Hyperleukocytosis and leukostasis in acute and chronic leukemias.

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.

High dose cyclophosphamide for cytoreduction in patients with acute myeloid leukemia with hyperleukocytosis or leukostasis.

Hyperleukocytosis may lead to multiple medical emergencies. Hydroxyurea, intensive chemotherapy, and leukapheresis are used for cytoreduction. However, there is little data regarding the best approach. Here, we report on the efficacy and safety of high dose cyclophosphamide (HDCy; 60 mg/kg). 27 patients with acute myeloid leukemia or blast phase chronic myeloid leukemia who presented with white blood cell count (WBC) of ≥50x109/L or symptoms of leukostasis were treated with HDCy. Primary endpoint was early mortality (death within seven days of admission). Median WBC was 107 × 109/L at time of HDCy; 74% had leukostasis symptoms at presentation. Eight (29.6%) patients died within seven days of admission. Sustained WBC reduction was achieved in 18/24 (75%) evaluable patients with median nadir of 0.25 × 109/L. Adverse effects attributed to HDCy included tumor lysis syndrome (n = 7; 25.9%), disseminated intravascular coagulopathy (n = 5; 18.5%), and hemorrhagic cystitis (n = 1; 3.7%). HDCy was effective for cytoreduction and adverse effects were acceptable.

Leukostasis retinopathy with leukemic infiltrates as onset manifestation of chronic myeloid leukemia: a case report.

PURPOSE: To describe a case of retinopathy as onset manifestation of chronic myeloid leukemia (CML), successfully treated with leukapheresis and medical therapy. METHODS: A 28-year-old male patient presented complaining painless acute visual impairment in his right eye (RE). He reported moderate asthenia and episodes of night sweats during the previous month. His past medical history was unremarkable. BCVA at presentation was 20/80 in RE and 20/32 in left eye (LE). Fundus examination revealed venous congestion, diffuse Roth spots, and whitish macular infiltrates in both eyes. OCT showed hyperreflective foveal infiltrates, in both eyes. Blood test showed markedly elevated white blood cells (WBCs) count (430 × 103/mm3). Clinical-instrumental examination revealed hepatosplenomegaly. These features were consistent with CML. The patient was treated with leukapheresis and nilotinib. RESULTS: After 2 weeks of treatment, the WBCs count dropped (71 × 103/mm3), and the patient reported subjective improvement of symptoms. At 1-month follow-up, BCVA and retinopathy signs were improved in both eyes. OCT showed the almost complete resolution of foveal infiltrates with ellipsoid zone focal defects. At 4-months follow-up, we observed complete resolution of retinopathy. BCVA was 20/32 in RE and 20/25 in LE. OCT showed the persistence of ellipsoid zone focal defects in RE and complete anatomical restoration in LE. At 6-months follow-up, the patient was clinically well and his WBCs count was normal. CONCLUSION: In our case, the CML-related retinopathy represented the onset sign of the underlying systemic pathology, leading to proper management and treatment, with hematological normalization and resolution of the retinopathy.

Hyperleukocytosis and leukostasis: management of a medical emergency.

INTRODUCTION: Hyperleukocytosis is defined as a white blood cell count greater than 100,000/mL in patients affected by acute leukemia and often it is associated with increased morbidity and mortality, that can be up to 40% if unrecognized. Areas covered: Risk factors include younger age, myelomonocytic or monocytic/monoblastic morphology, microgranular variant of acute promyelocitic leukemia and T-cell ALL, and some cytogenetic abnormalities. Poor prognosis due to high early death rate secondary to leukostasis. The mechanisms at the origin of leukostasis are still poorly understood. The management of acute hyperleukocytosis and leukostasis involves supportive measures and reducing the number of circulating leukemic blast cells, with careful monitoring of fluid balance, control of uric acid production and control of urine pH to prevent tumour lysis syndrome. Expert commentary: Several studies have been performed to ameliorate the outcome of this setting of patients. The high number of leukocytes may cause 3 main complications: disseminated intravascular coagulation (DIC), tumor lysis syndrome (TLS), and leukostasis. Although hyperleukocytosis and tumour lysis syndrome are still a challenge for clinicians, a better prognosis for these conditions is emerging in the last years.

[Successful induction therapy for acute myeloid leukemia complicated with brain hemorrhage and hyperleukocytosis].

Adequate management of hyperleukocytosis in patients with acute myeloid leukemia (AML) is essential for the prevention of life-threatening complications related to leukostasis and tumor lysis syndrome, but the optimal therapeutic strategy remains unclear. We report a 15-year-old girl with newly diagnosed AML who had extreme hyperleukocytosis (leukocyte count at diagnosis, 733,000/µl) leading to a brain hemorrhage. She was initially treated with hydroxyurea, but presented with brain hemorrhage due to leukostasis and underwent leukapheresis emergently with intensive care and mechanical ventilation. Full-dose standard induction chemotherapy was initiated after achieving gradual cytoreduction (leukocyte count, 465,000/µl) within five days after the initiation of therapy with hydroxyurea and leukapheresis. These treatments were successful and she experienced no complications. The patient ultimately recovered fully and was discharged with complete remission of AML. Although the effects of hydroxyurea and leukapheresis in the setting of hyperleukocytosis are still controversial, these initial treatments may contribute to successful bridging therapy followed by subsequent induction chemotherapy, especially in AML cases with extreme hyperleukocytosis or life-threatening leukostasis.

High Output Cardiac Failure in a Patient Presenting with Acute Myeloid Leukemia and Leukostasis.

In this case report a patient presents with high-output cardiac failure in the clinical setting of acute leukemia and leukostasis. Case particulars are presented, literature is reviewed and a potential mechanistic explanation is proposed to describe presentation and clinical findings.

Leukostasis Retinopathy: A New Clinical Manifestation of Chronic Myeloid Leukemia With Severe Hyperleukocytosis.

The authors report a new clinical manifestation of chronic myeloid leukemia. A 41-year-old man presented with significant visual loss, leading to a diagnosis of chronic myeloid leukemia. His white blood count exceeded that of any previously reported case of the disease with documented retinal findings (562,000/mm(3)), and clinical evaluation revealed the blockage of temporal retinal vessels by white blood cells. Hematologic findings resolved within 1 month of chemotherapy with dasatinib, and further treatment with intravitreal anti-VEGF agents resulted in the complete resolution of fundus findings. The authors propose that leukostasis retinopathy be recognized as a clinical manifestation of this life-threatening disease.

A safe therapeutic apheresis protocol in paediatric patients weighing 11 to 25 kg.

BACKGROUND AND OBJECTIVES: Erythrocytapheresis and leukapheresis (LPE) of small children are logistically complex and many centres are reluctant to perform these procedures. In children, both sickle cell and leukaemic emergencies demand prompt action to prevent additional morbidity but detailed protocols for small children are lacking, and often are performed using guidelines shown to work in larger patients. We report a 3-year experience with children weighing 11-25 kg at a large academic medical centre. MATERIALS AND METHODS: All patients were treated with the COBE® Spectra apheresis system; circuit was primed with blood not adjusted for haematocrit and anticoagulant citrate dextrose A was used as anticoagulation. Procedures were performed in the paediatric intensive care unit by apheresis nursing staff. RESULTS: Twenty-five apheresis procedures in 19 patients were performed; 17 of 19 patients presented with sickle cell-related acute complications and two (2/19) with newly diagnosed acute leukaemia and hyperleucocytosis. None of the patients required medications during the procedures. Vital signs and clinical condition remained stable and did not worsen during or postapheresis. One patient had a delayed haemolytic transfusion reaction 1 week posterythrocytapheresis as he developed alloantibodies as a result of the procedure. All sickle cell patients achieved a target haematocrit of 21-30% and Haemoglobin A of ≥68%. Both leukaemia patients who underwent LPE had no further signs of leukostasis and achieved marked reductions in leucocyte counts. CONCLUSIONS: Apheresis of children weighing 11-25 kg can be safely performed without increased morbidity. We outline a protocol that can be used to perform apheresis with minimal complications.

[Leukostasis and tumor lysis: important complications of hyperleukocytosis]. / Leukostase und Tumorlyse: Wichtige Komplikationen der Hyperleukozytose.

The occurrence of hyperleukocytosis (leukocytes > 100.000/µl) is associated with complications such as leukostasis, tumor lysis and consumption coagulopathy in patients with acute leukemia much more often than in patients with chronic malignant hematological diseases. To manage these situations may be complex as organ failure is often imminent or manifest, infectious complications arise and indications for induction chemotherapy are usually urgent. Prophylaxis and therapy of the tumor lysis syndrome consists of hydration, lowering of uric acid and the management of electrolyte disturbances. Leukostasis requires immediate reduction of the leukocyte count by leukapheresis, administration of hydroxycarbamide and, ultimately, by causative and specific treatment of the underlying disease itself. In patients with curable diseases or favorable long-term prognosis, transfer to the intensive care unit must be evaluated early in the course of impending organ dysfunction, especially in cases of acute respiratory failure.

Hyperleukocytosis, leukostasis and leukapheresis: practice management.

Hyperleukocytosis, arbitrarily defined in acute leukemia as a white blood cell count greater than 100,000/mL, often is associated with increased morbidity and mortality in patients with leukemic processes. It can induce leukostasis, tumor lysis syndrome and disseminated intravascular coagulopathy and has significant prognostic implications with or without one of these clinical complications. The main sites that tend to be injured from the obstructions are the central nerve system and lungs. Despite characteristic clinical presentations, the diagnosis of leukostasis is rarely made with high confidence. The main goal of the management of hyperleukocytosis and/or leukostasis is to reduce the white blood cell count before starting induction chemotherapy. The cytoreduction can be achieved by either leukapheresis and/or hyroxyurea. The technical aspects, complications and efficacy of leukapheresis are discussed in the current article.

Acute leukemia with a very high leukocyte count: confronting a medical emergency.

From 5% to 30% of adult patients with acute leukemias present with hyperleukocytosis--very high white blood cell counts (> 100,000 cells/mm3)--and symptoms of leukostasis. These conditions are a medical emergency that needs prompt recognition and initiation of therapy to prevent respiratory failure or intracranial hemorrhage. Patients should be referred as soon as possible for induction chemotherapy and leukapheresis.

Radioterapia paliativa en niños: presentación de un caso clínico y recuerdo de sus indicaciones / Palliative radiotherapy in children: presentation of a clinical case and recall of indications

- Propósito: conocer el papel de la radioterapia como tratamiento paliativo en la patología oncológica pediátrica.- Caso clínico: se comenta el caso de un niño de 10 años con neuroblastoma estadio IV de inicio que a pesar de sucesivos esquemas de tratamiento por progresión presentó metástasis cerebral única a los tres años del diagnóstico.- Resultados y conclusiones: revisada la literatura, se puede afirmar que la radioterapia es un tratamiento paliativo eficaz y adecuado cuando nuestro objetivo es controlar síntomas y ofrecer calidad de vida (AU)

Leukapheresis in chronic myelomonocytic leukemia with leukostasis syndrome: elevated serum lactate levels as an early sign of microcirculation failure.

We present the course of three patients suffering from chronic myelomonocytic leukemia (CMML), who presented with a markedly increase of their WBC (>200 G/l). All patients were started on chemotherapy consisting of ARA-C given as continuous infusion. Due to acute respiratory insufficiency, all patients were treated in the ICCU with ventilation support. Respiratory insufficiency was most likely due to pulmonary leukostasis since pulmonary infection or edema were excluded by X-ray in all patients. Therapeutic leukapheresis was therefore initiated and resulted in a dramatic improvement in one patient. Two patients died due to multiorganic failure despite effective leukocyte depletion (>40%) and maximum supportive care. At the onset of symptoms, two patients had markedly elevated serum lactate levels most likely due to microcirculatory failure. Both patients died because of deteriorating sequelae of pulmonary leukostasis, however, the patient with marginally elevated serum lactate levels survived. Leukapheresis is an established therapeutic approach in patients with hyperleukocytosis and leukostasis, which improves the prognosis of high-risk patients. In our opinion, patients presenting with asymptomatic hyperleukocytosis may benefit from early leukapheresis, particularly when increasing serum lactate levels indicate the early onset of microcirculatory failure.

Pulmonary leukostasis: role of perfusion lung scan in diagnosis and follow up.

A patient with hyperleukocytic myelomonocytic leukemia who presented to the emergency room with sudden pleuritic chest pain and dyspnea is reported. Clinical manifestations included dyspnea tachypnea and hyperventilation. Blood gas analysis revealed hypoxemia, hypocarbia, and respiratory alkalosis. Chest X ray was normal, and perfusion lung scan revealed a diffuse vascular occlusive pattern compatible with pulmonary leukostasis. The patient underwent immediate leukapheresis with subsequent mitigation of symptoms. A second perfusion lung scan showed evidence of significant improvement. To our knowledge this is the first published case of hyperleukocytosis presenting with pulmonary leukostasis that was successfully diagnosed and followed by serial perfusion lung scan.

Pulmonary leukostasis mimicking pulmonary embolism.

We report a case of a 32-year-old woman who presented with shortness of breath and pleuritic chest pain, and mismatched perfusion defects on a ventilation-perfusion scan suspicious for pulmonary embolism. However, subsequent data revealed the diagnosis of acute myelogenous leukemia with hyperleukocytosis and associated pulmonary leukostasis. Unfortunately, the patient died despite urgent leukopheresis. Autopsy examination revealed extensive infiltration of leukemic cells in all major organs with no evidence of pulmonary embolism. This case highlights the clinical, radiographic and histologic features of pulmonary leukostasis, and reminds the clinician that not all ventilation-perfusion mismatching is due to thromboembolic disease.

[Unexpected death by leukostasis and lung leukostatic tumors in acute myeloid leukemia. Study of four cases]. / Morte inattesa da leucostasi e da tumori leucostatici polmonari nelle leucemie mieloidi acute. Studio su quattro casi.

Four cases of unexpected death due to acute myeloid leukemia have been studied: myeloblastic M1 (case I and II), promyelocytic M3 (case III), myelomonocytic M4 (case IV). Diagnosis was performed before death only in case III. Histological leukostasis was the most evident feature in all cases, particularly at the lung level, where tumor-like aspects were evident and widely diffused in case II. The last three cases were pregnant at the third trimester. Serious hemorrhagic complications were evident in all cases: CID in the former 3 cases and primary hyperfibrinolysis in the 4th, as demonstrated by the absence of intravascular cloths in many organs and especially in lung and kidney; abundant, on the contrary, in the former three cases. Leukostasis was not associated to hyper-leucocytosis in all 4 cases, but associated to normal number of peripheral white cells (below normal level in case III). This phenomenon, that disagrees with literature data on acute or chronic reactivated myeloid leukemia leukostasis, may be due to the primary confination of the immature granuloblasts in the vascular bed, because of the hemoreologic effects connected with their deficient plasticity, that is essential for normal granulocytes to flow easily in the capillary bed. In all cases death was caused by breathing and cardiocirculatory insufficiency with the associated unceasing hemorrhages.