Clinical Characteristics And Outcomes Of 82 Patients With Mixed Phenotype Acute Leukemia

1.Background and ObjectiveMixed phenotype acute leukemia（MPAL）is a rare and heterogeneous disease expressing both myeloid and lymphoid markers.Due to the rarity of this type of leukemia and the lack of prospective,controlled trials,Currently,the Clinical biological characteristics and standard treatment of MPAL are still unclear.Nevertheless,In our dairy clinical practice,internists choose individualized treatments based on patients’ age,underlying diseases and its cell morphology,immunophenotype,cytogenetics,and molecular biology.Retrieving domestic or foreign literatures,As for the treatment options of MPAL’s patients,we found that ALL-like,AML-likeand so-called "hybrid" therapy mixing elements of both have been reported.However,there are still some controversies on the choices of the best induction chemotherapy.Outcomes for MPAL are worse than both acute lymphoblastic leukemia（ALL）and acute myeloid leukemia（AML）.In our study,we retrospective analysis 82 MPAL or BAL patients.We compared the effectiveness of treatments utilizing ALL-like,acute myeloid leukemia（AML）-like,and hybrid therapies in MPAL patients,and analyzed the patients’biological characteristics and outcomes.in order to explore the best induction therapy and the effect of hematopoietic stem cell transplantation on the outcomes of this disease.2.Objects and Methods2.1 ObjectsFor this retrospective study,data has been collected from January 2006 and December 2017 at our hospital.The study population included 82 MPAL/BAL patients,of whom 73 met the European Group for the Immunological Classification of Leukemia criteria,68 met the World Health Organization 2008 diagnostic criteria,and 59 fulfilled both definitions for MPAL.2.2 MethodsTo select the patients who met the European Group for the Immunological Classification of Leukemia criteria or the World Health Organization 2008 diagnostic criteria.to analysis age,gender,white blood cell and bone marrow blast counts,central nervous system involvement at initial diagnosis,and biological characteristics such as morphology,immunophenotype,cytogenetics and molecular biology.The effects of different induction and consolidation regimens were further analyzed to explore the related factors affecting the prognosis of these patients.So as to explore the relevant prognostic factors that affecting the outcomes of these patients.3.Results3.1 Clinical and biological characteristicseighty-two patients were studied,including 60 males and 22 females with a male to female ratio of 2.7:1 and a median age of 29 years（range,2 months-72 years）,61 patients（77%）were older than 18 years old,Immunophenotyping revealed that 51（62.2%）cases had a B-myeloid phenotype,24（29.3%）had a T-myeloid phenotype,5（6.1%）had a B-T phenotype,and 2（2.4%）had a trilineage combination.Among the 82 cases,57 cases with successful cytogenetic studies,20（35.1%）had normal karyotypes and 37patients（64.9%）had abnormal karyotypes.Twelve patients（21.05%）translocation between chromosomes 9 and 22,five（8.8%）patients had 11q23/MLL translocations.Twelve patients（21.05%）had a complex karyotype and eight patients（14%）had other karyotype.3.2 Treatment response and survival analysisInformation on response to first-line treatment was available for 79 patients,and The overall complete response rate（CR）was 49.3%.Response（CR）was achieved in 66.7%of patients treated with hybrid induction therapy,51.9%of patients treated with ALL-like induction therapy,and 16.7%of patients treated with AML-like induction therapy,with a significant difference among the treatment outcomes（P value 0.003）.The median OS durations in the hybrid induction,ALL-like induction,and AML-like induction therapy groups were 47 months（3-year OS 59.8±10.0%）,20 months（3-year OS 39.8±10.2%）,and 16 months（3-year OS 34.2±11.5%）,respectively.（P value 0.239）.forty-five patients received stem cell transplant（HSC）for consolidation or salvage treatment while twenty-one patients received the chemotherapy alone after induction chemotherapy.The median OS durations in the transplantation and chemotherapy groups were 43 months and 11 months,respectively,and the 3-year OS rates were 61.7±7.6%and 22.3±9.4%respectively（P value 0.002）.Median event-free survival compared between transplantation group and chemotherapy group was 43 months and 9 months respectively.Three years event-free survival was 59.7±7.6%and 19.3±8.4%respectively.（P value 0.001）.4.ConclusionsALL like induction therapy or "hybrid" therapy was associated with a more greater CR rate than AML like therapy.Consolidation with allo-HSCT can significantly improve the long-term survival of patients with MPAL,and it may even be one of the clinical curative therapy in patients with MPAL.