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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 -
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 Nov 2023Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst...
Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57% of the intra-tumor vascular areas, diminished the leukemoid reaction's progression, and the spleens' weight and length. A significant reduction in VEGF-C, SDF-1, angiopoietin-2, and endothelin-1 angiogenic factors was induced. Moreover, GK-1 prevents T cell exhaustion in the tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It also increased IFN-γ and granzyme-B expression and the cytotoxic activity of CD8 TILs cells against tumor cells. All these features were found to be associated with a better antitumor response and prognosis. Altogether, these results reinforce the potential of GK-1 to improve the clinical outcome of triple-negative breast cancer immunotherapy. Translation research is ongoing towards its evaluation in humans.
Topics: Humans; Female; Animals; Mice; Triple Negative Breast Neoplasms; T-Cell Exhaustion; Lymphocytes, Tumor-Infiltrating; Prognosis; Antineoplastic Agents; CD8-Positive T-Lymphocytes
PubMed: 37736849
DOI: 10.1007/s00262-023-03538-9 -
Pediatric Dermatology 2024Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an idiosyncratic drug reaction hallmarked by cutaneous eruption, fever, lymphadenopathy,...
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an idiosyncratic drug reaction hallmarked by cutaneous eruption, fever, lymphadenopathy, multiorgan involvement, and hematological abnormalities, most often eosinophilia and atypical lymphocytosis. Leukemoid reactions have rarely been described in DRESS syndrome and here we describe a 16-year-old male who was admitted to the hospital with DRESS syndrome due to minocycline, who had a severe leukocytosis up to 52.08 K/μL. He improved with cessation of minocycline and initiation of systemic steroids. We report this case to add to the literature on hematological abnormalities in pediatric DRESS syndrome.
Topics: Male; Humans; Child; Adolescent; Drug Hypersensitivity Syndrome; Minocycline; Leukemoid Reaction; Eosinophilia
PubMed: 37496096
DOI: 10.1111/pde.15392 -
Bulletin Du Cancer May 2024Neonatal acute myeloid leukemias (AML) occurred within the first 28 days of life and constitute only a small proportion of all AL. They are distinguished from leukemias... (Review)
Review
Neonatal acute myeloid leukemias (AML) occurred within the first 28 days of life and constitute only a small proportion of all AL. They are distinguished from leukemias of older children by their clinical presentation, which frequently includes cutaneous localizations ("blueberry muffin rash syndrome") and a leukocytosis above 50 ×10/L. This proliferation may be transient, causing a transient leukemoid reaction in a background of constitutional trisomy 21 ("Transient Abnormal Myelopoieseis" or TAM) or Infantile Myeloproliferative Disease in the absence of constitutional trisomy 21 ("Infantile Myeloproliferative Disease" or IMD). In cases of true neonatal AML, the prognosis of patients is poor. Overall survival is around 35 % in the largest historical series. This poor prognosis is mainly due to the period of onset of this pathology making the use of chemotherapy more limited and involving many considerations, both ethical and therapeutic. The objective of this work is to review this rare pathology by addressing the clinical, biological, therapeutic and ethical particularities of patients with true neonatal AML or transient leukemoid reactions occurring in a constitutional trisomy 21 (true TAM) or somatic background (IMD).
Topics: Humans; Leukemia, Myeloid, Acute; Infant, Newborn; Down Syndrome; Prognosis; Leukemoid Reaction; Myeloproliferative Disorders
PubMed: 38503585
DOI: 10.1016/j.bulcan.2023.12.010 -
The Journal of Maternal-fetal &... Dec 2023Neonatal leukemoid reaction is associated with higher risk of mortality, chronic lung disease and has been associated with chorioamnionitis. Literature on extremely low...
BACKGROUND
Neonatal leukemoid reaction is associated with higher risk of mortality, chronic lung disease and has been associated with chorioamnionitis. Literature on extremely low birth weight infants with leukemoid reaction is limited.
OBJECTIVES
The aim of our study was to characterize the maternal and placental factors associated with neonatal leukemoid reaction and to describe outcomes of these ELBW infants. Our objective was to assess if there were maternal factors that would assist the decision-making process regarding the delivery of preterm infants at risk of chorioamnionitis and the sequelae of this inflammatory process.
METHODS
This was a retrospective case-control study performed in a single, tertiary Maternity Hospital in Dublin. Two matched controls were identified for each case based on gestation and year of birth and data was collected on both the infants and their mothers.
RESULTS
7 extremely preterm neonates were identified as having a leukemoid reaction, defined as a total white cell count of >50,000 or in the first seven days of life. Baseline characteristics between the groups were similar. The median gestational age in the cases group was 24 + 4 weeks and in the control group was 24 + 1. The mean birthweight was 650 g in the cases group vs. 655 g in the control group. There was a higher percentage of males in the control group, 42.9% vs 28.6% in the cases. The preterm infants with leukemoid reaction had a longer duration of ventilation with a median of 18 days (7.5-23.5 days) compared to 6.5 days (2.8-24.5 days) in the control group. More infants in the leukemoid reaction group required inotropes for hypotension in the first 72 h after delivery (42.9% vs 7.1% in the controls, value .169). Death or Bronchopulmonary dysplasia (BPD) occurred in 85.7% of the cases identified with a leukemoid reaction vs 71.4% of the controls matched. Median maternal CRP was higher in cases prior to delivery vs the controls (66 vs 18.1 mg/L, -value = .2151). There was histological evidence of maternal inflammatory response in all cases with fetal inflammatory response in 71% of cases.
CONCLUSIONS
Leukemoid reaction in ELBW infants with evidence of maternal and fetal inflammatory response syndrome on placental histology is associated with a longer duration of initial ventilation, increased need for inotropes in the first 72 h after birth, higher rates of death, and BPD. Prospective studies are required to identify potential biomarkers such as proinflammatory cytokines, IL-6, which might aid the decision-making process in delivery.
Topics: Infant; Male; Infant, Newborn; Humans; Female; Pregnancy; Infant, Extremely Premature; Retrospective Studies; Leukemoid Reaction; Case-Control Studies; Chorioamnionitis; Intensive Care Units, Neonatal; Placenta; Gestational Age; Bronchopulmonary Dysplasia
PubMed: 37322830
DOI: 10.1080/14767058.2023.2225115 -
Journal of Hepatology Mar 2024
Topics: Humans; Jaundice; Leukocyte Disorders; Leukocytosis; Liver; Biopsy; Fatty Liver, Alcoholic; Methylprednisolone; Leukemoid Reaction
PubMed: 38368018
DOI: 10.1016/j.jhep.2023.10.014 -
Leukemia Mar 2024Constitutional trisomy 21 (T21) is a state of aneuploidy associated with high incidence of childhood acute myeloid leukemia (AML). T21-associated AML is preceded by...
Constitutional trisomy 21 (T21) is a state of aneuploidy associated with high incidence of childhood acute myeloid leukemia (AML). T21-associated AML is preceded by transient abnormal myelopoiesis (TAM), which is triggered by truncating mutations in GATA1 generating a short GATA1 isoform (GATA1s). T21-associated AML emerges due to secondary mutations in hematopoietic clones bearing GATA1s. Since aneuploidy generally impairs cellular fitness, the paradoxically elevated risk of myeloid malignancy in T21 is not fully understood. We hypothesized that individuals with T21 bear inherent genome instability in hematopoietic lineages that promotes leukemogenic mutations driving the genesis of TAM and AML. We found that individuals with T21 show increased chromosomal copy number variations (CNVs) compared to euploid individuals, suggesting that genome instability could be underlying predisposition to TAM and AML. Acquisition of GATA1s enforces myeloid skewing and maintenance of the hematopoietic progenitor state independently of T21; however, GATA1s in T21 hematopoietic progenitor cells (HPCs) further augments genome instability. Increased dosage of the chromosome 21 (chr21) gene DYRK1A impairs homology-directed DNA repair as a mechanism of elevated mutagenesis. These results posit a model wherein inherent genome instability in T21 drives myeloid malignancy in concert with GATA1s mutations.
Topics: Humans; Child; Down Syndrome; DNA Copy Number Variations; Myeloproliferative Disorders; Genomic Instability; Leukemia, Myeloid, Acute; Aneuploidy; Trisomy; GATA1 Transcription Factor; Leukemoid Reaction
PubMed: 38245602
DOI: 10.1038/s41375-024-02151-8 -
Pediatrics and Neonatology Jan 2024
Topics: Infant, Newborn; Humans; Leukemoid Reaction; Infant, Premature
PubMed: 37739873
DOI: 10.1016/j.pedneo.2023.05.007 -
Cureus Aug 2023Pulmonary mucoepidermoid carcinoma (PMEC) is rare and challenging to diagnose. Its association with paraneoplastic syndromes is poorly described. It is also uncommon for...
Pulmonary mucoepidermoid carcinoma (PMEC) is rare and challenging to diagnose. Its association with paraneoplastic syndromes is poorly described. It is also uncommon for a patient with lung cancer to present with multiple paraneoplastic syndromes. We report a case of a patient with metastatic high-grade PMEC associated with three paraneoplastic syndromes, namely, humoral hypercalcemia of malignancy, ectopic ACTH syndrome, and paraneoplastic leukemoid reaction.
PubMed: 37767242
DOI: 10.7759/cureus.44193