RATIONALE AND OBJECTIVES

Individuals with myeloproliferative neoplasia (MPN) have blood cell parameters representing abnormal proliferation of the cell line/lines affected. Considering the implication of symptom burden scores to treatment response and disease progression, with the same implication among changes in blood cell parameters, a question of correlation between the two variables becomes inevitable. This study aims to determine the correlation of controlled blood counts, severity of symptoms and quality of life of individuals with MPN.

This is a cross-sectional analytical study and a sub-study from the Filipino myeloproliferative neoplasia quality of life (MPN-QOL) multicenter study. Secondary data obtained from the parent study will be used as primary data of this sub-study. Comparative analyses were conducted using Chi-Square Test of Homogeneity or Fisher’s Exact Test. Association analysis used Cramer’s V coefficient.

Data in this study has shown 52.65 years old as the average age of participants. Most participants had mild symptom burden at 60.53% with the most common symptom being fatigue. Comparative analysis showed the absence of identified statistical difference in the overall symptom burden severity among the three types of MPN.

In this study, there was no statistically significant correlation between the severity of symptom burden or quality of life, and the degree of blood count control among the three types of MPN. In practice, controlling hematologic parameters has been a goal to achieve among patients with MPN. This study suggests symptom control and quality of life is not necessarily affected by blood count control.

OBJECTIVES: To investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL) in children. METHODS: A retrospective analysis was conducted on the clinical data, treatment, and prognosis of 8 children with AEL treated at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023. RESULTS: Among the 7 patients with complete bone marrow morphological analysis, 4 exhibited trilineage dysplasia, with a 100% incidence of erythroid dysplasia (7/7), a 71% incidence of myeloid dysplasia (5/7), and a 57% incidence of megakaryocytic dysplasia (4/7). Immunophenotyping revealed that myeloid antigens were primarily expressed as CD13, CD33, CD117, CD38, and CD123, with 4 cases expressing erythroid antigens CD71 and 2 cases expressing CD235a. Chromosomal analysis indicated that 2 cases presented with abnormal karyotypes, including +8 in one case and +4 accompanied by +6 in another; no complex karyotypes were observed. Genetic abnormalities were detected in 4 cases, with fusion genes including one case each of dup MLL positive and EVI1 positive, as well as mutations involving KRAS, NRAS, WT1, and UBTF. Seven patients received chemotherapy, with 6 achieving remission after one course of treatment; 2 underwent hematopoietic stem cell transplantation, and all had disease-free survival. Follow-up (median follow-up time of 6 months) showed that only 3 patients survived (2 cases after hematopoietic stem cell transplantation and 1 case during treatment). CONCLUSIONS Children with AEL have unique clinical and biological characteristics, exhibit poor treatment response, and have a poor prognosis; however, hematopoietic stem cell transplantation may improve overall survival rates.
Humans ; Male ; Female ; Prognosis ; Child, Preschool ; Retrospective Studies ; Child ; Leukemia, Erythroblastic, Acute/diagnosis* ; Infant ; Adolescent

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Pediatric chronic myeloid leukemia (CML) is more aggressive than adult CML, with unique molecular characteristics and a higher propensity for lymphoid blast crisis. The application of tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis of pediatric CML. Based on international consensus and clinical experience, this article proposes standardized diagnosis and treatment recommendations for pediatric CML, covering initial therapy selection, efficacy evaluation, drug switching, and management of adverse effects. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended only for patients with disease progression or failure of multiple lines of TKI therapy. For children newly diagnosed with CML in accelerated phase, high-dose imatinib or second-generation TKIs are recommended as first-line therapy. Those achieving optimal responses should continue maintenance therapy, while non-responders require switching to alternative TKIs and consider allo-HSCT. For blast-phase CML, induction therapy requires a combination of TKIs and chemotherapy, with allo-HSCT serving as the core curative intervention. This article highlights common but challenging problems (poor response, drug intolerance, and disease progression) in pediatric CML treatment using three typical cases, aiming to optimize treatment strategies. Furthermore, the goal of achieving treatment-free remission needs to be further addressed through multi-center clinical studies.
Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Child ; Hematopoietic Stem Cell Transplantation ; Protein Kinase Inhibitors/therapeutic use* ; Male ; Female ; Adolescent

OBJECTIVE: To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells. METHODS: K562 cells were treated with ginsenoside-Rg5 and imatinib. Cell survival was detected by CCK-8 assay, and IC₅₀ were calculated separately for each drug. Based on the value of IC₅₀ of ginsenoside-Rg5 and imatinib, an appropriate concentration gradient was selected for the combination. The synergistic effect of the two drug was analyzed using the online software synergy finder. The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy. RESULTS: Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dosedependent manner(r =-0.991， r =-0.942). The synergy score ZIP >10 was measured by Synergy Finder online software, indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells. The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96% and 8.13%, respectively, while the rate increased to 21.35% with the combination of two drugs, the apoptosis rate in the combination group was higher than that in the single-drug group ( P <0.05). The proportion of K562 cells in the G₀/G₁ phase was significantly increased with the combined treatment of two drugs( P <0.05). The protein expression levels of p-PI3K, p-AKT, p-mTOR in K562 cells treated with the combination were significantly decreased, with noticeable downregulation of BCL-2 and upregulation of BAX, leading to a decreased Bcl-2/BAX ratio, while no significant changes were observed in the non-phosphorylated forms of PI3K, AKT, and mTOR proteins. CONCLUSION The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.
Humans ; Ginsenosides/pharmacology* ; Imatinib Mesylate ; K562 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction/drug effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Drug Synergism ; Apoptosis/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Proliferation/drug effects*

OBJECTIVE: To analyze the occurrence of arterial events and platelet parameters in patients with polycythemia vera (PV) and essential thrombocythemia (ET), and to explore the characteristics of platelet parameters in patients with PV and ET and their relationship with arterial complications. METHODS: The clinical and laboratory data of newly diagnosed PV and ET patients who visited the Department of Hematology, Beijing Anzhen Hospital, Capital Medical University from August 2017 to August 2022 were retrospectively analyzed. RESULTS: 86 MPN patients (46 males and 40 females) were enrolled, including 44 PV patients and 42 ET patients, with an median age of 61(23-83) years. The mutation rate of JAK2V617F gene, the number of megakaryocytes in bone marrow, the incidence of splenomegaly, and the levels of white blood cell count (WBC), hemoglobin (HGB), hematocrit (HCT), platelet distribution width (PDW), mean platelet volume (MPV), platelet-large cell ratio (P-LCR) in PV patients were significantly higher than those in ET patients (P < 0.05), while the levels of PLT and PCT were significantly lower than those in ET patients (P < 0.01). 22 cases (50%) of PV patients were complicated with arterial events, of which 12 had arterial stenosis in≥2 locations. Among arterial events, the PDW of PV patients with ischemic stroke was greater than that of PV patients without ischemic stroke (P =0.003), and the PDW of PV patients with arterial stenosis in≥2 locations was greater than that of PV patients with arterial stenosis in≤1 location (P =0.037). 23 cases (54.8%) of ET patients were complicated with arterial events, and 7 cases had arterial stenosis in≥2 locations. In arterial events, the PCT of ET patients complicated with ischemic stroke was greater than that of ET patients without ischemic stroke (P =0.037), and the PCT of ET patients with≥2 locations of arterial stenosis was greater than that of ET patients with≤1 location of arterial stenosis (P =0.049). The binary logistic regression analysis showed that elevated PDW and PCT were risk factors for ischemic stroke in PV and ET patients, respectively (P < 0.05). CONCLUSION The platelet parameters of PV and ET patients exhibit significantly different characteristics. Elevated PDW and PCT can predict a higher risk of ischemic stroke in PV and ET patients, respectively.
Humans ; Middle Aged ; Female ; Male ; Aged ; Retrospective Studies ; Adult ; Thrombocythemia, Essential/blood* ; Myeloproliferative Disorders/complications* ; Aged, 80 and over ; Polycythemia Vera/blood* ; Blood Platelets ; Platelet Count ; Young Adult ; Mean Platelet Volume

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of patients with chronic myeloid leukemia (CML), and achieving treatment-free remission (TFR) has become a new goal for these patients. Various methods of discontinuing medication are continuously being explored, with successful cessation linked to factors such as the duration of TKI treatment, the sustainability of deep molecular response (DMR), transcript type, and immunological factors. Early switching of TKI, combining other therapies, and targeting leukemia stem cells may help increase the TFR rate. This article reviews the latest research developments on the exploration of TKI cessation, factors affecting TFR, selection of patients for discontinuation, strategies to enhance TFR, and monitoring after cessation, expecting to provide reference and guidance for achieving TFR in CML patients.
Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors/therapeutic use* ; Remission Induction ; Tyrosine Kinase Inhibitors

Ropeginterferon α-2b (Ropeg), a novel, long-acting pegylated prolene alpha interferon, is the first interferon specifically approved for the treatment of patients with polycythemia vera (PV), and has been found in clinical trials and experience to induce hematologic remission, control disease-related symptoms, and reduce JAK2V617F allelic burden in patients with myeloproliferative neoplasms (MPNs). It has a lower incidence and severity of adverse drug reactions than pegylated interferon alpha and hydroxyurea and a longer dosing interval. Some patients with lowrisk PV and myelofibrosis can benefit from it. This article reviews the latest progress of Ropeg in MPN.
Humans ; Interferon-alpha/therapeutic use* ; Myeloproliferative Disorders/drug therapy* ; Polyethylene Glycols/therapeutic use* ; Recombinant Proteins/therapeutic use* ; Interferon alpha-2 ; Polycythemia Vera/drug therapy*

OBJECTIVE: To screen the genetic risk factors related to severe hematology adverse effects (AEs) in patients with chronic myeloid leukemia (CML) treated with imatinib (IM), and explore the correlation of single nucleotide polymorphisms (SNPs) in IM drug metabolism and transport pathway gene polymorphism with the risk of severe hematology AEs. METHODS: 172 newly diagnosed Chinese Han patients in CML chronic phase (CML-CP) treated with IM were included and divided into severe hematology AEs group and non-severe hematology AEs group. The demographic characteristics and laboratory test results were compared between the two groups. 11 gene SNP sites in the included subjects were genotyped using SNaPshot multiplex SNPs technique. RESULTS: Compared with non-severe hematology AEs group, the severe hematology AEs group had higher white blood cell (WBC) and EOS% (both P < 0.05), but lower hemoglobin (Hb) and hematocrit (HCT) (both P < 0.01). For rs1045642 of ABCB1 gene, there were significant differences in the distribution of allele frequency and genotype frequency of this loci between severe hematology AEs group and non-severe hematology AEs group (both P < 0.05). Carriers of rs1045642 mutation allele A had an increased risk of severe hematology AEs (OR =2.09, 95% CI : 1.24-3.55, P =0.005). There was a significant difference in the distribution of NR1I2 gene rs3814055 genotype between severe hematology AEs group and non-severe hematology AEs group (P < 0.05). The additive model and recessive model of ABCB1 gene rs1045642 and the recessive model of NR1I2 gene rs3814055 were associated with the increased risk of severe hematology AEs (OR =2.14, 3.28, 5.54, all P < 0.05). CONCLUSION Peripheral blood WBC, EOS%, Hb and HCT in patients with newly diagnosed CML-CP are all related to the risk of severe hematology AEs. ABCB1 gene rs1045642 and NR1I2 gene rs3814055 related to the metabolism and transport pathway of IM are associated with severe hematology AEs after IM treatment in CML-CP patients, and they may be potential molecular markers to predict the risk of severe hematology AEs of CML patients treated by IM.
Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics* ; Polymorphism, Single Nucleotide ; Genotype ; ATP Binding Cassette Transporter, Subfamily B ; Gene Frequency ; Female ; Male ; Middle Aged ; Adult ; Asian People

OBJECTIVE: To analyze the clinical features and laboratory characteristics of patients with cold agglutinin disease (CAD)/cold agglutinin syndrome (CAS) who were positive for acidified-serum lysis test (Ham test), and to compare them with Ham test negative CAD/CAS patients and paroxysmal nocturnal hemoglobinuria (PNH) patients, in order to provide references for the differential diagnosis of these diseases. METHODS: 53 patients diagnosed with CAD/CAS and 67 patients diagnosed with classic PNH in our hospital from January 2015 to December 2020 were retrospectively analyzed. The patients were grouped according to clinical diagnosis and results of cold agglutinin test (CAT), direct antiglobulin test (DAT), Ham test and PNH clone detection. The clinical and laboratory characteristics of each group were compared. RESULTS: The patients were grouped as follows: Ham^- CAD/CAS group, CAD/CAS patients negative for Ham test (n=36); Ham⁺ CAD/CAS group, CAD/CAS patients positive for Ham test (n=17); classic PNH group (n=67). Compared with the classic PNH group, the Ham⁺ CAD/CAS group had a higher median age (P =0.024), weaker positivity of Ham test, higher positive rates of CAT and DAT, and lower positive rate of PNH clone detection (all P <0.001). The proportions of patients with splenomegaly and cyanosis in Ham⁺ CAD/CAS group were significantly higher than those in classic PNH group (P =0.002 and P <0.001). Ham⁺ CAD/CAS group displayed lower red blood cell count (RBC) and lactate dehydrogenase (LDH) level (P =0.007 and P <0.001), and higher mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and indirect bilirubin (IBIL) level (P =0.003, P =0.004 and P =0.006) than those in classic PNH group. The levels of serum complement C3 and C4 in Ham⁺ CAD/CAS group were lower than those in classic PNH group (P =0.001 and P <0.001). The positive rate of urinary occult blood in Ham⁺ CAD/CAS group was lower than that in classic PNH group (P =0.010). The clinical and laboratory characteristics of Ham⁺ CAD/CAS group were similar to those of Ham^- CAD/CAS group, except for median age, hemoglobin (Hb), MCHC, mean corpuscular volume (MCV), reticulocyte ratio (Ret), Ham test results, DAT positive types, and proportion of splenomegaly. CONCLUSION Some clinical features and laboratory indicators of CAD/CAS patients with positive results of Ham test are different from those of classic PNH patients, but relatively similar to those of CAD/CAS patients with negative results of Ham test. These results may provide a reference for differential diagnosis of related diseases.
Humans ; Anemia, Hemolytic, Autoimmune/blood* ; Retrospective Studies ; Hemoglobinuria, Paroxysmal/diagnosis* ; Female ; Male ; Coombs Test ; Diagnosis, Differential ; Middle Aged ; Adult