Clinical Features And Prognostic Factors Of Primary Bone Marrow Lymphoma

Background and ObjectiveLymphoma is a malignant progressive disease with various types.In some types of lymphoma,bone marrow invasion is often considered as a manifestation of the middle and advanced stages of the disease,such as diffuse large B-cell lymphoma(DLBCL),follicular lymphoma(FL),mantle cell lymphoma(MCL)and so on.Primary bone marrow lymphoma(PBML)is an extremely rare lymphoma with rapid progression and poor prognosis,it is also a special hematological entity characterized by bone marrow invasion as the first admission symptom.PBML has been described in the literature since the 1980s,but the diagnostic criteria at that time are not clear.In 2012,the diagnostic criteria of PBML were systematically defined by Martinez et al for the first time and have been used ever since.PBML mainly occurs in five types of lymphoma,including Hodgkin's lymphoma(HL),DLBCL,peripheral T-cell lymphoma,unspecified type(PTCL,NOS),ALK-negative anaplastic large cell lymphoma(ALK-Negative ALCL)and FL.However,its clinical features are often different from their respective lymphoma subtypes,of which the most common is hemocytopenia,followed by B symptoms.In the early stage of the disease,there are usually no manifestations other than the bone marrow hematopoietic system,so the disease characteristics are not typical and easy to be ignored.Besides,the disease itself is dangerous and the prognosis is poor,therefore,early detection and early treatment by clinicians are needed.In addition,the current treatment methods for PBML are not unified and not standardized,and most of the treatments are only for the subtype of the disease,lack of specificity and scientific basis.Therefore,in view of this situation,in order to explore the pathological,clinical and prognostic characteristics of PBML and provide a basis for the choice of treatment strategies for patients.We selected 7 patients who were treated in Lymphoma Diagnosis and Treatment Center of Henan Province from July 2011 to June 2017,and 59 cases from case reports published at home and abroad from 1997 to 2018 in our study.MethodSeven cases were collected from Lymphoma Diagnosis and Treatment Center of Henan Province,the first affiliated Hospital of Zhengzhou University.The pathological diagnosis and clinical diagnosis were confirmed by 2 senior pathologists and 2 senior oncologists,respectively.And with "primary bone marrow lymphoma" as the keywords in domestic commonly used databases such as"Wanfang database" and "Chinese National Knowledge Infrastructure(CNKI)" and"Primary bone marrow lymphoma" and "PBML" as the keywords in foreign commonly used databases such as "Pubmed" for retrieval.A total of 66 related cases from 1997 to 2018(including 7 in our center and 59 from literature review)were collected and analyzed retrospectively.The data of multiple examination indexes,treatment plan and survival follow-up time of patients with PBML were collected,and the R software was used for statistical analysis and visual operation.Finally,the clinical nomogram was established to predict the survival status of patients and the discrimination ability of the model was evaluated by C-index and time-dependent ROC curve.Results1.The incidence of PBML was more common in females than in males.It could occur in various pathological types of lymphoma,and the most common PBML was DLBCL.The initial symptoms were various,but hemocytopenia was the main symptom.2.Of the 66 patients,54 received the evaluation of the initial treatment,of which 29(53.7%)patients received complete response(CR),9(16.7%)patients received partial response(PR)after the first treatment,and the total response rate was 70.4%(53.7%CR+16.7%PR).3.The prognosis of patients with PBML sas poor,and the 1-,2-and 3-year survival rates were only 46.8%,23.4%and 14.9%.Univariate analysis showed that symptoms B(P=0.044),serum platelet level<75×10^9/L(P=0.010),grade 3 and grade 4 hemocytopenia(P=0.046),and not achieving CR after initial treatment(P<0.001)were associated with poor prognosis.The Kaplan-Meier method showed that symptoms B(P=0.037),serum platelet level<75×10^9/L(P=0.044),grade 3 and 4 hemocytopenia(P=0.041),not reaching CR after initial treatment(P<0.001)and elevated serum LDH level(P=0.048)were significantly correlated with poor prognosis.Multivariate analysis further showed that only serum platelet level(P=0.010),B symptoms(P<0.001)and initial therapeutic effect(P<0.001)were independent factors of prognosis.4.Four variables including B symptoms,serum platelet level,serum LDH level and initial therapeutic effect were selected to construct normogram to predict the 1-year and 2-year survival rate of patients.The model evaluation C-index was 0.877 and the area under the ROC curve(AUC)of 1-year and 2-year were 0.874.Moreover,the fitting degree of calibration curves for 1-year and 2-years was high,showing that the model was built successfully.Conclusion1.The prognosis of patients with PBML is poor.2.Serum platelet level,B symptoms and initial therapeutic effect are independent prognostic factors affecting the survival of PBML.3.The survival nomogram of PBML based on four factors including serum LDH level,serum platelet level,B symptoms and initial therapeutic effect has excellent predictive accuracy and would be helpful for individualized treatment and prognosis evaluation.