Pure white cell aplasia before and after thymectomy in the rare conundrum of thymoma: A case report and review of the literature.

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage. PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum. DIAGNOSES: The final diagnosis of our patient was PWCA and thymoma. INTERVENTIONS: She underwent a thymectomy and cyclosporine A administration during first remission. OUTCOMES: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence. LESSONS: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.

Development and validation of a model for the early prediction of progression from essential thrombocythemia to post-essential thrombocythemia myelofibrosis: a multicentre retrospective study.

Background: Essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN), has a substantial risk of evolving into post-essential thrombocythemia myelofibrosis (post-ET MF). This study aims to establish a prediction nomogram for early prediction of post-ET MF in ET patients. Methods: The training cohort comprised 558 patients from 8 haematology centres between January 1, 2010, and May 1, 2023, while the external validation cohort consisted of 165 patients from 6 additional haematology centres between January 1, 2010, and May 1, 2023. Univariable and multivariable Cox regression analysis was performed to identified independent risk factors and establish a nomogram to predict the post-ET MF free survival. Both bias-corrected area under the curve (AUC), calibration curves and concordance index (C-index) were employed to assess the predictive accuracy of the nomogram. Findings: Multivariate Cox regression demonstrated that elevated red blood cell distribution width (RDW), elevated levels of lactate dehydrogenase (LDH) and the level of haemoglobin (Hb), a history of smoking and the presence of splenomegaly were independent risk factors for post-ET MF. The C-index displayed of the training and validation cohorts were 0.877 and 0.853. The 5 years, 10 years AUC values in training and external validation cohorts were 0.948, 0.769 and 0.978, 0.804 respectively. Bias-corrected curve is close to the ideal curve and revealed a strong consistency between actual observation and prediction. Interpretation: We developed a nomogram capable of predicting the post-ET MF free survival probability at 5 years and 10 years in ET patients. This tool helps doctors identify patients who need close monitoring and appropriate counselling. Funding: This research was funded by the Key R&D Program of Zhejiang (No. 2022C03137); the Public Technology Application Research Program of Zhejiang, China (No. LGF21H080003); and the Zhejiang Medical Association Clinical Medical Research special fund project (No. 2022ZYC-D09).

Clinical characteristics and outcomes of COVID-19 infection in Chinese patients with hematologic malignancies in the Omicron era.

Patients with hematologic malignancies are often immunodeficient and therefore have a higher risk of severe symptoms from coronavirus disease 2019 (COVID-19). We retrospectively examined a cohort of 289 patients from 16 hospitals in Zhejiang Province who had hematologic malignancies and COVID-19 during a period when the Omicron variant was predominant. Univariate analysis showed that some clinical characteristics, including elder age (P = 0.014), multiple comorbid conditions (P = 0.011), and receipt of active antineoplastic therapy (P = 0.018) were associated with an increased risk of severe COVID-19. Patients with severe/critical COVID-19 had significantly lower levels of lymphocytes and serum albumin, and significantly higher levels of D-dimer, lactate dehydrogenase, C-reactive protein, and interleukin-6 (all P < 0.05). Fifty-four patients (18.7%) had symptoms lasting ≥3 weeks, suggesting that persistent long-term COVID-19 infection is likely present in a significant proportion of patients. Receipt of the inactivated vaccine was unrelated to disease severity (P = 0.143), which indicated that many patients with hematologic malignancies may not have effective humoral immunity to inactivated vaccines.

Construction of circRNA-miRNA-mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia.

Introduction: CircRNA is closely correlated with a wide variety of processes of acute myeloid leukemia (AML), whereas the novel circRNAs, their molecular mechanism and the specific function they played in AML should be explored in depth. Methods: The microarray chip data of AML patients and normal samples in the Gene Expression Omnibus (GEO) database were selected to differentially expressed (DE) circRNA, miRNA, and mRNA genes. The miRNA gene was the intersection of the circRNA target gene predicted using CSCD and the miRNA gene screened from AML patients, while the mRNA gene was the intersection of the target gene mRNA of miRNA predicted using miRanda and miRTarBase software and the mRNA gene screened from AML patients. The hub mRNAs related to survival were further screened through Cox proportional hazard regression. CircRNA/miRNA/mRNA interaction network was constructed by using Cytoscape software.10 circRNAs and 6 miRNAs in bone marrow mononuclear cells (BMMNCs) of AML patients (n=43) and healthy controls (n=35) were determined by RT-qPCR. Correlations between them were analyzed by Pearson correlation coefficient. Results: 10 circRNAs, 6 miRNAs, and 33 mRNAs were identified. Subsequently, the network of circRNAs, miRNAs, and hub genes was built using Cystoscope. Four key circRNAs, seven hub genes and their regulatory pathways were identified. The result of RT-qPCRs showed that hsa_circ_0009581 and hsa_circ_0005273 were significantly upregulated in AML patients while hsa_circ_0000497 and hsa_circ_0001947 were significantly downregulated. Hsa-miR-150-5p was significantly downregulated; hsa-miR-454-3p was upregulated in AML patients. Hsa_circ_0009581 and hsa-miR-150-5p; hsa_ circ_0001947 and hsa-miR-454-3p were inversely correlated using Pearson's correlation coefficient. Conclusion: This study suggests that differentially expressed circRNAs take on a critical significance to AML development and may be the effective therapeutic targets. We suppose that hsa_circ_0009581 promotes leukemia development through hsa-miR-150-5p and hsa_circ_0001947 through hsa-miR-454-3p. hsa_circ_0001947 and hsa_circ_0009581 may provide new directions in the pathogenesis of AML.

Venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14): A case report.

BACKGROUND: Conventional therapies for primary plasma cell leukemia (pPCL) are usually ineffective, with a short remission time with the use of multiple myeloma medications, showing aggressiveness of pPCL. B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma (RRMM) with t(11;14). There are very few studies published on the use of venetoclax in pPCL without t(11;14). Similarly, histone deacetylase inhibitors are considered effective for the treatment of RRMM, but there are no reports on their use in pPCL. CASE SUMMARY: A 57-year-old woman with severe anemia, thrombocytopenia, multiple bone destruction, impaired renal function, and 42.7% of peripheral plasma cells is reported. After multiple chemotherapy regimens and chimeric antigen receptor T-cell treatment, the disease progressed again. The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy. CONCLUSION: The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.

Chronic myelomonocytic leukemia (CMML)-0 with pleural effusion as first manifestation: A case report.

RATIONALE: Extramedullary invasion of chronic myelomonocytic leukemia (CMML) usually occurs in the liver, spleen, and lymph nodes, while the pleural infiltration of CMML is rare. The presence of pleural effusion is usually associated with uncontrolled leukocytosis and increased monocytes. PATIENT CONCERNS: Here we reported a rare case of CMML-0 with pleural effusion as the first manifestation in a 44-year-old woman. The pleural effusion was caused by blasts infiltration confirmed by the flow cytometer and the pleural biopsy. DIAGNOSES: CMML with pleural invasion. INTERVENTIONS: The patient was treated with azacitidine 75 mg/m d for 2 cycles, followed by daily oral intake of hydroxyurea (500 mg/d). OUTCOMES: Pleural effusion was resolved and chest pain was relieved. LESSONS: The current case indicated that leukemic infiltration into pleura could occur despite mild leukocytes, while demethylation may be an effective therapy.

Outcome of adult T-lymphoblastic lymphoma depends on ALL-type chemotherapy, prognostic factors, and performance of allogeneic hematopoietic stem cell transplantation.

To study the prognostic factors of adult patients with T-lymphoblastic lymphoma (T-LBL) and to evaluate therapeutic effects of acute lymphoblastic leukemia (ALL)-type chemotherapy in combination with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients who achieved overall response (OR) with first line ALL-type chemotherapy.This was a retrospective study of 59 adult patients with T-LBL treated with hyper-fractionated administration of cyclophosphamide, vincristine, doxorubicin and dexamethasone/methotrexate (hyper-CVAD/MA) chemotherapy alone or in combination with allo-HSCT between June 2008 and October 2015. Complete response (CR) and OR rates were evaluated after the initial chemotherapy. Clinical characteristics and the risk factors associated with prognosis and overall survival (OS) were analyzed in all patients and the effects of allo-HSCT on OS were evaluated in patients who had achieved OR after initial chemotherapy.Forty-eight patients (81.4%) achieved OR by hyper-CVAD chemotherapy, among which, 22 patients (45.8%) further received allo-HSCT. The median follow-up was 31.5 months, ranging from 11 to 97 months. The 3-year OS and progression-free survival (PFS) were 45.7% and 45.0% for patients who achieved OR after chemotherapy and both 0 for patients who did not achieve OR (both P < .001). Three year OS and PFS were higher in patients who received chemotherapy + allo-HSCT than in patients who received chemotherapy alone (3-year OS: 72.8% vs 17.5%, P = .008; PFS: 65.1% vs 27.8%, P = 0.007). Shorter survival was independently associated with elevated lactic dehydrogenase (LDH), Ki-67≥75%, pleural effusion and no OR (all P < .05) in all patients. But shorter survival was only associated with elevated LDH level, leukocytosis (>10 G/L), and chemotherapy alone in patients who achieved OR (all P < .05).The mid-term outcomes of adult patients with T-LBL are associated with response to chemotherapy (in all patients) and performance of allo-HSCT (in patients who achieved OR). Allo-HSCT could be a feasible and effective consolidation therapy for adult T-LBL.