高白细胞血症.ppt

Hyperleukocytosis Hyperleukocytosis and and leukostasisleukostasis Hyperleukocytosis refers to a laboratory abnormality that has been variably defined as a total leukemia blood cell count greater than 50-100 x 109/L (100,000/microL). . INTRODUCTIONINTRODUCTION INTRODUCTIONINTRODUCTION leukostasis also called symptomatic hyperleukocytosis a medical emergency , a pathologic diagnosis the one-week mortality rate is approximately 20 to 40 percent. EPIDEMIOLOGYEPIDEMIOLOGY leukemia type and patient population. large, poorly deformable blasts in infants, ages of 10 and 20 years, males, T cell phenotype 病因 端粒酶 ATRT，三氧化二砷 机理 1.白细胞可塑性小，变性能力差，过高的白细胞在微循环 中大量淤滞，导致血流减慢，血液粘滞度增高，特别易在 脑、肺、肾、腹腔血管梗塞，预后很差。 2. 白血病细胞耗氧量高，导致组织缺氧，加之白血病细胞 浸润破坏血管壁致脏器出血、水肿，更由于血小板计数减 少和大量白血病细胞崩解释放出促凝血物质，极易形成DIC 。 SIGNS AND SYMPTOMSSIGNS AND SYMPTOMS the main clinical symptoms of leukostasis and causes of early death are related to involvement of the central nervous system (40%) lungs (30%) Pulmonary signs and symptomsPulmonary signs and symptoms dyspnea and hypoxia with or without diffuse interstitial or alveolar infiltrates on imaging studies. Measurement of the arterial pO2 can be falsely decreased since the WBCs in the test tube utilize oxygen. Pulse oximetry provides a more accurate assessment of O2 saturation in this setting. Neurological signs and symptomsNeurological signs and symptoms visual changes, headache, dizziness(头晕), tinnitus（耳鸣）, gait instability, confusion, somnolence（嗜睡）, and, occasionally, coma（昏迷）. an increased risk of intracranial hemorrhage that persists for at least a week after the reduction of white cell count （ reperfusion injury ） noncontrasted CT or MRI is indicated in patients with neurologic abnormalities. cautious about using intravenous contrast dye at a time when renal function may be compromised by leukostasis or tumor lysis syndrome, and dehydration. fever（80%） inflammation associated with leukostasis concurrent infection. treat empirically for infection in all such patients Less common signs or symptoms Less common signs or symptoms ： electrocardiographic signs of myocardial ischemia or right ventricular overload worsening renal insufficiency priapism, acute limb ischemia, or bowel infarction DIAGNOSIS DIAGNOSIS Leukostasis (symptomatic hyperleukocytosis) is diagnosed empirically when a patient with leukemia and a white blood cell (WBC) count over 100 x 109/L (100,000/microL) presents with symptoms thought to be due to tissue hypoxia, most commonly respiratory or neurological distress. MANAGEMENTMANAGEMENT 水化：足量液体20003000ml/m2.d 碱化：予5%碳酸氢钠80-100ml/m2.d，使尿PH7 去白 ALLALL 1、ALL 在诱导缓解治疗之前应用肾上腺激素并逐渐加量，如强的松由 15mg/m2渐增至30mg/m2 , 50 mg/m2 , 75 mg/m2 , 100 mg/m2，一般需 一周待白细胞降至50109/L，可考虑加用其他种类化疗药物。 多数研究表明，儿童ALL诊断时白细胞50109/L为判断预后的独 立危险因素之一。但部分高细胞ALL被强化疗克服，相当一部分患儿仍 可获长期无病存活。 德国BFM-95方案中，儿童ALL白细胞20109/L；年龄1岁，6岁 ；免疫分型T细胞型ALL定为中危组，5年无病生存率仍达70%。 Cytoreduction 1. chemotherapy (hydroxyurea 羟基脲or remission induction chemotherapy诱导缓解化疗)the only treatment proven to improve survival 50 to 100 mg/kg /d po, WBC 50-80%(24-48h), 2 to 4 grams ,q12,po, 50 x 109/L Rare complications include fever and abnormal liver function tests. Hydroxyurea should not be used in pregnancy or in women who are breastfeeding. 2. leukapheresis(白细胞分离) respiratory failure and neurologic compromise are present，facilities are available, we suggest leukapheresis for patients with leukemic blast counts greater than 50 to 100 x 109/L Supportive care Supportive care 1.TLS： UA、K、P ，Ca intravenous hydration to ensure adequate urine flow allopurinol(别嘌醇) or rasburiscase（拉布立酶), UA correction of any electrolyte disturbances or causes of reversible renal failure. 2.Coagulation abnormalities:DIC, Fbg，FDPs、D-dimer 3.red blood cell transfusions:be given slowly, over a few hours, or during the leukapheresis procedure， Hydration encouraged , diuretics discouraged 4.platelet transfusions : 20 to 30,000/microL PROGNOSISPROGNOSIS depends upon the type of leukemia and the presence of symptoms. The mortality rate is unrelated to the level of the white blood cell count, but patients with symptoms AML： initial mortality rate 20-40% patients who lived more than one week VS. patients who died within the first week (retrospective analysis 1977) coagulopathy (64 vs. 18% ) respiratory distress (100 vs. 15%) renal failure (43 vs.29%) neurologic symptoms (64 vs. 12%) ALL hyperleukocytosis is rarely complicated by leukostasis in childhood ALL ,the early death rate 5 percent The challenge:TLS, DIC, and the higher risk of relapse (approximately 50 percent by four years) 拉布立酶 重组尿酸氧化酶 recombinant urate oxidase) 尿酸氧化酶(urate oxidase)广泛存在于非灵长类动物的体内，首先从黄 曲霉菌中被分离出来，它可将尿酸进一步氧化为尿素囊(allantoin)及过 氧化氢(H202)(见图1)，前者的水溶性是尿酸的510倍，以终产物形式 稳定从肾脏排出。 非重组尿酸氧化酶，可有效降低患者血尿酸水平，并且将透析率由16 23降至026。但非重组尿酸氧化酶的过敏反应发生率为 455，限制了其临床应用。 1996年研究者将黄曲霉菌中编码尿酸氧化酶的基因转移并表达于酿酒 酵母菌中，成功研发出重组尿酸氧化酶一拉布立酶(resburicase)，明显 减少了过敏反应的发生 2001年Goldman等报道了拉布立酶的首个、也是迄今为止唯一的多中 心、开放性、期随机对照研究，对比有TLS风险的儿童进展期NHL及 ALL患者分别使用拉布立酶及别嘌呤醇的临床疗效。 结果发现拉布立酶首剂4小时后实验组及对照组尿