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Introduction: Preclinical studies suggest that cannabinoid receptor type 2 (CB2R) activation has a therapeutic effect in animal models on chronic inflammation and vascular permeability, which are key pathological features of diabetic retinopathy (DR). A novel CB2R agonist, triazolopyrimidine RG7774, was generated through lead optimization of a high-throughput screening hit. The aim of this study was to characterize the pharmacology, absorption, distribution, metabolism, elimination, and toxicity (ADMET) profile of RG7774, and to explore its potential for managing the key pathological features associated with retinal disease in rodents. Methods: The in vitro pharmacology of RG7774 was investigated for CB2R binding and receptor activation using recombinant human and mouse CB2R expression in Chinese hamster ovary cells, and endogenous CB2R expression in human Jurkat cells, and rat and mouse spleen cells. The ADMET profile was evaluated and the effects of RG7774 on retinal permeability, leukocyte adhesion, and choroidal neovascularization (CNV) were investigated in rodent models of retinal disease. Pharmacokinetic (PK) parameters and the exposure-response relationship were characterized in healthy animals and in animals with laserinduced CNV. Results: RG7774was found to be a potent (EC50: 2.8 nMand Ki: 51.3 nM), selective, and full CB2R agonist with no signs of cannabinoid receptor type 1 (CB1R) binding or activation. The ligand showed a favorable ADMET profile and exhibited systemic and ocular exposure after oral delivery. Functional potency in vitro translated from recombinant to endogenous expression systems. In vivo, orally administered RG7774 reduced retinal permeability and leukocyte adhesion in rodents with lipopolysaccharide (LPS)-induced uveitis and streptozotocin (STZ)-induced DR, and reduced lesion areas in rats with laser-induced CNV with an ED50 of 0.32 mg/kg. Anatomically, RG7774 reduced the migration of retinal microglia to retinal lesions. Discussion: RG7774 is a novel, highly selective, and orally bioavailable CB2R agonist, with an acceptable systemic and ocular PK profile, and beneficial effects on retinal vascular permeability, leukocyte adhesion, and ocular inflammation in rodent animal models. Results support the development of RG7774 as a potential treatment for retinal diseases with similar pathophysiologies as addressed by the animal models. [ABSTRACT FROM AUTHOR]

Innovations in oncology have expanded treatment eligibility, leading to a rise in cancer patients requiring critical care. This necessitates that all critical care clinicians possess a fundamental knowledge of prevalent oncological conditions and identify emergent scenarios requiring immediate action. This article will explore key oncological complications and their management approaches. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and hypertension as individuals age. DR is a severe microvascular complication of both type I and type II diabetes mellitus and the leading cause of vision impairment. The critical approach to combatting and halting the advancement of DR lies in effectively managing blood glucose and blood pressure levels in diabetic patients; however, this is seldom achieved. Both human and animal studies have revealed the intricate nature of this condition involving various cell types and molecules. Aside from photocoagulation, the sole therapy targeting VEGF molecules in the retina to prevent abnormal blood vessel growth is intravitreal anti-VEGF therapy. However, a substantial portion of cases, approximately 30-40%, do not respond to this treatment. This review explores distinctive pathophysiological phenomena of DR and identifiable cell types and molecules that could be targeted to mitigate the chronic changes occurring in the retina due to diabetes mellitus. Addressing the significant research gap in this domain is imperative to broaden the treatment options available for managing DR effectively. [ABSTRACT FROM AUTHOR]

IntroductionPreclinical studies suggest that cannabinoid receptor type 2 (CB2R) activation has a therapeutic effect in animal models on chronic inflammation and vascular permeability, which are key pathological features of diabetic retinopathy (DR). A novel CB2R agonist, triazolopyrimidine RG7774, was generated through lead optimization of a high-throughput screening hit. The aim of this study was to characterize the pharmacology, absorption, distribution, metabolism, elimination, and toxicity (ADMET) profile of RG7774, and to explore its potential for managing the key pathological features associated with retinal disease in rodents.MethodsThe in vitro pharmacology of RG7774 was investigated for CB2R binding and receptor activation using recombinant human and mouse CB2R expression in Chinese hamster ovary cells, and endogenous CB2R expression in human Jurkat cells, and rat and mouse spleen cells. The ADMET profile was evaluated and the effects of RG7774 on retinal permeability, leukocyte adhesion, and choroidal neovascularization (CNV) were investigated in rodent models of retinal disease. Pharmacokinetic (PK) parameters and the exposure-response relationship were characterized in healthy animals and in animals with laser-induced CNV.ResultsRG7774 was found to be a potent (EC50: 2.8 nM and Ki: 51.3 nM), selective, and full CB2R agonist with no signs of cannabinoid receptor type 1 (CB1R) binding or activation. The ligand showed a favorable ADMET profile and exhibited systemic and ocular exposure after oral delivery. Functional potency in vitro translated from recombinant to endogenous expression systems. In vivo, orally administered RG7774 reduced retinal permeability and leukocyte adhesion in rodents with lipopolysaccharide (LPS)-induced uveitis and streptozotocin (STZ)-induced DR, and reduced lesion areas in rats with laser-induced CNV with an ED50 of 0.32 mg/kg. Anatomically, RG7774 reduced the migration of retinal microglia to retinal lesions.DiscussionRG7774 is a novel, highly selective, and orally bioavailable CB2R agonist, with an acceptable systemic and ocular PK profile, and beneficial effects on retinal vascular permeability, leukocyte adhesion, and ocular inflammation in rodent animal models. Results support the development of RG7774 as a potential treatment for retinal diseases with similar pathophysiologies as addressed by the animal models.

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Simple Summary: Leukostasis in hyperleukocytotic acute myeloid leukemia (AML) is a medical emergency. The optimal treatment strategy and the potential benefits of incorporating emergency leukapheresis (LA) are still unclear. In our retrospective study, we observed a striking difference in the outcome of FLT3-ITD mutated (mut) AML patients undergoing LA in the early phase of treatment compared to patients with FLT3 wildtype (wt). Knowledge of mutational status might guide treatment decisions in the early phase of hyperleukocytosis. Purpose: We aimed to identify subsets of patients who benefit from emergency LA and to establish a therapeutic algorithm for AML patients with hyperleukocytosis. Methods: In this single-center retrospective cohort study, a total of 20 consecutive patients underwent LA because of their clinical symptoms. Overall survival (OS) analysis was conducted using the Kaplan–Meier plot method. Univariate and multivariate analyses (using multiple logistic regression) were performed. At the time of diagnosis, all patients received a standard diagnostic workup for AML including FLT3-ITD mutational analysis. Results: FLT3-ITD mut AML patients receiving LA had a median OS of 437 days (range 5–2379 days) with a corresponding 14-day survival of 92.3%, while FLT3 wt AML patients displayed a significantly lower median OS of only 5 days (range 1–203 days) with a corresponding 14-day survival of 14.3% (p = 0.0001). Conclusions: Among patients with clinical symptoms of leukostasis, the subset of FLT3-ITD mut AML patients showed a better outcome with lower early mortality after emergency LA. Based on these observations, we established a therapeutic algorithm for AML patients with hyperleukocytosis. [ABSTRACT FROM AUTHOR]

Hyperleukocytosis, a white blood cell count greater than 100,000/mcl, can be associated with the following three primary oncologic emergencies: leukostasis, disseminated intravascular coagulation, and tumor lysis syndrome. These complications significantly increase a patient’s risk of morbidity and mortality. Therefore, timely evidence-based interventions ensure patient safety. This article provides clinical evidence and guidelines for advanced practice nurses working in hematology-oncology to support diagnostic workup and management of hyperleukocytosis in patients with acute myeloid leukemia. A patient case study demonstrates key concepts. [ABSTRACT FROM AUTHOR]

Background: For the past 30 years, white blood cell depletion (WBCD) or leukocytapheresis has been conducted to rapidly reduce excessive circulating white blood cell (WBC) concentrations in patients at risk for or with symptoms of leukostasis due to hyperleukocytosis. The goal of leukocytapheresis is to prevent or treat acute complications from leukostasis, thereby enabling patients to receive potentially curative chemotherapy. Methods: This report details the results from a retrospective and a prospective clinical study conducted in the European Union and the People's Republic of China, which assessed the use of the Spectra Optia Apheresis System for leukocytapheresis in patients with hyperleukocytosis. The primary objective of both studies was to the assess the safety and performance of the WBCD procedure in patients with elevated WBC counts. Results: Data were collected from 72 participants completing 87 WBCD procedures. The mean percent change in participant WBC counts post‐procedure was 50.3 ± 21.2% and the collection efficiency (CE1) of the WBCD procedures was 53.7 ± 19.8%. Sixty‐one participants (95.3%) experienced a total of 279 adverse events (AEs) with the majority of the AEs related to post‐procedure changes in laboratory values, which is an anticipated AE in this patient population. Conclusion: The data collected within these studies indicate that the WBCD procedure is safe and well tolerated in patients with hyperleukocytosis as evaluated by percent decrease in WBC count, CE1, and AE incidence. [ABSTRACT FROM AUTHOR]

Introduction: Our study investigated leukapheresis's effect on delayed induction therapy outcomes in patients with acute leukemia presenting with symptomatic hyperleukocytosis. Methods: This retrospective cohort study included 30 adult patients diagnosed with acute leukemia who underwent leukapheresis for leukostasis. The patients were divided into the first 24 h and >24 h groups, according to the time from diagnosis to induction therapy (TDT). Results: There was no significant difference between the TDT groups regarding complete remission (CR), 4‐week mortality, and overall survival (OS) at a median follow‐up of 409 days. Tumor lysis syndrome, disseminated intravascular coagulation, and hemoglobin levels were significant in early mortality. In univariate analysis, age, hemoglobin levels, patients' eligibility for intensive chemotherapy, and achieving CR were critical factors for OS. Conclusion: The study findings suggest that waiting for the clinical and laboratory results may be a safe and reasonable approach before assigning patients the best treatment option with leukapheresis. [ABSTRACT FROM AUTHOR]

Pediatric chronic myeloid leukemia (CML) is a very rare malignancy (age-related incidence 0.1/100,000) typically presenting with leucocyte counts >100,000/µL. However, clinical signs of leukostasis are observed at diagnosis in only approximately 10% of all cases and among these, priapism is infrequent. Here, we analyze data from pediatric CML registries on the occurrence of priapism heralding diagnosis of CML in 16/491 (3.2%) boys (median age 13.5 years, range 4–18) with pediatric CML. In the cohort investigated, duration of priapism resulting in a diagnosis of CML was not reported in 5 patients, and in the remaining 11 patients, occurred as stuttering priapism over 3 months (n = 1), over 6 weeks (n = 1), over 1–2 weeks (n = 2), over several days (n = 2), or 24 h (n = 1), while the remaining 4 boys reported continuous erection lasting over 11–12 h. All patients exhibited splenomegaly and massive leukocytosis (median WBC 470,000/µL, range 236,700–899,000). Interventions to treat priapism were unknown in 5 patients, and in the remaining cohort, comprised intravenous fluids ± heparin (n = 2), penile puncture (n = 5) ± injection of sympathomimetics (n = 4) ± intracavernous shunt operation (n = 1) paralleled by leukocyte-reductive measures. Management without penile puncture by leukapheresis or exchange transfusion was performed in 3 boys. In total, 7 out 15 (47%) long-term survivors (median age 20 years, range 19–25) responded to a questionnaire. All had maintained full erectile function; however, 5/7 had presented with stuttering priapism while in the remaining 2 patients priapism had lasted <12 h until intervention. At its extreme, low-flow priapism lasting for longer than 24 h may result in partial or total impotence by erectile dysfunction. This physical disability can exert a large psychological impact on patients' lives. In a narrative review fashion, we analyzed the literature on priapism in boys with CML which is by categorization stuttering or persisting as mostly painful, ischemic (low-flow) priapism. Details on the pathophysiology are discussed on the background of the different blood rheology of hyperleukocytosis in acute and chronic leukemias. In addition to the data collected, instructive case vignettes demonstrate the diagnostic and treatment approaches and the outcome of boys presenting with priapism. An algorithm for management of priapism in a stepwise fashion is presented. All approaches must be performed in parallel with cytoreductive treatment of leukostasis in CML which comprises leukapheresis and exchange transfusions ± cytotoxic chemotherapy. [ABSTRACT FROM AUTHOR]

An otherwise healthy 27-year-old woman presented with bilateral blurry vision and was found to have diffuse posterior venous stasis with significant retinal ischemia. On further examination, she was found to have chronic myeloid leukemia with life-threatening leukocytosis. Prompt systemic treatment can result in near-complete resolution of any ocular pathology Purpose: The following case report highlights a rare presentation of chronic myeloid leukemia-associated hyper-viscosity syndrome and provides a brief review of expected findings and treatment outcomes. Methods: An otherwise healthy 27-year-old woman presented to the ophthalmology clinic with mild bilateral blurriness (20/20 in both eyes) and prolonged light adaption in the morning for several months. Examination demonstrated severe bilateral venous stasis, white-centered hemorrhages, intraretinal hemorrhage, and peripheral ischemia with diffuse leakage. Results: Same-day CBC demonstrated a leukocytosis of >600,000. Subsequent bone marrow biopsy confirmed the 9,22 translocation (Philadelphia chromosome). On further examination, the patient had an enlarged cardiac silhouette, cytopenia, and splenomegaly past the umbilicus, consistent with a severe and life-threatening leukostasis. Conclusion: Ocular involvement can occur in acute and chronic leukemia. Five to ten percentage of patients present to an eye physician first, without a known diagnosis. Prompt systemic treatment can result in near-complete reversal of any intraocular injury in most mild-to-moderate cases, as was the case here. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the first-line treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor -α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.

Abstract Priapism is a rare presenting feature of chronic myeloid leukemia (CML) in male patients. Treatment aims to relieve symptoms and to prevent erectile dysfunction. Several treatment modalities exist, however no standard treatment is recommended. We evaluated literature concerning different treatment approaches and evaluate the value of leukapheresis in treatment of priapism. The literature search resulted in 57 included articles, consisting of 53 studied patients. Patients had a mean age of 25.3 years, average time from onset to presentation at the hospital was 2 days, and mean white blood cell (WBC) count was 344 × 109/L. Most patients (67.9%) were treated with a combined approach (different modalities were radiological, urological, and oncological treatment). Twelve patients, with a mean WBC count of 365 × 109/L, received leukapheresis. Only two of them reported erectile dysfunction after treatment. Priapism is an urological emergency requiring urgent multidisciplinary treatment. We highlight the importance of local urological therapy combined with systemic therapy for CML. Therapeutic leukapheresis should be applied when available and with no other contraindications.

Inflammation is essential in the protection of the organism and wound repair, but in cases of chronic inflammation can also cause microvasculature deterioration. Thus, inflammation monitorization studies are important to test potential therapeutics. The intravital microscopy (IVM) technique monitors leukocyte trafficking in vivo, being a commonly used procedure to report systemic conditions. Although the cremaster muscle, an established protocol for IVM, may affect the hemodynamics because of its surgical preparation, only male animals are used, and longitudinal studies over time are not feasible. Thinking how this impacts future studies, our aim is to understand if the IVM technique can be successfully performed using the ear lobe instead of the cremaster muscle. Elevated IL-1β plasmatic concentrations confirmed the systemic inflammation developed in a diabetic animal model, while the elevated number of adherent and rolling leukocytes in the ear lobe allowed for the same conclusion. Thus, this study demonstrates that albeit its thickness, the ear lobe protocol for IVM is efficient, non-invasive, more reliable, cost-effective and timesaving. [ABSTRACT FROM AUTHOR]

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 × 109/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 × 109/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. [ABSTRACT FROM AUTHOR]

IntroductionLeukapheresis 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.MethodsForty-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).ResultsThe 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

Background: Chronic myeloid leukemia (CML) is mostly asymptomatic at diagnosis. Intracerebral hemorrhage (ICH), as the first presentation of CML in its chronic phase (CP) has only once been reported in the literature. In addition, CML (CP) patients developing ICH are equally rare, with only eight cases reported. ICH is more commonly associated with CML progressing to its end stage (accelerated phase [AP] and blast crisis [BC]). The pathophysiology of ICH in CML-CP is postulated to be due to leukostasis, unlike in the CML-AP/BC, where thrombocytopenia and coagulopathy are the underlying mechanisms. This case adds to the scarce literature on a rare and challenging complication of ICH in CML-CP, especially as these patients tend to rebleed and management is uncertain. Case Description: A 22-year-old male presented with a 2-week history of headaches and vomiting, associated with a 1-week history of the left-sided weakness. Initial blood work revealed hyperleukocytosis. The patient was investigated for CML with intracranial involvement. During his stay, his Glasgow coma score (GCS) dropped (from 14 to 11), prompting an urgent CT scan which revealed a large resolving ICH with perifocal edema and midline shift. A decompressive hemicraniectomy with expansion duraplasty was performed to alleviate the mass effect and reduce intracranial pressure. Three hours postoperatively, the patient developed an extradural hematoma which needed prompt evacuation. A postoperative CT revealed an improved midline shift, and after 7 days, his GCS improved to 15, and he began oncological treatment. Neurological symptoms were experienced by our patient at presentation with hyperleukocytosis on full blood count, which may implicate leukostasis as an underlying mechanism. Conclusion: Even in the CP, CML patients presenting with mild neurological symptoms should be investigated to exclude intracranial bleeds. As these patients tend to rebleed, they should be conservatively managed unless there is a need to alleviate intracranial pressure. [ABSTRACT FROM AUTHOR]

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy. [ABSTRACT FROM AUTHOR]

Digital ischemia with gangrene is a rare manifestation of chronic myeloid leukemia (CML). We report a rare CML case with severe thrombocytosis presenting clinically as digital ischemia and gangrene, the sole primary symptom. A 40-year-old patient presented with pain and discoloration of the tips of the ring and little fingers of the right hand for 20 days, which later progressed to dry gangrene with a line of demarcation and pre-gangrenous changes in the index and middle fingers. He was a chronic smoker and alcoholic with no other comorbidities. On investigation, he was found to have abnormal leukocytosis (153,000/mm 3 ) and moderate thrombocytosis (969,000/mm 3 ) with anemia. In view of abnormal leukocytosis, he was investigated for leukemia. He was found to be positive for BCR-ABL by reverse transcription polymerase chain reaction (RT-PCR), thus confirming the diagnosis of CML. He received imatinib 400 mg/day and subsequently experienced resolution of symptoms and complete hematological response by the 12th week of therapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patil et al.)

Twelve to 22% of pediatric acute myeloid leukemia (AML) patients present with hyperleukocytosis, which is one of the main risk factors of early death due to its clinical complications: leukostasis, causing pulmonary or central nervous system injuries, tumor lysis syndrome, and disseminated intravascular coagulation. Sorafenib is a multi-kinase inhibitor that blocks the Fms-Related Tyrosine Kinase 3 receptor (FLT3) in AML patients with a FLT3-internal tandem duplication (FLT3-ITD), leading to a reduction of proliferation. Here we report four de novo diagnosed or relapsed pediatric FLT3-ITD–positive AML patients with hyperleukocytosis, which were treated with sorafenib in combination with cytoreductive chemotherapy prior to the start of the induction phase. We observed a fast reduction of white blood cells in peripheral blood and bone marrow. This resulted in a rapid clinical stabilization of the patients. Adverse side effects—such as dermatologic toxicity, elevation of transaminases and hypertension—occurred but were mild and inductive chemotherapy could be started in parallel or subsequently. This implies sorafenib as a safe and effective treatment option in combination with chemotherapy during cytoreductive prephase for children with this life-threatening condition.

Leukostasis is a life-threatening complication of high concentrations of circulating leukemic cells, most often myeloblasts. Effective care of patients with leukostasis involves early recognition and treatment, and aggressive management of concurrent complications of the underlying leukemia. The relatively poor prognosis in patients with leukostasis underscores the importance of the timely and effective care of this hematologic emergency. While cytoreductive measures such as hydroxyurea, corticosteroids, intravenous chemotherapy, and leukapheresis are available to urgently reduce high cell counts, characterization of the leukemia and initiation of tailored, definitive treatment is a parallel priority. However, data supporting any specific cytoreductive approach are limited, making clinical practice guided primarily by expert opinion. In this review, we discuss the pathophysiology, clinical manifestations, diagnosis, and management of leukemic hyperleukocytosis and leukostasis, with an emphasis on how to acutely manage this oncologic emergency in patients with acute myeloid leukemia, which is the most common cause of symptomatic leukostasis. [ABSTRACT FROM AUTHOR]

As outcomes have improved across the hematologic malignancy population, candidacy for ICU admission has increased. This complex population may develop a variety of complications related to their treatment or underlying disease that can result in critical illness necessitating ICU support. This review highlights common causes of critical illness associated with hematologic malignancies, including the following: (1) neutropenic sepsis; (2) hyperleukocytosis and leukostasis across patients with acute myeloid leukemia; (3) complications of acute promyelocytic leukemia; (4) tumor lysis syndrome; and (5) critical care complications that can arise following hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Dongdong Zhang,1 Yufan Zhu,2 Yanxia Jin,3 Natasha Mupeta Kaweme,3 Youhong Dong1 1Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, Hubei, 441000, People’s Republic of China; 2Orthopedics department, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of China; 3Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Youhong DongDepartment of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, Hubei, 441000, People’s Republic of ChinaEmail dongyouhong2005@163.comAbstract: Hyperleukocytosis is a hematologic crisis caused by excessive proliferation of leukemic cells and has a relatively high early mortality due to a series of severe complications. Therefore, prompt and effective intervention is required. Leukapheresis performed using apheresis equipment to separate leukocytes from peripheral blood, at the same time returns autologous plasma, platelets and erythrocytes to the patient, is applied clinically for the treatment of hyperleukocytosis. Leukapheresis not only removes excessive leukocytes rapidly and corrects metabolic abnormalities but also alleviates the symptoms of leukostasis. In addition, the procedure of leukapheresis is generally well tolerated. Leukapheresis has become one of the most imperative adjuvant therapies to treat hyperleukocytosis, especially in the patient who was not inappropriate to cytoreduce with Ara-C or hydroxyurea. In this review, we present the background of leukapheresis development and highlight its clinical application in hyperleukocytic leukemia patients.Keywords: hyperleukocytosis, leukapheresis, leukostasis, hyperleukocytic leukemia

Ikhwan Rinaldi,1 Resti Mulya Sari,2 Vanya Utami Tedhy,3 Kevin Winston3 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Division of Hematology and Medical Oncology, Department of Internal Medicine, Dharmais National Cancer Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Ikhwan RinaldiDivision of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, IndonesiaTel +628111001758Email ikhwan.rinaldi@ui.ac.idIntroduction: Leukostasis is a medical emergency with high mortality which often occurs in acute myeloid leukemia patients with hyperleukocytosis. One of the therapies that can be used for leukostasis in acute myeloid leukemia is leukapheresis. However, whether leukapheresis can provide better survival benefit when compared with patients not receiving leukapheresis is still unclear. Hence, we aimed to evaluate the effect of chemotherapy plus leukapheresis combination versus chemotherapy only on 28-day survival of acute myeloid leukemia patients with leukostasis.Methods: This study was a dual-center retrospective cohort using secondary data from medical records collected from November 2018 to March 2019. Inclusion criteria were adult patients aged 18 years old or above, diagnosed with acute leukemia with hyperleukocytosis status defined by WBC count greater than 100,000/uL, and with symptoms of leukostasis. One-month survival analysis was conducted using Kaplan–Meier curve method. Univariate and multivariate analyses were then conducted using Cox proportional hazards model to obtain value of hazard ratio (HR) with a 95% confidence interval (CI).Results: A total of 38 patients were obtained for analysis. The median overall survival was 25 days (95% CI: 17.001– 32.999 days) in the chemotherapy only group and 20 days (95% CI: 1.497– 38.503) in the chemotherapy with leukapheresis group. The use of leukapheresis did not affect 28-day survival (HR: 1.140; 95% CI: 0.396– 3.283; p value: 0.809) and 7-day survival (HR: 1.073; 95% CI: 0.277– 4.152; p value: 0.919). In the multivariate analysis, age ≥ 60 years, blast percentage ≥ 90%, creatinine ≥ 1.4 mg/dL, and presence of disseminated intravascular coagulation were associated with worse 28-day survival.Conclusion: AML patients with leukostasis who received both chemotherapy and leukapheresis did not have better 28-day survival and 7-day survival when compared with patients receiving chemotherapy only. Old age, high blast percentage, high creatinine, and presence of disseminated intravascular coagulation were prognostic factors for worse 28-day survival.Keywords: leukemia, hyperleukocytosis, leukostasis, leukapheresis, chemotherapy, survival

Müller cells and macrophages/microglia are likely important for the development of diabetic retinopathy; however, the interplay between these cells in this disease is not well understood. An inflammatory process is linked to the onset of experimental diabetic retinopathy. CD40 deficiency impairs this process and prevents diabetic retinopathy. Using mice with CD40 expression restricted to Müller cells, we identified a mechanism by which Müller cells trigger proinflammatory cytokine expression in myeloid cells. During diabetes, mice with CD40 expressed in Müller cells upregulated retinal tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), intracellular adhesion molecule 1 (ICAM-1), and nitric oxide synthase (NOS2), developed leukostasis and capillary degeneration. However, CD40 did not cause TNF-α or IL-1β secretion in Müller cells. TNF-α was not detected in Müller cells from diabetic mice with CD40+ Müller cells. Rather, TNF-α was upregulated in macrophages/microglia. CD40 ligation in Müller cells triggered phospholipase C-dependent ATP release that caused P2X7-dependent production of TNF-α and IL-1β by macrophages. P2X7-/- mice and mice treated with a P2X7 inhibitor were protected from diabetes-induced TNF-α, IL-1β, ICAM-1, and NOS2 upregulation. Our studies indicate that CD40 in Müller cells is sufficient to upregulate retinal inflammatory markers and appears to promote experimental diabetic retinopathy and that Müller cells orchestrate inflammatory responses in myeloid cells through a CD40-ATP-P2X7 pathway.

Inflammation is essential in the protection of the organism and wound repair, but in cases of chronic inflammation can also cause microvasculature deterioration. Thus, inflammation monitorization studies are important to test potential therapeutics. The intravital microscopy (IVM) technique monitors leukocyte trafficking in vivo, being a commonly used procedure to report systemic conditions. Although the cremaster muscle, an established protocol for IVM, may affect the hemodynamics because of its surgical preparation, only male animals are used, and longitudinal studies over time are not feasible. Thinking how this impacts future studies, our aim is to understand if the IVM technique can be successfully performed using the ear lobe instead of the cremaster muscle. Elevated IL-1β plasmatic concentrations confirmed the systemic inflammation developed in a diabetic animal model, while the elevated number of adherent and rolling leukocytes in the ear lobe allowed for the same conclusion. Thus, this study demonstrates that albeit its thickness, the ear lobe protocol for IVM is efficient, non-invasive, more reliable, cost-effective and timesaving.

Hyperleukocytosis in pediatric acute leukemia is associated with increased morbidity and mortality and at present there is no consensus on the use of leukapheresis (LPH) for its management. Our aim was to review characteristics and outcomes of newly diagnosed leukemia patients with hyperleukocytosis (HL) comparing those who received LPH and those who did not. An IRB approved retrospective case control study reviewed data from a single institution over a 10 year period. At our institution, LPH was used in 8 of 62 (13%) patients with hyperleukocytosis with minimal complications. Mean leukocyte count in patients who received LPH versus those who did not was 498 k cells/mm3 and 237 k cells/mm3, respectively. Patients who had symptoms of neurologic (63 vs. 17%) or pulmonary leukostasis (75 vs. 17%) were more likely to have undergone leukapheresis. The time from presentation to the initiation of chemotherapy was not different between those who received LPH and those who did not (mean of 35 h vs. 34 h). There was one death in the LPH group, that was the result of neurologic sequelae of hyperleukocytosis and not LPH itself. The use of LPH in patients with hyperleukocytosis is safe, well tolerated and does not alter time to chemotherapy at our institution. [ABSTRACT FROM AUTHOR]

Therapeutic leukapheresis is performed in patients having hyperleukocytosis, leading to leukostasis. The aim of this study was to evaluate the efficacy of therapeutic leukapheresis in reducing white cell count in leukemic patients with symptoms of leukostasis. Two cases of acute lymphoblastic leukemia, admitted to the hematology intensive care unit between January and May 2015, were taken up for therapeutic leukapheresis, using COBE Spectra Cell Separator. The first patient was a 24-year-old male, admitted with fever, weakness, headache, blurred vision, and a total leukocyte count (TLC) of 564,000/μL. The second patient was a 36-year-old male admitted with fever, headache, dyspnea, and a TLC of 530,000/μL. The first patient had a 31.38% and 30.19% reduction in TLC after first and second procedures, respectively. The second patient had a reduction in TLC of 31.7% and 31.41% after first and second procedures, respectively. This significant decrease in white cell count achieved reversal of symptoms of leukostasis. Patients with hyperleukocytosis may present as a medical emergency, requiring prompt recognition and initiation of therapy to prevent respiratory failure or intracranial hemorrhage. Leukapheresis removes circulating blasts quickly to alleviate symptoms.

Sudden death due to leukostasis and lymphocyte thrombi in patients with chronic hematologic malignancies is rare. Leukostasis is characterized by highly elevated leukemic cell count and decreased tissue perfusion symptoms, leading to severe complications and even death. Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder that shows a highly heterogeneous clinical course, ranging from indolent form to very aggressive disease. Due to its low metabolic and mitotic rate, there is a lower incidence of clinically significant leukostasis in patients with CLL. Two main theories have been proposed in the development of leukostasis: (1) increased blood viscosity due to large leukemic cell populations; (2) high metabolic activity and cytokine production by leukemic cells. Both mechanisms lead to local hypoxic damage. We present a case of a 70-year-old man who died suddenly in the absence of symptoms. Autopsy and histology examinations revealed findings consistent with CLL and diffuse leukostasis involving the major organs' vessels. In the presence of gross and/or microscopic findings suggesting a potential hematologic malignancy, undiagnosed or relapsing hematologic malignancies should be considered in the differential diagnosis of sudden deaths. [ABSTRACT FROM AUTHOR]

Hyperleukocytosis (HL), defined by a peripheral white blood cell (WBC) count exceeding 100,000/mm3, is occasionally observed in childhood acute leukemia. The increased viscosity in the micro-circulation by HL and the interaction between the leukemic blasts and endometrium of blood vessels sometimes result in leukostasis. Leukostasis can incur life-threatening manifestations, such as respiratory distress, brain infarction and hemorrhage, and renal failure, needing an emergency care. Although early stage of leukostasis is difficult to detect due to nonspecific manifestations, an emergency care is mandatory because leukostasis can proceed to a fatal course. Initial management includes an aggressive fluid therapy that can reduce WBC count, and prevent other metabolic complications implicated by HL. Packed red blood cells should be judiciously transfused because it increases blood viscosity. Conversely, transfusion of platelet concentrates or fresh frozen plasma, which does not affect blood viscosity, is recommended for prevention of hemorrhage. To reduce tumor burden, leukapheresis or exchange transfusion is commonly performed. However, the efficacy is still controversial, and technical problems are present. Leukapheresis or exchange transfusion is recommended if WBC count is 200,000-300,000/mm3 or more, especially in acute myelocytic leukemia, or manifestations of leukostasis are present. In addition, early chemotherapy is the definite treatment of leukostasis.

Hematological malignancies can present with severe complications, including hyperleukocytosis, which demands immediate intervention due to elevated leukocyte counts that increase blood viscosity and cause microcirculatory abnormalities. This case report highlights the critical role of therapeutic leukapheresis in managing a pediatric patient with acute myeloid leukemia (AML) in crisis. A six-year-old male child presented with symptoms of severe hyperleukocytosis, including high-grade fever, respiratory distress, and a significant leukocyte count (555,820/µL). Immediate interventions included intravenous hydration, antibiotics, steroids, and non-invasive ventilation, followed by therapeutic leukapheresis. The leukapheresis procedure successfully reduced the leukocyte count by 81% without any adverse events. Post-procedure treatment with etoposide further decreased the leukocyte count, leading to symptomatic improvement and stabilization of the patient. The patient was later discharged in stable condition and continued receiving induction-phase chemotherapy. This case underscores the efficacy and necessity of leukapheresis as a life-saving adjunctive therapy in pediatric AML crises, demonstrating its role in rapidly reducing leukocyte counts and preventing life-threatening complications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, V et al.)

Purposel-Methylfolate, pyridoxal 5'-phosphate, and methylcobalamin, individually have been reported to have beneficial effects on diabetes-induced defects. The possibility that combining these therapeutic approaches might have additional benefit led us to investigate the effect of Metanx against development of early stages of diabetic retinopathy in a mouse model.MethodsC57BL/6J mice were made diabetic with streptozotocin, and some were given Metanx (a combination food product) mixed in the food at a dose of 5 mg/kg of body weight. Mice were killed at 2 months and 10 months of study for assessment of retinal function, retinal vascular histopathology, accumulation of albumin in neural retina, and biochemical and physiological abnormalities in retina.ResultsTwo months of diabetes significantly increased leukostasis within retinal vessels and superoxide generation by the retina. Diabetes also significantly increased expression of intercellular adhesion molecule-1 (ICAM-1) and phosphorylation of IκB. Daily consumption of Metanx significantly inhibited all of these abnormalities. Ten months of diabetes significantly increased the degeneration of retinal capillaries and impaired visual function (spatial frequency threshold (SFT) and a parameter of contrast sensitivity) compared to nondiabetic controls. Daily consumption of Metanx for 10 months inhibited impairment of SFT but had no significant beneficial effect on capillary degeneration, pericyte loss, or the estimate of contrast sensitivity.ConclusionsMetanx inhibited a diabetes-induced defect in retinal spatial frequency threshold and inhibited measures of oxidative stress and inflammation. It had no significant effect on contrast sensitivity or retinal capillary degeneration. Nutritional management with Metanx may help inhibit diabetes-induced defects in visual function.

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy.

Brown recluse spiders, also known as Loxosceles reclusa, are endemic to the Southwest and Central Midwestern United States. A bite from this spider can cause a range of clinical manifestations, anywhere from a painless papular lesion to life-threatening reactions. We report a possible spider bite presenting as leukostasis initially suspected to be acute leukemia. A 22-year-old female patient presented to the emergency department with confusion and right upper arm pain, redness, and swelling after a suspected spider bite. Initial labs showed WBC count of 103.5x10e3/µL, hemoglobin of 3.3 g/dL, positive Direct Coombs' test, creatinine of 1.8 mg/dL, transaminitis, and lactic acid of 20 mmol/L. Acute leukemia with leukostasis was suspected. She was started emergently on hydroxyurea in conjunction with prophylaxis for tumor lysis syndrome. However, peripheral smear showed left-shifted granulocytosis with lymphocytosis, monocytosis, and no blast cells or evidence of myelodysplasia. Bone marrow aspirate showed mildly hypercellular marrow with myeloid hyperplasia and no myelodysplasia. Flow cytometry analysis confirmed a left-shifted myeloid maturation pattern with 0.3% myeloblasts. BCR-ABL1 and JAK2 testing was negative. Hence, she had no evidence of leukemia but rather had leukostasis from a spider bite. Hydroxyurea was stopped and follow-up labs normalized. Sphingomyelinase D in the brown recluse spider venom is unique to Loxosceles and Sicarius and may be responsible for the unique clinical presentation of loxoscelism. The presentation of hyperleukocytosis complicated by shock with an unclear history poses a diagnostic challenge. In diagnostic uncertainty, consider delaying chemotherapy until a diagnosis can be confirmed to avoid potential harm. [ABSTRACT FROM AUTHOR]

Therapeutic leukapheresis is performed in patients having hyperleukocytosis, leading to leukostasis. The aim of this study was to evaluate the efficacy of therapeutic leukapheresis in reducing white cell count in leukemic patients with symptoms of leukostasis. Two cases of acute lymphoblastic leukemia, admitted to the hematology intensive care unit between January and May 2015, were taken up for therapeutic leukapheresis, using COBE Spectra Cell Separator. The first patient was a 24-year-old male, admitted with fever, weakness, headache, blurred vision, and a total leukocyte count (TLC) of 564,000/µL. The second patient was a 36-year-old male admitted with fever, headache, dyspnea, and a TLC of 530,000/µL. The first patient had a 31.38% and 30.19% reduction in TLC after first and second procedures, respectively. The second patient had a reduction in TLC of 31.7% and 31.41% after first and second procedures, respectively. This significant decrease in white cell count achieved reversal of symptoms of leukostasis. Patients with hyperleukocytosis may present as a medical emergency, requiring prompt recognition and initiation of therapy to prevent respiratory failure or intracranial hemorrhage. Leukapheresis removes circulating blasts quickly to alleviate symptoms. [ABSTRACT FROM AUTHOR]

Cystoid macular edema (CME) is the abnormal collection of intraretinal fluid in the macular region, especially in the inner nuclear and outer plexiform layers. CME leads to severe visual impairment in patients with various retinal diseases, such as diabetic retinopathy, retinal vascular occlusion, choroidal neovascularization, and uveitis. Although various retinal conditions lead to CME, a shared pathogenesis of CME is involved in these diseases. Accordingly, the pathogenesis of CME based on vasogenic mechanisms is first discussed in this review, including vascular hyperpermeability, leukostasis, and inflammation. We then describe cytotoxic mechanisms based on retinal Müller cell dysfunction. This comprehensive review will provide an understanding of the pathogenesis of CME for potential therapeutic strategies.

In recent years a systematic growing incidence of diabetes mellitus is being observed. Diabetic retinopathy - a microvascular complication of diabetes mellitus - is one of the leading causes of blindness among professionally active people. Pathophysiology of diabetic retinopathy remains unclear. Decreased retinal perfusion is one of the first observed changes in diabetic retinopathy. Hypoxia and hyperglycemia contribute to diabetic retinopathy development in multiple biochemical mechanism such as: increased sorbitol pathway, increased nonenzymatic protein glycation, increased activation of diacylglycerol and protein kinase C pathway, increased expression of growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), haemodynamic changes, accelerated oxidative stress, activation of the renin-angiotensin-aldosterone system, subclinical inflammation with leukostasis. There is strong evidence that retinal neurodegeneration contributes to pathophysiology of diabetic retinopathy. A thorough analysis of these underlying pathogenic mechanisms may be useful for new effective pharmacological therapy discoveries. [ABSTRACT FROM AUTHOR]

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 CMMLRapid diagnosis and institution of cytoreductive therapy with hydroxyurea is critical to avoid high morbidity and mortality.

Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by the presence of Philadelphia chromosome or BCR-ABL oncogene fusion. Patients with CML commonly present in the chronic phase with chief complaint of abdominal pain or early satiety. Priapism as the first manifestation of CML is a rare phenomenon. Priapism as a consequence of leukostasis is a urological emergency that requires immediate intracavernosus therapy followed by systemic therapy. We report a 44-year-old male patient presenting with priapism as the first manifestation of CML.