Pediatric faculty,Shanghai Medical
College,Fudan University
Hematologic diseases of Children
小儿 血液系统疾病
Associated Professor Lu Feng Quan
Hematologic Disorders of Children
小儿血液系统疾病
? Diseases of erythrocytic system:
? 红细胞系统疾病：
* Hematopoietic substances deficiency;
* 造血原料缺乏 ;
Nutritional iron deficiency anemia
营养性缺铁性贫血
nutritional megaloblastic anemia
营养性巨幼性贫血
* Anerythropoiesis;
* 红细胞生成减少 ;
aplastic anemia
再生障碍性贫血
Pure erythrocytic aplastic anemia
纯红再障
* Excessive destroy of erythrocytes;
* 红细胞破坏过多 ;
hemolytic anemia
溶血性贫血
* blood loss;
* 失血 ;
acute & chronic blood loss
急慢性失血
* tumors of the bone marrow of bone marrow
metastasis
骨髓自身肿瘤 肿瘤或骨转移
? Disorders of the white blood cells：
? 白细胞性疾病：
* hematologic malignancy ;
* 血液系统恶性肿瘤 ;
acute & chronic leukemia
急慢性白血病
? Bleeding and coagulation disorders：
? 出凝血疾病：
* Endogenous coagulation factors deficiency ;
内源性凝血因子缺乏 ;
hemophilia
血友病
* Disorders of platelet production;
血小板生成障碍 ;
Thrombocytopenic purpura
血小板减少性紫癜
blood characteristics of infants and children
婴儿和儿童期 血象特点
? Content of erythrocyte count and hemoglobin
? 红细胞数和血红蛋白含量
? Content of RBC and Hb at 2 weeks after birth is the
same as those of umbilical blood
新生儿生后 2周时的 RBC和 Hb含量与脐血相同
? There is slight anemia 2-3months after birth
（ physiologic anemia）
生后 2－ 3月时出现轻度贫血（生理性贫血）
? Recover to normal at 6 month of age and reach the
level of adult by 12 years of age
6个月时恢复,12岁时达成人水平
hemoglobin pattern and content of hemoglobin in
various age period
各不同年龄的血红蛋白种类含量
HbA
(Α 2β 2) %
HbF
(α 2 r 2 ) %
HbA2
(α 2 ?2 ) %
6 months fetus 5-10 90
newborn 30 70 1
3mon-1year 95 5 2-3
2years-adult 95 2 2-3
? White blood count and differentiation
? 白细胞数及分类
* White blood cells count is higher at birth:15－
20× 109/L
初生时白细胞总数较高 15－ 20× 109/L
* Average of 12× 109/L at 1 week of age
一周时平均为 12× 109/L
* Maintain at 10× 109/L in infancy and young children
婴幼儿维持在 10× 109/L
* Approximate 4－ 10× 109/L of the adult level after 8
years of age
8岁后接近成人 4－ 10× 109/L
2 4 6 8 10 1 2 3 4 8 10 14
70
60
50
40
30
20
10
%
Lymphocyte
Neutrophil
5 years
5 days
days years
The two cross-over of neutrophils and lyphocytes
during childhood
anemia
贫血
? Definition of anemia：
? 贫血的定义：
? erythrocytes and hemoglobin per
volume of pheripheral blood lower than
normal
外周血中单位体积内的红细胞数或血红
蛋白量低于正常
? Consensus of National Symphosium on
Pediatric, At sea level of 0:
? 全国小儿血液会议定,根据 WHO海拔为 0时
The following Hb level will be considered as
anemic:
? neonate <145g/L,1-4months<90g/L、
4-6months<100g/L,6mon-6years<110g/L、
6years-14years<120g/L
程度分类
? Degree of anemia
Neonate
Mild ~90 g/L ~120 g/L
Moderate ~60 g/L ~90 g/L
Severe ~30 g/L ~60 g/L
Extremely severe? 30 g/L ? 60 g/L
Morphologic classification
? 32? 28? 80hypochromatic
microcytic
32-28? 28? 80microcytic
32-2828-3280-94Normal-cytic
32-283294macrocytic
MCHC
(32-38%)
MCH28-
(32pg)
MCV80-94fl
形 态 分 类
Etiologic classification
病 因 分 类
? Inadequate production of RBC and HB
? 红细胞和血红蛋白生成不足
?Deficiency of hematopoietic factors,folic
acid,B12 and iron deficiency
造血因子缺乏,叶酸,B12,铁缺乏
? Duplication and differentiation anomaly of stem
cells,
干细胞复制分化异常：
? aplastic anemia
再生障碍性贫血
? Infectious anemia
感染性贫血
? damage of bone marrow hematopoisis by
drugs and tumor infiltration
药物损伤骨髓造血、肿瘤浸润
? Hemolytic anemia
溶血性贫血
? Intrinsic anomaly of RBC
红细胞内在异常
? Extrinsic anomaly of RBC
红细胞外在异常
? Blood loss:
失血性：
? acute & chronic blood loss
急慢性失血
Diagnosis of Animia
贫 血 诊 断? History
病史
? Age of onset
发病年龄
? Accompanying symptoms
伴随症状
? Feeding history 喂养史
? Past history 过去史
? Family history 家族史
? Physical examination
体格体检
? Growth and development 生长发育史
? Nutritional status 营养状况
? Skin and mucus membrane 皮肤粘膜
? Nails and hair 指甲毛发
? Liver-Spleen & Lymph nodes
肝脾淋巴结
? Laboratory testing 实验室
? RBC morphology 红细胞形态
? Reticulocyte count 网织红计数
? Bone marrow smear 骨髓涂片
? RBC fragility 红细胞脆性
? Hb electropheresis Hb电泳
? Enzyme determination 酶测定
? Coomb’s test 抗人球蛋白试验
? Serum iron determination 铁的血清学
Nutritional Anemias
营养性贫血
Iron deficiency anemia
缺铁性贫血
Megaloblastic anemia
巨幼红细胞贫血
营养性缺铁性贫血
Nutritional iron deficiency
anemia
Iron deficiency anemia （ IDA）
缺铁性贫血
? Increased demand of the body
体内铁的需要增加
? Inadequate iron ingestion or excessive loss
摄入铁不足或丢失过多
? Iron deficiency of the body
体内铁不足或缺铁
? Inadequate Hb synthesis,microcytic hypochromatic
anemia
Hb合成不足、小细胞低色素贫血
? Mostly seen during 6 months-2 years
高发年龄 6月 -2岁
Etiology of nutritional iron deficiency anemia
营养性缺铁性贫血的病因
? Inadequate storage of iron,Premature,twin、
（ fetal to fetal,fetal to mother transfusion)
铁储存不足：早产、双胎（胎胎、胎母输血）
? Inadequate ingestion,Lack of iron in dairy
products and low absorption rate,supplemental
food not in time
铁摄入量不足：乳制品含铁少吸收率低，不及时
添加辅食
? Growth & developmental factors：
生长发育因素：
? more body weight increase resulting in more
blood volume and more iron demand
体重增加、血容量随之增加、需铁增加
? excessive loss or more consume of iron,
铁的丢失或消耗过多,
? intestinal bleeding due to hypersensitivity to
cow milk,parasite consume iron and excessive
excretion through diarrhea
牛奶过敏致肠出血、寄生虫、消耗增多、腹泻时
排铁
IDA Pathogenesis
? Iron depletion,ID
? Iron deficient erythropoiesis,IDE
? Iron deficiency anemia,IDA
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
IDA clinical manifestations
? Pallor is the most important clue
? Irritability and anorexia are prominent when Hb level
falls below 50g/L
? Tachycardia,cardiac dilatation and systolic murmur
are often present
? Palpable spleen in 10 ~15% of patients
? Pica is sometimes prominent
? Changes in neurologic and intellectual function
patient Normal
Diagnosis of IDA
? Clinical diagnosis
临床 诊断
? determine the etiology of
iron deficiency
明确缺铁的病因,
? Physical examination,
体检,
? Laboratory diagnosis
实验室诊断
Laboratory diagnosis
实 验 室 诊 断
? Blood,microcytic hypochromatic
anemia,various size of RBC,pale
area of RBC extended,normal
reticular cell count or alight decreased,
MCV↓,MCH↓,MCHC↓
血象,小细胞低色素性贫血,RBC大
小不等，苍白区扩大，网织正常或轻
度下降,MCV↓, MCH↓, MCHC↓
? Bone marrow,ratio of granulocyte:RBC
inversed,unparallel development of
nuclear and cytoplasma（ developmental
retardation of cytoplasma）
骨髓,粒,红倒置，核浆发育不平衡（胞
桨发育落后胞核）
? Serological examination of iron:
铁的血清学检查：
155-13 Normal red cell
morphology
155-14 Microcytes in IDA
155-15 Megalocytes in
pernicious anemia
SF (?g/L) 100?60 ? 20 ? 10 ? 10
SI (?g/dl) 115?50 ? 115 ? 60 ? ? 40
TS(%) 35?15 ? 30 ? 15 ? ? 10
Sideroblast(%) 40-60 40-60 ? 10 ? ? 10
TIBC (?g/dl) 330?30 360 390 ? 410
FEP (?g/dl RBC) 30 30 100 ? 200
Normal IDAIDEID
Microcytic
hypochromic
Storage iron
Transport iron
Erythron iron
Prevention of nutritional iron deficiency
anemia
营养性缺铁性贫血预防
? Prevention of premature birth,prevention of iron
deficiency in pregnancy
预防早产，预防孕妇缺铁
? Encouraging breast feeding and adding
supplemental food in time
鼓励母乳喂养，及时添加辅食
? Iron supplement for premature baby begin at 2
month after birth 早产儿于出生 2月起补铁
? Iron fortified food 铁强化食品
? Regular screening for anemia 定期进行贫血普查
Therapy of nutritonal iron deficiency anemia
营养性缺铁性贫血的治疗
? Etiologic therapy 病因治疗
? Iron supplement,Fe++ elemental iron 3-6mg/kg.d
铁剂治疗,Fe++ 元素铁 3-6mg/kg.d
?common preparation：
常用制剂：
Ferrous Fumarate(elemental iron33％ )
富马铁 (含元素铁 33％ )
Mixture of ferrous sulfate（ elemental iron 5mg/ml）
硫酸亚铁合剂（含元素铁 5mg/ml）
Ferrous Gluconate（ elemental iron12％）
葡萄糖酸亚铁（含元素铁 12％）
?commonly used injection：
常用针剂：
Iron Dextrane Injection（ elemental iron
50mg/ml）
右旋糖酐铁（含元素铁 50mg/ml）
? Blood transfusion
输血
total elemental iron supplement（ mg）＝（ Lower
limit of normal Hb－ patient Hb level） × body
weight× 0.4
补充元素铁总量（ mg）＝（ Hb正常低限－患儿 Hb值）
×体重× 0.4
Bleeding disorders
(Hemorrhagic diseases)
ITP
Hemophilia
Idiopathic thrombocytopenic Purpura (ITP)
特发性血小板减少性紫癜
? Etiology,病因：
? Viral infection,病毒感染：
DNA virus,herpes virus,human micro-Virus
B19,CMV,EBV
DNA病毒 疱疹类、人类微小病毒 B19,CMV,EBV
? RNA virus,rubella, hepatitis,parotitis,HIV、
measles
RNA病毒 风疹、肝炎,腮腺炎,HIV,麻疹
? Vaccine immunization,疫苗接种：
? Medicine,药物：
Pathogenesis发病机理
?Combination of viral Ag with related Ab forming immuno-
complex,depositing on platelet and megakaryocyte
causing damage
病毒 Ag与相应 Ab结合形成免疫复合物，沉积到血小
板和巨核细胞上，使其破坏增多
?Anti-virus produced by the organism, Through cross-
reaction between molecular analog machine and glycoprotein
on the platelet surface or through activating complement
system reducing platelet survival
? 机体 产生的抗病毒 Ab,通过分子模拟机与血小板表
面糖蛋白发生 交 叉效应，或激活补体系统，血小板
寿命缩短
?Virus changes the structure of glycoprotein of the platelet
membrane,causing changes to its Antigen,forming anti
itself antibody,thus destroying the platelet
病毒改变血小板膜糖蛋白结构，使其 Ag发生改变，形成
自身 Ab,破坏血小板
?Virus acts directly on magakarycytes forming inclusion
body within their nucleus,leading to the damage of
platelet
病毒直接作用于巨核细胞形成核内包涵体，导致血小板
破坏
acute onset type
急性型
? Onset age most children aged from 2~5 years
发病年龄 常见年龄 2-5岁儿童
? mostly with history of viral infection
多伴有病毒感染史
? Onset acute
起病 急骤
? Petechiae and purpura are common
瘀点和紫癜是常见的
? Bleeding heavy
出血程度 重
? Organ bleeding there may be
脏器出血 可有
? Course
病程
80％ recover in 4-6weeks
80％ 4-6周恢复
90％ cure spontaneously in 6months
90％半年内自愈
? platelet count
血小板计数 <20X109/L
? megakaryocyte count,
巨核细胞数
normal or increase,megakaryoblast increase
正常或增多,幼巨核增多
ITP (acute) laboratory findings
?Peripheral blood
platelet count
Blood smear
?(Bone marrow,platelet associated antibody)
Therapy 治 疗
? General therapy：
一般治疗：
? Drug therapy：
药物治疗：
Adrenal corticosteroid;
肾上腺皮质激素 ;
Prednisone 1.5-2mg/kg.d
强的松 1.5-2mg/kg.d，
? BPC>60× 109/L tapering 减量
? total therapeutic course <4 weeks
总疗程 <4周
? boost therapy,
冲击疗法
dexamethasone 1.5-2.0mg/kg.d
地塞米松
Methylprednisolone 15-30mg/kg.d
甲基强的松龙
? HD-IVIG,400mg/kg.d,for 5 d,boost once
each week
HD-IVIG,400mg/kg.d,适用 5天，每周加强
一次
or 1g/kg.次,once a month
或 1g/kg.次，每月 1次
? simply infusing platelet
单采血小板
Therapy（ for chronic type）
治 疗 （慢性）
? Immunoinhibitant：
免疫抑制剂：
for chronic type only,generally do not use
慢性型用,一般不用
? Anti－ rabbit D globulin,25mg/kg.d× 2d
抗－ D免疫球蛋白,
? ?－ interferon,100-3,000,000U/dose
?－干扰素：
? Splenectomy,age>6years
切脾,年龄 >6岁,
course>11/2years,
病程 >11/2年
prepuberty female
青春期前少女
with less efficacy in those with
megakaryocyte↓ and PAIgG↑
巨核细胞 ↓,PAIgG↑ 疗效差
血 友 病
（ Hemophilia）
Classification of hemophilia
血友病的种类
HA－ FⅧ （ anti-hemophilia globulin AHG） ↓ 80%
抗血友病球蛋白 AHG
HB－ FⅨ （ plasma thromboplastin component PTC） ↓ 15%
血浆凝血活酶成分 PTC
HC－ FⅪ （ plasma thromboplastin antecidant PTA） ↓ 1-2%
凝血活酶前质 PTA
●
●
●
●●●
XX XX XX
XX XX XX XX XX XX
XY XY XY
XY XY XY XY XY XY
Heredity of hemophilia
Clinical manifestations
临床表现
Bleeding after minor injury is the common manifestation of hemophilia
轻微损伤出血不止是本组病的主要共性
? HA,Severe type most onset before 2-year of age,even in neonates,
mild and moderate patient mostly begin at an older age,
HA,重型多在 <2岁起病，可在新生儿期起病，轻中型起病
晚
? Bleeding within joints,deep muscle,organs and subcutaneous tissue
Inflammation caused by recurrent bleeding,leading to malformation
深部出血 关节、深部肌肉、内脏、皮下，大关节反复出
血致炎症，导致畸形
8-year old boy with Hemophilia A,heavy bleeding in the left knee joint
9-year old boy with severe hemophilia
A,heavy bleeding in the right knee joint
after decompression operation
9-year old boy with severe hemophilia
A,extensive bleeding in soft tissue of left
cheek after extraction of his tooth
?HB,HC,hemorrhagic symptoms is the same as HA
HB,HC,出血症状同 HA
?HB severe type－ FⅨ content<2％（ rare）
HB重型 － FⅨ 含量 <2％（罕见）
?HC heterozygote,without bleeding,homozygote
with hemorrhagic diathesis
HC 杂合子, 无出血，纯合子有出血倾向
Clinical classification of hemophilia
血友病临床分型
Errhysis after severe injury or major
operation
20-50Subclinical
Prolongation of bleeding time after
minor injury and operation,without
articular malformation
6-20Mild
Bleeding in joints,muscle,deep tissue
after minor injury and articular
malformation
2-5Moderate
Recurrent spontaneous bleeding in
joints,muscle,deep tissue and articular
malformation
1Severe
Bleeding siteⅧ,C
content%
Laboratory diagnosis
实验室检查
? Screening：
筛选实验：
? Prolonged coagulation time (test tube method) (severe type）
试管法凝血时间延长（重型）
? Prolonged Activated partial prothrombin time (APTT)
活化部分凝血酶原时间（ APTT） 延长
? Abnormal Thromboplastin generaton test
凝血活酶生成试验异常
? Prothrombin consumption test abnormal（ normal in
mild cases）
凝血酶原消耗不良（轻者正常）
? Prothrombin time（ PT） normal
凝血酶原时间（ PT） 正常
? Bleeding time normal
出血时间正常
? Blood clot retraction time normal
血块收缩时间正常
Differential diagnosis of various type of hemophilia
区分血友病类型
prothrombin consumption and thromboplastin
generation correction test
凝血酶原消耗及凝血活酶生成纠正试验
HA HB HC
(AHG↓) (PTC↓) (PTA↓)
normal plasma( Ⅷ, Ⅸ, Ⅺ ) correctable correctable correctable
normal plasma （ Ⅸ, Ⅺ ） uncorrectable correctable correctable
barium sulfate absorbed (Ⅷ, Ⅺ ) correctable uncorrectable correctable
plasma
? Coagulation factors content determination
凝血因子含量测定
? Ⅷ, Ⅸ, Ⅺ coagulation activation determination
Ⅷ, Ⅸ, Ⅺ 凝血活性测定
? coagulation activation of various type coagulation
factors decreased
各型相应因子凝血活性降低
? Various type of vWF,normal
各型 vWF正常
Therapy 治 疗
?Prevent hemorrhage 预防出血：
?Local hemostasis 局部止血：
?Substitution therapy,替代疗法：
?Based on the expected percent of coagulation factors to be
achieved to calculate the FⅧ dosage to be infused：
根据凝血因子需达的 %，计算需要输注的 FⅧ 剂量：
mild 20%-30%
moderate 30%-50%
severe 60%-80%
Infusing 1u/kg of condensed Ⅷ factor,can raise FⅧ, C 2%
输入 1u/kg 浓缩 Ⅷ 因子,可提高 FⅧ, C 2%
? Drug therapy药物治疗
Ranitidine雷尼替丁
1-deanimo-8-arginine（ DDAVP)
1-脱氨 -8-精氨酸（ DDAVP)
? Gene therapy,recombinant FⅧ （ r FⅧ ）
without contamination with virus
基因治疗 基因重组 FⅧ （ r FⅧ ）不受病毒污染
can raise the body relevant coagulation
factors by more than 5%
使体内有关凝血因子活性达到 5％以上
Preventive Therapy
预 防 治 疗
? Severe hemophilia
重型血友病
? Optional age for preventive therapy:1-2 years
预防治疗的最佳年龄 1-2岁
? Gene diagnosis,
基因诊断
reducing the incidence of hemophilia
降低血友病的发病率
Update of hemophilia diagnosis and therapy
Gene monitoring
血友病的诊治进展
? gene mutation spot－ chemistry mismatch
fragmentation method
基因突变点－化学错配裂解法
? simple chain conformation polymorphism analysis
单链构象多态性分析
? denaturation gradient gel electrophoresis
变性梯度凝胶电泳
? DNA polymorphism analysis－ through analysis
on genetic markers to identify mutation locus
DNA多态性分析－分析遗传学标记鉴定突变位点
? Gene deletion,insert mutation,gene inversion－
Southern blot
基因缺失、插入突变、基因倒位－ Southorn印迹法
? Highly purified coagulation factor
高纯化凝血因子
? Highly purified AHG（ contains FⅧ 2000-4000U),substitute
medium purified AHG（ contains FⅧ 0.5-5U)
高纯化 AHG（含 FⅧ 2000-4000U),
取代中度纯化 AHG（含 FⅧ 0.5-5U)
? Highly purified FⅨ
高纯化 FⅨ
? Synthesized coagulation factors,
人工合成凝血因子：
—— The most safe therapy
—— 最安全的治疗
? Gene Therapy：
基因治疗：
coagulation factor Ⅷ -recombinant AAV
凝血因子 Ⅷ -重组 AAV
Management of hemophilia
血友病的管理
? Establish hemophilia therapy and prevention
specialist network and training center
建立血友病防治的专家网、培训中心
? Organization of hemophilia nursing care and
therapy
对血友病病人的护理、治疗要有组织团体
? Improve safety of hemostasis products
改进止血产品的安全性
Lower the prices
使之价格的低廉性
Childhood Leukemia
小儿白血病
? Epidemiology
流行病学
? 35%of childhood tumor was leukemia
白血病约占该期肿瘤的 35%
? ? Incidence of childhood leukemia
<15years,4/10万
? 15岁儿童白血病发病率 4/10万
? 10,000 new cases of childhood leukemia occur in
China annually
我国每年约有 1万例儿童白血病发生
? Onset from any age,even infant and congenital
任何年龄均可发病如先天性或婴儿
? More often seen in preschool and school aged
学龄前期和学龄期儿童多见
? Classification
分类
? Mostly childhood acute leukemia,accounting for >95%
小儿急性白血病为主,占 95%以上
? Acute lymphocytic leukemia,accounting for 75%
急性非淋巴细胞白血病占 35%
? Acute non-lymphocytic leukemia accounting for 35%
慢性白血病占 3%-5%
? Chronic leukemia 3%-5% Mixed cell leukemia rare
混合细胞白血病少见
ALL：
? Gemany BFM cooperation group
德国 BFM协作组
ALL 5-year event free survival(EFS)80%
ALL 5年无事生存率 (EFS)80%
? The United States:CCSG,St.Juds Children’s Hospital
美国 CCSG,St.Juds儿童医院
ALL 5-year EFS 74%
? Beijing,Shanghai of China 国内北京、上海
ALL 5-year EFS 74%
ANLL：
Abroad,5-year survival from 30% to 50%~60%
国外 5年存活率从 3%提高到 50%-60%
Domestic,5-year EFS 40%-50%
国内
Therapeutic principle of childhood ALL
小儿 ALL治疗原则
? Selection of therapeutic regime according
to the leukemia type
按型选方案
? Therapy divide into two steps
治疗分二步
? Remission induction (combined
chemotherapy）
诱导缓解 (联合化疗）
? maximal killing leukemic cells (99%) reducing from 1012 to 108
最大限度杀伤 (99%)白血病细胞从 1012减少 108
? Restore hematopoitic function of the bone marrow (CR)
恢复骨髓造血功能 (CR)
? Therapy after achieving remission
缓解后治疗
further killing the residual 108 leukemic cells to
prevent relapse
进一步杀灭剩下 108白血病细胞防止复发
? Include,
此阶段包括
? Consolidation,maintaining
巩固 维持
? prevention of CNS complications
中枢神经系统预防
? fortified therapy at advanced stage
后期强化治疗
? Total therapeutic course,boy 3 years,girl
31/2 years
总疗程 男孩 3年、女孩 3年半
Recent knowledge and development of
childhood lukemia
近代对小儿白血病的认识和进展
? Childhood leukemia is a curable and not an incurable
disease
? 小儿白血病不是一个不治之症而是有治之症
? 5-year EFS of childhood ALL (low risk) reached >70% both
domestically and internationally
? 小儿白血病中的 ALL（低危）国内外的 5年 EFS可
达 70%以上
? Diagnosis update,Research progress in morphology,
immunology,cytogenetics and molecular biology
? 诊断进展：形态学、免疫学、细胞遗传学到分子
生物学的研究进展
? Therapy update,New therapeutic agents,such as
continuous improvement of chemotherapy regime,
hematopoietic stem cells transplantation,gene
therapy,biologic regulator
治疗进展：化疗方案不断改进、造血干细胞移植
基因治疗、生物调节剂等新的治疗手段
? Chemotherapy is still the basic and most important
therapeutic method for ALL
迄今为止化疗仍是 ALL的最基本、最重要的治疗
手段
College,Fudan University
Hematologic diseases of Children
小儿 血液系统疾病
Associated Professor Lu Feng Quan
Hematologic Disorders of Children
小儿血液系统疾病
? Diseases of erythrocytic system:
? 红细胞系统疾病：
* Hematopoietic substances deficiency;
* 造血原料缺乏 ;
Nutritional iron deficiency anemia
营养性缺铁性贫血
nutritional megaloblastic anemia
营养性巨幼性贫血
* Anerythropoiesis;
* 红细胞生成减少 ;
aplastic anemia
再生障碍性贫血
Pure erythrocytic aplastic anemia
纯红再障
* Excessive destroy of erythrocytes;
* 红细胞破坏过多 ;
hemolytic anemia
溶血性贫血
* blood loss;
* 失血 ;
acute & chronic blood loss
急慢性失血
* tumors of the bone marrow of bone marrow
metastasis
骨髓自身肿瘤 肿瘤或骨转移
? Disorders of the white blood cells：
? 白细胞性疾病：
* hematologic malignancy ;
* 血液系统恶性肿瘤 ;
acute & chronic leukemia
急慢性白血病
? Bleeding and coagulation disorders：
? 出凝血疾病：
* Endogenous coagulation factors deficiency ;
内源性凝血因子缺乏 ;
hemophilia
血友病
* Disorders of platelet production;
血小板生成障碍 ;
Thrombocytopenic purpura
血小板减少性紫癜
blood characteristics of infants and children
婴儿和儿童期 血象特点
? Content of erythrocyte count and hemoglobin
? 红细胞数和血红蛋白含量
? Content of RBC and Hb at 2 weeks after birth is the
same as those of umbilical blood
新生儿生后 2周时的 RBC和 Hb含量与脐血相同
? There is slight anemia 2-3months after birth
（ physiologic anemia）
生后 2－ 3月时出现轻度贫血（生理性贫血）
? Recover to normal at 6 month of age and reach the
level of adult by 12 years of age
6个月时恢复,12岁时达成人水平
hemoglobin pattern and content of hemoglobin in
various age period
各不同年龄的血红蛋白种类含量
HbA
(Α 2β 2) %
HbF
(α 2 r 2 ) %
HbA2
(α 2 ?2 ) %
6 months fetus 5-10 90
newborn 30 70 1
3mon-1year 95 5 2-3
2years-adult 95 2 2-3
? White blood count and differentiation
? 白细胞数及分类
* White blood cells count is higher at birth:15－
20× 109/L
初生时白细胞总数较高 15－ 20× 109/L
* Average of 12× 109/L at 1 week of age
一周时平均为 12× 109/L
* Maintain at 10× 109/L in infancy and young children
婴幼儿维持在 10× 109/L
* Approximate 4－ 10× 109/L of the adult level after 8
years of age
8岁后接近成人 4－ 10× 109/L
2 4 6 8 10 1 2 3 4 8 10 14
70
60
50
40
30
20
10
%
Lymphocyte
Neutrophil
5 years
5 days
days years
The two cross-over of neutrophils and lyphocytes
during childhood
anemia
贫血
? Definition of anemia：
? 贫血的定义：
? erythrocytes and hemoglobin per
volume of pheripheral blood lower than
normal
外周血中单位体积内的红细胞数或血红
蛋白量低于正常
? Consensus of National Symphosium on
Pediatric, At sea level of 0:
? 全国小儿血液会议定,根据 WHO海拔为 0时
The following Hb level will be considered as
anemic:
? neonate <145g/L,1-4months<90g/L、
4-6months<100g/L,6mon-6years<110g/L、
6years-14years<120g/L
程度分类
? Degree of anemia
Neonate
Mild ~90 g/L ~120 g/L
Moderate ~60 g/L ~90 g/L
Severe ~30 g/L ~60 g/L
Extremely severe? 30 g/L ? 60 g/L
Morphologic classification
? 32? 28? 80hypochromatic
microcytic
32-28? 28? 80microcytic
32-2828-3280-94Normal-cytic
32-283294macrocytic
MCHC
(32-38%)
MCH28-
(32pg)
MCV80-94fl
形 态 分 类
Etiologic classification
病 因 分 类
? Inadequate production of RBC and HB
? 红细胞和血红蛋白生成不足
?Deficiency of hematopoietic factors,folic
acid,B12 and iron deficiency
造血因子缺乏,叶酸,B12,铁缺乏
? Duplication and differentiation anomaly of stem
cells,
干细胞复制分化异常：
? aplastic anemia
再生障碍性贫血
? Infectious anemia
感染性贫血
? damage of bone marrow hematopoisis by
drugs and tumor infiltration
药物损伤骨髓造血、肿瘤浸润
? Hemolytic anemia
溶血性贫血
? Intrinsic anomaly of RBC
红细胞内在异常
? Extrinsic anomaly of RBC
红细胞外在异常
? Blood loss:
失血性：
? acute & chronic blood loss
急慢性失血
Diagnosis of Animia
贫 血 诊 断? History
病史
? Age of onset
发病年龄
? Accompanying symptoms
伴随症状
? Feeding history 喂养史
? Past history 过去史
? Family history 家族史
? Physical examination
体格体检
? Growth and development 生长发育史
? Nutritional status 营养状况
? Skin and mucus membrane 皮肤粘膜
? Nails and hair 指甲毛发
? Liver-Spleen & Lymph nodes
肝脾淋巴结
? Laboratory testing 实验室
? RBC morphology 红细胞形态
? Reticulocyte count 网织红计数
? Bone marrow smear 骨髓涂片
? RBC fragility 红细胞脆性
? Hb electropheresis Hb电泳
? Enzyme determination 酶测定
? Coomb’s test 抗人球蛋白试验
? Serum iron determination 铁的血清学
Nutritional Anemias
营养性贫血
Iron deficiency anemia
缺铁性贫血
Megaloblastic anemia
巨幼红细胞贫血
营养性缺铁性贫血
Nutritional iron deficiency
anemia
Iron deficiency anemia （ IDA）
缺铁性贫血
? Increased demand of the body
体内铁的需要增加
? Inadequate iron ingestion or excessive loss
摄入铁不足或丢失过多
? Iron deficiency of the body
体内铁不足或缺铁
? Inadequate Hb synthesis,microcytic hypochromatic
anemia
Hb合成不足、小细胞低色素贫血
? Mostly seen during 6 months-2 years
高发年龄 6月 -2岁
Etiology of nutritional iron deficiency anemia
营养性缺铁性贫血的病因
? Inadequate storage of iron,Premature,twin、
（ fetal to fetal,fetal to mother transfusion)
铁储存不足：早产、双胎（胎胎、胎母输血）
? Inadequate ingestion,Lack of iron in dairy
products and low absorption rate,supplemental
food not in time
铁摄入量不足：乳制品含铁少吸收率低，不及时
添加辅食
? Growth & developmental factors：
生长发育因素：
? more body weight increase resulting in more
blood volume and more iron demand
体重增加、血容量随之增加、需铁增加
? excessive loss or more consume of iron,
铁的丢失或消耗过多,
? intestinal bleeding due to hypersensitivity to
cow milk,parasite consume iron and excessive
excretion through diarrhea
牛奶过敏致肠出血、寄生虫、消耗增多、腹泻时
排铁
IDA Pathogenesis
? Iron depletion,ID
? Iron deficient erythropoiesis,IDE
? Iron deficiency anemia,IDA
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
IDA clinical manifestations
? Pallor is the most important clue
? Irritability and anorexia are prominent when Hb level
falls below 50g/L
? Tachycardia,cardiac dilatation and systolic murmur
are often present
? Palpable spleen in 10 ~15% of patients
? Pica is sometimes prominent
? Changes in neurologic and intellectual function
patient Normal
Diagnosis of IDA
? Clinical diagnosis
临床 诊断
? determine the etiology of
iron deficiency
明确缺铁的病因,
? Physical examination,
体检,
? Laboratory diagnosis
实验室诊断
Laboratory diagnosis
实 验 室 诊 断
? Blood,microcytic hypochromatic
anemia,various size of RBC,pale
area of RBC extended,normal
reticular cell count or alight decreased,
MCV↓,MCH↓,MCHC↓
血象,小细胞低色素性贫血,RBC大
小不等，苍白区扩大，网织正常或轻
度下降,MCV↓, MCH↓, MCHC↓
? Bone marrow,ratio of granulocyte:RBC
inversed,unparallel development of
nuclear and cytoplasma（ developmental
retardation of cytoplasma）
骨髓,粒,红倒置，核浆发育不平衡（胞
桨发育落后胞核）
? Serological examination of iron:
铁的血清学检查：
155-13 Normal red cell
morphology
155-14 Microcytes in IDA
155-15 Megalocytes in
pernicious anemia
SF (?g/L) 100?60 ? 20 ? 10 ? 10
SI (?g/dl) 115?50 ? 115 ? 60 ? ? 40
TS(%) 35?15 ? 30 ? 15 ? ? 10
Sideroblast(%) 40-60 40-60 ? 10 ? ? 10
TIBC (?g/dl) 330?30 360 390 ? 410
FEP (?g/dl RBC) 30 30 100 ? 200
Normal IDAIDEID
Microcytic
hypochromic
Storage iron
Transport iron
Erythron iron
Prevention of nutritional iron deficiency
anemia
营养性缺铁性贫血预防
? Prevention of premature birth,prevention of iron
deficiency in pregnancy
预防早产，预防孕妇缺铁
? Encouraging breast feeding and adding
supplemental food in time
鼓励母乳喂养，及时添加辅食
? Iron supplement for premature baby begin at 2
month after birth 早产儿于出生 2月起补铁
? Iron fortified food 铁强化食品
? Regular screening for anemia 定期进行贫血普查
Therapy of nutritonal iron deficiency anemia
营养性缺铁性贫血的治疗
? Etiologic therapy 病因治疗
? Iron supplement,Fe++ elemental iron 3-6mg/kg.d
铁剂治疗,Fe++ 元素铁 3-6mg/kg.d
?common preparation：
常用制剂：
Ferrous Fumarate(elemental iron33％ )
富马铁 (含元素铁 33％ )
Mixture of ferrous sulfate（ elemental iron 5mg/ml）
硫酸亚铁合剂（含元素铁 5mg/ml）
Ferrous Gluconate（ elemental iron12％）
葡萄糖酸亚铁（含元素铁 12％）
?commonly used injection：
常用针剂：
Iron Dextrane Injection（ elemental iron
50mg/ml）
右旋糖酐铁（含元素铁 50mg/ml）
? Blood transfusion
输血
total elemental iron supplement（ mg）＝（ Lower
limit of normal Hb－ patient Hb level） × body
weight× 0.4
补充元素铁总量（ mg）＝（ Hb正常低限－患儿 Hb值）
×体重× 0.4
Bleeding disorders
(Hemorrhagic diseases)
ITP
Hemophilia
Idiopathic thrombocytopenic Purpura (ITP)
特发性血小板减少性紫癜
? Etiology,病因：
? Viral infection,病毒感染：
DNA virus,herpes virus,human micro-Virus
B19,CMV,EBV
DNA病毒 疱疹类、人类微小病毒 B19,CMV,EBV
? RNA virus,rubella, hepatitis,parotitis,HIV、
measles
RNA病毒 风疹、肝炎,腮腺炎,HIV,麻疹
? Vaccine immunization,疫苗接种：
? Medicine,药物：
Pathogenesis发病机理
?Combination of viral Ag with related Ab forming immuno-
complex,depositing on platelet and megakaryocyte
causing damage
病毒 Ag与相应 Ab结合形成免疫复合物，沉积到血小
板和巨核细胞上，使其破坏增多
?Anti-virus produced by the organism, Through cross-
reaction between molecular analog machine and glycoprotein
on the platelet surface or through activating complement
system reducing platelet survival
? 机体 产生的抗病毒 Ab,通过分子模拟机与血小板表
面糖蛋白发生 交 叉效应，或激活补体系统，血小板
寿命缩短
?Virus changes the structure of glycoprotein of the platelet
membrane,causing changes to its Antigen,forming anti
itself antibody,thus destroying the platelet
病毒改变血小板膜糖蛋白结构，使其 Ag发生改变，形成
自身 Ab,破坏血小板
?Virus acts directly on magakarycytes forming inclusion
body within their nucleus,leading to the damage of
platelet
病毒直接作用于巨核细胞形成核内包涵体，导致血小板
破坏
acute onset type
急性型
? Onset age most children aged from 2~5 years
发病年龄 常见年龄 2-5岁儿童
? mostly with history of viral infection
多伴有病毒感染史
? Onset acute
起病 急骤
? Petechiae and purpura are common
瘀点和紫癜是常见的
? Bleeding heavy
出血程度 重
? Organ bleeding there may be
脏器出血 可有
? Course
病程
80％ recover in 4-6weeks
80％ 4-6周恢复
90％ cure spontaneously in 6months
90％半年内自愈
? platelet count
血小板计数 <20X109/L
? megakaryocyte count,
巨核细胞数
normal or increase,megakaryoblast increase
正常或增多,幼巨核增多
ITP (acute) laboratory findings
?Peripheral blood
platelet count
Blood smear
?(Bone marrow,platelet associated antibody)
Therapy 治 疗
? General therapy：
一般治疗：
? Drug therapy：
药物治疗：
Adrenal corticosteroid;
肾上腺皮质激素 ;
Prednisone 1.5-2mg/kg.d
强的松 1.5-2mg/kg.d，
? BPC>60× 109/L tapering 减量
? total therapeutic course <4 weeks
总疗程 <4周
? boost therapy,
冲击疗法
dexamethasone 1.5-2.0mg/kg.d
地塞米松
Methylprednisolone 15-30mg/kg.d
甲基强的松龙
? HD-IVIG,400mg/kg.d,for 5 d,boost once
each week
HD-IVIG,400mg/kg.d,适用 5天，每周加强
一次
or 1g/kg.次,once a month
或 1g/kg.次，每月 1次
? simply infusing platelet
单采血小板
Therapy（ for chronic type）
治 疗 （慢性）
? Immunoinhibitant：
免疫抑制剂：
for chronic type only,generally do not use
慢性型用,一般不用
? Anti－ rabbit D globulin,25mg/kg.d× 2d
抗－ D免疫球蛋白,
? ?－ interferon,100-3,000,000U/dose
?－干扰素：
? Splenectomy,age>6years
切脾,年龄 >6岁,
course>11/2years,
病程 >11/2年
prepuberty female
青春期前少女
with less efficacy in those with
megakaryocyte↓ and PAIgG↑
巨核细胞 ↓,PAIgG↑ 疗效差
血 友 病
（ Hemophilia）
Classification of hemophilia
血友病的种类
HA－ FⅧ （ anti-hemophilia globulin AHG） ↓ 80%
抗血友病球蛋白 AHG
HB－ FⅨ （ plasma thromboplastin component PTC） ↓ 15%
血浆凝血活酶成分 PTC
HC－ FⅪ （ plasma thromboplastin antecidant PTA） ↓ 1-2%
凝血活酶前质 PTA
●
●
●
●●●
XX XX XX
XX XX XX XX XX XX
XY XY XY
XY XY XY XY XY XY
Heredity of hemophilia
Clinical manifestations
临床表现
Bleeding after minor injury is the common manifestation of hemophilia
轻微损伤出血不止是本组病的主要共性
? HA,Severe type most onset before 2-year of age,even in neonates,
mild and moderate patient mostly begin at an older age,
HA,重型多在 <2岁起病，可在新生儿期起病，轻中型起病
晚
? Bleeding within joints,deep muscle,organs and subcutaneous tissue
Inflammation caused by recurrent bleeding,leading to malformation
深部出血 关节、深部肌肉、内脏、皮下，大关节反复出
血致炎症，导致畸形
8-year old boy with Hemophilia A,heavy bleeding in the left knee joint
9-year old boy with severe hemophilia
A,heavy bleeding in the right knee joint
after decompression operation
9-year old boy with severe hemophilia
A,extensive bleeding in soft tissue of left
cheek after extraction of his tooth
?HB,HC,hemorrhagic symptoms is the same as HA
HB,HC,出血症状同 HA
?HB severe type－ FⅨ content<2％（ rare）
HB重型 － FⅨ 含量 <2％（罕见）
?HC heterozygote,without bleeding,homozygote
with hemorrhagic diathesis
HC 杂合子, 无出血，纯合子有出血倾向
Clinical classification of hemophilia
血友病临床分型
Errhysis after severe injury or major
operation
20-50Subclinical
Prolongation of bleeding time after
minor injury and operation,without
articular malformation
6-20Mild
Bleeding in joints,muscle,deep tissue
after minor injury and articular
malformation
2-5Moderate
Recurrent spontaneous bleeding in
joints,muscle,deep tissue and articular
malformation
1Severe
Bleeding siteⅧ,C
content%
Laboratory diagnosis
实验室检查
? Screening：
筛选实验：
? Prolonged coagulation time (test tube method) (severe type）
试管法凝血时间延长（重型）
? Prolonged Activated partial prothrombin time (APTT)
活化部分凝血酶原时间（ APTT） 延长
? Abnormal Thromboplastin generaton test
凝血活酶生成试验异常
? Prothrombin consumption test abnormal（ normal in
mild cases）
凝血酶原消耗不良（轻者正常）
? Prothrombin time（ PT） normal
凝血酶原时间（ PT） 正常
? Bleeding time normal
出血时间正常
? Blood clot retraction time normal
血块收缩时间正常
Differential diagnosis of various type of hemophilia
区分血友病类型
prothrombin consumption and thromboplastin
generation correction test
凝血酶原消耗及凝血活酶生成纠正试验
HA HB HC
(AHG↓) (PTC↓) (PTA↓)
normal plasma( Ⅷ, Ⅸ, Ⅺ ) correctable correctable correctable
normal plasma （ Ⅸ, Ⅺ ） uncorrectable correctable correctable
barium sulfate absorbed (Ⅷ, Ⅺ ) correctable uncorrectable correctable
plasma
? Coagulation factors content determination
凝血因子含量测定
? Ⅷ, Ⅸ, Ⅺ coagulation activation determination
Ⅷ, Ⅸ, Ⅺ 凝血活性测定
? coagulation activation of various type coagulation
factors decreased
各型相应因子凝血活性降低
? Various type of vWF,normal
各型 vWF正常
Therapy 治 疗
?Prevent hemorrhage 预防出血：
?Local hemostasis 局部止血：
?Substitution therapy,替代疗法：
?Based on the expected percent of coagulation factors to be
achieved to calculate the FⅧ dosage to be infused：
根据凝血因子需达的 %，计算需要输注的 FⅧ 剂量：
mild 20%-30%
moderate 30%-50%
severe 60%-80%
Infusing 1u/kg of condensed Ⅷ factor,can raise FⅧ, C 2%
输入 1u/kg 浓缩 Ⅷ 因子,可提高 FⅧ, C 2%
? Drug therapy药物治疗
Ranitidine雷尼替丁
1-deanimo-8-arginine（ DDAVP)
1-脱氨 -8-精氨酸（ DDAVP)
? Gene therapy,recombinant FⅧ （ r FⅧ ）
without contamination with virus
基因治疗 基因重组 FⅧ （ r FⅧ ）不受病毒污染
can raise the body relevant coagulation
factors by more than 5%
使体内有关凝血因子活性达到 5％以上
Preventive Therapy
预 防 治 疗
? Severe hemophilia
重型血友病
? Optional age for preventive therapy:1-2 years
预防治疗的最佳年龄 1-2岁
? Gene diagnosis,
基因诊断
reducing the incidence of hemophilia
降低血友病的发病率
Update of hemophilia diagnosis and therapy
Gene monitoring
血友病的诊治进展
? gene mutation spot－ chemistry mismatch
fragmentation method
基因突变点－化学错配裂解法
? simple chain conformation polymorphism analysis
单链构象多态性分析
? denaturation gradient gel electrophoresis
变性梯度凝胶电泳
? DNA polymorphism analysis－ through analysis
on genetic markers to identify mutation locus
DNA多态性分析－分析遗传学标记鉴定突变位点
? Gene deletion,insert mutation,gene inversion－
Southern blot
基因缺失、插入突变、基因倒位－ Southorn印迹法
? Highly purified coagulation factor
高纯化凝血因子
? Highly purified AHG（ contains FⅧ 2000-4000U),substitute
medium purified AHG（ contains FⅧ 0.5-5U)
高纯化 AHG（含 FⅧ 2000-4000U),
取代中度纯化 AHG（含 FⅧ 0.5-5U)
? Highly purified FⅨ
高纯化 FⅨ
? Synthesized coagulation factors,
人工合成凝血因子：
—— The most safe therapy
—— 最安全的治疗
? Gene Therapy：
基因治疗：
coagulation factor Ⅷ -recombinant AAV
凝血因子 Ⅷ -重组 AAV
Management of hemophilia
血友病的管理
? Establish hemophilia therapy and prevention
specialist network and training center
建立血友病防治的专家网、培训中心
? Organization of hemophilia nursing care and
therapy
对血友病病人的护理、治疗要有组织团体
? Improve safety of hemostasis products
改进止血产品的安全性
Lower the prices
使之价格的低廉性
Childhood Leukemia
小儿白血病
? Epidemiology
流行病学
? 35%of childhood tumor was leukemia
白血病约占该期肿瘤的 35%
? ? Incidence of childhood leukemia
<15years,4/10万
? 15岁儿童白血病发病率 4/10万
? 10,000 new cases of childhood leukemia occur in
China annually
我国每年约有 1万例儿童白血病发生
? Onset from any age,even infant and congenital
任何年龄均可发病如先天性或婴儿
? More often seen in preschool and school aged
学龄前期和学龄期儿童多见
? Classification
分类
? Mostly childhood acute leukemia,accounting for >95%
小儿急性白血病为主,占 95%以上
? Acute lymphocytic leukemia,accounting for 75%
急性非淋巴细胞白血病占 35%
? Acute non-lymphocytic leukemia accounting for 35%
慢性白血病占 3%-5%
? Chronic leukemia 3%-5% Mixed cell leukemia rare
混合细胞白血病少见
ALL：
? Gemany BFM cooperation group
德国 BFM协作组
ALL 5-year event free survival(EFS)80%
ALL 5年无事生存率 (EFS)80%
? The United States:CCSG,St.Juds Children’s Hospital
美国 CCSG,St.Juds儿童医院
ALL 5-year EFS 74%
? Beijing,Shanghai of China 国内北京、上海
ALL 5-year EFS 74%
ANLL：
Abroad,5-year survival from 30% to 50%~60%
国外 5年存活率从 3%提高到 50%-60%
Domestic,5-year EFS 40%-50%
国内
Therapeutic principle of childhood ALL
小儿 ALL治疗原则
? Selection of therapeutic regime according
to the leukemia type
按型选方案
? Therapy divide into two steps
治疗分二步
? Remission induction (combined
chemotherapy）
诱导缓解 (联合化疗）
? maximal killing leukemic cells (99%) reducing from 1012 to 108
最大限度杀伤 (99%)白血病细胞从 1012减少 108
? Restore hematopoitic function of the bone marrow (CR)
恢复骨髓造血功能 (CR)
? Therapy after achieving remission
缓解后治疗
further killing the residual 108 leukemic cells to
prevent relapse
进一步杀灭剩下 108白血病细胞防止复发
? Include,
此阶段包括
? Consolidation,maintaining
巩固 维持
? prevention of CNS complications
中枢神经系统预防
? fortified therapy at advanced stage
后期强化治疗
? Total therapeutic course,boy 3 years,girl
31/2 years
总疗程 男孩 3年、女孩 3年半
Recent knowledge and development of
childhood lukemia
近代对小儿白血病的认识和进展
? Childhood leukemia is a curable and not an incurable
disease
? 小儿白血病不是一个不治之症而是有治之症
? 5-year EFS of childhood ALL (low risk) reached >70% both
domestically and internationally
? 小儿白血病中的 ALL（低危）国内外的 5年 EFS可
达 70%以上
? Diagnosis update,Research progress in morphology,
immunology,cytogenetics and molecular biology
? 诊断进展：形态学、免疫学、细胞遗传学到分子
生物学的研究进展
? Therapy update,New therapeutic agents,such as
continuous improvement of chemotherapy regime,
hematopoietic stem cells transplantation,gene
therapy,biologic regulator
治疗进展：化疗方案不断改进、造血干细胞移植
基因治疗、生物调节剂等新的治疗手段
? Chemotherapy is still the basic and most important
therapeutic method for ALL
迄今为止化疗仍是 ALL的最基本、最重要的治疗
手段
