[Clinical Characteristics of CD4-CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To explore the clinical manifestations, pathological features, immunophenotype, as well as diagnosis, treatment and prognosis of patients with CD4-CD56+ blastic plasmacytoid dendritic cell neoplasm (BPDCN), in order to further understand the rare disease. METHODS: The clinical data, laboratory examinations and treatment regimens of two patients with CD4-CD56+ BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed. RESULTS: The two patients were both elderly males with tumor involved in skin, bone marrow, lymph nodes, etc. Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive, while CD4, CD34, TdT, CD3, CD20, MPO and EBER were negative. Flow cytometry of bone marrow demonstrated that CD56, CD123, and CD304 were all positive, while specific immune markers of myeloid and lymphoid were negative. Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens, but prone to rapid relapse. The overall survival of both patients was 36 months and 4 months, respectively. CONCLUSION: CD4-CD56+ BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis. Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

[Clinical Characteristics of Aggressive NK-Cell Leukemia].

OBJECTIVE: To explore and summarize the clinical characteristics and treatment of aggressive NK-cell leukemia (ANKL), and provide new insights for clinical diagnosis and treatment of this disease. METHODS: The clinical data of 7 patients with ANKL admitted to the First Affiliated Hospital of Wannan Medical College from March 2014 to July 2021 were retrospectively analyzed, and their clinical characteristics, laboratory and imaging results, treatment and outcomes were analyzed. RESULTS: Among the 7 patients, 5 were males and 2 were females, with a median age of 47 (33-69) years old. The morphology of bone marrow cells in 7 patients showed similar large granular lymphocytes. Immunophenotyping revealed abnormal NK cells in 5 cases. By the end of follow-up, 6 cases died and 1 case survived, with a median survival time of 76.9 (4-347) days. CONCLUSION: ANKL is a rare disease with short course and poor prognosis. If combined with hemophagocytic syndrome (HPS), the prognosis is even worse. There is no unified treatment method at present, and the use of PD-1 inhibitors may prolong the survival in some patients.

[Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed. RESULTS: Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later. CONCLUSION: PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

Combined scRNAseq and Bulk RNAseq Analysis to Reveal the Dual Roles of Oxidative Stress-Related Genes in Acute Myeloid Leukemia.

Background: Oxidative stress (OS) can either lead to leukemogenesis or induce tumor cell death by inflammation and immune response accompanying the process of OS through chemotherapy. However, previous studies mainly focus on the level of OS state and the salient factors leading to tumorigenesis and progression of acute myeloid leukemia (AML), and nothing has been done to distinguish the OS-related genes with different functions. Method: First, we downloaded single-cell RNA sequencing (scRNAseq) and bulk RNA sequencing (RNAseq) data from public databases and evaluated the oxidative stress functions between leukemia cells and normal cells by the ssGSEA algorithm. Then, we used machine learning methods to screen out OS gene set A related to the occurrence and prognosis of AML and OS gene set B related to treatment in leukemia stem cells (LSCs) like population (HSC-like). Furthermore, we screened out the hub genes in the above two gene sets and used them to identify molecular subclasses and construct a model for predicting therapy response. Results: Leukemia cells have different OS functions compared to normal cells and significant OS functional changes before and after chemotherapy. Two different clusters in gene set A were identified, which showed different biological properties and clinical relevance. The sensitive model for predicting therapy response based on gene set B demonstrated predictive accuracy by ROC and internal validation. Conclusion: We combined scRNAseq and bulk RNAseq data to construct two different transcriptomic profiles to reveal the different roles of OS-related genes involved in AML oncogenesis and chemotherapy resistance, which might provide important insights into the mechanism of OS-related genes in the pathogenesis and drug resistance of AML.

Defining Diffuse Large B-Cell Lymphoma Immunotypes by CD8+ T Cells and Natural Killer Cells.

BACKGROUND: There is a poor prognosis for diffuse large B-cell lymphoma (DLBCL), one of the most common types of non-Hodgkin lymphoma (NHL). Through gene expression profiles, this study intends to reveal potential subtypes among patients with DLBCL by evaluating their prognostic impact on immune cells. METHODS: Immune subtypes were developed based on CD8+ T cells and natural killer cells calculated from gene expression profiles. The comparison of prognoses and enriched pathways was made between immune subtypes. Following this validation step, samples from the independent data set were analyzed to determine the correlation between immune subtype and prognosis and immune checkpoint blockade (ICB) response. To provide a model to predict the DLBCL immune subtypes, machine learning methods were used. The virtual screening and molecular docking were adopted to identify small molecules to target the immune subtype biomarkers. RESULTS: A training data set containing 432 DLBCL samples from five data sets and a testing dataset containing 420 DLBCL samples from GSE10846 were used to develop and validate immune subtypes. There were two novel immune subtypes identified in this study: an inflamed subtype (IS) and a noninflamed subtype (NIS). When compared with NIS, IS was associated with higher levels of immune cells and a better prognosis for immunotherapy. Based on the random forest algorithm, a robust machine learning model has been established by 12 hub genes, and the area under the curve (AUC) value is 0.948. Three small molecules were selected to target NIS biomarkers, including VGF, RAD54L, and FKBP8. CONCLUSION: This study assessed immune cells as prognostic factors in DLBCL, constructed an immune subtype that could be used to identify patients who would benefit from ICB, and constructed a model to predict the immune subtype.

[Clinical Characteristics for Cutaneous Involvement in Diffuse Large B-Cell Lymphoma and Hemophagocytic Syndrome patients with First Presentation of Dermatomyositis].

OBJECTIVE: To present one patient initially diagnosed with dermatomyositis(DM) who was eventually revealed to be diffuse large B-cell lymphoma(DLBCL) complicated with hemophagocytic syndrome(HPS), and to improve the understanding of the disease. METHODS: The clinical characteristics, diagnostic approach, treatment of the patient were retrospectively analyzed, and some related literatures were reviewed. RESULTS: A 52-year-old female patient suffered from muscle weakness, elevated serum creatine kinase activity, electromyography changes and characteristic skin rashes and diagnosed as DM. The patient was treated with glucocorticoid therapy and the muscle strength, skin rashes, and creatine kinas index turns into remission. Subsequently, subcutaneous nodules appeared during treatment, and the patient was confirmed as DLBCL based on pathological biopsy; And the patient was considered HPS because of presenting with repeated fever, splenomegaly, cytopenias, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, high levels of sCD25, low NK-cell activity and hemophagocytosis in bone marrow. But the patient refused chemotherapy, and only treated with "DXM+VP-16" to control hemophagocytic syndrome, and unfortunately died due to the disease progression. CONCLUSION: Cutaneous involvement in diffuse large B-cell lymphoma and hemophagocytic syndrome patients with first presentation of dermatomyositis is relatively rare. Malignacy screening should be performed as soon as possible after newly diagnosed DM, so that the patient can get early diagnosis and effective treatment to improve survival rate.

Extramedullary Blast Crisis of Chronic Myelogenous Leukemia With a Skin Lesion: A Case Report and Literature Review.

ABSTRACT: Extramedullary blast crisis of chronic myeloid leukemia (CML) is defined as extramedullary disease composed of blasts regardless of the proliferation of blasts in the bone marrow. The commonly affected sites are the lymph node, central nervous system, bone, skin, and soft tissue. However, skin infiltration of CML patients as the initial presentation while their bone marrow is still in the chronic phase is extremely rare. In this article, we present a case of a 51-year-old woman who was admitted to our hospital complaining about a skin nodule in her right calf and easy fatigability for 1 week. The peripheral blood and bone marrow analysis both supported the diagnosis of CML in the chronic phase, whereas the excisional biopsy specimen obtained from her right calf showed immature cells infiltration, and fluorescence in situ hybridization test was positive for p210 BCR/ABL1 gene rearrangement. Based on the presence of extramedullary myeloid sarcoma, the patient was diagnosed with extramedullary myeloid blast crisis of CML despite the chronic phase in the bone marrow.

[Comparison of the Curative Efficacy of Elderly Patients with High-Risk MDS and MDS-Transformed AML between Decitabine Combined with Low-Dose CEG Regimen and Decitabine Combined with Low-Dose CAG Regimen].

OBJECTIVE: To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML). METHODS: A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. The risk stratification of patients was poor or very poor, according to IPSS-R score. The treament results of decitabine combined with CEG and decitabine combined with CAG were compared. RESULTS: The comparison of the two regiem showed that the DCEG regimen had advantages on total effective rate (ORR, 86.4% vs 47.8%, respectively), overall survival time (OS) (10.0 months vs 6.0 months, respectively) and progression-free survival time (PFS) (9.0 months vs 3.0 months, respectively). About 50% of MDS patients treated by DCEG regimen achieved PR or CR, with a median OS of 31 months. Multivariate analysis showed that patients with PR or CR after induction therapy and DCEG regimen had longer survival time (31months). The incidence of bone marrow suppression, infection and treatment-related mortality rate were similar between the two groups. CONCLUSION: Decitabine combined with CEG regimen could improve the survival of patients with high-risk MDS and MDS-transformed AML. The conclusion of the reaserch needs to be validated by a larger prospective randomized clinical trial.

[Clinical Characteristics of Patients with Myeloid Sarcoma].

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment methods of patients with myeloid sarcoma(MS)． Methods: The clinical data, laboratory examination, clinical pathology and treatment methods of 15 patients with MS treated in the First Affiliated Hospital of Wannan Medical College from June 2012 to January 2020 were retrospectively analyzed. RESULTS: Among the 15 cases of MS, including eight males and seven females, the middle age of patients were 53（19 to 72）. Among the 15 patients with MS, 4 showed solitary MS, while 11 showed secondary MS. Immunohistochemical results showed that MPO+（12/15）、CD68+（3/6）、Lys+（3/3）、CD34+（6/14）、TdT+（0/9）、CD43+（13/13）、CD117+（6/10）、CD15+（7/10）、CD3+（1/15）、CD20+（0/15）. 6 of 13 patients were survival till follow-up date．The median overall survival (OS) time was 16 months (1-88 months)．Conclusion: Myeloid sarcoma is rare and often secondary from acute myeloid leukemia(AML) and chronic myeogenous leukemia(CML). Isolated MS can easily be misdiagnosed as lymphoma. Treatment response should be evaluated in combination with bone marrow examination, PET/CT and other imagines．Systematic chemotherapy and hematopoietic stem cell transplantation are the main method to treat MS.

[Analysis of Clinical Characteristics in De novo Chronic Myelogenous Leukemia Patients with Extramedullary T-Lymphoblastic Blast Crisis].

OBJECTIVE: To report the clinical characteristics in a case of extramedullary T-lymphoblastic blast crisis of de novo chronic myelogenous leukemia (CML) so as to improve the understanding of this disease. METHODS: The clinical characteristics, diagnostic approach and treatment of the patient were retrospectively analyzed, and some related literatures were reviewed. RESULTS: According to resuts of blood routine, bone marrow, chromosome and fusion gene tests, this patient was considered to be CML patient. The cervical lymph node biopsy indicated a T-cell lymphoblastic lymphoma (TLBL), and fluorescence in situ hybridization (FISH) analysis showed the BCR-ABL fusion gene within tumor cells of the patient's lymphnodes, thus was confirmedly diagnosed as extramedullary T-lymphoblastic blast crisis of chronic myelogenous leukemia. Treatment with dasatinib 140 mg/d combined with chemotherapy was then initiated, while the patient never achieved a complete remission. CONCLUSION: De novo chronic myelogenous leukemia in blast crisis is infrequent presence, the cases of extramedullary T-lymphoblastic blast crisis of newly diagnosed CML with additional chromosome 11q23 are extremely rare. And prognosis of these patients are poor, allogeneic hematopoietic stem cell transplantation maybe the only curable treatment.

Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes multiple myeloma resistance through the JAK2/STAT3 pathway.

AIMS: Bone marrow stromal cells (BMSCs) have been reported to interact with multiple myeloma (MM) and exert a vital function of the survival of MM cells. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, has the potential to become a hematological malignancies targeted gene. This study aimed to investigate the role of HO-1 in MM resistance of BMSCs and its possible mechanisms. MAIN METHODS: In this study, the expression of related proteins was detected by RT-qPCR and Western blot. HO-1 expression was regulated by lentivirus transfection. Cell viability and apoptosis were detected by Flow cytometry and CCK-8. Cytokine secretion was assayed by ELISA. The survival and carcinogenic abilities was detected by clone formation assay. KEY FINDINGS: HO-1 expression in the BMSCs of stage III MM patients was substantially increased, compared with that of healthy donors and stage I/II patients. The results of co-culture of BMSCs and MM cells indicated that, the upregulated HO-1 inhibited the apoptosis of co-cultured MM cells, while downregulated HO-1 promoted the chemosensitivity of co-cultured MM cells, moreover, the upregulated HO-1 in BMSCs increased the colony-formation ability of MM cells. This protective capability may be regulated by CXCL12/CXCR4 signaling. High HO-1 expression in BMSCs can promote the phosphorylation of the JAK2/STAT3 pathway, thereby increasing secretion of SDF-1 in BMSCs and activating CXCL12/CXCR4 signaling. In addition, direct contact between BMSCs and MM cells may cause drug resistance. SIGNIFICANCE: These results indicated that the regulation of HO-1 in BMSCs may be a new effective method of MM therapy.

[Neutrophil-Lymphocyte Ratio as a Prognostic Predictor in Patients with Newly Diagnosed Angioimmunoblastic T Cell Lymphoma].

OBJECTIVE: To investigate the prognostic evaluation value of neutrophil-lymphocyte ratio (NLR) in patients with newly diagnosed angioimmunoblastic T cell lymphoma (AITL). METHODS: Clinical data of 39 patients with newly diagnosed AITL in our hospital from March 2010 to August 2018 were colleated and retrospective analyzied, and the relationship between NLR before treatment and the prognosis of AITL patients was analyzed. RESULTS: Among 39 AITL patients, the median value of NCR was 5.43. Based on the cut-off value (5.43), all the patients were divided into 2 groups: high NLR group (5.43, n=20) and a low NLR group (＜5.43, n=19). The total effective rate of treatment was lower in the high NLR group as compered with low NLR group (P=0.041). Univariate analysis showed that, age ＞60 years old, extranodal involvement＞1 as well as high NLR were the independent risk factors that affected overall survival (OS) in newly diagnosed AITL patients. Multivariate Cox analysis showed that extranodal involvement＞1 and high NLR were the independent risk factors that affected OS in newly diagnosed AITL patients. CONCLUSION: The NLR may be an independent prognostic factor in patients with newly diagnosed AITL. High NLR associated with poor prognosis.

Combination of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation With Unrelated Cord Blood Unit in Patients Aged 35 to 50 Years With Severe Aplastic Anemia: Preliminary Summary of a Single-Arm Trial.

This study reports a single-arm trial in the interim phase in 4 patients with median age of 40.5 years who have undergone combined HLA-matched sibling donor (MSD) stem cell graft and an unrelated cord blood (UCB) unit for the treatment of severe aplastic anemia (SAA). The median time was 10 days for neutrophil engraftment (9-18 days) and 17 days for platelets (12-24 days). Median follow-up of 22 months (ranging from 16 to 29 months) showed survival of the 4 patients with complete hematological response. Acute graft-vs-host disease (GVHD) (grade II) occurred only in 1 patient, yet chronic GVHD was free. One patient showed a pattern of transient MSD graft followed by dominant UCB chimerism, and another 1 achieved mixed chimerism in the first 6 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT) then evolved to a stable MSD graft. The other 2 patients sustained a full MSD graft during the post-HSCT period. Nevertheless, none of the patients developed primary and secondary graft failure up to the final follow-up. Although this is a small cohort, the dual transplantation combining HLA-matched sibling allogeneic hematopoietic stem cell transplantation with unrelated cord blood unit may deserve further exploration for treatment of SAA patients aged 35 to 50 years old.

Primary bronchial myeloid sarcoma mimicking bronchogenic carcinoma: a case report.

BACKGROUND: Myeloid sarcoma (MS) rarely involves the bronchus, and primary bronchial MS has almost never been reported in mainland China. CASE PRESENTATION: A 65-year-old female patient was admitted with a 3-month history of cough. She was initially diagnosed with bronchogenic carcinoma according to chest computed tomography (CT). However, after a biopsy was taken from the endobronchial lesion by bronchoscopy and further immunohistochemical analysis was performed, the diagnosis of MS was made. Because her bone marrow was normal and she had no history of haematologic diseases, we further considered the diagnosis of primary bronchial MS. The patient received chemotherapy with HAG regimens, and the original mass completely resolved, as confirmed by chest CT scan after 3 cycles of treatment. Meanwhile, no abnormalities were found on re-examination via bronchoscopy. CONCLUSIONS: MS should be considered in the differential diagnosis in the presence of a suspicious pulmonary mass. Immunohistochemical analysis is necessary to confirm the diagnosis. Chemotherapy can lengthen the survival time for patients.

[Imatinib as Second-Line Treatment Drug for CML Patients Intolerant to Nilotinib].

OBJECTIVE: To explore the individualized treatment for patient with chronic phase chronic myeloid leukemia(CML-CP). METHODS: The clinical data and treatment process of one CML-CP patient which intolerated to nilotinib were analyzed. RESULTS: Nilotinib was given to the patient once the diagnosis of CML-CP was set. Although major molecular remission (MMR) and complete cytogenetic remission (CCyR) were obtained during treatment for 3 months, a grade 3-4 hepatotoxicity appeared in the course of treatment.With drug reduction and symptomatic treatment, nilotinib was discontinued after 3 withdrawals and replaced with imatinib in January 11, 2015. The patients achieved MMR and CCyR at 7 months after imatinib replacement. At present, the patient tolerated well without any adverse events. CONCLUSION: Imatinib can be used as a second-line treatment drug for CML patients who was intolerant to nilotinib, and with less adverts, good effect and so on.

Aggressive natural killer cell leukemia or extranodal NK/T cell lymphoma? a case with nasal involvement.

BACKGROUND: Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare and highly aggressive NK cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with NK/T cell lymphoma (NKTL), which has a very different prognosis. Here, we present a case with nasal and bone marrow involvement, provide a literature review and make a differential diagnosis. CASE PRESENTATION: A 41-year-old male presented nasal congestion pharyngalgia, palatal perforation, high fever and multiorgan dysfunction. Our diagnosis primarily relied on clinical features, the morphology and immunophenotype of the neoplastic cells and imaging studies. Characteristic large granular lymphocytes with azurophilic granules were visible in the bone marrow smears. In addition, the neoplastic cells expressed a typical immunophenotype, and the T cell receptor γ (TCR-γ) gene rearrangement analysis and presence of Epstein-Barr virus (EBV) were negative. The patient's symptoms and signs were temporarily relieved after chemotherapy treatment, but after a short time, he underwent a rapid clinical decline and died 8 weeks later after admission due to multiorgan function failure. CONCLUSION: Our case demonstrates that to avoid a misdiagnosis, bone marrow analyses and other examinations should be performed early when a patient initially presents nasal lesions and other systemic symptoms. To the best of our knowledge, this may be the first reported case of ANKL with sternal tenderness.

Effect of Decitabine Combined with Unrelated Cord Blood Transplantation in an Adult Patient with -7/EVI1+ Acute Myeloid Leukemia: a Case Report and Literature Review.

Patients with relapsed or refractory acute myeloid leukemia (rAML) have a poor prognosis if they do not undergo hematopoietic stem cell transplantation (HSCT). We describe a case herein of acute myeloid leukemia (AML) with monosomy 7 and EVI1(+)(-7/EVI1(+)) in a patient who failed to achieve a complete remission (CR) after two cycles of standard induction chemotherapy. He subsequently received decitabine (DAC) as "bridge therapy" and directly underwent unrelated cord blood transplantation (UCBT) due to the absence of an available sibling donor. Although DAC treatment did not induce CR, it did produce hematologic improvement and control disease progression with acceptable side effects, thus effectively bridging the time of donor search. Following UCBT, the marrow showed complete hematologic and cytogenetic remission. At present, 18 months after the transplantation, the patient's general condition is still good.

[Change and significance of Th17 cells and its secretive IL-17 in patients with autoimmune hemolytic anemia].

AIM: To observe the percentage of Th17 cells in the peripheral blood and levels of plasma IL-17 of patients with autoimmune hemolytic anemia (AIHA)before treatment and after glucocorticoid treatment and to explore their clinical significance. METHODS: Flow cytometric assay were used to detect the rate of Th17 cells in AIHA patients. The level of plasma IL-17 in AIHA patients were measured by ELISA. RESULTS: The rate of Th17 cells and the level of plasma IL-17 were significantly increased before treatment as compared with that in normal controls [(2.78 ± 0.59)%, (126.4 ± 11.6)ng/L vs (0.59 ± 0.15)%, (52.3 ± 4.8) ng/L](P < 0.01). After treatment, The percentage of Th17 cells (1.05±0.28)% was significantly decreased (P < 0.01). The same tendency was also found in the levels of plasma IL-17(78.5 ± 6.4) ng/L(P < 0.01). CONCLUSION: The rate of Th17 cells and the lever of plasma IL-17 significantly elevate in AIHA patients. Glucocorticoid might play a role in AIHA treatment by down-regulating Th17 cells number and concentrations of IL-17.