Leukostasis by hyperleukocytic childhood acute leukemia: pathophysiology, clinical presentation, and emergency care

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.

Leukostasis retinopathy: An uncommon visual threatening complication of chronic myeloid leukemia with severe hyperleukocytosis – A case report and review of the literature

To describe a rare case of an unusual visual threatening complication of chronic myeloid leukemia (CML). A 21-year-old male visited the hospital complaining of 1-week painless binocular acute visual loss without any other symptoms. The patient was diagnosed with CML. He then received emergent leukapheresis with imatinib treatment, which achieved obvious hematological remission. However, the visual acuity did not recover along with the CML remission and ocular structure relief. CML-related leukostasis could induce severe leukostasis retinopathy. Hematologists and ophthalmologists should pay more attention to this relatively rare and severe complication of CML.

Application of leukostasis grading score system to evaluate the efficacy of leukocyte reduction in hyperleukocytic acute myeloid leukemia / 白血病·淋巴瘤

Objective To evaluate the treatment efficacy of leukocyte reduction in hyperleukocytic acute myeloid leukemia (HAML) patients with leukostasis grading score (LGS).Methods The data of 54 HAML patients were analyzed retrospectively.The relationship between LGS and leukocyte stasis symptoms or early mortality was observed, and the impact of leukapheresis on LGS was analyzed.Results Among 54 patients with HAML, there were 1 case of M1, 16 cases of M2, 10 cases of M4, 20 cases of M5 and 7 cases of unclassified AML.Based on clinical symptoms and LGS system, 3 cases were LGS 0, 15 cases LGS 1, 17 cases LGS 2, and 19 cases LGS 3.In patients with LGS ≤ 2, the rates of type Ⅰ respiratory failure, central nevers system (CNS) symptoms and early mortality caused by leukostasis were significantly lower than those in patients with LGS 3 (P ＜ 0.05).The LGS of HAML patients was reduced by leukocyte reduction therapy (P ＜ 0.000 1).The LGS of HAML patients treated by leukapheresis and low dose chemotherapy was improved significantly than that of patients treated without leukapheresis (P =0.008).Among 37 cases receiving induction chemotherapy, 20 cases reached complete remission (CR) after the first cycle of induction chemotherapy.CR rate of patients with LGS ≤ 2 was no significantly different compared with that of patients with LGS 3 (P =0.703).Conclusions LGS can be used to evaluate the degree and the improvement status of leukostasis after treatment in HAML patients.The early death often occurres in patients with high LGS.Leukapheresis combined with low-dose chemotherapy can effectively improve the LGS of HAML patients.

Pathologic rupture of the spleen in a patient with acute myelogenous leukemia and leukostasis

Rupture of the spleen can be classified as spontaneous, traumatic, or pathologic. Pathologic rupture has been reported in infectious diseases such as infectious mononucleosis, and hematologic malignancies such as acute and chronic leukemias. Splenomegaly is considered the most relevant factor that predisposes to splenic rupture. A 66-year-old man with acute myeloid leukemia evolved from an unclassified myeloproliferative neoplasm, complaining of fatigue and mild upper left abdominal pain. He was pale and presented fever and tachypnea. Laboratory analyses showed hemoglobin 8.3 g/dL, white blood cell count 278 × 109/L, platelet count 367 × 109/L, activated partial thromboplastin time (aPTT) ratio 2.10, and international normalized ratio (INR) 1.60. A blood smear showed 62% of myeloblasts. The immunophenotype of the blasts was positive for CD117, HLA-DR, CD13, CD56, CD64, CD11c and CD14. Lactate dehydrogenase was 2384 U/L and creatinine 2.4 mg/dL (normal range: 0.7-1.6 mg/dL). Two sessions of leukapheresis were performed. At the end of the second session, the patient presented hemodynamic instability that culminated in circulatory shock and death. The post-mortem examination revealed infiltration of the vessels of the lungs, heart, and liver, and massive infiltration of the spleen by leukemic blasts. Blood volume in the peritoneal cavity was 500 mL. Acute leukemia is a rare cause of splenic rupture. Male gender, old age and splenomegaly are factors associated with this condition. As the patient had leukostasis, we hypothesize that this, associated with other factors such as lung and heart leukemic infiltration, had a role in inducing splenic rupture. Finally, we do not believe that leukapheresis in itself contributed to splenic rupture, as it is essentially atraumatic...

Clinical Effects and Safety of Therapeutic Leukapheresis in Hyperleukocytosis / 대한수혈학회지

BACKGROUND: Therapeutic leukapheresis is the cytoreduction procedure performed before chemotherapy in patients with hyperleukocytosis for prevention of complication. However, there have been clinical concerns about bleeding tendency due to anticoagulant used during the procedure. The aim of our study was to compare the clinical characteristics and hematological parameters before and after therapeutic leukapheresis in order to evaluate its effect on bleeding tendency and to provide a guideline for treatment strategy. METHODS: The clinical data for 39 procedures of therapeutic leukapheresis performed on 17 patients with hyperleukocytosis from May 2005 to October 2013 at the National Cancer Center were reviewed retrospectively. RESULTS: The patients consisted of 11 males and six females. The mean age was 41 years old (range, 8~74). The mean number of therapeutic leukapheresis per patient was two (range, 1~4). Clinical symptoms improved in 14 patients (82%) after therapeutic leukapheresis and three patients (18%) were not yet to improve. The mean WBC count was significantly reduced by 32.6% (+/-17.4) after therapeutic leukapheresis, from 250,146/microL (+/-117,000) to 174,702/microL (+/-104,700) (P<0.001). The mean volume of single removal was 298 ml with 4.25x10(11)/L (+/-1.54) WBCs. After therapeutic leukapheresis, the mean platelet count showed a decline from 85x10(9)/L (+/-43) to 71x10(9)/L (+/-26). However, the prothrombin time (PT) and activated partial thromboplastin time (aPTT) did not show a significant increase (PT, P=0.637; aPTT, P=0.054). CONCLUSION: Therapeutic leukapheresis is demonstrated as an effective and safe treatment that can improve symptoms and reduce leukocytes in hyperleukocytosis.

Hiperleucocitosis asociada a leucostasis pulmonar y cerebral en leucemia mieloide aguda / Hyperleucocytosis associated with pulmonary and cerebral leukostasis in acute myeloid leukemia

La leucostasis es una complicación de la leucemia mieloide aguda que se considera de mal pronóstico y está asociada a hiperleucocitosis. Entre los órganos principalmente afectados se encuentran el sistema nervioso central (SNC) y el pulmón. Su presentación se ha asociado con una menor sobrevida. Su reconocimiento puede ser difícil, ya que puede simular la presencia de infecciones y complicaciones hemorrágicas asociadas a la leucemia aguda. A continuación se presenta un caso clínico de un paciente con hiperleucocitosis con compromiso pulmonar y cerebral (Acta Med Colomb 2011; 36: 90-92).

Leukostasis is a complication of acute myeloid leukemia. It is associated with hyperleukocytosis and a poor prognosis. The organs primarily affected are the central nervous system and lung. The presence of pulmonary leukostasis has been associated with a lower survival rate. Its recognition can be difficult because it can mimic the presence of infections and bleeding complications associated with acute leukemia. We present the case of a patient with hyprleukocytosis with pulmonary and cerebral involvement (Acta Med Colomb 2011; 36: 90-92).

A Case of Avascular Necrosis of the Femoral Head as Initial Presentation of Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a malignant clonal disorder of hemopoietic stem cells characterized by abnormal proliferation and accumulation of immature granulocyte. Leukostasis is one of the complications of CML and is characterized by partial or total occlusion of microcirculation by aggregation of leukemic cells and thrombi leading to respiratory, ophthalmic or neurologic symptoms. We experienced a rare case of avascular necrosis of the femoral head as the initial presentation of chronic myelogenous leukemia. A 24-year-old male patient was admitted to our hospital with pain in the right hip joint. The patient was diagnosed to be suffering from chronic myelogenous leukemia by packed marrow with granulocytic and megakaryocytic hyperplasia and the presence of Philadelphia chromosome. The right hip joint pain was attributed to avascular necrosis of the femoral head. And the avascular necrosis could be considered as the complication of chronic myelogenous leukemia due to microcirculatory obstruction of the femoral head. The avascular necrosis of the right femoral head was treated with bipolar hemiarthoplasty.

Leukapheresis with high dose hydroxyurea in the management of lower leg artery obstruction in Chronic Myelogenous Leukemia / 대한내과학회지

There was no specific criteria of white cell count to determine the therapy of hyperleukocytosis in chronic myelogenous leukemia (CML). Therapeutic leukapheresis usually indicated in acute myelogenous leukemia with over 100,000/mm3 of white blood cell, leukocyte infiltration and leukostasis with over 100,000/mm3 of white blood cell, and hairy cell leukemia with no response to drug and splenectomy. Leukapheresis can reverse the hyperleukocytic syndrome rapidly, be used immediately without having to wait for the result of allopurinol to reduce the risk of uric acid nephropathy and decrease the tumor cell mass so as to minimize the extent of cytolysis- induced hyperuricemia, hyperkalemia and hyperphosphatemia. We report a case of 56-year-old man presented right lower leg pain, gait disturbance who was diagnosed CML 4 years before. He showed right popliteal artery obstruction in doppler sonogram and immediatly started leukapheresis. After two therapeutic leukapheresis, symptoms were improved and popliteal blood flow was improved by follow-up doppler sonogram. As a result, we consider that leukapheresis without use of anticoagulant or thrombolytic agents is effective therapy in CML associated leukocytosis and vascular obstruction.

Evaluation of therapeutic leukapheresis in hyperleukocytic leukemias / 대한수혈학회지

BACKGROUND: Leukemia with hyperleukocytosis is risk factor for early mortality and morbidity. Therepeutic leukapheresis has been recognized as the choice of treatment modality to prevent leukostatic complications by selective removal of abnormal leukocytes. METHODS: We analyzed the clinical and laboratory data in total of 44 therapeutic leukapheresis performed at Samsung Medical Center in 31 patients (15 males, 16 females) with hyperleukocytic leukemias from March 1, 1995 to August 31, 1998. The change of laboratory findings related to therapeutic leukapheresis as well as the correlation between preprocedural and postprocedural hematologic parameters, the degree of leukoreduction and clinical efficacy were evaluated. RESULTS: The age distribution was from 6 months to 77 years with the 35 years of mean age. The most common diagnosis of patients who were performed therapeutic leukapheresis was acute myeloblastic leukemia (15/32, 46.9%) followed by acute lymphoblastic leukemia (9/32, 28.1%), and major leukostatic symptoms were dyspnea and headache. The mean leukocyte count before leukapheresis were 167,400/microliter and the mean leukoreduction per procedure was 50,080/microliter (30.3%). The changes of hemoglobin and platelet count were not significant. The efficacies of therapeutic leukapheresis were 66.7% in acute myeloblastic leukemia, 44.4% in acute lymphoblastic leukemia and 37.5% in other leukemia patients. Patients with low initial leukocyte count and blast count or low final leukocyte count showed higher clinical improvement rate than patients without those parameters. CONCLUSION: The present study for therapeutic leukaphresis indicate that it is relatively safe and can be used to relieve leukostatic symptoms and improve clinical status in leukemic patients.