver function; the patient with geographic tongue must be reassured; for celiac serology there is no consensus on the staring age and the frequency, we propose every year from the age of 2; we advise to test people with DS for H. pylori infection if they are attending specialized institutions; abdominal ultrasounds must be systematic during the first months of life; detection of NAFLD is recommended; people with DS must be vaccinated against hepatitis B; breastfeeding is possible with maternal support; it is important to start speech therapy very early; feeding difficulties are often overlooked by the family and educators; gastroesophageal reflux is often pathological; preventing obesity must start from birth using body mass index for the general population; it is necessary to do everything for their meals to be joyful.
Topics: Adolescent; Child; Child, Preschool; Down Syndrome; Feeding and Eating Disorders of Childhood; Female; Gastrointestinal Diseases; Humans; Infant; Infant, Newborn; Male; Young Adult
PubMed: 31784293
DOI: 10.1016/j.arcped.2019.11.008 -
JAMA Oncology Sep 2023Down syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS... (Review)
Review
IMPORTANCE
Down syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recognized for decades, consisting of an approximately 150-fold higher risk of acute myeloid leukemia (AML) before age 4 years, and a 10- to 20-fold higher risk of acute lymphoblastic leukemia (ALL), compared with children without DS.
OBSERVATIONS
A recent National Institutes of Health-sponsored conference, ImpacT21, reviewed research and clinical trials in children, adolescents, and young adults (AYAs) with DS-AL and are presented herein, including presentation and treatment, clinical trial design, and ethical considerations for this unique population. Between 10% to 30% of infants with DS are diagnosed with transient abnormal myelopoiesis (TAM), which spontaneously regresses. After a latency period of up to 4 years, 20% to 30% develop myeloid leukemia associated with DS (ML-DS). Recent studies have characterized somatic mutations associated with progression from TAM to ML-DS, but predicting which patients will progress to ML-DS remains elusive. Clinical trials for DS-AL have aimed to reduce treatment-related mortality (TRM) and improve survival. Children with ML-DS have better outcomes compared with non-DS AML, but outcomes remain dismal in relapse. In contrast, patients with DS-ALL have inferior outcomes compared with those without DS, due to both higher TRM and relapse. Management of relapsed leukemia poses unique challenges owing to disease biology and increased vulnerability to toxic effects. Late effects in survivors of DS-AL are an important area in need of further study because they may demonstrate unique patterns in the setting of chronic medical conditions associated with DS.
CONCLUSIONS AND RELEVANCE
Optimal management of DS-AL requires specific molecular testing, meticulous supportive care, and tailored therapy to reduce TRM while optimizing survival. There is no standard approach to treatment of relapsed disease. Future work should include identification of biomarkers predictive of toxic effects; enhanced clinical and scientific collaborations; promotion of access to novel agents through innovative clinical trial design; and dedicated studies of late effects of treatment.
Topics: Infant; Child; Adolescent; Young Adult; Humans; Child, Preschool; Down Syndrome; Leukemoid Reaction; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37440251
DOI: 10.1001/jamaoncol.2023.2163 -
International Journal of Laboratory... Apr 2020Leukemoid reaction (leukocyte count >50 cells ×10 L) is a rare but extremely relevant finding. Since little has been published on this condition's clinical relevance... (Clinical Trial)
Clinical Trial
INTRODUCTION
Leukemoid reaction (leukocyte count >50 cells ×10 L) is a rare but extremely relevant finding. Since little has been published on this condition's clinical relevance and prognosis, we investigated leukemoid reaction in patients with a white blood cell count of >50 × 10 L, including etiology and outcomes.
METHODS
This retrospective cohort study included all patients at a Brazilian tertiary hospital between January 2016 and July 2018 > 18 years with a total leukocyte count >50 cells×10 L. Demographics, complete blood count, clinical features, and the exams used to diagnose and determine leukemoid reaction etiology were analyzed. A Kaplan-Meyer survival analysis was performed, and a binary logistic regression model identified variables associated with death.
RESULTS
Of the 267 cases with white blood cell count of >50 × 10 , 162/267 (60%) were secondary to hematopoietic neoplasm and 105/267 (40%) presenting as a true leukemoid reaction. The primary causes of the true leukemoid reaction cases were infection (59), nonhematopoietic neoplasm (17), or other causes (29). Patient deaths (66) differed significantly between groups (P < .001, log-rank [Mantel-Cox] Test). Lower hemoglobin, older age, and increased segmented neutrophil count were associated with increased risk of death.
CONCLUSIONS
This was a modern cohort analysis of leukemoid reactions, inclusive of all etiologies. The most common cause was infection, which involved several microorganisms. Paraneoplastic leukemoid reaction was also common. Both conditions have a poor prognosis with high mortality, being a major medical challenge.
Topics: Adult; Age Factors; Aged; Disease-Free Survival; Female; Hemoglobins; Humans; Leukemoid Reaction; Leukocyte Count; Male; Middle Aged; Retrospective Studies; Survival Rate
PubMed: 31765058
DOI: 10.1111/ijlh.13127 -
Indian Pediatrics Feb 2021
Topics: Humans; Leukemoid Reaction; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Paraneoplastic Syndromes
PubMed: 33632959
DOI: No ID Found -
Journal of Clinical Pathology Jun 2020Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone... (Review)
Review
Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone marrow infiltration by that solid tumour. The clinical presentation is widely variable, and therefore challenging. If the underlying malignancy is not clinically apparent, PLR could be mistaken for myeloproliferative neoplasms, altering the patient's management. CSTs are highly aggressive tumours associated with a poor prognosis due to multiple mechanisms. Localising and treating the underlying malignancy is the mainstay of treatment. Both the treating clinician and the pathologist should keep a high level of suspicion for this entity in patients having unexplained leukocytosis. We herein discuss the underlying mechanisms, clinical presentation, pathological features, differential diagnosis and prognosis of this rare entity. An emphasis on the role of the pathologist is provided since the lack of knowledge on this entity can lead to dramatic effects on the patient, including unnecessary diagnostic testing and treatments.
Topics: Cytokines; Diagnosis, Differential; Humans; Leukemia, Myeloid; Leukemoid Reaction; Leukocytes; Myeloproliferative Disorders; Neoplasms; Prognosis
PubMed: 31941653
DOI: 10.1136/jclinpath-2019-206340 -
Pathology, Research and Practice Jan 2021We recently encountered a patient with unexplained hyperleukocytosis (105.4 K/μL at presentation), subsequently found to have colon cancer with a marked... (Review)
Review
OBJECTIVES
We recently encountered a patient with unexplained hyperleukocytosis (105.4 K/μL at presentation), subsequently found to have colon cancer with a marked tumor-associated neutrophilic infiltrate; the leukocytosis abruptly improved after tumor removal. Paraneoplastic leukemoid reaction (PLR) is a rare entity, occurring due to tumor cytokine secretion (typically granulocyte-colony stimulating factor [G-CSF]). We describe a case and aggregate results of previously published cases.
METHODS
We reviewed the English-language literature for all prior reports of PLR, recording age, gender, histologic diagnosis, WBC count, G-CSF level, and overall survival. We analyzed clinicopathologic variables' impact on survival.
RESULTS
We identified 179 cases (mean age 64; 72 % M). Adeno-, squamous cell, sarcomatoid, and undifferentiated carcinomas accounted for >70 %. Esophagus, gallbladder, lung, liver, and pancreas were the most common primaries. At time of publication 81 % of patients had died, with mean overall survival of 4 months. There was no correlation between WBC count and G-CSF level. On univariate analysis, WBC count was the only variable associated with survival (P = 0.03). Patients with WBC counts >100 K/μL were twice as likely to die as those with counts from 11 K to 40 K/μL.
CONCLUSIONS
PLR, typically carcinoma-associated, is characterized by dismal prognosis. The WBC count is inversely related to survival. Knowledge of this phenomenon militates against protracted, expensive work ups. In malignant neoplasms with prominent neutrophilic stroma, the pathologist should correlate with the WBC count and, if markedly elevated (>40 K/μL), raise consideration for PLR.
Topics: Adult; Aged; Aged, 80 and over; Colectomy; Colonic Neoplasms; Fatal Outcome; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemoid Reaction; Leukocyte Count; Male; Middle Aged; Neutrophil Infiltration; Paraneoplastic Syndromes; Treatment Outcome
PubMed: 33341546
DOI: 10.1016/j.prp.2020.153295 -
Cureus Mar 2021Hypersensitivity reactions to dapsone are common and potentially fatal adverse drug reactions. Herein, we report a case of a 45-year-old female who presented with fever,...
Hypersensitivity reactions to dapsone are common and potentially fatal adverse drug reactions. Herein, we report a case of a 45-year-old female who presented with fever, generalized desquamating rashes, and icterus three weeks after initiation of dapsone therapy for leprosy neuritis. She was diagnosed to have dapsone hypersensitivity syndrome (DHS) with leukemoid reaction and thrombocytosis. Dapsone was immediately discontinued, and she has treated with prednisolone 50 mg daily for a month and tapered over the next month. She has improved completely. DHS, leukemoid reaction, and severe thrombocytosis, or these adverse drug reactions to dapsone have rarely been reported.
PubMed: 33889465
DOI: 10.7759/cureus.14026 -
Cureus Dec 2023A leukemoid reaction is a rare condition characterized by an elevation in white blood cell count exceeding 50,000 cells/μL in response to severe medical conditions,...
A leukemoid reaction is a rare condition characterized by an elevation in white blood cell count exceeding 50,000 cells/μL in response to severe medical conditions, which can mimic the presentation of chronic myeloid leukemia (CML). Distinguishing between leukemoid reaction and CML depends on a thorough clinical history and comprehensive laboratory evaluation. We present a case of leukemoid reaction associated with severe diabetic ketoacidosis, where the patient's white blood cell count returned to the normal range after the correction of hyperglycemia and electrolyte imbalances.
PubMed: 38205495
DOI: 10.7759/cureus.50325 -
Cancer Immunology, Immunotherapy : CII Feb 2023Paraneoplastic leukemoid reaction (PLR) is a rare phenomenon in metastasized melanoma associated with poor prognosis and rapid disease progression. Currently, no...
BACKGROUND
Paraneoplastic leukemoid reaction (PLR) is a rare phenomenon in metastasized melanoma associated with poor prognosis and rapid disease progression. Currently, no specific therapeutic options exist other than treating the underlying malignancy.
METHODS
Five cases of paraneoplastic neutrophilia in patients with advanced-stage IV melanoma were enrolled in our study. Cytokine concentrations in patients' serum samples were analyzed before and during PLR using a multiplex cytokine array. Further, immunohistochemical staining of tumor tissue biopsied during PLR was performed.
RESULTS AND CONCLUSIONS
We observed a strong correlation between worsening of tumor burden and aggravation of neutrophilia. Cytokine measurements revealed an increase of proinflammatory cytokines (IL6, IFNγ), proangiogenic cytokines (VEGF) and immune stem cell growth factors (G-CSF) during PLR. Immunohistochemistry confirmed neutrophil infiltration of tumor tissue. The presented cytokine alterations provide a basis for further functional analysis, which is necessary for the development of targeted therapeutic approaches against PLR.
Topics: Humans; Cytokines; Leukemoid Reaction; Melanoma; Leukocytosis; Granulocyte Colony-Stimulating Factor; Prognosis; Neutrophils
PubMed: 35841421
DOI: 10.1007/s00262-022-03249-7