Background: Patients with amyloid light-chain (AL) amyloidosis with a bone marrow plasma cell ratio > 10% (AL-PCMM) have a poorer prognosis than patients with AL amyloidosis with a bone marrow plasma cell ratio of <10% (AL-only), similar to that of patients with AL amyloidosis and multiple myeloma (AL-MM). However, the prognostic factors for AL-PCMM and AL-MM have not been studied. Methods: A total of 49 patients with AL-PCMM or AL-MM in the Peking University First Hospital registry in 2010-2018 were enrolled. Clinical and follow-up data were collected. The relationship between clinical parameters and survival time was also assessed. Results: Compared with patients with AL-PCMM, patients with AL-MM only had a higher incidence of bone marrow plasma cell ratio ≥ 20%. In AL-PCMM and AL-MM, the survival time was significantly shorter in patients with alkaline phosphatase (ALP) ≥ 187.5 IU/L, γ-glutamyl transpeptidase (GGT) ≥ 85 IU/L, total bilirubin (TBIL) ≥ 20 µmol/L, cardiac troponin I (CTNI) ≥ 0.1 ng/mL, ejection fraction (EF) < 50%, initial therapeutic effect (ITE) < very good partial response (VGPR), and Boston University (BU) staging system stage ≥ III. ALP at diagnosis was correlated with brain natriuretic peptide (BNP) level, CTNI level, and EF rather than TBIL level. Cox regression analyses revealed that BU staging system stage ≥ III (P=0.001, hazard ratio [HR]=5.579), ALP ≥ 187.5 IU/L (P=0.011, HR=3.563), and ITE < VGPR (P=0.002, HR=7.462) were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM. Conclusion: ALP level, which is related to cardiac amyloidosis rather than liver involvement, can be a prognostic factor for this group of patients. A BU staging system stage ≥ III, ALP ≥ 187.5 IU/L, and ITE < VGPR were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM.

Objectives: Myelomatous pleural effusion is a rare presentation of extramedullary disease in multiple myeloma, which has been reported with dismal prognosis. We aimed to explore whether it has distinctive clinical characteristics and outcomes compared to other anatomic locations of extramedullary involvements. Methods: Multiple myeloma patients diagnosed at our institution from 2010 to 2020 were retrieved retrospectively. In total, 42 pairs of patients with and without extramedullary disease were enrolled, including 13 with myelomatous pleural effusion. The clinical and laboratory parameters were collected and compared between different groups. Prognostic effect of myelomatous pleural effusion was assessed in cox regression model and Kaplan–Meier curves. Results: Myelomatous pleural effusion patients presented a higher level of β2-microglobulin ( P = .041), greater prevalence of multisites extramedullary lesions (69.2% vs 38.0%, P = .036) and International Staging System stage III (76.9% vs 44.8%, P = .016). Median overall survival was 60.6 months in patients without extramedullary disease versus 35.0 months in patients with extramedullary disease ( P = .045). Notably, median overall survival was 13.0 months in myelomatous pleural effusion patients versus 37.0 months in other extramedullary disease patients with a significant difference ( P = .029). Furtherly, multivariate analysis recognized myelomatous pleural effusion as an independent prognostic indicator (Hazard ratio: 2.669, 95% CI [1.132-6.293], P = .025). Conclusion: Myelomatous pleural effusion patients presented heavier tumor burden and worse outcomes than other extramedullary diseases.

Angioimmunoblastic T-cell lymphoma is one of the peripheral T-cell lymphomas. Reactive plasma cells can occasionally be observed in AITL patients' peripheral blood and bone marrow. Plasmacytic pleural effusion as the presentation of AITL has not been reported before. The mechanisms of plasmacytic pleural effusion are not fully understood. Here we present an 82-year-old male with exuberant plasma cells in his pleural effusion in addition to his peripheral blood and bone marrow aspiration. By presenting this case, we would like to expand the spectrum of disease presentations in AITL and discuss the significance of flow cytometry in the differential diagnosis of pleural effusion. To our knowledge, this is the first case report in the literature, which will be crucial to assist the hematopathologist in accurate diagnosis and treatment.

Background Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis are not particularly clear. Methods Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information was collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationship between the clinical parameters and survival was also assessed. Results Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P<0.001), ALP>187.5IU/L (P=0.032) and ALB<25g/L (P<0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P=0.030) and Alb<25g/L (P=0.024). The existence of AL amyloidosis, especially those with the heart involvement, was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on the symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/mL in symptomatic multiple myeloma having independent poorer prognostic significance (HR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P<0.001). Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent poorer prognostic significance (HR=8.741, P=0.002). Conclusion AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma. It is mainly because of involvement of important organs, especially the heart. AL amyloidosis probably has a greater impact on the prognosis of smoldering multiple myeloma than on the symptomatic multiple myeloma.

To the Editor: A 64-year-old Chinese man (65 kg) with fever and lymphadenopathy was admitted to the hematology department of the Peking University First Hospital. Before admission, he had had intermittent fever for the past 3 months with a body temperature high of 38.5°C. He had no accompanying discomfort and his temperature sometimes dropped to normal without drugs. Onemonth before admission, he found several palpable enlarged cervical lymph nodes. Upon admission, a lymph node biopsy was conducted and the pathological diagnosis showed a nodular sclerosis, a subtype of classical Hodgkin lymphoma. Positron emission tomography/computed tomography (PET/CT) revealed (i) enlarged lymph nodes that were widely distributed within the body with high fructose diphosphate (FDG) uptake, (ii) high FDG uptake in the L2 vertebra, right sacrum, sciatica, and femoral neck with local partial bone destruction, and (iii) low-density foci in the right lobe of the liver with increased glucose metabolism. Unilateral bone marrow aspiration and biopsy showed no signs of lymphoma infiltration. Therefore, the patient was diagnosed as having classical Hodgkin lymphoma nodular sclerosis subtype, stage IV, group B. He was treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy regimen. PET/CT showed complete remission after two cycles of ABVD therapy. Therefore, the primary chemotherapy regimen was continued. However, the patient started to develop hyperthermia with abdominal pain and diarrhea 1 week after day 1 of the third cycle of ABVD therapy. The patient’s white blood cell count was 1.31 10/L (reference range: 3.5–9.5 10/L), hemoglobin count was 66 g/L (reference range: 130–175 g/L), platelet count was 17 10/L (reference range: 125– 350 10/L), and neutrophil granulocyte count was 0.72 10/L (reference range: 1.8–6.3 10/L). Further,

BACKGROUND:Myelomatous pleural effusion (MPE), as a presentation of extramedullary infiltration of multiple myeloma (MM), is rare and currently associated with poor outcomes without effective therapy. The potential value of cytokine detection in pleural effusion to MPE has not been reported to date.CASE PRESENTATION:We herein report a case of refractory and relapsed multiple myeloma that developed bilateral MPE due to disease progression caused by intolerance to various chemotherapy regimens. Cytomorphology and flow cytometry were adopted for diagnosis confirmation. Chemotherapy containing immunomodulators combined with thoracic catheterization drainage was applied to the patient, showing a certain therapeutic effect. During the course of disease, the change of cytokine profile in pleural effusion was monitored by cytometric bead array (CBA) technology, revealing that cytokines related to tumor load such as interleukin 6 (IL-6) and interleukin 10 (IL-10) in pleural effusion decreased with the improvement of disease, while other cytokines such as interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 17A (IL-17A), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), granzyme A, granzyme B, perforin and granulysin increased with the improvement of disease.CONCLUSION:There is a prospect that cytokine level in pleural effusion may indicate treatment response of MPE, and in light of this case, immunomodulators may be utilized in treating patients suffering MPE. Due to limitations of our single case, we urge more groups to evaluate the potential role of cytokine profile in MPE.

Background Multiple myeloma causes different types of renal injury. C3 glomerulonephritis (C3GN) is characterised by an abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of the complement system. While the association between C3GN and multiple myeloma has been well established, mild renal injury by C3GN in multiple myeloma patients with high levels of light chain has not been reported. Case presentation A 55-year-old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy, and renal biopsy, he was diagnosed with IgA-type multiple myeloma accompanied by C3GN and light chain proximal tubulopathy without crystal deposits. Although he had a higher level of lambda serum-free light chain, the renal injury in this patient was mild. After treatment with four courses of BD, one course of PAD, and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function. Conclusions In multiple myeloma, the light chain reaches a certain level and persists, resulting in C3GN renal impairment. Early diagnosis and early intensive treatment are critical for the prognosis of such patients.

Primary pulmonary Hodgkin's lymphoma (PPHL) is an extremely rare disease. The nonspecific clinical and radiological features render the diagnosis a great challenge. Here, we present a case of PPHL mimicking rheumatoid arthritis-associated organizing pneumonia.

Background Immune thrombocytopenia (ITP) has been known to be associated with assorted virus infections. This study aims to investigate the Epstein-Barr virus infection status in chronic ITP patients by real-time quantitative polymerase chain reaction. Methods 42 chronic ITP patients and 42 healthy donors were retrospectively included via propensity score matching with gender and age. EBV-DNA levels in whole blood of patients and donors were assessed by RT-qPCR, and correlations between virus load and platelet count were analyzed. Results The positive rate of EBV-DNA in lymphocytes of chronic ITP patients was significantly higher than that in donors (52.4% vs 31.0%, p = 0.046). Platelet count [18(8-45)x10(9)/L] of patients with high virus load in lymphocytes was significantly lower than that [51(30-87)x10(9)/L] of patients with low virus load (p = 0.0001), whereas no difference was observed in platelet count between EBV-DNA-positive and negative subgroups of donors (p = 0.984). And a significant inverse correlation was observed between EBV-DNA levels in lymphocytes and platelet count (r = -0.4958, p = 0.019) in patients, which was independent from the presence of platelet-associated IgG. Conclusions EBV infection has a potential role in the development of chronic ITP. Identification and control of this underlying infection should be emphasized in the treatment of chronic ITP.

Abstract Background Universal gene targets are in persistent demand by real‐time quantitative polymerase chain reaction (RT‐qPCR)‐based methods in acute leukemia (AL) diagnosis and monitoring. Human Krüppel‐like factor 3 (hKLF3), a newly cloned human transcription factor, has proved to be a regulator of hematopoiesis. Methods Sanger sequencing was performed in bone marrow (BM) samples from 17 AL patients for mutations in hKLF3 coding exons. hKLF3 expression in peripheral blood (PB) and BM samples from 45 AL patients was dynamically detected by RT‐qPCR. PB samples from 31 healthy donors were tested as normal controls. Results No mutation was sequenced in hKLF3 coding exons. hKLF3 expression in PB of AL was significantly lower than that in healthy donors [0.30 (0.02‐1.07) vs 1.18 (0.62‐3.37), P < .0001]. Primary acute myeloid leukemia (AML) exhibited the least expression values compared with secondary AML and acute lymphoblastic leukemia. Receiver operating characteristic (ROC) analyses suggested that hKLF3 expression in PB was a good marker for AML diagnosis with an AUC of 0.99 (95% CI 0.98‐1.00) and an optimum cutoff value of 0.67 (sensitivity 93.94% and specificity 93.55%). hKLF3 expression was upregulated significantly when AML patients acquired morphological complete remission (CR), and the level of hKLF3 seemed to be higher in patients with deeper CR than in patients with minimal residual disease (MRD). Paired PB and BM samples showed highly consistent alteration in hKLF3 expression (r = .6533, P = .001). Besides, a significantly converse correlation between decreased hKLF3 expression in PB and markers for leukemic load was observed. Conclusions hKLF3 expression in PB may act as a potential marker for AL diagnosis and monitoring.

Objective:To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL).Methods:A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams.Results:There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. Conclusions:ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.

Background: Multiple myeloma has different kinds of renal injuries. C3 glomerulonephritis (C3GN) is characterized by abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of complement system. The association between C3GN and multiple myeloma had been well established. However, the mild renal injury of C3GN in the multiple myeloma patients with high level of light chain had not been reported.Case presentation: A 55 years old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy and renal biopsy, this patient was diagnosed with IgA type multiple myeloma accompanied by C3GN and light chain tubular reabsorption. Although he had a higher level of lamda serum free light chain, the renal injury of this patient was mild. After treated with 4 courses of BD, one course of PAD and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function. Conclusions: In multiple myeloma, the condition for light chain to result in renal impairment of C3GN is that the light chain reaches a certain level and lasts for a long time. Early diagnosis and early intensive treatment are extremely important for the prognosis of such patients.

Two major type of lymphoma involve the pleura as primary neoplasms: primary effusion lymphoma (PEL) in the setting of human immunodeficiency virus (HIV) infection, and pyothorax-associated lymphomas (PAL), with a strong Epstein-Barr virus (EBV) or pyothorax association. However, indolent B cell lymphoma initially manifested as pleural effusion is an extremely rare clinical occurrence. In this study, we report a case of 52-year-old woman with no history of HIV infection or pyothorax, who only manifested long-term massive bilateral pleural effusion. This patient was characterized by lymphocytic pleural effusion, which had been misdiagnosed as tuberculous hydrothorax. A total of 75 liters of pleural effusion were drained over a two-year period. After admission to our hospital, we performed flow cytometry of pleural effusion and revealed proliferation of B lymphocytes with abnormal immune markers consistent with marginal zone B cell phenotype, although lymphocyte morphology is normal. Flow cytometry on bone marrow revealed ckappa restrictive expression on B cells further, which indicating small B cell lymphoma. The right-side pleural fluid was encapsulated after thoracoscopy and the patient's symptom were relieved. Considering the foreseeable side effects of chemotherapeutic drugs and indolent potential of the small B cell lymphoma, the patient opted not to undergo further treatment. Follow up was done 1, 3 and 6 months after discharge, the depths of bilateral pleural effusion on ultrasound stabilized around 3 cm without thoracentesis. This case is thought to be an unusual presentation because the pleural lymphoma occurred on an immunocompetent adult woman and the type was small B cell lymphoma, which were totally different from PEL or PAL. We also describe the use of flow cytometry to effectively diagnose the unexplained pleural effusion, and discuss the findings using relevant previously reported literature. Overall, our findings provide new insights to deal with unexplained pleural effusion and the value of flow cytometry in diagnosis.

Background: Fanconi anemia (FA) is the most common inherited bone marrow failure (BMF) syndrome with 22 related genes identified. The ALDH2 rs671variant has been proved related to accelerate the progression of BMF in FA patients. The phenotype and genetic basis of Chinese FA patients have not been investigated yet. Methods: We analyzed the 22 FA-related genes of 63 BMF patients suspected to be FA.Clinical manifestations, morphological and cytogenetic feathers, ALDH2 genotypes, treatment, and outcomes of the definite cases were retrospectively studied. Results: A total of 21 patients were confirmed the diagnosis of FA with the median age of BMF onset was 4-year-old. The number of patients manifested as congenital malformations and growth retardation were 20/21 and 14/21, respectively. BM dysplasia and cytogenetic abnormalities were found in 13/20 and 8/19 patients. All the patients with abnormal karyotypes also manifested as BM dysplasia or had evident blasts. Thirty-five different mutations were identified involving six genes and including twenty novel mutations. FANCA mutations contributed to 66.67% of cases. Eight patients harboring ALDH2 -G/A genotype have a significantly younger age of BMF onset ( p =0.025). Within the 19 patients adhering to continuous follow-up, 15 patients underwent hematopoietic stem cell transplantations (HSCTs). During the 29 months of follow-up, 8/19 patients died, seven of which were HSCT-related, and one patient who did not receive HSCT died from severe infection. Conclusion: The phenotypic and genetic spectrum of Chinese FA patients is broad. Bone marrow dysplasia and cytogenetic abnormalities are prevalent and highly consistent. The overall outcome of HSCTs is disappointing. Nationwide multicenter studies are needed for the rarity and adverse outcome of this disease.

Objective:To investigate the infection spectrum revealed by metagenomics high-throughput next-generation sequencing (mNGS), and to provide a reference for infection diagnosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 64 patients who developed systemic or local infection symptoms after allo-HSCT in Hebei Yanda Lu Daopei Hospital from January 2018 to November 2018 were enrolled. Gene sequences of pathogenic microorganisms in blood, cerebrospinal fluid and bronchoalveolar fluid specimens were detected by using mNGS. The pathogenic microorganisms or suspected pathogens were determined based on the clinical manifestations of patients.Results:There were 97 samples of mNGS detection for 64 patients who underwent allo-HSCT. The most common gram-positive bacteria were staphylococcus haemolyticus (19 times) and staphylococcus (14 times), and the most common gram-negative bacterium was acinetobacter baumannii (8 times). The most common viruses were cytomegalovirus, EB virus and Torque teno virus (35, 22 and 23 times, respectively), and the most common fungi were malassezia globus (14 times) and candida parapsilosis (8 times). There were 3 mycobacterium tuberculosis complexes detected in 3 patients with acute myeloid leukemia who received allo-HSCT. Mycoplasma orale was detected in one patient's sputum, and none parasite was detected.Conclusion:mNGS can comprehensively reveal the infection spectrum of hematologic diseases after allo-HSCT, especially for pathogenic microorganisms that are rare or difficult to cultivate, and it can effectively help the diagnosis of clinically infectious pathogens.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy arising from plasmacytoid dendritic cell precursors. The disease typically manifests in the skin, but it also evolves into a leukemic phase or can be complicated by other myeloid malignancies, especially myelomonocytic tumors. The association between these neoplasms is not fully elucidated. We report a case of BPDCN with a history of cytopenia that was supposed to be chronic myelomonocytic leukemia. The patient received intensive chemotherapy and achieved complete remission, but soon relapsed. The successive occurrence of myelomonocytic neoplasm and BPDCN is in accordance with the fact that they evolve from a common cell origin with a multilineage potential for myelomonocytic and plasmacytoid dendritic cell differentiation. This case may shed further light on the mystery of biology and the histogenesis of BPDCN.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits is a rare monoclonal gammopathy of renal significance with dense deposits on electron microscopy similar to polyclonal immune complex-mediated glomerulonephritis. 70% of patients with proliferative glomerulonephritis with monoclonal IgG are negative for a monoclonal (M) spike, and patients with this condition rarely develop an M spike during follow-up. We report a Chinese man in his 50s who presented with nephrotic syndrome and normal glomerular filtration rate. His first kidney biopsy showed masked IgG3 deposition, such that IgG3 staining was apparent only after digestion by enzyme on paraffin tissue, with a membranoproliferative pattern. During follow-up, his glomerular filtration rate worsened and proteinuria increased. 18 months after the first biopsy, the patient developed an M spike; a second kidney biopsy showed proliferative glomerulonephritis with monoclonal IgG deposits with unmasked IgG3λ deposition. The patient was successfully treated with bortezomib and dexamethasone, followed by lenalidomide and dexamethasone maintenance therapy.

目的:探讨巨细胞病毒(CMV)再活化对于完全缓解期行异基因造血干细胞移植术(allo-HSCT)的急性髓系白血病(AML)患者复发和生存的影响.方法:对106例于完全缓解期行allo-HSCT的成人AML患者的资料进行回顾性分析,包括移植术后CMV再活化的发生情况和影响因素,以及CMV再活化对于复发和生存的影响.结果:67.0％(71/106)的患者在移植后12个月内出现了CMV再活化,中位时间为移植后46(1～117)d.HLA不全相合和预处理应用兔抗人胸腺细胞免疫球蛋白(ATG)是移植后CMV再活化的影响因素.106例患者移植后的中位随访时间为36(1～171)个月,19例患者移植后出现复发,中位复发时间为4.5(2～38)个月,3年累积复发率为17.8％.单因素分析显示,Ⅱ～Ⅳ度急性移植物抗宿主病和慢性移植物抗宿主病的发生可降低患者的复发率,而CMV再活化对于移植后的复发率无明显影响.106例患者的3年总生存率(OS)为77.2％,无病生存率(DFS)为76.0％.单因素分析显示,年龄＞40岁和移植后CMV再活化影响患者的OS,但不影响DFS.Cox多因素回归分析显示,移植后CMV再活化是影响患者3年OS的独立危险因素.结论:HLA不全相合和预处理过程中应用ATG是导致移植后CMV再活化的危险因素,而CMV再活化对于完全缓解期AML移植后的复发并没有影响,但仍是影响此类患者生存的独立危险因素.

Objective To investigate the application of metagenomic next-generation sequencing (mNGS) in detection of the rare or difficult-to-cultivate pathogens. Methods One patient with acute lymphoblastic leukemia who went through allogeneic hematopoietic stem cell transplantation (allo-HSCT) developed symptoms of infection after transplantation. Conventional microbial culture, polymerase chain reaction (PCR), and mNGS combined with biological information analysis were performed with plasma and cerebrospinal fluid samples, the anti-infective treatment was adjusted according to the test results, and the efficacy was assessed. Results No suspected pathogens were detected by microbial culture and PCR in the cerebrospinal fluid and plasma samples since the patient developed infection symptoms. However, Legionella pneumophila was analyzed by mNGS in the cerebrospinal fluid specimen on day 23 after allo-HSCT (reads count: 19 655), and it was considered as the principal pathogen after comprehensively evaluating the patient's clinical manifestations and the test results. Then the antimicrobial treatments were adjusted according to the patient's clinical manifestations and laboratory test results, and the number of gene sequences of Legionella pneumophila was monitored by mNGS method. Azithromycin, tigecycline, and other antibiotics effective for Legionella pneumophila were used after detecting this pathogen. A total of 15 mNGS analysis were performed during the 5-month period, and the highest number of Legionella pneumophila sequences monitored in the cerebrospinal fluid was 2 226, the lowest was 253 and eventually turned negative. The clinical symptoms and treatment outcomes were consistent with the mNGS monitoring results. Conclusions The mNGS technology has significant value in detection of the rare and difficult-to-cultivate pathogens. The mNGS technology provides a valuable supplement to microbial culture and PCR methods. Key words: High-throughput nucleotide sequencing; Metagenome; Hematopoietic stem cell transplantation; Legionella pneumophila

OBJECTIVE:To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD).METHODS:The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively.RESULTS:Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P＜0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1β and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P＜0.01）, IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P＜0.05）, no significant difference of the rest cytokines was found between iMCD and the control group.CONCLUSION:IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.