Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based o...Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase II inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapy-related myeloid neoplasms would help developing risk-adapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.展开更多
BACKGROUND Myeloid neoplasm(MN)with eosinophilia and rearrangement of platelet-derived growth factor receptor beta(PDGFRB)shows a good therapeutic response to imatinib in adults.MN is rarely found in children,and the ...BACKGROUND Myeloid neoplasm(MN)with eosinophilia and rearrangement of platelet-derived growth factor receptor beta(PDGFRB)shows a good therapeutic response to imatinib in adults.MN is rarely found in children,and the efficacy of imatinib on pediatric patients remain unclear.CASE SUMMARY We report 2 pediatric cases diagnosed with MN with eosinophilia and PDGFRB rearrangement who were treated with imatinib.Case 1 was a 1-year-old girl admitted to the hospital because of“abdominal distension with hyperleukocytosis for 3 mo”.She had leukocytosis,anemia,and eosinophilia(the absolute eosinophil count(AEC)was 8960/μL),and her fluorescence in situ hybridization(FISH)test revealed that PDGFRB rearrangement was detected in 70%of 500 interphase cells.Case 2 was a 2-year-old girl admitted to the hospital because of“recurrent fever and rashes for 1 mo”.Her blood cell count showed an AEC of 3540/μL.The FISH test revealed that PDGFRB rearrangement was detected in 71%of 500 interphase cells.Both patients were diagnosed as MN with eosinophilia and PDGFRB rearrangement.Imatinib was added into their treatment regimen.As expected,complete hematologic remission was achieved after 1 mo of treatment,and symptoms disappeared.CONCLUSION Although MN with eosinophilia and PDGFRB rearrangement usually occurs in adults,it can be found in children.The therapeutic benefits of imatinib in these 2 pediatric patients were consistent with its reported effects in adult patients.展开更多
EZH2 is a component of the polycomb repressive complex 2(PRC2),which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3.EZH2 mutations are associated with oncogenesis and progressio...EZH2 is a component of the polycomb repressive complex 2(PRC2),which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3.EZH2 mutations are associated with oncogenesis and progression of cancers.However,the relationship between the clinical outcome of patients with myeloid malignancies and EZH2 mutations is controversial.Therefore,we performed a meta-analysis of 8 studies(n Z 2243 patients)that evaluates the correlation between EZH2 mutations and overall survival(OS)in patients with myeloid neoplasms.EZH2 mutations were associated with significantly worse OS(hazard ratio[HR]Z 2.37,95%confidential interval(CI),1.48e3.79).In a word,EZH2 mutations indicate a poor prognosis for patients with myeloid neoplasms.展开更多
Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification ...Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.展开更多
BACKGROUND The Janus kinase 2(JAK2) V617 F mutation is common in patients with breakpoint cluster region-Abelson1(BCR-ABL1)-negative myeloproliferative neoplasms,including polycythemia vera, essential thrombocythemia ...BACKGROUND The Janus kinase 2(JAK2) V617 F mutation is common in patients with breakpoint cluster region-Abelson1(BCR-ABL1)-negative myeloproliferative neoplasms,including polycythemia vera, essential thrombocythemia and primary myelofibrosis, but is rarely detected in BCR-ABL1-positive chronic myeloid leukemia(CML) patients. Here, we report a CML patient with both a BCR-ABL1 rearrangement and JAK2 V617 F mutation.CASE SUMMARY A 45-year-old Chinese woman was admitted to our department with a history of significant thrombocytosis for 20 d. Color Doppler ultrasound examination showed mild splenomegaly. Bone marrow aspiration revealed a karyotype of 46,XX, t(9;22)(q34;q11.2) in 20/20 metaphases by cytogenetic analysis,rearrangement of BCR-ABL1(32.31%) by fluorescent polymerase chain reaction(PCR) and mutation of JAK2 V617 F(10%) by PCR and Sanger DNA sequencing.The patient was diagnosed with CML and JAK2 V617 F mutation. Following treatment with imatinib for 3 mo, the patient had an optimal response and BCRABL1(IS) was 0.143%, while the mutation rate of JAK2 V617 F rose to 15%.CONCLUSION Emphasis should be placed on the detection of JAK2 mutation when CML is diagnosed to distinguish JAK2 mutation-positive CML and formulate treatment strategies.展开更多
Background: Patients with stem cell myeloproliferative disorders have a particularly poor prognosis and limited treatment options, i.e. mainly aggressive chemotherapy or allogeneic stem cell transplantation. In 2004, ...Background: Patients with stem cell myeloproliferative disorders have a particularly poor prognosis and limited treatment options, i.e. mainly aggressive chemotherapy or allogeneic stem cell transplantation. In 2004, Chen et al. reported a patient presenting a t(8;13) (p11;q12) cytogenic anomaly who responded positively to treatment with PKC412 (midostaurin), an oral multi-targeted tyrosine kinase inhibitor. Here, we report a second case treated with the above-mentioned drug. Patient: A 71-year-old woman was diagnosed as having chronic myelogenous leukaemia with eosinophilia secondary to t(8;13) with FGFR1 involvement. Due to her age, an allogeneic stem cell transplantation was not possible. Treatment: A treatment combining aggressive chemotherapy and midostaurin was explored. The patient received one cycle of hyper-CVAD chemotherapy followed by maintenance therapy with midostaurin. A relapse occurred after six months, and she was treated with four more cycles of hyper-CVAD chemotherapy. The patient entered a complete clinical, haematological and cytogenetic remission. A maintenance therapy with midostaurin continued for four months until she developed a chemoresistant relapse followed by acute leukaemia. Conclusion: This is the second case of a t(8;13) myeloid and lymphoid neoplasm with FGFR1 abnormalities treated successfully with midostaurin. Midostaurin is administered orally, allows for outpatient care and in this case showed only occasional and minimal side effects. The combination of hyper-CVAD and midostaurin extended survival by 21 months without allogeneic transplantation. This case further supports the possibility of using midostaurin for the treatment of other diseases with FGFR1 dysregulations;however, specific clinical trials are needed to confirm this hypothesis.展开更多
基于修订的第4版世界卫生组织(World Health Organization,WHO)造血淋巴肿瘤分类之后相关领域积累的研究成果和临床应用进展,WHO在2022年提出了第5版造血淋巴肿瘤分类(以下简称第5版分类)。第5版分类中骨髓增生异常性肿瘤/综合征(myelod...基于修订的第4版世界卫生组织(World Health Organization,WHO)造血淋巴肿瘤分类之后相关领域积累的研究成果和临床应用进展,WHO在2022年提出了第5版造血淋巴肿瘤分类(以下简称第5版分类)。第5版分类中骨髓增生异常性肿瘤/综合征(myelodysplastic neoplasms/syndrome,MDS)和急性髓系白血病(acute myeloid leukemia,AML)与第4版分类有较大更新,在临床实践中对疾病诊断和治疗,乃至疾病登记、科研等都具有重要意义。本文根据发表于Leukemia杂志出版的第5版分类和国际癌症研究机构官方网站上发布的第5版分类测试版进行解读。展开更多
文摘Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase II inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapy-related myeloid neoplasms would help developing risk-adapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.
文摘BACKGROUND Myeloid neoplasm(MN)with eosinophilia and rearrangement of platelet-derived growth factor receptor beta(PDGFRB)shows a good therapeutic response to imatinib in adults.MN is rarely found in children,and the efficacy of imatinib on pediatric patients remain unclear.CASE SUMMARY We report 2 pediatric cases diagnosed with MN with eosinophilia and PDGFRB rearrangement who were treated with imatinib.Case 1 was a 1-year-old girl admitted to the hospital because of“abdominal distension with hyperleukocytosis for 3 mo”.She had leukocytosis,anemia,and eosinophilia(the absolute eosinophil count(AEC)was 8960/μL),and her fluorescence in situ hybridization(FISH)test revealed that PDGFRB rearrangement was detected in 70%of 500 interphase cells.Case 2 was a 2-year-old girl admitted to the hospital because of“recurrent fever and rashes for 1 mo”.Her blood cell count showed an AEC of 3540/μL.The FISH test revealed that PDGFRB rearrangement was detected in 71%of 500 interphase cells.Both patients were diagnosed as MN with eosinophilia and PDGFRB rearrangement.Imatinib was added into their treatment regimen.As expected,complete hematologic remission was achieved after 1 mo of treatment,and symptoms disappeared.CONCLUSION Although MN with eosinophilia and PDGFRB rearrangement usually occurs in adults,it can be found in children.The therapeutic benefits of imatinib in these 2 pediatric patients were consistent with its reported effects in adult patients.
基金This work is supported in part by The National Natural Science Foundation of China,China(81770172,81270613)Key Research&Technology Projects in Jiangsu Province,China(BE2017747)Milstein Medical Asian American Partnership(MMAAP)Foundation Research Project Award,USA in Hematology(2017).
文摘EZH2 is a component of the polycomb repressive complex 2(PRC2),which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3.EZH2 mutations are associated with oncogenesis and progression of cancers.However,the relationship between the clinical outcome of patients with myeloid malignancies and EZH2 mutations is controversial.Therefore,we performed a meta-analysis of 8 studies(n Z 2243 patients)that evaluates the correlation between EZH2 mutations and overall survival(OS)in patients with myeloid neoplasms.EZH2 mutations were associated with significantly worse OS(hazard ratio[HR]Z 2.37,95%confidential interval(CI),1.48e3.79).In a word,EZH2 mutations indicate a poor prognosis for patients with myeloid neoplasms.
文摘Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.
文摘BACKGROUND The Janus kinase 2(JAK2) V617 F mutation is common in patients with breakpoint cluster region-Abelson1(BCR-ABL1)-negative myeloproliferative neoplasms,including polycythemia vera, essential thrombocythemia and primary myelofibrosis, but is rarely detected in BCR-ABL1-positive chronic myeloid leukemia(CML) patients. Here, we report a CML patient with both a BCR-ABL1 rearrangement and JAK2 V617 F mutation.CASE SUMMARY A 45-year-old Chinese woman was admitted to our department with a history of significant thrombocytosis for 20 d. Color Doppler ultrasound examination showed mild splenomegaly. Bone marrow aspiration revealed a karyotype of 46,XX, t(9;22)(q34;q11.2) in 20/20 metaphases by cytogenetic analysis,rearrangement of BCR-ABL1(32.31%) by fluorescent polymerase chain reaction(PCR) and mutation of JAK2 V617 F(10%) by PCR and Sanger DNA sequencing.The patient was diagnosed with CML and JAK2 V617 F mutation. Following treatment with imatinib for 3 mo, the patient had an optimal response and BCRABL1(IS) was 0.143%, while the mutation rate of JAK2 V617 F rose to 15%.CONCLUSION Emphasis should be placed on the detection of JAK2 mutation when CML is diagnosed to distinguish JAK2 mutation-positive CML and formulate treatment strategies.
文摘Background: Patients with stem cell myeloproliferative disorders have a particularly poor prognosis and limited treatment options, i.e. mainly aggressive chemotherapy or allogeneic stem cell transplantation. In 2004, Chen et al. reported a patient presenting a t(8;13) (p11;q12) cytogenic anomaly who responded positively to treatment with PKC412 (midostaurin), an oral multi-targeted tyrosine kinase inhibitor. Here, we report a second case treated with the above-mentioned drug. Patient: A 71-year-old woman was diagnosed as having chronic myelogenous leukaemia with eosinophilia secondary to t(8;13) with FGFR1 involvement. Due to her age, an allogeneic stem cell transplantation was not possible. Treatment: A treatment combining aggressive chemotherapy and midostaurin was explored. The patient received one cycle of hyper-CVAD chemotherapy followed by maintenance therapy with midostaurin. A relapse occurred after six months, and she was treated with four more cycles of hyper-CVAD chemotherapy. The patient entered a complete clinical, haematological and cytogenetic remission. A maintenance therapy with midostaurin continued for four months until she developed a chemoresistant relapse followed by acute leukaemia. Conclusion: This is the second case of a t(8;13) myeloid and lymphoid neoplasm with FGFR1 abnormalities treated successfully with midostaurin. Midostaurin is administered orally, allows for outpatient care and in this case showed only occasional and minimal side effects. The combination of hyper-CVAD and midostaurin extended survival by 21 months without allogeneic transplantation. This case further supports the possibility of using midostaurin for the treatment of other diseases with FGFR1 dysregulations;however, specific clinical trials are needed to confirm this hypothesis.
