-
Frontiers in Pediatrics 2023Leukapheresis reduces hyperleukocytosis in children with acute leukemia. Although the usefulness of this procedure is under debate, a repeated small-volume exchange...
INTRODUCTION
Leukapheresis reduces hyperleukocytosis in children with acute leukemia. Although the usefulness of this procedure is under debate, a repeated small-volume exchange transfusion along with leukapheresis yielded satisfactory results.
METHODS
Forty-seven patients with acute leukemia [32 acute lymphocytic leukemia (ALL) and 15 acute myeloblastic leukemia (AML)] were enrolled between January 2017 and June 2022 and underwent repeated small-volume exchange transfusion. The following were measured: demographic and clinical characteristics, time of the procedure, PWBC (peripheral white blood cell) count, hemoglobin, platelet count, blood biochemistry, electrolytes, coagulation, leukostasis, TLS (tumor lysis syndrome), DIC (disseminated intravascular coagulopathy), adverse events (AEs), and serious AEs (SAEs).
RESULTS
The demographic and clinical characteristics were not significantly different between ALL and AML patients, but differences were observed in PWBC counts (424.2 ± 135.6 vs. 223.8 ± 58.0 × 109/L). The procedures needed 3-8 processes, and the average procedure time was not significantly different between ALL and AML. The PWBC count gradually reduced to <100 × 109/L; hemoglobin, platelet count, K+, Na+, and Ca2+ were unchanged. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, troponin-I, creatine kinase-MB, prothrombin time, and activated partial thromboplastin time maintained normal or recovered from abnormal ranges. The manifestations of leukostasis, TLS, and DIC improved or disappeared. No AEs and SAEs occurred. The required total blood volume was based on initial PWBC count, manifestations of leukostasis, and age.
CONCLUSIONS
Our finding suggests that repeated small-volume exchange transfusion is effective and safe for treating hyperleukocytosis in children with acute leukemia.
PubMed: 37033185
DOI: 10.3389/fped.2023.1155481 -
Glia Sep 2022Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia...
Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia contribute to both physiological and pathological angiogenesis, the molecular mechanisms by which these glia regulate pathological NV have not been fully elucidated. In this study, we utilized a retinal microglia-specific Transforming Growth Factor-β (Tgfβ) receptor knock out mouse model and human iPSC-derived microglia to examine the role of Tgfβ signaling in activated microglia during retinal NV. Using a tamoxifen-inducible, microglia-specific Tgfβ receptor type 2 (Tgfβr2) knockout mouse [Tgfβr2 KO (ΔMG)] we show that Tgfβ signaling in microglia actively represses leukostasis in retinal vessels. Furthermore, we show that Tgfβ signaling represses expression of the pro-angiogenic factor, Insulin-like growth factor 1 (Igf1), independent of Vegf regulation. Using the mouse model of oxygen-induced retinopathy (OIR) we show that Tgfβ signaling in activated microglia plays a role in hypoxia-induced NV where a loss in Tgfβ signaling microglia exacerbates and prolongs retinal NV in OIR. Using human iPSC-derived microglia cells in an in vitro assay, we validate the role of Transforming Growth Factor-β1 (Tgfβ1) in regulating Igf1 expression in hypoxic conditions. Finally, we show that Tgfβ signaling in microglia is essential for microglial homeostasis and that the disruption of Tgfβ signaling in microglia exacerbates retinal NV in OIR by promoting leukostasis and Igf1 expression.
Topics: Animals; Disease Models, Animal; Hypoxia; Insulin-Like Growth Factor I; Leukostasis; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Neovascularization, Pathologic; Oxygen; Retinal Diseases; Retinal Neovascularization; Transforming Growth Factor beta
PubMed: 35611927
DOI: 10.1002/glia.24218 -
Transfusion Medicine and Hemotherapy :... Aug 2022Leukostasis refers to clinical symptoms caused by hyperleukocytosis seen in some haematological diseases such as leukaemia. Cytoreduction can be achieved by therapeutic...
INTRODUCTION
Leukostasis refers to clinical symptoms caused by hyperleukocytosis seen in some haematological diseases such as leukaemia. Cytoreduction can be achieved by therapeutic leukapheresis. The aim of this study was to retrospectively analyse the procedures performed in our Centre and to evaluate their efficacy and safety.
METHODS
This was a retrospective study of all the therapeutic leukapheresis procedures carried out in our Centre between January 1998 and December 2020. The sample collection was obtained through the review of the clinical files of the respective patients. Statistical analysis was performed using the software R v.4.0.1. A total of 54 therapeutic leukapheresis procedures were performed in 31 patients in our Centre.
RESULTS
After these procedures clinical improvement was observed in 16 patients and we verify that there was a significant difference in survival between the group that improved and the group that maintained the same clinical condition or worsened. The lack of immediate clinical improvement was a sign of a poor prognosis. Laboratory efficacy occurred in 16 patients who had a reduction in white blood cell count, with a 39.1% reduction after 24 h, and did not succeed in 15 patients, who had no reduction. However, in this case there is no significant difference in survival between the two groups. There was some complication in 53.9% of the procedures, with hypocalcaemia being the most frequent, which was observed in 22 procedures. Only 4 patients experienced serious side effects but these adverse reactions cannot be attributed to the procedures carried out. The overall survival rate 6 months after this treatment was 51.6%.
CONCLUSION
Despite the reduced number of patients, we conclude that therapeutic leukapheresis is a safe and effective option that may still have a therapeutic role in some cases.
PubMed: 36159955
DOI: 10.1159/000520933 -
Cureus Sep 2019Hyperleukocytosis is defined as a white blood cell (WBC) count of ≥ 100,000/µL. Leukostasis refers to symptomatic hyperleukocytosis and is considered a medical...
Hyperleukocytosis is defined as a white blood cell (WBC) count of ≥ 100,000/µL. Leukostasis refers to symptomatic hyperleukocytosis and is considered a medical emergency. In pediatric practice, hyperleukocytosis is most commonly described in leukemia and other myeloproliferative disorder, but other etiologies, such as infection, are less commonly mentioned. In this case report, a one-day-old, preterm, male baby (26 weeks of gestation) was referred for preterm care. A sepsis-induced leukemoid reaction hyperleukocytosis diagnosis was presumed, and he was successfully treated with an empirical antibiotic with a gradual improvement in WBC counts.
PubMed: 31700707
DOI: 10.7759/cureus.5594 -
Cureus Nov 2021Acute coronary syndrome (ACS) is a condition that develops from reduced blood flow and oxygen delivery through the coronary arteries which leads to cardiac ischemia. In...
Acute coronary syndrome (ACS) is a condition that develops from reduced blood flow and oxygen delivery through the coronary arteries which leads to cardiac ischemia. In the case presented here, the patient's ACS was precipitated by his underlying condition of chronic myelogenous leukemia (CML). Several complications can arise in patients with CML, one of them being blast crisis. Blast crisis is defined by 20% or greater blasts in the peripheral blood, or extramedullary proliferation of blasts.There is a known phenomenon of blood hyperviscosity that can develop in such patients which can lead to complications of stroke-like symptoms, congestive heart failure, and acute respiratory failure. In such cases, leukostasis rarely leads to myocardial ischemia. We present a challenging case of a patient with an acute coronary syndrome (ACS) precipitated by a blast crisis. This case highlights a potentially life-threatening cardiac complication of CML in patients with coronary artery disease and aimed to provide an optimal treatment strategy to improve outcomes.
PubMed: 34926059
DOI: 10.7759/cureus.19589 -
Leukemia Research Reports 2021Leukemoid reactions following surgery are commonly caused by infections or tissue injury. Management is directed towards underlying condition and cytoreduction is not...
Leukemoid reactions following surgery are commonly caused by infections or tissue injury. Management is directed towards underlying condition and cytoreduction is not indicated. Chronic myelo-monocytic leukemia (CMML) is a clonal hematological malignancy characterized by persistent monocytosis and overlapping features of myelodysplastic and myeloproliferative neoplasms.In this case report we describe a 51-year-old Hispanic female without any significant prior medical history, who underwent a cholecystectomy for calculous cholecystitis. Post-operative course was complicated by hyperleukocytosis leading to splenic infarction and intracranial hemorrhage. Further investigations led to a diagnosis of CMML-2. A literature review of patients with CMML who developed post-operative leukocytosis and leukostasis (POLL) is presented.Case high lights two critical points: Post-operative hyperleukocytosis with leukostasis can be the first presentation of CMML Rapid diagnosis and institution of cytoreductive therapy with hydroxyurea is critical to avoid high morbidity and mortality.
PubMed: 34934616
DOI: 10.1016/j.lrr.2021.100283 -
Cureus Nov 2022Leukostasis is a life-threatening complication that causes vascular occlusion leading to organ damage in leukemia patients. Organs with impairment due to leukostasis are...
Leukostasis is a life-threatening complication that causes vascular occlusion leading to organ damage in leukemia patients. Organs with impairment due to leukostasis are usually the lungs and kidneys, but other organs may also be damaged. We experienced an autopsy case of severe infarction in multiple organs including the spleen probably due to leukostasis in a patient with acute myeloid leukemia.
PubMed: 36532923
DOI: 10.7759/cureus.31518 -
Investigative Ophthalmology & Visual... Feb 2013Retinal hemorrhages occur in a variety of sight-threatening conditions including ocular trauma, high altitude retinopathy, and chronic diseases such as diabetic and...
PURPOSE
Retinal hemorrhages occur in a variety of sight-threatening conditions including ocular trauma, high altitude retinopathy, and chronic diseases such as diabetic and hypertensive retinopathies. The goal of this study is to investigate the effects of blood in the vitreous on retinal vascular function in rats.
METHODS
Intravitreal injections of autologous blood, plasma kallikrein (PK), bradykinin, and collagenase were performed in Sprague-Dawley and Long-Evans rats. Retinal vascular permeability was measured using vitreous fluorophotometry and Evans blue dye permeation. Leukostasis was measured by fluorescein isothiocyanate-coupled concanavalin A lectin and acridine orange labeling. Retinal hemorrhage was examined on retinal flatmounts. Primary cultures of bovine retinal pericytes were cultured in the presence of 25 nM PK for 24 hours. The pericyte-conditioned medium was collected and the collagen proteome was analyzed by tandem mass spectrometry.
RESULTS
Intravitreal injection of autologous blood induced retinal vascular permeability and retinal leukostasis, and these responses were ameliorated by PK inhibition. Intravitreal injections of exogenous PK induced retinal vascular permeability, leukostasis, and retinal hemorrhage. Proteomic analyses showed that PK increased collagen degradation in pericyte-conditioned medium and purified type IV collagen. Intravitreal injection of collagenase mimicked PK's effect on retinal hemorrhage.
CONCLUSIONS
Intraocular hemorrhage increases retinal vascular permeability and leukostasis, and these responses are mediated, in part, via PK. Intravitreal injections of either PK or collagenase, but not bradykinin, induce retinal hemorrhage in rats. PK exerts collagenase-like activity that may contribute to blood-retinal barrier dysfunction.
Topics: Animals; Blood; Blood-Retinal Barrier; Bradykinin; Capillary Permeability; Cattle; Cells, Cultured; Collagenases; Concanavalin A; Evans Blue; Fluorescein-5-isothiocyanate; Fluorophotometry; Intravitreal Injections; Leukostasis; Male; Pericytes; Plasma Kallikrein; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Retinal Diseases; Retinal Hemorrhage; Retinal Vessels; Tandem Mass Spectrometry; Vitreous Body
PubMed: 23299478
DOI: 10.1167/iovs.12-10537 -
Investigative Ophthalmology & Visual... Oct 2021Previous studies indicate that leukocytes, notably neutrophils, play a causal role in the capillary degeneration observed in diabetic retinopathy (DR), however, the...
PURPOSE
Previous studies indicate that leukocytes, notably neutrophils, play a causal role in the capillary degeneration observed in diabetic retinopathy (DR), however, the mechanism by which they cause such degeneration is unknown. Neutrophil elastase (NE) is a protease released by neutrophils which participates in a variety of inflammatory diseases. In the present work, we investigated the potential involvement of NE in the development of early DR.
METHODS
Experimental diabetes was induced in NE-deficient mice (Elane-/-), in mice treated daily with the NE inhibitor, sivelestat, and in mice overexpressing human alpha-1 antitrypsin (hAAT+). Mice were assessed for diabetes-induced retinal superoxide generation, inflammation, leukostasis, and capillary degeneration.
RESULTS
In mice diabetic for 2 months, deletion of NE or selective inhibition of NE inhibited diabetes-induced retinal superoxide levels and inflammation, and inhibited leukocyte-mediated cytotoxicity of retinal endothelial cells. In mice diabetic for 8 months, genetic deletion of NE significantly inhibited diabetes-induced retinal capillary degeneration.
CONCLUSIONS
These results suggest that a protease released from neutrophils contributes to the development of DR, and that blocking NE activity could be a novel therapy to inhibit DR.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Male; Mice; Mice, Inbred C57BL; Neutrophils; Peptide Hydrolases; Retina
PubMed: 34643662
DOI: 10.1167/iovs.62.13.7 -
Annals of Hematology Apr 2023Hyperleukocytosis is associated with a significant early mortality rate in patients with acute myeloid leukemia (AML). To date, no controlled trial has ever evaluated a...
Hyperleukocytosis is associated with a significant early mortality rate in patients with acute myeloid leukemia (AML). To date, no controlled trial has ever evaluated a strategy to reduce this risk, and the initial management of these patients remains heterogeneous worldwide. The aim of the present study was to evaluate the influence of a short course of intravenous dexamethasone on the early outcomes of patients with hyperleukocytic AML with white blood cell (WBC) count above 50 × 10/L. Clinical and biological data of all consecutive patients (1997-2017) eligible for intensive chemotherapy from a single center were retrospectively collected. A total of 251 patients with a median age of 51 years and a median WBC count of 120 × 10/L were included, 95 of whom received dexamethasone. Patients treated with dexamethasone had higher WBC count and a more severe disease compared with those who did not, and they presented more often with leukostasis and hypoxemia, resulting in a more frequent need for life-sustaining therapies (p < 0.001). To account for these imbalances, patients were compared after adjusting for a propensity score, which included all variables with a prognostic influence in the overall cohort. In the matched cohort, dexamethasone was associated with lower early death (OR = 0.34, p = 0.0026) and induction failure rate (OR = 0.44, p = 0.02) and better overall survival (HR = 0.60, p = 0.011), with no impact on relapse risk (cHR = 0.73, p = 0.39). The overall survival benefit was confirmed among all tested subgroups. This study suggests that dexamethasone administration is safe and associated with a lower risk of induction mortality in patients with hyperleukocytic AML and deserves prospective evaluation.
Topics: Humans; Middle Aged; Leukocytosis; Propensity Score; Retrospective Studies; Leukemia, Myeloid, Acute; Dexamethasone
PubMed: 36773040
DOI: 10.1007/s00277-023-05119-3