ABSTRACT
Objective:To investigate the therapeutic efficacy and prognosis of multiple myeloma (MM) patients with early relapse and the influencing factors of early relapse.Methods:The clinical data of 164 patients with newly diagnosed MM admitted to Affiliated Hospital of Hebei University from January 2018 to January 2021 were retrospectively analyzed, and 53 cases (32.3%) relapsed at the end of the follow-up. According to the recurrence within 12 months or not, the patients were divided into early relapse group and advanced relapse group; the clinical characteristics, overall response rate (ORR) and overall survival (OS) of both groups were compared. Logistic regression was used to analyze if the following indexes including age, gender, albumin, lactate dehydrogenase (LDH), β 2-microglobulin (β 2-MG), hemoglobin, creatinine, serum calcium, bone marrow plasma cell ratio, extramedullary disease, high-risk fluorescent in situ hybridization (FISH) were the influencing factors of the early relapse. Based on 7 published clinical trials, simplified early relapse MM (S-ERMM) scoring system was constructed to subgroup all relapsed patients. The difference in risk stratification between early relapsed patients and advanced relapsed patients was compared. Results:The median follow-up time of 164 newly diagnosed MM patients was 26 months (12-48 months). Among 53 relapsed MM patients, 24 cases had early relapse and 29 cases had advanced relapse. The ORR of patients with early relapse was decreased compared with that of those with advanced relapse [70.8% (17/24) vs. 89.7% (26/29), χ2 = 3.04, P = 0.001]. The median OS of the early relapse group was shorter than that of the advanced relapse group (24 months vs. not reached, P < 0.001). The OS of patient in the early relapse group with the best response ≥ complete remission (CR), ≥ very good partial remission (VGPR) and ≥ partial remission (PR) during initial induction therapy was worse than that of those in the advanced relapse group, and the differences were statistically significant ( P values were 0.008, 0.011, 0.012, respectively). Multivariate Logistic regression analysis showed low albumin (<35 g/L vs. ≥35 g/L: OR = 1.644, 95% CI 1.076-2.511, P = 0.022) and high LDH (< the upper limit of normal value vs. ≥ the upper limit of normal value: OR = 0.998, 95% CI 0.985-1.011, P = 0.030) were independent influencing factors of early relapse. Among 24 early relapse patients, there were 5 cases (20.8%), 13 cases (54.2%), 6 cases (25.0%), respectively in the S-ERMM scoring system low-risk, middle-risk, high-risk groups; among 29 advanced relapse patients, there were 18 cases (62.1%),9 cases (31.0%), 2 cases (6.9%), respectively in the S-ERMM scoring system low-risk, middle-risk, high-risk groups; the difference in risk stratification of the S-ERMM scoring system between the early relapse group and the advanced relapse group was statistically significant ( χ2 = 9.09, P = 0.003). Conclusions:MM patients with early relapse have poor therapeutic efficacy and prognosis. The prognosis is not affected by the depth of remission to first-line therapy. Low albumin and high LDH may be independent risk factors of MM patients with early relapse.
ABSTRACT
Objective:To explore the efficacy of venetoclax plus azacitidine (VA) in the treatment of patients with newly diagnosed chronic myelomonocytic leukemia (CMML).Methods:The clinical data of 4 newly diagnosed CMML-2 patients treated with VA regimen in the Affiliated Hospital of Hebei University from February 2022 to March 2023 were retrospectively analyzed, and the related literature was reviewed.Results:All 4 CMML-2 patients achieved the effect of ≥ partial bone marrow remission (PMR) after 1 course of treatment, and with the deepened extension of treatment course, the overall response rate and complete remission (CR) rate was 100% and 50%, respectively. In terms of dose adjustment, the dose and usage day of venetoclax were determined by using dynamic frailty assessment and adverse events. Among the 2 patients who achieved CR, 1 patient initially received venetoclax 200 mg for 14 days, and 1 patient received venetoclax 400 mg for 28 days and then the usage reduced to venetoclax 200 mg for 14 days due to hematological adverse events. All 4 patients maintained CR status. The most common grade 3 and 4 adverse events were neutropenia and thrombocytopenia.Conclusions:The first-line application of VA regimen in the treatment of newly diagnosed CMML-2 patients may achieve faster remission and better safety compared with traditional HMA monotherapy.
ABSTRACT
Objective To investigate the role of microRNA-155 (miR-155) on post-transcription regulation of SH2 domain-containing inositol 5'-phosphatase 1 (SHIP1) gene expression in the pathogenesis of acute myeloid leukemia (AML).Methods Quantitative real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of miR-155 and SHIP1 mRNA in the AML patients and controls.miR-155 mimics was transfected into U937cells (U937m) by using X-treme GENE siRNA transfection reagent.Cells without transfection (U937c) and cells with negative transfection (U937mc) were used as controls.RT-PCR was performed to detect the expression of miR-155 and SHIP1 mRNA in these cells.The expression of SHIP1,TAKT and pAKT were detected by Western blot in U937 cells.Apoptosis was studied by flow cytometry (FCM).Results The average level of SHIP1 protein content in 15 samples of patients with AML-M4 or AML-M5 from 30 AML patients was significantly lower compared with that of patients with the other types of AML,and the levels of miR-155 were significantly higher in the same group of patients (P ＜ 0.05).Significantly decreased levels of SHIP1 protein were found in U937m cells compared that of U937c and U937mc (P ＜ 0.05).Significantly decreased rate of apoptosis was observed in U937m cells compared with that of U937mc and U937c.U937m cells also exhibited no alteration in total AKT content,while increased p-AKT levels were found (P＜ 0.05).Conclusion SHIP1 was also a primary target of miR-155 in AML.Overexpression of miR-155 could activate PI3K-AKT pathway to depressing SHIP1 and decrease the apoptosis rate of AML cells.