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BACKGROUND Pulmonary alveolar proteinosis (PAP) is a rare condition that can cause progressive symptoms including dyspnea, cough and respiratory insufficiency. Secondary PAP is generally associated with hematological malignancies including chronic myelomonocytic leukemia (CMML). To the best of our knowledge, this is the first reported case of PAP occurring secondary to CMML. CASE SUMMARY We report the case of a 63-year-old male who presented with a recurrent cough and gradually progressive dyspnea in the absence of fever. Based upon clinical symptoms, computed tomography findings, bone marrow aspiration, flow cytometry studies and cytogenetic analyses, the patient was diagnosed with PAP secondary to CMML. He underwent whole lung lavage in March 2016 to alleviate his dyspnea, after which he began combined chemotherapeutic treatment with decitabine and cytarabine. The patient died in January 2020 as a consequence of severe pulmonary infection. CONCLUSION This case offers insight regarding the mechanistic basis for PAP secondary to CMML and highlights potential risk factors.

Background: In December 2019, the novel coronavirus pneumonia was detected in Wuhan and named COVID-19. It is an international outbreak of the respiratory illness caused by severe acute respiratory syndrome coronavirus 2. Recent papers pointed out the cytopenia in COVID-19 patients including lymphopenia, neutrophilia, thrombocytopenia and lower level of hemoglobin had prognostic significance. This systemic review and meta-analysis summaries the latest evidence from available data and determine the hematological abnormality caused by severe acute respiratory syndrome coronavirus 2 and potential efficacy on the outcomes in patients with COVID-19. Methods: This protocol for a systematic reviews and meta-analysis will be performed according to the preferred reporting items for systematic reviews and meta-analysis protocols 2015 guidelines. The database of Cochrane Library, PUBMED, EMBASE, Medline, Web of Science, Google Scholar, CNKI, WanFang, as well as gray literatures from the inception to present will be comprehensively and systematically searched without limitations of regions or language. The main study outcomes will be the mortality of COVID-19 patients. The meta-analysis was performed by RevMan V.5.3 program and Stata V.12.0 software after 2 reviewers independently selected literature, data extraction, bias risk evaluation and study quality assessment. Any disagreement will be resolved by consensus to the third researcher. Results: This systematic review and meta-analysis may help provide clarify on the effect of cytopenia in patients with COVID-19. The result will be published at a peer-reviewed journal. Conclusions: This proposed study will evaluate the existing evidence on the effectiveness of cytopenia in COVID-19 patients. Ethic and dissemination: The content of this article does not involve moral approval or ethical review because no individual data will be collected. PROSPERO registration: CRD42020187524.

Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure. In the present study, published data was reviewed with a focus on the factors associated with early mortality. When treated with ATO as a primary treatment, the fms-like tyrosine kinase-internal tandem deletion has no impact on early mortality. Low lymphoid enhancer binding factor-1 expression may be a reliable marker for early mortality and the target of therapy if it could be proven by further studies. Cluster of differentiation (CD)56+ and CD34+/CD2+ may be candidates to select high-risk patients. The risk of early mortality in APL still cannot be predicted via the cell surface makers, despite multiple studies on their prognostic significance. Typically, a complex translocation did not alter the survival rate in patients with APL; however, if an abnormal karyotype [e.g., Ide(17), ZBTB16/RARα and STAT5B/RARα] appeared singularly or as part of a complex mutation, there is a high possibility of early mortality if clinicians are unable to identify or monitor it.

Mucormycosis is an angioinvasive fungal infection with a high mortality rate. Patients with hematological malignancies following voriconazole therapy are at high risk from mucormycosis. Here, the present study reports on a 68-year-old man diagnosed with multiple myeloma and secondary myelodysplastic syndrome, who was infected with disseminated mucormycosis with cerebellum involvement confirmed by mycological culture and histopathological examination. For patients with hematological malignancies who are receiving antifungal therapy, an opportunistic infection of mucormycosis should be considered if a 'breakthrough' infection occurs in the predilection sites (such as the sinuses, lungs, skin, brain and gastrointestinal tract). It is difficult to diagnose mucormycosis because of the limited reliable detection methods, and because mucormycosis often presents with an acute onset and progresses rapidly, particularly in immunocompromised patients. Antifungal therapy with amphotericin B or posaconazole should be started as soon as possible considering the empirical diagnosis.

Mucormycosis is an angioinvasive fungal infection with a high mortality rate. Patients with hematological malignancies following voriconazole therapy are at high risk from mucormycosis. Here, the present study reports on a 68-year-old man diagnosed with multiple myeloma and secondary myelodysplastic syndrome, who was infected with disseminated mucormycosis with cerebellum involvement confirmed by mycological culture and histopathological examination. For patients with hematological malignancies who are receiving antifungal therapy, an opportunistic infection of mucormycosis should be considered if a ‘breakthrough’ infection occurs in the predilection sites (such as the sinuses, lungs, skin, brain and gastrointestinal tract). It is difficult to diagnose mucormycosis because of the limited reliable detection methods, and because mucormycosis often presents with an acute onset and progresses rapidly, particularly in immunocompromised patients. Antifungal therapy with amphotericin B or posaconazole should be started as soon as possible considering the empirical diagnosis.

Background Multiple myeloma can lead to lots of clinical problems including pain, fatigue, anemia, infections, renal failure, and so on. Huanglian Jiedu Decoction is a common conservative treatment for this disease in China. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy of Huanglian Jiedu Decoction in the treatment of multiple myeloma. Methods A systematic literature search for studies will be performed in 8 databases, including PubMed, Web of Science, Embase, the Cochrane library, ClinicalTrials.gov databases, Chinese National Knowledge Infrastructure Database, Wanfang database, and VIP database. The methodological quality of the included studies using the risk bias assessment tool of Cochrane. And the level of evidence for results is assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Statistical analysis is conducted with Revman 5.3. Results This systematic review and meta-analysis will provide a synthesis of existed evidences for Huanglian Jiedu Decoction on multiple myeloma. Conclusion The conclusion of this study will provide evidence to assess effectiveness of Huanglian Jiedu Decoction on multiple myeloma, which can further guide clinical decision-making. Inplasy registration number INPLASY202060094.

The current study presents the case of a 9-year-old Chinese boy who presented with eosinophilia and elevated serum levels of immunoglobulin G4 (IgG4). A bone marrow puncture identified an elevated eosinophil rate of 23% (normal range

Premise of the study: To survey population variation and the adaptive evolution of Cephalotaxus fortunei (Cephalotaxaceae), an endemic and endangered conifer in China, microsatellite markers were developed and characterized for this species. Methods and Results: Based on the Fast Isolation by AFLP of Sequences Containing repeats (FIASCO) protocol, 15 microsatellite markers were developed for C. fortunei, 13 of which were polymorphic within a sample of 75 individuals representing five natural populations. The number of alleles per locus ranged from one to seven. The expected and observed heterozygosities were 0.108–0.738 and 0.000–1.000, respectively. Ten polymorphic loci were also successfully amplified in C. oliveri. Conclusions: These polymorphic loci provide a valuable tool for population genetic analysis of C. fortunei, which will contribute to its management and conservation.

This case report describes a 44-year-old female with hepatitis C virus-related thrombocytopenia. The laboratory tests showed a platelet count of 3×109/l, positive HCV serology and high serum concentration of HCV-RNA of 6.74×106 copy/ml. She was refractory to standard therapies including corticosteroids, intravenous immunoglobulin (IVIG), thrombopoietin (TPO) and even interferon (IFN) regimens, due to the persistence of a low platelet count. At first, splenectomy was thought to be impossible, but then splenectomy was successfully performed and patient showed good tolerance and a constant normal platelet count after surgery. In conclusion, splenectomy is feasible in selected patients and may allow us to acquire a reasonable platelet count and completion of an anti-HCV protocol. Low platelet count itself should not be the contraindication of operation specifically for these patients. Further studies in larger numbers of patients and over a longer period of time are warranted.

To investigate the effect of Dahuang Zhechong pills (DZ) on arterial thrombotic model in vivo.Sixty-five rabbits were randomly divided into 7 groups: normal, model (collagen encapsulated thread-drawing),model+aspirin (ASA), model+clopidogrel (CP),model+ASA+CP, model+ low dosage DZ (DZL), and model+high dosage DZ (DZH). All rabbits except the normal group were fed with the drugs repectively for 8 days,and sacrificed at 2 hours after the last feeding, obtained aortae. The pathological changes in the aortae were observed under microscope,and the level of FDP, D-dimer and tissue factor (TF) were measured by enzyme-linked immunosorbent assay (ELISA).The vascular vessels were filled with thrombi in the model group and the elastic membranes of the vessel wall were seriously injured. The arterial thrombi were observed around the vascular wall in the DZL group, but some of the thrombi were dissolved. The number of thrombi was remarkably decreased in the DZH group, and most thrombi were dissolved and the vascular intimal membranes were intact. Compared with the model group, the dry and wet weight of the thrombi and the level of D-dimer, FDP, and TF in the plasma were significantly attenuated (P0.01) in all the treatment groups. There were no significant difference between the DZL group and the ASA group in the dry weight, D-Dimer, and FDP (P0.05). The pathological changes in the vascular vessel and the elevation of plasma parameters in the DZL group were similar to those in the ASA and CP groups (P0.05). The dry and wet weight, D-dimer, FDP, and TF in the plasma in the DZH group were significantly lower than those in the DZL group (P0.01 or P0.05, separatively), and closed to those in the ASA+CP group.Dahuang Zhechong pills are potential novel anti-thromobotic agent for arterial thrombosis.

Cytokine-induced killer (CIK) cells are activated T cells with natural killer (NK) properties that can be expanded in vitro in presence of recombinant human interleukin-2 (rhIL-2) starting from peripheral blood mononuclear cells stimulated by interferon-γ and anti-CD3 antibody. They express CD3 and CD56 as well as the NKG2D antigen and show major histocompatibility complex (MHC)–unrestricted cytotoxicity toward neoplastic but not normal targets. CIK cells express several chemokine receptors, and in vivo models suggest that they can migrate to the site of tumors after intravenous administration, there carrying out their cytotoxic potential and helping to control tumor growth. CIK cells have shown cytotoxic activity in vitro and in vivo against hematopoietic neoplastic cells, including AML (acute myeloid leukemia), CML (chronic myelogenous leukemia), and CLL (chronic lymphocytic leukemia). Their cytotoxicity against patient with B-NHL (B-cell non-Hodgkin lymphoma) , however, has not been fully investigated. The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy reduse dose of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells for consolidation treatmemt in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from 20 elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 10(9)-1 × 10(10)) were then infused back to individual patients. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 6 cycles of transfusion and 6 received 4 cycles. After treatment of CIK cells plus IL-2, the general conditions of 20 patients were to different extent improved No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum β2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01)., Complete remission(CR) observed in 11 patients before the treatmemt of CIK was still CR; Partial remission(PR) in 9 patients ,After the treatmemt of CIK, the transformation of disease state from partial remission to complete remission was seen in 4 patients. At the end of follow-up, the mean survival time was 24 months. Transfusion with autologous CIK cells is safe and effective for treating haematological malignancies in elderly patients. Disclosures No relevant conflicts of interest to declare.

Background. Neutropenic enterocolitis (NE) is a life-threatening complication occurring after intensive chemotherapy; however, only a few data are available for adults with hematological malignancy in China. The aim of this retrospective study was to elucidate the incidence, risk factors, and outcome of NE in adults with hematological malignancy after intensive chemotherapy. Methods. The medical records of 226 adult patients who were diagnosed with hematological malignancy and neutropenic enterocolitis after intensive chemotherapy from 2004 to 2013 were reviewed. Diagnosis of NE was established in case of neutropenic fever, abdominal pain or diarrhea, and bowel wall thickening >4mm on abdominal sonography or CT. Results. Amongst 1804 patients with hematological malignancy treated at the department of hematology, Hangzhou first people's hospital from 2004 to 2013, NE was diagnosed in 226 patients (12.5%), amedian +14(10–19) days after chemotherapy, with a death rate of 11.9%. Bloodstream infections were present in 23 patients, with gram-negative bacteria in 17 patients. Previous therapy with cytarabine and an intestinal wall thickness of ≥10 mm in the ultrasonographic examination affected survival, were associated with greater mortality. In multivariate analysis, the clinical findings of 4 or more symptoms was associated with higher risk of death. Conclusions. NE is a rare but severe complication in patients undergoing intensive chemotherapy. Use of cytarabine, an intestinal wall thickness of ≥10 mm and the clinical findings of 4 or more symptoms were associated with a higher death rate. Disclosures No relevant conflicts of interest to declare.

Abstract 3998 The recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is the worst prognostic subgroup in MM, although the basis for this poor prognosis is unknown. The t(4;14) is unusual in that it involves 2 potential target genes: fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET). MMSET is universally overexpressed in t(4;14) MM, whereas FGFR3 expression is lost in one-third of cases. Nonetheless, The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear. Here we demonstrate a role for MMSET in t(4;14) MM cells. We found that Down-regulation of MMSET expression in KMS11 cell by RNA interference and by selective disruption of the translocated MMSET allele using gene targeting dramatically reduced DNA synthesis in KMS11 decreased to 20% of that of the control, whereas the viability of cells decreased to 2% (p_ 0.01) of that of the control and increase in apoptosis was twice that of the control. These findings were associated with reduced expression of genes (e.g. CCND2, CCNG1, MAF and VEGF). These results provide direct evidence that MMSET plays a significant cell survival and antiapoptotic role in t(4;14) MM and suggest that therapies targeting this gene could impact this particular subset of poor-prognosis patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 4893 The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in china. A propensity score method was used to compensate for the non-randomized study design. From January 2004 to December 2009, 68 patients were newly diagnosed with DLBCL Using Hans' algorithm based on CD10, BCL-6, and MUM1, the non-germinal center (N-GCB) subgroup 45(66.2%) and germinal center B-cell-like (GCB) 23(33.8%). 32 in the rituximab plus CHOP-based chemotherapy (R+) group, and 36 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (81.1 vs. 68.1%, P < 0.005,); The complete response rate of N-GCB and GCB in the R+ group was78.2% and 82.1%, p>0.05 respectively. The complete response rate of N-GCB and GCB in the R- group was58.2% and 71.3 %, p P < 0.001. The rituximab can overcome poor outcomes for N-GCB subgroup of DLBCL. The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 69.5% for the R- group, P < 0.001. The 2-year overall survival (OS) was 72% in N-GCB Subgroup and 78% in GCB Subgroup for the R+ group, and 48% in N-GCB Subgroup and 68% in GCB Subgroup for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43–0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited N-GCB subgroup patients). IPI also showed significant impact for PFS (hazard ratio 1.72, 95% CI 1.34–2.14 for one score increase, P < 0.001 as well as OS P < 0.001. In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for DLBCL patients, particularly patients N-GCB subgroup of DLBCL. Disclosures: No relevant conflicts of interest to declare.

Abstract 4943 The clinical safety of intravenous itraconazole use exceeding 14 days is unknown. However, many cases need further treatment, but the absorption of itraconazole oral in severely ill patients is variable and unpredictable. Gastric acidity and food influence the absorption of oral formulation. The intravenous formulation, on the other hand, achieves adequate blood levels more rapidly and its bioavailability is predictable and invariable compared to the oral formulation. We performed this study to investigate the clinical safety of long-term intravenous itraconazole for the treatment of invasive fungal infection (IFI) in severely ill patients with hematological malignancies. 20 patients (median age, 70 years; range, 38–82 years) with hematological malignancies who had met the IFI inclusion criteria were enrolled. All the infection sites were the lung. These patients were given intravenous itraconazole for 14 days. There were significant effective but the lesions were not fully absorbed and no severe adverse events were found. So the long-term intravenous itraconazole therapy was enabled. Clinical efficacy and adverse events were recorded. Itraconazole 200 mg via intravenous infusion (administered over 1 hour) twice a day for 4 doses followed by 200 mg once a day until the lesions was fully absorbed. The treatment median time was 27(18-58) days. During this period, closely monitor changes in vital signs, chest CT, liver enzymes, renal function, electrocardiogram and electrolytes were assessed. We found that the patients achieved composite endpoints including survival, defervescence and undetectable lesions, except one patient died of primary disease - acute myeloid leukemia. Treatment-related adverse events were found in 7 patients (35%) during the study and none of them were severe adverse events. Such as hypokalemia (10.0%), gastrointestinal disorders (10.0%), elevation of liver enzymes (10.0%) and pleural effusion (5.0%). All the adverse events occurred during the first two weeks of the treatment and no significant exacerbation in the following days. In conclusion, long-term intravenous itraconazole therapy was effective for IFI and the drug-related adverse events have been shown to be generally predictable and manageable. Disclosures: No relevant conflicts of interest to declare.

Abstract 4138 To report a case of All–Trans-Retinoic Acid(ATRA)-induced rhabdomyolysis and acute renal failure in a patient with Acute Promyelocytic Leukemia(APL). A 44-year-old man with underlying APL. Results of the laboratory investigation were as follows: WBC 1.400/dl, hemoglobin 5.7 g/dl and platelets 15000/dl; prothrombin time 15.8 sec, activated partial thromboplastin time 23.4 sec, fibrinogen 75mg/dL (200-590 mg/dL), 3P(+), D-dimer>0.8 mg/dl(0.8 mg/dl( Conclusion,: although ATRA-induced rhabdomyolysis in the induction treatment of APL is a very rare complication, rhabdomyolysis - related ARF carries the risk of high morbidity and mortality. The authors recommended CK monitoring in all patients undergoing ATRA therapy, and withdrawal of ATRA when CK levels exceed 5 times the normal values. Disclosures: No relevant conflicts of interest to declare.