儿童白血病介绍(自制)ppt演示课件

.,1,儿童白血病,.,2,白血病的故事,19世纪中叶，法国医生多奈观察到某些病人出现原因不明的贫血、倦怠、发热、牙龈、皮下出血、肝、脾、淋巴结肿大现象，在他们的血液中血液中发现大量的白色的细胞。由于病人体质越来越弱，不久都会死亡，这是一种什么病呢?,.,3,白血病的故事,到1847年，英国医学家本尼特和德国医学家威尔萧几乎同时指出，这种特征为血液中的白细胞及幼稚细胞异常增生的血液病。分别被他们命名为白血病和白细胞病。,.,4,提要,什么是白血病?为什么会得白血病?白血病的临床表现?怎么诊断?如何治疗?,.,5,定义,Leukemia is cancer of the blood and bone marrow.It is a typically non-inherited disease in which large numbers of immature, abnormal white blood cells are produced in the bone marrow.Abnormal white blood cells flood the bloodstream, affecting the production of oxygen-producing red blood cells and platelets.A large production of abnormal white blood cells makes the body very susceptible to infections and diseases,.,6,概况,Leukemia is the most common cancer of childhood. In the U.S. there are approximately 3,250 children diagnosed each year with leukemia and 2,400 with acute lymphoblastic leukemia (ALL).There has been a steady increase of 1% per year in the incidence of ALL in the past 25 years.,.,7,概况,我国白血病的发病率:目前尚无全国范围的统计资料 上海:2.643.65/10万 天津:2.854.33/10万 平顶山:3.57.09/10万 我国儿童白血病中ALL约占70%,.,8,Types of Leukemia,Myeloid Lymphoid,AcuteChronic,Adults, +Children, +,Adults, +Children, rare,Adults, +Children, +,Adults, +Children, never,.,9,肿瘤发生机制,癌基因的激活,肿瘤抑制基因的失活,点突变,缺失,插入,易位,扩增,（原发性）,（细胞生长分化失控）,.,10,Growth signal protein switched on,.,11,白血病发病机制,.,12,病因,1.病毒感染2.化学因素3.物理因素4.遗传因素,.,13,VirusesHuman T-cell Leukemia Virus (HTLV),The genetic structure of HTLV is similar, but distinct from other retroviruses. HTLV contains the normal gag, pol, and env genes that other retroviruses possess. However, there is an additional region found on the 3 end of the genome possessing the genes tax and rex. These two genes are essential for viral replication.,.,14,Benzene,Known leukemogen in occupational settingsClusters of leukemia in shoemakers, rubber workers, refinery workers,.,15,Cancer treatments cause leukemia,AML is a common secondary cancer, caused by chemotherapy and radiationVarious antitumor agents have been strongly implicated, including procarbazine, melphalan, thio-TEPA, chlorambucil, and cyclophosphamide Antibiotic chloramphenicol and analgesic phenylbutazone,.,16,Radiation causes leukemia,Scientists studying radioactive substances developed leukemiaUranium miners Atomic bomb survivorsDownwinders,.,17,From 1945 to 1962, the US conducted 235 above ground nuclear weapons tests, primarily in Nevada and the Pacific200,000 Department of Defense (DoD) military and civilian participants.,Above-ground Nuclear Testing,.,18,Predisposing Factors,Genetic SyndromesDown syndrome: 10-20 times increased incidence (600 times in megakaryoblastic type)Bloom syndromeNeurofibromatosisSchwachman syndromeAtaxia TelangiectasiaKlinefelter syndromeFamilial aggregationConcordance in Twins,.,19,Ataxia-Telangactasia,.,20,.,21,肿瘤发生机制,癌基因的激活,肿瘤抑制基因的失活,点突变,缺失,插入,易位,扩增,（原发性）,（细胞生长分化失控）,二次打击,多重打击,.,22,临床表现 clinical manifestation,患者的症状源于：（一）.骨髓功能降低 decreased bone marrow production of red blood cells (RBCs), white blood cells (WBCs), platelets （二）.白细胞浸润 leukemic infiltration of extramedullary (outside bone marrow) sites.,.,23,临床表现 clinical manifestation,（一）骨髓功能低下 1. 发热及感染 fever and infection： 免疫系统受抑制，继发感染，以 口腔、肛周、呼吸道、泌尿系、 皮肤感染多见，严重时败血症。 白血病本身发热，肿瘤性发热。,.,24,大肠埃希菌肛周脓肿,金葡肛周脓肿,金黄葡萄球菌皮肤感染,小肠耶尔森菌小肠结肠炎,临床表现细菌感染,.,25,水痘-带状疱疹病毒感染,Epstein-Barr Virus,临床表现病毒感染,.,26,临床表现 clinical manifestation,：2. 贫血 anemia： 面色苍白 pallor， 疲倦 fatigue， 食欲不振 poor appetite,.,27,临床表现 clinical manifestation,3. 出血 bleeding： 皮肤瘀点、瘀斑 petechia bruising ，牙龈出血 gingiva bleeding鼻衄 haemorrhagia nasalis; ，月经过多 menorrhagia眼底出血 subhyaloid hemorrhage消化道出血 alimentary tract hemorrhage血尿 hematuria，颅内出血 ICH intracranial hemorrhageDIC：尤以M3常见 common in M3.,.,28,临床表现 clinical manifestation,(二）白血病细胞浸润 leukemic infiltration1. 肝、脾淋巴结肿大： 75%ALL有淋巴结肿大Lymphadenopathy , 多数为全身淋巴结肿大; 纵隔淋巴结肿大mediastinal adenopathy 多见于T-ALL; 肝脾肿大Hepatomegaly and splenomegaly普遍， 多为轻至中度。 2. 骨骼和关节： 胸骨下端压痛；关节及骨骼疼痛，局部无红肿； 绿色瘤（粒细胞肉瘤),.,29,3. 中枢神经系统浸润： 多见于T-ALL ； 多发生在缓解期； 脑膜、脑实质局部浸润或颅神经直接浸润的表现 Leukemic infiltration of cranial nerves may cause cranial nerve palsies with mild nuchal rigidity.4. 睾丸浸润： 多在治疗缓解后-年发病； 单侧睾丸无痛性肿大。 The testes may occasionally be unilaterally or bilaterally enlarged secondary to leukemic infiltration.,临床表现 clinical manifestation,.,30,5. 皮肤粘膜浸润： 皮疹、牙龈肿胀、口腔溃疡、咽峡炎，多见于 ANLL-M4和M5。 6. 其他器官浸润表现： 腮腺、唾液腺、肾、肺、心包等。 A mediastinal mass can cause tachypnea, orthopnea, and respiratory distress. The optic fundi may show exudates of leukemic infiltration and hemorrhage from thrombocytopenia.,临床表现 clinical manifestation,.,31,脾肿大，瘤栓栓塞,.,32,Gum Hypertrophy,.,33,Chloromas,CNS浸润,睾丸浸润,纵隔占位,.,35,诊断,1.临床表现2.实验室检查 外周血 骨髓MICM3.影像学检查,.,36,实验室检查 Laboratory findings,一、血象 complete blood count (CBC) 白细胞增多，多在15万 高白细胞性白血病 WBC100109/L 白细胞不增多白血病 WBC2 for the myeloid lineage and 1 for the lymphoid lineage.,.,49,染色体及基因,.,50,.,51,.,52,WHO分型MICM的分型,.,53,.,54,.,55,.,56,（2001年）,.,57,临床危险度分组标准,ALL标危中危高危,AML低危中危高危,.,58,临床危险度分组标准ALL,标危组：必须同时满足以下所有条件：1.年龄1岁且10岁；2.WBC50109/L；3.泼尼松反应良好（第8天外周血白血病细胞1109/L）；4.非T-ALL；5.非成熟B-ALL；6.无t（9;22）或BCR/ABL融合基因；无t（4;11）或MLL/AF4融合基因；无t（1;19）或E2A/PBX1融合基因；7.治疗第15天骨髓呈M1(原幼淋细胞5%)或M2（原幼淋细胞5%-25%），第33天骨髓完全缓解。,.,59,临床危险度分组标准ALL,中危组：必须同时满足以下4个条件：1.无t（9;22）或BCR/ABL融合基因；2.泼尼松反应良好（第8天外周血白血病细胞1109/L）；3.标危诱导缓解治疗第15天骨髓呈M3（原幼淋细胞25%）或中危诱导缓解治疗第15天骨髓呈M1/M2；4.微小残留病（MRD）检测，第33天MRD102。同时至少符合以下条件之一：5.WBC50109/L；6.年龄10岁；7.T-ALL；8.t（1;19）或E2A/PBX1融合基因阳性；9.年龄1岁且无MLL基因重排。,.,60,临床危险度分组标准ALL,高危组：必须满足下列条件之一：1.泼尼松反应不良（第8天外周血白血病细胞1109/L）；2.t（9;22）或BCR/ABL融合基因阳性；3.t（4;11）或MLL/AF4融合基因阳性；4.中危诱导缓解治疗第15天骨髓呈M3；5.第33天骨髓形态学未缓解（5），呈M2/M3；6.MRD检测，第33天MRD102，或第12周MRD103。,.,61,临床危险度分组标准AML,低危组：APL、M2b、M4eo及其它伴inv(16)者；中危组：非低危型且不存在危险因素者；高危组：存在危险因素任何一项者。危险因素：1.诊断时年龄小于1岁；2.诊断时WBC100*109/L；3.染色体核型-7；4.MDS-AML；5.标准化疗方案1个疗程不缓解。,.,62,治疗,Antileukemic TherapySupportive careMetabolic Complications（Tumor lysis syndrome，TLS）Hyperleukocytosis Infection ControlHematologic Support,.,63,小儿ALL化疗,（一）化疗原则：按不同危险度分型治，采用早期强化疗、后期弱化疗，分阶段、长期规范治疗 的方针。程序依次是：诱导缓解、早期强化、巩固、延迟强化和维持治疗，总程 2.0 -2.5 年。（二）化疗方案：,.,64,小儿ALL化疗,t（9；22）/BCR-ABL1阳性患儿：给予高危方案化疗，或进行造血干细胞移植，有条件的在化疗的同时应用酪氨酸激酶抑制剂；CNSL和TL：初诊时合并CNSL的在诱导治疗中每周1次TIT，直至CSF转阴至少5次，完成延迟强化治疗后接受颅脑放疗，1岁不放疗，1-2岁12Gy，2岁18Gy；复发的CNSL隔天1次TIT，直至CSF转阴，颅脑放疗同上；初诊时合并TL的巩固治疗结束后楔形活检，确定是否睾丸放疗，TL复发的一般做双侧睾丸放疗（20-26Gy），年龄较小的幼儿12-15Gy,.,65,小儿ALL化疗主要化疗药物的不良反应,VCR(VDS)：末梢神经炎，便秘；DNR(ADR)：心脏毒性；L-ASP(PEG-ASP)：肝毒性、胰腺炎、凝血及抗凝因子减少、过敏；Pred(Dex)：高血压、高血糖、柯兴貌、骨质疏松、液体潴留、高眼压、消化性溃疡；HD-MTX：黏膜炎、肝肾损伤；CTX：出血性膀胱炎；Ara-