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MDS vs AML
Blood. 2013;121:3811
发病情况
• 发病年龄：成 人发病为主， 老年更多见， 轻微男性发病 优势 • 发病率：美国 报告为2-12/10 万；70岁以上 者50/10万 (Int J Hematol 2001,73:405)
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病因、发病机理
• • • • • • • 高龄，外因； 原发性、继发性MDS：tMDS（烷化剂、表鬼臼毒素类） 先天/家族性MDS HSC增生失控、分化受阻、细胞凋亡增加 细胞遗传学异常：-5/5q-，-7/7q基因水平的改变；AML1-MDS1-EVI1融合基因 表观遗传学调控异常
Br J Haematol 1976, 33:451
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MDS (FAB 1982)
% Ringed PB Sideroblasts Blasts < 1% > 15% < 1% < 5% > 5% < 5% BM Blasts < 5% < 5% 5-20% 21-30% ≤ 20% > 1x109 /L
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Morphologic Features
• Blasts：Myeloblasts • Dysmyelopoiesis; Dyserythropoiesis; Dysgranulopoiesis; Dysmegakaryopoiesis • Trephine biopsy: Cellularity; Myelofibrosis (reticulin, MDS with fibrosis); Report estimated % of CD34+ blasts; Dysmegakaryopoiesis (CD61); ALIP(abnormal
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PB Monocytes
RA RARS RAEB RAEB-T界限：骨髓原始细胞降为20% RAEB-t归入AML；但有t(8;21)、t(15;17)、 inv(16)/t(16;16)等核型异常者即使小于20%也应 诊断为白血病 CMML: MDS/MPD
Childhood MDS, including refractory cytopenia of childhood (RCC, provisional)
MDS, unclassifiable
WHO 2016
1. MDS with single lineage dysplasia (MDS-SLD) 2. MDS with multilineage dysplasia (MDS-MLD) 3. MDS with ring sideroblasts (MDS-RS) MDS-RS and single lineage dysplasia (MDS-RSSLD) MDS-RS and multilineage dysplasia (MDS-RSMLD) 4. MDS with excess blasts (MDS-EB1, MDS-EB2) 5. MDS with isolated del(5q) (5q- syndrome) 6. MDS, unclassifiable (MDS-U) 7. Provisional entity: Refractory cytopenia of childhood (RCC)
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临床表现
• • • • • • • 差异大、早期低危患者无症状 贫血 发热、感染 出血 一般无肝脾淋巴结肿大 转化为急性白血病 老年患者多有合并症
Recommendations and Definitions in MDS
• Recommendations • Differential: 500 in BM, 200 cells in PB • Number: 200 for G and E, 30 cells for meg. • Ring sideroblasts: ≥ 5 iron granules encircling ≥ 1/3 of the nucleus • Minimal dysplastic changes (good quality of smear)
WHO 2000→2008
增加RN、RT，与RA一起组成RCUD; 重新定义MDS-U （不再包括RN和RT） 增加Childhood MDS （RCC） RCMD与RCMD-RS合并 t-MDS/t-AML不再区分原因（烷化剂or鬼臼毒素类）
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WHO 2008
RCUD
RA RN RT RARS
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WHO 2000
PB blasts 1 2 3 4 5 6 7 8 RA RARS RCMD RCMD-RS Del(5q) RAEB-1 RAEB-2 MDS-U <5% 5-19% 5-9% 10-19% high risk <5% <5% RS≥15% RS≥15% low risk BM blasts
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Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
1. Chronic myelomonocytic leukemia (CMML) 2. Atypical chronic myeloid leukemia (aCML), BCR-ABL1(-) 3. Juvenile myelomonocytic leukemia (JMML) 4. MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) 5. MDS/MPN, unclassifiable
骨髓增生异常综合征 （Myelodysplastic syndromes, MDS）
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定义
一组起源于造血干细胞(HSC)的异质性的克隆性疾病, 以①外 周血一系或多系减少②骨髓增生正常或亢进伴病态造血和③ 高风险向急性白血病转化为特征。 • A group of clonal neoplasms; heterogeneous; • Hematopoietic stem cells (HSC) or progenitors; • Cytopenia • Myelodysplasia; ineffective hematopoiesis • Increased risk of blastic transformation: - preleukemia, smouldering leukemia
Refractory cytopenias with unilineage dysplasia
refractory anemia refractory neutropenia refractory thrombocytopenia Refractory anemia withb ring sideroblasts
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WHO myeloid neoplasm and acute leukemia classification
1. 2. 3. Myeloproliferative neoplasms (MPN) Mastocytosis Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 4. Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) 5. Myelodysplastic syndromes (MDS) 6. Myeloid neoplasms with germ line predisposition 7. Acute myeloid leukemia (AML) and related neoplasms ① AML with recurrent genetic abnormalities ② AML with myelodysplasia-related changes ③ Therapy-related myeloid neoplasms ④ AML, NOS ⑤ Myeloid sarcoma ⑥ Myeloid proliferations related to Down syndrome ⑦ Transient abnormal myelopoiesis (TAM) ⑧ Myeloid leukemia associated with Down syndrome 8. Acute leukemias of ambiguous lineage 9. B-lymphoblastic leukemia/lymphoma 10. T-lymphoblastic leukemia/lymphoma 18 11. Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymphoma
Myeloproliferative neoplasms (MPN) (JAK2, MPL, CALR mutations)
Chronic myeloid leukemia (CML), BCR-ABL11 Chronic neutrophilic leukemia (CNL) (CSF3R mutation) Polycythemia vera (PV) Primary myelofibrosis (PMF) PMF, prefibrotic/early stage PMF, overt fibrotic stage Essential thrombocythemia (ET) Chronic eosinophilic leukemia, not otherwise specified (NOS) • MPN, unclassifiable • • • • • • • •
MDS Proliferation ↑ Differentiation ↓ Apoptosis ↑