混合细胞白血病英文讲义.doc

1、 Good afternoon，everyone，today I will introduce something about acute mixed leukemia.2、 My comtents include Overview，Clinical feature，Laboratory examination and diagnosis，Treatment,curative effect and prognoses，Conclusion.3、 At first，I will introduce the overview of acute mixed leukemia.what is acute mixed leukemia(MAL)? Human acute leukemias (AL) are classified as myeloid or lymphoid according to cytomorphology and the expression of leukocyte differentiation antigens/CD-markers. However, in the minority of cases leukemic cells express both myeloid and lymphoid antigens,these leukemia are defined as mixed acute leukemia（MAL)4、 MAL account for about 2-8% of total AL.It usually happens among old persons.The pathogenesis of MAL is not clear.5、 As the picture shows MAL express both myeloid and lymphoid antigens,It contains three situation，myeloid and T-lymphoid antigens, myeloid and B-lymphoid antigens, myeloid and T+B-lymphoid antigens, as for T and B Lymphoid antigens express respectively or co-expressed in leukemia cells ，Which be Classified to MAL by some studies，there is no agreement about whether it be Classified to MAL.6、 MAL includes three subtypes ：biphenotypic acute leukemia (BAL), acute biclonal leukemia and acute bilineal leukemia 7、 biphenotypic acute leukemia (BAL)refers to acute leukemia with a single population of blasts coexpressing markers of two different lineages.And the co-expression of several myeloid and lymphoid antigens in the same cells.8、 This is schematic diagram of biphenotypic acute leukemia (BAL)9、 acute bilineal leukemia means some leukemia cells express myeloid antigens，others express lymphoid antigens，the two kinds of cells are derived from a single population of multipotent stem cell. the two kinds of leukemia cells exist at the same time, or they dont exist at the same time, they appear one after another within 6 months10、 11、The two figures are schematic diagrams of acute bilineal leukemia.12、 acute biclonal leukemia refers tov Some leukemia cells express myeloid antigens，others express lymphoid antigens，the two kinds of cells are derived from separate populations of blasts.v the two kinds of leukemia cells exist at the same time, or they dont exist at the same time, they appear one after another within 6 months. v leukemia cells express myeloid/lymphoid antigens, After chemotherapy,the former antigen disappeared, leukemia cells express another type of antigens. they appear 6 months. 13、14、15、The three figures are schematic diagrams of acute biclonal leukemia 16、17、18、The three figures are schematic diagrams of biphenotypic acute leukemia (BAL)，acute bilineal leukemia，acute biclonal leukemia separately.19、clincal features include：v Anemia， fever， hemorrhagev Hepatosplenomega，lylymphadenectasisv Sternal tenderness v Skin invasion v Central nervous system leukemia（CNSL）And MAL patients showed a much higher incidence of extramedullary infiltration. 20、Next I will introduce Laboratory examination and diagnosis of MAL，Currently,there is no unified criterion for diagnosis of MAL ,immunophenotype analysis is very important to it.Blood routine test，Marrow routine test， cytochemical staining ，Cytogenetic testAnd other laboratory methods Play a supporting role in diagnosis.21、From Blood routine test of MAL,we can see：v Most MAL leukocyte surpass100109/L，Peripheral blood progenitor cells are more than 85% of Non-erythroid nuclear cells ，The cell characteristics are similar to FAB-L1 cell or myeloblast.But some leukemia cells are between type I-myeloblast and FAB-L2 type cell.v The mainly characteristic for Anemia of MAL is moderate pigment and size cell anemia ，10% patients have serious anemia. We can not distinguish between different types of leukemia Only by red blood cell morphology. Especially when patients have hemorrhage，peripheral blood Reticulocyte and polychromatic erythrocyte will raise sightly，May appear a small amount of immature red blood cells.v It is different from other AL, during Early diagnosis of MAL，platelet of about 50% patients reduced slightly，between 5080109/L. Whether or not platelet count is normal, platelet aggregation rate would decline. 22、the figure shows morphology of MAL peripheral cells (Wright stain),series of blast cells are similar to blast cells between type-I myeloblasts and ALL-L2 cells,there also have someALL-L1 cells23、24、25 From Marrow routine test of MAL,we can see：v Minority （In a few cases）：typical morphocytology both lymphoblast and myeloblast can be found v Majority（In most situation）：Atypical morphocytology only have lymphoblast or myeloblast，can be easily misdiagnosed as AML（M1/ M2a）or ALL（ALL2）v morphology of MAL cells（Wright stain）Myeloid characteristics leukemia cells are similar as type-I myeloblasts，which have basophilic cytoplasm without granules，scattered chromatin， 24 conspicuous nucleoli.v lymphoid characteristics leukemia cells are similar as ALL-L1 cells，the cells are small in size， their diameter is about 1012m， they have little and Light blue stained cytoplasm without granules and slightly clumped chromatin ，inconspicuous nucleoli, high nuclear/cytoplasmic ratio. v Leukemia cells which have co-expression of Myeloid and lymphoid characteristics，morphology of MAL cells are similar to blast cells between type-I myeloblasts and ALL-L2 cells, their diameter is about 1214m，have basophilic cytoplasm with little amount of L. azure granules granules，scattered chromatin， 24 conspicuous nucleoli，class round or slightly irregular shaped nuclear.v Leukemia cells which have co-expression of Tand B lymphoid characteristics，morphology of MAL cells are similar to ALL-L2 cells，about 80%of cells are big in size，their diameter is about 1215m， they have Light blue stained cytoplasmwith little amount of L. azure granules granules，ruled round shaped nuclear,have slightly clumped chromatin,1-2 conspicuous nucleoli26、the figure shows morphology of MAL cells（Wright stain）series of blast cellsvary in size.some cells are small and similar to ALL-L1 cells, have slightly clumped chromatin ，inconspicuous nucleoli ；some cells are big，have scattered chromatin，conspicuous nucleoli ，there are little amount of granules lie in cytoplasma ， similar to I、II type myeloblasts.27、the figure shows Morphology of some BAL blasts. The T/M leukemia cells (A) and B/T leukemia cells (B) show more variation in size and morphology than typical lymphoblasts.28、cytochemical staining of MAL have no specificity.v Pox staining：MAL blast cells are negative or Most cells negative while few positive;v Specific esterase（SE,ASD-NCE）staining：Most cells negative while few positive;v Non-specific esterase（NSE,-NAE）staining：cells negative，cant be inhibited when add sodium fluoride（NaF）.v PAS staining： Some MAL blast cells are positive，another negative，a few are negative.29、the figure shows that POX stain of MAL patients marrow leukemia cells，Some blast cells present postive reactive30、the figure shows that-NBE stain of MAL patients marrow leukemia cells，it can clearly be seen a red-brown-stained postive T cell，others are B-lympho-blast.31、There are several classification criteria for MAL diagnoses.The most commonly used is immunophenotype analysis by the European Group for the Immunological Characterization ofLeukemias(EGIL,1995). The following table shows Immunological diagnostic scoring system for MAL(EGIL,1995），When Myeloid system score2，and lymphoid system score 1，we can diagnosis MAL32、Acording to some studies，B lymphoid and myeloid co-express is the most commen form of MAL, account for about 60-70% of MAL patients，T lymphoid and myeloid co-express Accounted for the second，B+T lymphoid and myeloid co-express is the least commen form of MAL， account for about 4-10% of MAL patients.33、In the proliferation and differentiation process， while some stage have problems and abnormal state, Corresponding hematologic malignancies will happen. Lymphoid and Myeloid progenitor cells have problems and abnormal states, ALL and AML will happen.Similarly, while the problems arise in mature cells，CLL ora CML will happen. Other stages of lymphocyte development have problems, Lymphoma and Multiple myeloma will happen.MAL patients showed a much higher incidence of CD34 antigen expression, indicate MAL can occur in stages of pluripotent hematopoietic stem cells.34、From Cytogenetic test of MAL,we can see：v t(9;22)（translocation between 9 and 22 chromosome） was the most common abnormality in chromosome structure.v Other unfavorable karyotypes contains translocation between 8 and 21 chromosome，translocation between 2 and 16 chromosome,Hyperdiploid in chromosome 5, chromosome 1, chromosome 19, hyperdiploid in chromosome 15,chromosome 7, deletion at zone1 region2 ，long arm of Chromosome 3.v Some studies confirm that: MAL with unfavorable karyotypes have poor prognosis。35、Next I will introduce Treatment,curative effect and prognoses of MAL. Treatment of MAL include Symptomatic and supportive treatment，chemotherapy and Hematopoietic stem cell transplantation.36、Symptomatic and supportive treatment is based treament of MAL,It contains: prophylaxis and treatment of infection, correct anemia, Control of hemorrhage, hydration and alkalization and Maintain nutrition.37、MAL patients can only esist for about 1.5months if give symptomatic and supportive treatment only，so we need to give advance treatment.chemotherapy is very important for MAL patient. Which can improve curative effect to some extent. As the table shows , we can give lymphoid or myeloid program therapy according to FAB classification, we can also give accommodate the two therapy，such as 【VPDA】.Induction theatment have three paths，as the table shows , we can give lymphoid or myeloid program induction therapy according to FAB classification, we can also give accommodate the two therapy，such as 【VPDA】，It is ineffective to give lymphoid or myeloid program induction therapy, Accommodate the two induction therapy Program got better effects in recent years. But some studies found there is no significance between one linege program induction therapy and that of the accommodation between the two lineges. We have no clear conclusions If the latter induction therapy have advantages to others.As for Post-remission therapy and Salvage therapy after relapse,we also haveno clear results which one is better，38、39、40、the following three tables shows the protocol in detail for induction therapy，Post-remission therapy，Salvage therapy after relapse respectively.41、A study by Xiao-Qian Xu et.al retrospectively analyzed 452 adult acute leukemia patients diagnosed according to French-American-British (FAB) classification and mixed acute leukemia diagnosed according to European Group for the Immunological Characterization of Leukemias (EGIL) classification, respectively. Biological characteristics, response to treatment, and outcome were examined in MAL patients and compared with that in acute myeloid leukemia and acute lymphoblastic leukemia patients with complete follow-up profiles diagnosed in the same period.Of 452 acute leukemia patients, 21 cases (4.6%) were diagnosed as MAL. Among them, 14 (66.7%) were B lymphoid and myeloid, 5 (23.8%) were T lymphoid and myeloid, one (4.8%) was trilineage differentiation，one (4.8%) was T/B lymphoid.42、This table shows the EGIL score of 21 patients43、This table shows the therapy of 21 patients42、The following table shows OS and DFS for MAL when compared with that of ALL,we can found that OS and DFS for BAL is significant worse than that of AMLand ALL.44、Responses to treatment and outcomes in MAL patients were compared with those of AML and ALL,diagnosed in the same period. v No statistical difference was noted in CR rate after the first inductionand overall CR rate (p0.05). v The incidence of relapse in MAL patients was significantly higher than that of patients with AML (p0.05).v CR rates after relapse were lower in MAL patients than those with AML (p0.05). v A significant worse OS and DFS for MAL when compared with that of ALL (p=0.0003, p=0.007)and AML(p=0.0044, p=0.0119) is denoted by the Kaplan-Meier curve.45、It is unclear whether hematopoietic stem cell transplantation (HSCT) should be included as an integral part of BAL treatment.a study by Changcheng Zheng,et.al. They retrospectively reviewed the medical records and analyzedclinicopathological data on 25 children with MAL, 9 of them accepted HSCT,46、From the following two tables, we found that Hematopoietic stem cell transplantation(HSCT) did not improve either overall survival or event-free survival compared to chemotherapy alone (hazard ratio 0.98, 95% CI 0.352.76, P0.966; hazard ratio 1.07, 95% CI 0.412.78, P0.88).47、This is Another study by Zhang Cheng，et.al v The transplantation with HLA haploid peripherad blood stem cells and bone marrow for four patient s with MAL were carried out ,and the efficacy and correlated complication were observed. v All patients were successful engraftment . One patient with partial remission (PR) was complete remission (CR) and the other three patients were continue complete remission after t ransplantation. Actue GVHD occurred in two patient s. Chronic GVHD was not seen. Single prolong of APTT was detected in one patient . The median follow-up duration was 181 (129 - 337) d. One died with fungus infection post transplantation 190d. One patient with CR2 and one with PR was relapse post transplantation 183d and 129d ,respectively. The other one was free disease survival for 337d.48、About HSCTv We were disappointed to find that HSCT did not offer significant survival benefits in these studies.v This may possibly be attributed to small patient numbers and our consequent inability to perform detailed subgroup analyses.v whether HSCT therapy can improve the otherwise poor outlook of the MAL population remains to be established.49、At last,I will have my conclusions:v Mixed acute leukemia is a rare disorder that is difficult to diagnose. It displays