The Risk and Survival Analysis of Multiple Malignancies in Hematologic Malignancy Patients: A Single Chinese Center Retrospective Study, 2009 through 2017 / 中国实验血液学杂志

OBJECTIVE@#To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients.@*METHODS@#The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively.@*RESULTS@#A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival.@*CONCLUSION@#In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

Correlation of Peripheral Blood T Lymphocyte Subsets with Prognosis of Elderly Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression level of T lymphocyte subsets in elderly patients with newly diagnosed multiple myeloma (NDMM), and to evaluated the prognostic value of T lymphocytic abnormalities in elderly NDMM patients.@*METHODS@#Pretreated peripheral blood of 39 newly diagnosed elder patients with MM was tested by multi-parameter flow cytometry (MFC) to quantitatively detect T lymphocyte subsets, including CD4T cell, CD8T cell, and CD4/CD8 ratio. The prognostic values T-lymphocyte subset were evaluated in newly diagnosed elderly patients with MM.@*RESULTS@#The median follow-up time was 21.5 (range, 3.0-66.0) months. Absolute counts of CD4T cell and CD4/CD8 ratio positively correlated with prognosis. In the multivariate COX analysis, lower CD4/CD8 ratio and CD4T cell counts were identified to be independent adverse prognostic factors for OS.@*CONCLUSION@#Lower CD4/CD8 ratio and CD4T cell counts at initial diagnosis are independent unfavorable prognostic factors for elderly patients with MM, and T lymphocyte subsets are crucial indicators for MM patients' prognosis.

Diagnostic Value of CD27 Antigen in Patients with Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the expression of CD27 antigen in patients with multiple myeloma(MM), and its clinical diagnostic value, as well as the correlation of CD27 with clinical features and genetic abnormalities.</p><p><b>METHODS</b>Using 8 color flow cytometry, the immunophenotype of 123 MM patients' marrow cells was examined, while 51 cases of normal plasma cell reactive prolieration were used as control. Antibodies are as follows:ckappa-FITC/clambda-PE/ CD38-ECD/CD45-PERCP/CD19-PC7/ CD27-APC/CD138-BV421/ CD56-BV510. For differentiation of abnormal plasma cells from normal or reactive plasma cells, FS INT /FS PEAK with CD138/CD38 gating strategy was used to measure cell markers CD138,CD38, CD56, CD19, ckappa, clambda and CD45, then the expression rate of CD27 and mean fluorescence intensity(MFI) were analyzed for its diagnostic value in MM. At the same time, the laboratory data of 107 cases of MM patients were analyzed and the fluorescence in situ hybridization (FISH) was used to detecte 1q21 amplification, 13q14 deletion, p53 deletion and IGH rearrangement in 34 cases, then the clinical features and genetic abnormalities were compared between CD27and CD27MM patients.</p><p><b>RESULTS</b>The CD27 positive rate of abnormal plasma cells in MM patients was 48% (59/123) (percentage ≥20% as positive criterion), MFI was 31.3±35.6; while the positive rate of normal or reactive plasma cells were 100% (51/51), the MFI was 93.7±6.3. The positive rate and MFI of CD27 in MM patients were significantly lower than that in normal or reactive plasma cells (P<0.01). Laboratory examination of 58 cases of CD27 negative and 49 cases of CD27 positive MM patients indicated that no significant differences were shown on disease progress parameter, such as hemoglobin, albumin, serum calcium, serum creatinine,and no notable differences were involved in the analysis of prognostic factors between the 2 groups, such as β2-MG microglobulin and LDH levels (P<0.05). The 1q21 amplification, 13q14 deletion, p53 deletion, and IGH rearrangement results all were not significantly different between 17 cases of CD27 negative and 17 cases of CD27 positive MM patients(P<0.05).</p><p><b>CONCLUSION</b>CD27 has a unique expression profile, and its negative or weak expression is highly suggestive for MM. The 8 color flow cytometry can be used to analyze the expression of multiple antigens, which can provide a reliable evidence for the diagnosis and differential diagnosis of MM disease.</p>

Primary Breast Diffuse Large B Cell Lymphoma: Summarization of 12 Cases / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological manifestation, immunophenotypic features and prognostic factors of patients with primary breast DLBCL (PB-DLBCL).</p><p><b>METHODS</b>Twelve cases of PB-DLBCL, diagnosed according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues, were retrospectively studied.</p><p><b>RESULTS</b>Most patients were admitted to hospital because of painless unilateral breast mass. Out of 12 cases, 5 were in Ann Arbor stage I (41.7%), 7 case were in stage II (58.3%). Most (89.9%) were assigned to non-GCB subtypes, 11.1% were classified as GCB subtype. The patients who recepted treatment were sensitive to chemotherapy and they were all alive following 12 to 92 months.</p><p><b>CONCLUSION</b>Primary breast DLBCL is extremely rare without specific clinical features. They all respond well to chemotherapy and show good prognosis.</p>

Clinical significance of serum free light chain in patients with multiple myeloma / 中国实验血液学杂志

Multiple myeloma (MM) is a malignant disorder characterized by the proliferation of a single clone of plasma cells that can produce excessive amounts of serum free light chain (sFLC). sFLC plays an important role in MM diagnosis and disease monitoring. The quantitative immuno-nephelometric assay is sensitive and specific means for sFLC testing. The aim of this study was to investigate the levels of sFLC in multiple myeloma and the relationship between sFLC and serum total light chain (sTLC). sFLC in 45 newly diagnosed patients were detected by immuno-nephelometric assay, and then the ratio of free kappa to free lambda for every sample was calculated. Meanwhile, sTLC was also determined in these patients. The results showed that the difference of sFLC levels between MM patients and the normal controls was significant (tΚ = 8.86, P < 0.001; tλ = 15.48, P < 0.001;tΚ/λ = 5.54,P < 0.005). No correlation between sFLC and sTLC was found in MM patients. It is concluded that the level of sFLC in MM patients is significantly higher than that in normal controls. sFLC and its ratio may be served as a indicator for diagnosis of MM. sTLC can not replace the role of sFLC.

Expression level of microRNA-92a and its clinical significance in multiple myeloma patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the expression level of microRNA 92a (miR-92a) and del(13q14) and the prognosis of MM patients, and to explore the pathway that miR-92a involved.</p><p><b>METHODS</b>Bone marrow samples from 53 newly diagnosed MM patients were collected, del(13q14) was analyzed by interphase fluorescence in situ hybridization in sorted CD138 positive plasma cell. The expression of miR-92a in plasma cells was measured by quantitative real-time PCR. The expression of c-jun was detected by Western blot in miR-92a transfected MM cell lines (LP-1, U266 and JJN3).</p><p><b>RESULTS</b>Of the 53 MM patients, del(13q14) was detected in 31 (58.4%) patients. The median levels of miR-92a in MM patients with or without del(13q14) were 27.36±2.61 and 21.87±15.98, respectively (P>0.05). With the median follow-up of 13.5 (0.5-72.5) months, the median duration of progression-free survival of patients with high expression level of miR-92a was significantly shorter than those with low expression level of miR-92a (4.5 months vs 14.0 months, P=0.006). Overexpression of miR-92a in MM cell lines induces time-dependent down-regulation of c-jun.</p><p><b>CONCLUSIONS</b>High expression of miR-92a was associated with poor prognosis in MM patients. The expression level of miR-92a was not associated with del(13q14), and the effect of miR-92a on the progress of MM might be involved in c-jun pathway.</p>

Clinical features of multiple myeloma invasion of the central nervous system in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although neurologic manifestations often complicate the course of patients with multiple myeloma, direct central nervous system invasion is rare. This study explored the neurologic symptoms, signs, clinical features, therapy and prognosis of Chinese patients with central nervous system myeloma invasion.</p><p><b>METHODS</b>The diagnosis, therapy and prognosis were analyzed retrospectively in 11 Chinese multiple myeloma patients with central nervous system infiltration from a total of 625 patients who have been treated at Changzheng Hospital (Shanghai, China) between January 1993 and May 2009. Survival curve was constructed with the use of Kaplan-Meier estimates.</p><p><b>RESULTS</b>There were 11 patients with central nervous system involvement from 625 multiple myeloma patients. The occurrence rate was 1.8%. Ten of the 11 patients had other extramedullary diseases. Symptoms included cerebral symptoms, cranial nerve palsies, and spinal cord or spinal nerve roots symptoms. Cerebrospinal fluid was abnormal in 7 patients, usually exhibiting pleocytosis and elevated protein content, plus positive cytologic findings. Specific magnetic resonance imaging findings suggestive of central nervous system invasion were found in 9 patients. After a median follow-up of 19 months, 3 patients were alive. The median overall survival for all patients was 23 months, while the median overall survival for patients after central nervous system invasion was merely 6 months.</p><p><b>CONCLUSIONS</b>It is exceedingly rare for there to be central nervous system infiltration in multiple myeloma patients. When it occurs, the prognosis is extremely poor despite the use of aggressive local and systemic treatment including stem cell transplantation.</p>