Prognostic Implications of Circulating Plasma Cell Percentage in Multiple Myeloma and Primary Plasma Cell Leukemia Defined by New Criteria.

INTRODUCTION: The definition of primary plasma cell leukemia (pPCL) has been revised from ≥20% to ≥5% circulating plasma cells (CPC). However, the precise prognosis associated with CPC remains controversial. This study aimed to investigate prognostic biomarkers for myeloma patients based on CPC presence. METHODS: A comprehensive analysis was conducted on 309 consecutive patients diagnosed with either multiple myeloma or pPCL, utilizing peripheral blood smears stained with Wright-Giemsa. RESULTS: Patients were grouped by CPC percentage: 0% (221, 71.5%), 1-4% (49, 15.9%), 5-19% (16, 5.2%), ≥20% (23, 7.4%). CPC >5% correlated with unfavorable characteristics, including anemia, renal dysfunction, and advanced International Staging System. Common cytogenetic abnormalities such as 1q21 amplification, 17p deletion, and Myc rearrangement were prevalent among CPC-positive patients. Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with CPC ≥5% (29.47 vs. 10.03 months; 64.10 vs. 12.30 months). Additionally, PFS and OS were shorter in CPC-positive patients without autologous hematopoietic stem cell transplantation (ASCT) and those with response < partial remission to the first-line regimen. Furthermore, an association emerged between soft tissue-related extramedullary disease and inferior PFS, while Myc rearrangement correlated with abbreviated OS. CONCLUSION: Biological characteristics displayed greater aggressiveness in patients with positive CPC, leading to significantly shorter PFS and OS. The presence of CPC, ASCT, and overall response rate were independent prognostic factors. While no new threshold for pPCL with CPCs is proposed, but Myc rearrangements and CPC positivity could serve as ultra-high-risk factors for multiple myeloma.

Food-related inhibitory control deficits in young male adults with obesity: Behavioral and ERP evidence from a food-related go/no-go task.

PURPOSE: Obesity poses a pervasive challenge to global public health, which is linked to adverse physical health outcomes and cognitive decline. Cognitive function, particularly food-related cognitive function, plays a critical role in sustaining a healthy weight and mitigating the progression of obesity. The aim of this study was to investigate the behavioral and neuroelectronic aspects of food-related inhibitory functions in young adult males with obesity. METHODS: Forty-nine participants with obesity and healthy-weight were recruited (BMI = 35.83 ± 5.06 kg/m2 vs. 22.55 ± 1.73 kg/m2, age = 24.23 ± 4.55 years vs. 26.00 ± 3.97 years). A food-related Go/No-go task which included 6 distinct blocks in a randomized order was conducted to investigate the general and food-related inhibitory control. 180 stimulus images from the Food Picture Database encompassing high-calorie food, low-calorie food, and neutral images were selected. Behavioral (Go RT, Go ACC, No-go ACC) and event-related potential measures (N2 and P3 amplitude) during the food-related Go/No-go task were measured. RESULTS: The main findings indicated that the group with obesity exhibited lower No-go accuracy, slower go reaction times, and smaller P3 amplitudes in high-calorie, low-calorie foods, and neutral picture, compared to the normal-weight group, but with no group difference in N2. Additionally, high-calorie food induced larger N2 and P3 amplitude than the neutral stimuli. CONCLUSIONS: Young male adults with obesity exhibit poorer inhibitory control in both food and non-food domains, specifically in slower reaction time and reduced accuracy, featuring difficulties in neural resource recruitment during the inhibitory control process. Additionally, the P3 component could serve as sensitive indicators to reveal the neural mechanisms of inhibitory control deficits in obesity, while the N2 and P3 components may differentiate the neural differences between high-calorie foods and non-foods in inhibitory control processing. Food, especially high-calorie food, induces more neural resources and may exacerbate the poor inhibitory ability towards food in obesity. Targeted interventions such as exercise interventions, cognitive training as well as neuromodulation interventions are warranted in the future to improve impaired general and food-related inhibitory functions in the obese populations, offering both theoretical and practical frameworks for obesity prevention and treatment.

Pure red cell aplasia and minimal residual disease conversion associated with immune reconstitution in a patient with high-risk multiple myeloma.

A second bone marrow aspiration and biopsy showed pure red cell aplasia in this case.

E2F1 promotes Warburg effect and cancer progression via upregulating ENO2 expression in Ewing sarcoma.

Altered glucose metabolism is an important characteristic of cancer cells, which is referred to as Warburg effect or aerobic glycolysis. Ewing sarcoma (EWS) is a highly malignant tumor that occurs in children and adolescents. However, the functions of aerobic glycolysis in EWS remain to be elucidated. The present study identified a transcription factor, E2F transcription factor 1 (E2F1), as a new regulator of cancer the aerobic glycolysis and progression in EWS. The present study showed that E2F1 modulated aerobic glycolysis in EWS cells by effecting glucose uptake, lactate production and ATP generation. Altered E2F1 expression increased or decreased cell viability and invasion in EWS. Mechanistically, the results demonstrated that E2F1 may promote the Warburg effect and cancer progression in EWS via upregulating enolase 2 expression. Generally, these findings indicated that E2F1 involvement in the progression of EWS and could serve as a clinical therapeutic target in EWS.

Distinct Mutation Landscapes Between Acute Myeloid Leukemia With Myelodysplasia-Related Changes and De Novo Acute Myeloid Leukemia.

OBJECTIVES: To explore the distinct mutation profiles between acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and de novo AML and their relationships with prognosis. METHODS: Next-generation sequencing of 42 myeloid neoplasm-related genes in 293 newly diagnosed patients with AML. RESULTS: Eighty-four patients had AML-MRC, and 161 patients had de novo AML. The mutation rates of ASXL1 (25% vs 8.7%, P = .001), NRAS (17.9% vs 8.1%, P = .022), PTPN11 (11.9% vs 5%, P = .048), SETBP1 (6% vs 0.6%, P = .033), SRSF2 (11.9% vs 5.6%, P = .08), TP53 (16.7% vs 1.2%, P < .001), and U2AF1 (17.9% vs 7.5%, P = .014) in AML-MRC were higher than those in de novo AML, while the rates of FLT3-ITD (3.6% vs 15.5%, P = .005), KIT (0% vs 6.2%, P = .046), WT1 (3.6% vs 9.9%, P = .077), NPM1 (1.2% vs 21.7%, P < .001), and CEBPA (4.8% vs 24.2%, P < .001) mutation were lower. The appearance of ASXL1, TP53, U2AF1, SRSF2, and SETBP1 mutation could predict AML-MRC-like features in de novo AML, which was related to older age (60 vs 51 years, P = .001), low WBC counts (4.7 × 109/L vs 11.6 × 109/L, P = .001), and inferior outcomes (median overall survival, 15 months vs not reached, P = .003). CONCLUSIONS: The presence of AML-MRC-related mutations can reveal a subset of patients with de novo AML similar to patients with AML-MRC.

Acquired pure red cell aplasia and T cell large granular lymphocytic leukaemia in patients with autoimmune polyglandular syndrome type 1.

BACKGROUND: Pure red cell aplasia (PRCA) and large granular lymphocytic leukaemia (LGLL) are very rare complications of autoimmune polyendocrine syndrome type 1 (APS1). Here, we report a case of APS1 with PRCA and LGLL. Previous cases were reviewed, and possible mechanisms are discussed. CASE PRESENTATION: A 31-year-old female presented with anaemia and was diagnosed with PRCA in our centre. She also had hypoparathyroidism for 24 years, premature ovarian failure for 10 years, osteoporosis for 5 years, recurrent pneumonia with bronchiectasis for 4 years and chronic diarrhoea for 1 year. Boosted whole-exome analysis showed AIRE heterozygous mutations, confirming the diagnosis as APS1. LGLL was diagnosed during follow-up. The PRCA responded well to glucocorticoid. treatment CONCLUSION: AIRE is causally related to the development of LGLL and consequent PRCA, which may be due to some immunological mechanisms.

A case report on concurrent occurrence of systemic mastocytosis and myeloid sarcoma presenting with extensive skin involvements and the results of genetic study.

INTRODUCTION: Systemic mastocytosis is a rare disease due to mast cell accumulation in various extracutaneous sites. Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease is the second most common subtype of systemic mastocytosis. The most common mutation associated with both systemic mastocytosis and myeloid sarcoma is mutation in Kit. Here, we identified the novel KIT D816V and ARID1A G1254S mutations co-occurring in systemic mastocytosis with myeloid sarcoma. PATIENT CONCERNS: A 33-year old male patient presented multiple skin lesions for 10 years. Symptoms accelerated in 2017 with decreased body weight. Physical examination revealed enlarged lymph nodes in his neck, axilla and inguinal region; conjunctival hemorrhage; gingival hyperplasia. Skin biopsy showed mast cell infiltration. Flow cytometry detected CD2, CD25 and CD117 positive cells in lymph nodes. Codon 816 KIT mutation D816V and codon 1245 ARID1A mutation G1254S were found in peripheral blood. MPO, CD117, CD68 positive cells in lymph nodes indicated co-existing myeloid sarcoma. DIAGNOSIS: Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease of myeloid sarcoma INTERVENTIONS:: Cytarabine and daunorubicin for myeloid sarcoma and dasatinib for systemic mastocytosis were initiated. Anti-histamine and anti-leukotrienes therapy were used to prevent NSAIDs-induced shock. Platelets were infused to treat bone marrow suppression. OUTCOMES: Patient was discharged after recovered from bone marrow suppression. Dasatinib continued on outpatient. CONCLUSION: This is the first case of patient with systemic mastocytosis and myeloid sarcoma simultaneously presenting extensive skin involvements. Mutations of Kit and Arid1a emphasis the importance to notice possibility of various tumors occurring in patients with multiple mutations. In addition, cysteine-leukotrienes-receptor antagonists should always be used to prevent anaphylactic shock due to mast cell activation.

Effective treatment of refractory acquired pure red blood cell aplasia with eltrombopag and sirolimus: a case report.

Acquired pure red cell aplasia (aPRCA) is a kind of anemia characterized by severe reticulocytopenia and reduced bone marrow erythroblastic cells. For patients who are refractory to the first-line therapy (cyclosporin A with/without glucocorticoids), second-line therapy is considered less effective. We report on a patient with primary aPRCA who was refractory to cyclosporin A, glucocorticoids, and several second-line regimens. The patient was treated with sirolimus for 10 months with no improvement in hemoglobin but complete response was achieved after adding eltrombopag at a dosage of 25 mg/day. Eltrombopag was well tolerated with no evidence of clonal evolution at the end of follow up. This case provided a new attempt at treating patients with refractory/relapse aPRCA with eltrombopag, probably in combination with sirolimus.

Analytical evaluation of three soluble transferrin receptor measurement systems for diagnosis of iron deficiency anemia: A retrospective study.

BACKGROUND: Soluble transferrin receptor (sTfR) is a promising indicator of iron deficiency anemia (IDA). Here, we investigated the application value of sTfR assays based on three different methods for the diagnosis of IDA. METHODS: The sTfR concentrations in two groups of patient specimens with high-level and low-level sTfR concentrations and in quality control materials were measured four times a day for five consecutive days to evaluate the precision of the three methods. We selected patients with IDA, anemia of chronic disease (ACD), or chronic diseases with iron deficiency anemia (CIDA), and apparently healthy subjects, and measured the serum sTfR concentrations in all subjects using the three different methods. The cutoff points for an IDA diagnosis using the three assays and their corresponding clinical sensitivities and specificities were calculated by receiver operating characteristic analysis. RESULTS: For the diagnosis of IDA, the cutoff points of sTfR measured by the chemiluminescent, immunoturbidimetric, and immunonephelometric assays were 2.91, 6.70, and 2.48 mg/L, respectively. The corresponding sensitivities were 85.59%, 85.59%, and 85.59%, the specificities were 91.47%, 90.31%, and 90.70%, and area under the curve was 0.943, 0.944, and 0.936, respectively. The sTfR concentrations measured by the different methods were significantly higher in the IDA and CIDA groups than in the other two groups (P < .05). CONCLUSIONS: The sTfR based on the three different measurement methods presented promising analytical performances and met the clinical requirements for sensitivity and specificity. However, the different measurement methods had markedly different cutoff points for IDA diagnosis, which should be critically considered in clinical practice.

[Clinical role of Morphology in Diagnosing Bone Marrow Involvement of Diffuse Large B Bell Lymphoma].

OBJECTIVE: To determine the significance of morphology of bone marrow smear for diagnosis of bone marrow involvement in patients with diffuse large B-cell lymphoma (DLBCL), and to study the morphological characteristics of DLBCL cells involved in bone marrow. METHODS: Four hundred and twenty cases of DLBCL diagnosed at Peking Union Hospital from 2006 to 2016 were analyzed and identified. RESULTS: Blinded analysis of bone marrow smear and bone marrow biopsy data showed involvement in 42 cases on smears (S), in 47cases by biopsy (B) and the in 49 cases by (S+B). There was an excellent correlation between 2 methods diagnosing the bone marrow infiltration of DLBCL independently (κ=0.889). The morphological features of DLBCL cells involved in bone marrow were of medium sizes, round or irregular nuclear. The chromatin presented dark purple rea and coarse granular, and most of them had 1-5 nucleoli. The amount of cytoplasm was moderate with the color of dark blue or greyish blue. Vacuoles and pseudopodia were common. CONCLUSION: The morphological examination of bone marrow cells has a certain role in the diagnosing bone marrow involvement in patients with DLBCL, and the atypical lymphoid cells making up ≥1% of the total nucleated cells highly suggests the bone marrow involvement in the patients with DLBCL.

Clinical presentation and prognosis of immunoglobulin light-chain amyloidosis with high percentage of bone marrow plasma cells.

OBJECTIVE: To summarize the clinical features and outcomes in Chinese patients with immunoglobulin light-chain (AL) amyloidosis with ≥10% bone marrow plasma cells (BMPCs). METHODS: We retrospectively compared the clinical features and outcomes between patients with ≥10% BMPCs (high-BMPC group; n = 56) and those with <10% BMPCs (low-BMPC group; n = 311). RESULTS: Patients in the high-BMPC group had significantly higher levels of N-terminal pro-brain natriuretic peptide, significantly lower levels of 24 h urine protein, and significantly higher levels of difference between the involved and uninvolved serum free light chains (485.3 versus 121.1 mg/L, P < 0.001). Patients in the high-BMPC group had significantly higher early mortality within 3 months of diagnosis (21.4% versus 10.9%, P = 0.018). In a 3-month landmark analysis, median progression-free survival durations were 17.3 and 34.5 months (P = 0.01), and the median overall survival durations were 24.4 months and not reached in the high- and low-BMPC groups, respectively (P = 0.005). CONCLUSION: Patients with AL amyloidosis and ≥10% BMPCs have higher mortality within 3 months of diagnosis and poorer prognosis compared with patients with <10% BMPCs.

Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis.

Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders associated with pathogenic defects in the genes encoding hemochromatosis (HFE), hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well described. However, there have been only a few detailed reports of HH in Chinese populations. Thus, there is insufficient patient information for population-based analyses in Chinese populations or comparative studies among different ethical groups. In the current work, we describe eight Chinese cases of hereditary hemochromatosis. Gene sequencing results revealed eight mutations (five novel mutations) in HFE, HFE2, TfR2, and SLC40A1 genes in these Chinese HH patients. In addition, we used Polymorphism Phenotyping v2 (Polyphen), Sorting Intolerant From Tolerant (SIFT), and a sequence alignment program to predict the molecular consequences of missense mutations.

[Morphology Manifestation of Bone Marrow Cells in 155 Newly- Diagnosed Patients with POEMS Syndrome].

OBJECTIVE: To investigate the morphological manifestation of bone marrow cells in newly-diagnosed patients with POEMS syndrome. METHODS: The bone marrow cells in 155 patients with POEMS syndrome were classified and counted by OLYMPUS BX51 microscope, and the abnormal morphology of bone marrow cells was observed. RESULTS: The count of plasma cells with normal morphology was 83.9% (130/155), the count of plasma cells with abnormal morphology (< 5 percent) was 12.3% (19/155), the count of plasma cells with obvious abnormal morphology (> 10 percent) was 3.8% (6/155) in patients with POEMS syndrome. CONCLUSION: The morphology of plasma cells in the most patients with the POEMS syndrome are normal, the minor patients of the POEMS syndrome have little abnormal plasma cell morphology, the extremely few patients showed obvious morphological abnormality in the bone marrow plasma cells. The higher proportion of plasma cells, the more easily and more abnormal plasma cells will be found.

An fMRI study showing the effect of acupuncture in chronic stage stroke patients with aphasia.

Acupuncture is used as a treatment in stroke patients with aphasia, yet the underlying neural mechanisms are unknown. This study aims to examine the relationship between changes in language function and brain activation using functional magnetic resonance imaging in chronic stroke patients with aphasia who underwent an 8-week acupuncture protocol. Seven chronic stroke patients were identified from a stroke database of a regional acute hospital in Hong Kong between January and July 2007. Patients were treated three times a week over a period of 8 weeks. Four acupoints were stimulated on the weak side of the patient's body. No other rehabilitation was given during the study period. Changes in language function were measured by aphasia quotient (AQ) of Cantonese Aphasia Battery (CAB). Functional magnetic resonance imaging blood oxygen level dependent signals were used to demonstrate the correlation between changes in AQ and brain activation after treatment. The patients were divided into well-recovered and poorly- recovered groups based on their CAB scores at entry. The well-recovered group showed significant improvement in CAB scores after receiving acupuncture treatment. A significant correlation between changes in AQ and blood oxygen level dependent activation in the lesioned Wernicke's speech area was found. These preliminary results suggest that acupuncture may be beneficial to language recovery in chronic stroke patients.