[Clinical Observation of Venetoclax Combined with Demethylating Agents on the Treatment of Relapsed/Refractory Acute Myeloid Leukemia].

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION: VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.

[The Clinical Features of Metabolic Syndrome in Receptors of Hematopoietic Stem Cells].

OBJECTIVE: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION: The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.

Decitabine Compared With Conventional Regimens in Older Patients With Acute Myeloid Leukemia: A Meta-Analysis.

BACKGROUND: The incidence of acute myeloid leukemia (AML) increases with age. The overall prognosis remains poor for older patients. Studies on the efficacy of decitabine, an epigenetic agent, in older patients with AML have reported conflicting results. MATERIALS AND METHODS: For this meta-analysis, we performed a literature search and collected 38 studies (including 3298 patients with AML) to evaluate the role of decitabine in elderly patients with AML. We used complete response (CR) or overall response (OR) rate as indicators of effectiveness. RESULTS: Patients treated with decitabine have a higher CR/OR rate than those treated with low-dose cytarabine (CR, 2.60; 95% confidence interval [CI], 1.64-4.14; OR, 4.88; 95% CI, 1.98-12.04) or CAG/HAG (low-dose epirubicin and cytarabine with granulocyte stimulating factor/low-dose homoharringtonine and cytarabine with granulocyte stimulating factor) regimens (CR, 2.53; 95% CI, 1.98-3.23; OR, 2.89; 95% CI, 2.24-3.73). However, patients treated with decitabine had a CR rate equivalent to those treated with intensive chemotherapy (CR, 0.58; 95% CI, 0.28-1.22; P = .15). Use of decitabine in combination with other regimens resulted in a higher CR/OR rate than did use of decitabine alone (P < .001); there was no significant difference in infection rates and early death rates (P > .05). CONCLUSION: The findings presented in this article show that decitabine is effective and safe for the treatment of older patients with AML.

[Change and significance of Th22 cells in patients with aplastic anemia].

OBJECTIVE: To explore the proportion of Th22 cells in peripheral blood of patients with aplastic anemia (AA) and evaluate its significance. METHODS: From January 2011 to June 2012, a total of 47 AA patients were recruited and divided into 4 groups: severe aplastic anemia (SAA) pre-therapy (group A, n = 11), non-severe aplastic anemia (NSAA) pre-therapy (group B, n = 12), SAA post-therapy (group C, n = 12), NSAA post-therapy (group D, n = 12) and healthy donor controls (n = 12). The proportion of Th22 cells in peripheral blood of each group was evaluated by flow cytometry. The cytokines interleukin-22 (IL-22), transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by ELISA. And the level of IL-22 mRNA was examined by reverse transcription-PCR (RT-PCR). RESULTS: The percentage of Th22 cells and the level of IL-22, TNF-α, IL-6 and IL-22 mRNA in group A (4.3% ± 1.4%, (57 ± 17) ng/L, (497 ± 123) ng/L, (323 ± 88) ng/L, 1.65 ± 0.51) and group C (2.6% ± 0.6%, (34 ± 10) ng/L, (314 ± 79) ng/L, (187 ± 45) ng/L, 0.92 ± 0.28) were significantly higher than that in control group (1.2% ± 0.3%, (19 ± 6) ng/L, (228 ± 50) ng/L, (134 ± 26) ng/L, 0.47 ± 0.09,all P < 0.05). The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group C (all P < 0.05). NSAA patients had similar results. The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group B (all P < 0.05). But the level of TGF-ß in groups A and C were significantly lower than that in control group ((3.4 ± 1.1) and (5.8 ± 1.7) vs (9.7 ± 2.8) ng/L, P < 0.05). And the level of TGF-ß in group A was lower than that of group B (P < 0.05). CONCLUSIONS: The number of Th22 cells is elevated in AA patients. Th22 cells may be positively correlated with the development of AA. And a higher level of TNF-α, IL-6 and a lower level of TGF-ß promote the differentiation of Th22 cells.

[Change of Th22 cells in peripheral blood of patients with primary immune thrombocytopenia and clinical implication].

AIM: To investigate the change of Th22 cells in the peripheral blood of the patients with primary immune thrombocytopenia (ITP) and evaluate the significance of Th22 cells in ITP. METHODS: The proportion of Th22 cells in the peripheral blood of ITP patients before therapy (group 1), ITP patients in complete response after therapy (ITP-CR, group 2) and healthy donors (group 3) was evaluated by flow cytometry. The cytokines IL-22, TGF-ß, TNF-α and IL-6 of each group were measured by ELISA. The level of IL-22 mRNA of each group was examined by RT-PCR. RESULTS: The proportion of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in group l and group 2 were significantly higher than those in group 3 (P<0.01). The proportion of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in group 2 were lower than those in group 1(P<0.05). But the level of TGF-ß in group l [(3.27±1.02) ng/L] and group 2 [(5.41±1.69) ng/L] was significantly lower than that in group 3 [(9.65±2.78) ng/L] (P<0.01), and the level of TGF-ß in group 1 was lower than that in group 2 (P<0.05). CONCLUSION: In ITP patients, the number of Th22 cells and the levels of TNF-α and IL-6 increase, and the level of TGF-ß decrease.

[Apoptosis of Kasumi-1 cells induced by puerariae radix flavones and its molecular mechanism].

OBJECTIVE: To explore the effects and the molecular mechanism of puerariae radix flavones (PRF) on acute myeloid leukemia cell line Kasumi-1 cells in vitro. METHODS: Kasumi-1 cells treated by PRF for 48 hours were observed with Wright's and Hoechst 33258 dying. The apoptotic cells were analyzed by flow cytometry with AnnexinV/PI staining. The expression levels of bcl-2, Bim and Caspase-3/-8/-9 protein were assayed by Western blot and the AML1-ETO fusion gene was detected by real-time polymerase chain reaction. RESULTS: PRF could induce Kasumi-1 cells to apoptosis effectively. The proportion of apoptotic cells in 50, 200 and 500 µg/ml PRF treatment groups were (14.1 ± 0.8)%, (17.7 ± 1.3)% and (32.4 ± 1.4)%, respectively, and significantly higher than that of control \[(7.8 ± 0.7)%\]. The relative expression levels of the anti-apoptotic Bcl-2 protein were 0.85 ± 0.05, 0.62 ± 0.07 and 0.43 ± 0.05; the apoptotic Bim protein were 0.21 ± 0.06, 0.39 ± 0.04 and 0.75 ± 0.05; the caspase-3 and caspase-9 were 0.92 ± 0.04, 1.21 ± 0.07, 1.33 ± 0.04 and 0.35 ± 0.05, 0.53 ± 0.03, 0.69 ± 0.07, respectively. Compared to the blank control group, all these changes were significant (P < 0.01). Nevertheless, nearly no changes could be observed on the expression level of AML1-ETO fusion gene and caspase-8 protein. CONCLUSION: Apoptosis of Kasumi-1 cells induced by PRF might correlate to the down-regulation of Bcl-2 protein expression and the activation of caspase-3 and caspase-8 protein in the cells. It seemed that all these effects had no relationship with the AML1-ETO fusion gene.

[The significance of change of Th22 cells in patients with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the proportion of Th22 cells in peripheral blood of patients with acute lymphoblastic leukemia (ALL) and evaluate its significance. METHODS: The proportions of Th22 cells in peripheral blood of B-ALL and T-ALL patients before therapy (group 1), B-ALL and T-ALL patients in complete remission (ALL-CR, group 2) and healthy donors (group 3) were evaluated by flow cytometry. The cytokines IL-22, TGF-ß, TNF-α and IL-6 in peripheral blood of each group were measured by enzyme-linked immunosorbent assay (ELISA). The levels of IL-22 mRNA in peripheral blood mononuclear cells of each group were examined by reverse transcription-PCR (RT-PCR). RESULTS: The percentages of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in B-ALL and T-ALL patients before therapy were (0.44 ± 0.10)%, (10.9 ± 3.4) ng/L, (110.7 ± 26.5) ng/L, (60.2 ± 13.8) ng/L, 0.17 ± 0.04 and (0.46 ± 0.11)%, (11.2 ± 3.5) ng/L, (114.6 ± 27.0) ng/L, (58.7 ± 12.4) ng/L, 0.19 ± 0.04, respectively; Which in B-ALL and T-ALL patients in complete remission were(0.59 ± 0.15)%, (14.3 ± 4.1) ng/L, (142.5 ± 32.7) ng/L, (83.7 ± 18.9) ng/L, 0.25 ± 0.06 and(0.60 ± 0.15)%, (14.6 ± 4.3) ng/L, (140.4 ± 31.4) ng/L, (81.4 ± 18.2) ng/L, 0.26 ± 0.06, significantly lower than those in healthy donors \[(1.24 ± 0.31)%, (19.7 ± 6.6) ng/L, (238.3 ± 50.4) ng/L, (138.0 ± 27.1) ng/L, 0.49 ± 0.09\] (P < 0.01). The percentages of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in group l were lower than those in group 2 (P < 0.05), there was not significant difference between B-ALL and T-ALL (P > 0.05). But the levels of TGF-ß in B-ALL and T-ALL patients before therapy \[(30.6 ± 8.2) ng/L, (31.4 ± 8.8) ng/L\] and in complete remission \[(24.2 ± 5.8) ng/L, (25.1 ± 6.1) ng/L\] were significantly higher than those in group 3\[(9.6 ± 2.8) ng/L\] (P < 0.01). However, the level of TGF-ß in group 1 was higher than that of group 2 (P < 0.05), there was not significant difference between B-ALL and T-ALL (P > 0.05). CONCLUSION: Both the number and function of Th22 cells reduced in ALL patients. Th22 cells might be negatively correlated with ALL progression. The lower levels of TNF-α and IL-6, and overexpression of TGF-ß in ALL patients might suppress the differentiation of Th22 cells.

[Regulations of function and maturation of plasmacytoid dendritic cells from primary immune thrombocytopenia patients by triptolide].

OBJECTIVE: To explore the mechanism of immunomodulatory activity of triptolide on primary immune thrombocytopenia (ITP)patients-derived plasmacytoid dendritic cells (pDCs). METHODS: pDCs in peripheral blood of ITP patients before therapy (group 1), ITP patients in complete response (ITP-CR, group 2) and healthy donors (group 3) were sorted by flow cytometry, then incubated with triptolide at 0, 5, 10 or 30 µg/L. After 24 hours, we collected the supernatants and then detected the concentrations of IFN-α, IL-6 and TNF-α using ELISA. After 5 days, the cultured cells were collected and CD11c, CD80 and CD86 expressions of myeloid dendritic cells (mDCs) were analyzed by flow cytometry, the morphology of mDC was observed by light microscope and electron microscope. RESULTS: After incubation with triptolide at 10 µg/L, the levels of IFN-α, IL-6 and TNF-α in group 1 \[(451.32 ± 85.77) ng/L, (105.68 ± 23.85) ng/L and (135.78 ± 30.62) ng/L\] and group 2 \[(391.71 ± 72.49) ng/L, (84.73 ± 17.77) ng/L and (108.16 ± 23.21) ng/L\] were significantly higher than those in group 3 \[(335.51 ± 67.54) ng/L, (73.62 ± 21.82) ng/L and (95.58 ± 32.85) ng/L\] (all P < 0.05); the levels of IFN-α, IL-6 and TNF-α in group 1 were significantly higher than those in group 2 (all P < 0.05) in a dose-dependent manner (P < 0.05). CD11c, CD80 and CD86 expressions of mDC in group1 and group 2 were significantly higher than those in group 3 (all P < 0.05); CD11c, CD80 and CD86 expressions of mDC in group 1 were significantly higher than those in group 2 (all P < 0.05) also in a dose-dependent manner (all P < 0.05). Triptolide could inhibit pDCs from differentiation into mDCs, the latter displayed more immature morphology than untreated-pDCs. CONCLUSION: Triptolide could decrease the immune function of pDCs from ITP, inhibit pDCs from differentiation and maturation.