Analysis Of Clinical Features And Prognostic Factors In Lymphoma Patients With Different Degrees Of Myelofibrosis

A.ObjectiveTo assess the clinical features and laboratory characteristics of lymphoma patients with different grade of myelofibrosis,and to analyze the factors affecting the survival of patients.B.MethodsThe clinical data of 509 lymphoma patients treated in the department of hematology of Qilu Hospital of Shandong University from January 1,2016 to December 31,2019 were retrospectively analyzed,including clinical features,laboratory tests,disease progression and overall survival.In the study,the classification of lymphoma was referred to the lymphoma section of the 2016 revision of the WHO classification of lymphoid neoplasms,and the WHO(2016)myelofibrosis grading criteria were used for grading myelofibrosis.The patients were divided into the MF grade 0 group,MF grade 1 group and MF grade 2-3 group.We analyzed the clinical features,laboratory tests,the impact of myelofibrosis on disease progression and overall survival among the three groups,and discussed factors affecting patients’ survival.C.Resultsa.Clinical featuresA total of 509 patients with lymphoma were included in this study,including 40 cases of Hodgkin lymphoma and 469 cases of non-Hodgkin lymphoma(12 cases of precursor lymphoid neoplasm,355 cases of mature B-cell lymphoma and 102 cases of mature T/NK-cell lymphoma).Among them,267 cases(52.46%)were patients with myelofibrosis(MF grade 1-3),and all of them were associated with secondary myelofibrosis except for one case with primary myelofibrosis.The analysis showed that the rate of lymphoma invading the bone marrow was higher in the MF grade 2-3 group than in the MF grade 0 and MF grade 1 groups in Hodgkin lymphoma and mature B-cell lymphoma(all P values<0.05).The rate of MF grade 2-3 with splenomegaly was higher in mature B-cell lymphoma and mature T/NK-cell lymphoma than in other two groups(all P values<0.05).b.Laboratory testsIn the Hodgkin lymphoma patients,the proportion of patients with complex karyotype in the MF grade 2-3 group was higher than in other two groups(all P values<0.05).In patients with mature B-cell lymphoma,the neutrophil ratio,hemoglobin and neutrophil-to-lymphocyte ratio were lower in the MF grade 2-3 group than in other two groups;the platelet count decreased with fibrosis increasing.Regarding biochemical indexes,alkaline phosphatase,lactate dehydrogenase and β2-microglobulin were higher in the MF grade 2-3 group than in the MF grade 0 and MF grade 1 group.Hemoglobin and platelet counts were also observed to be lower in patients for grade 2-3 than for grade 0 and 1 in mature T/NK-cell lymphoma.The higher the degree of myelofibrosis was,the higher the proportion of patients with mature B cell lymphoma whose bone marrow biopsy showed active myeloproliferative activity was.Among 37 patients in the non-Hodgkin lymphoma group who underwent gene mutation examination of bone marrow,13 patients had 15 gene mutations detected,in which,the most frequently detected gene mutations were DNMT3A(15.79%),NOTCH2(10.53%)and CARD 11(10.53%).c.Survival analysisIn the patients with non-Hodgkin lymphoma,the overall survival and progression-free survival of patients in the MF grade 2-3 group were lower than those in the MF grade 0 and MF grade 1 groups(both P values<0.05).Among the patients with mature B-cell lymphoma and diffuse large B-cell lymphoma,the overall survival rate was lower in the MF grade 2-3 group than in the MF grade 0 group,and the progression-free survival rate was lower than in the MF grade 0 group and the MF grade 1 group(both P values<0.05).In the patients with mature T/NK-cell lymphoma,there were no significant differences between the three groups in terms of overall survival and progression-free survival.d.Analysis of prognostic factorsUnivariate analysis revealed that poor prognostic factors in non-Hodgkin patients include age≥65 years,ECOG scores>2 points,with B symptoms,number of lymph node involved≥4,with hepatomegaly,with splenomegaly,Ann Arbor stage Ⅲ-Ⅳ,LYM%≥27%,Hb<115g/L,PLT<125×109/L,AKP>125U/L,ALB≤35g/L,LDH,245U/L,β2-MG≥2.7mg/L,NLR>3.5,MF grade 2-3,involvement of bone marrow and complex karyotype.In patients with non-Hodgkin lymphoma,multivariate COX regression analysis showed that age>65 years(P<0.001),numbers of lymph nodes involved>4(P=0.042)and MF grade 2-3(P=0.011)were independent risk factors for poor prognosis of patients.Age>65 years(P=0.006),AKP>125 U/L(P=0.023),ALB≤35 g/L(P=0.047)and MF grade 2-3(P=0.013)were independent risk factors for poor prognosis in patients with mature B-cell lymphoma.Age≥65 years(P=0.001),with B symptoms(P=0.035)and with hepatomegaly(P=0.048)were independent risk factors for poor prognosis in patients with mature T/NK-cell lymphoma.D.Conclusion1.Several pathological types of lymphoma can be combined with myelofibrosis at the time of initial diagnosis of the disease,in which,the majority of myelofibrosis was secondary myelofibrosis,and patients with primary myelofibrosis were rare.2.Among the non-Hodgkin lymphoma patients,patients for grade 2-3 myelofibrosis were often associated with hepatosplenomegaly and Ann Arbor disease stage Ⅲ or Ⅳ.3.Patients with non-Hodgkin lymphoma in the MF grade 2-3 group had worse overall survival and progression-free survival compared with patients in the MF grade 0 and MF grade 1 groups.4.Age≥65 years,numbers of lymph nodes involved≥4 and MF grade 2-3 were independent risk factors for poor prognosis in patients with non-Hodgkin lymphoma.Age≥65 years,AKP>125 U/L,ALB≤35 g/L and MF grade 2-3 were independent risk factors for poor prognosis in patients with mature B-cell lymphoma.Age>65 years,with B symptoms and with hepatomegaly were independent risk factors for poor prognosis in patients with mature T-/NK-cell lymphoma.