Maintenance of efficacy and its predictors after discontinuation of eltrombopag in adults with primary immune thrombocytopenia / 中华血液学杂志

Objective: To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods: Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results: Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion: Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.

Prognostic Significance of Follicular Lymphoma International Prognostic Index 2 (FLIPI2) in Follicular Lymphoma Patients Treated with Rituximab Maintenance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the prognostic significance of Follicular Lymphoma International Prognostic Index 2 (FLIPI2) in FL patients treated with rituximab maintenance.</p><p><b>METHODS</b>A tatol of 140 newly diagnosed FL patients who received Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy in our department were retrospectively analyzed from December 2002 to December 2014. Among 140 patients with FL 122 patients achieved response, from them 56 patients received R maintenance (RM) every 2 months for median 8 times (RM group) while the rest 66 patients did not receive further anti-lymphoma treatment (non-RM group).</p><p><b>RESULTS</b>There was no statistical difference in age, sex, pathologic grading, staging, FLIPI or FLIPI2 between RM and non-RM groups. The 2-year progression-free survival (PFS) of RM and non-RM groups were 89.7% and 77.6% (P=0.043) while the 2-year overall survival were 100% and 98.6% (P=0.131). FLIPI2 is a significant prognostic model either in the total cohort, RM or non-RM groups (P<0.001 all). In subgroup analysis, RM was able to decrease disease progression in low and intermediate-risk group of FLIPI2, while the 2-year PFS of RM and non-RM groups in high-risk group were similar (55.6% vs 46.9%)(P=0.920).</p><p><b>CONCLUSION</b>FLIPI2 presents robust prognostic significance either in RM or OBS patients, the patients in FLIPI2 low and intermediate-risk group may benefite from RM, but the role of RM in high-risk patients should be further to investigate.</p>

Polymorphisms in NF-KB pathway genes and their association with risk of lung cancer in the Chinese population

Objective:To investigate the association of NFKB1 -94 ins/del ATTG, NFKBIA -826C>T and NFKBIA -881A>G polymorphisms with risk of lung cancer in a Chinese population

Methods:Genotyping of the polymorphisms were performed on 1,436 subjects [718 cases and 718 controls] by using PCR-RFLP technique, followed by DNA sequencing

Results:We found a significant risk reduction associated with heterozygous ins/del [OR=0.705, 95% CI=0.566-0.878, P=0.002] and variant del/del [OR=0.342, 95% CI=0.221-0.528, P<0.001] genotypes of the NFKB1 polymorphism. In contrast, the heterozygous and variantgenotypes of theNFKBIA polymorphisms showed association with increased lung cancer risk [NFKBIA -826 CT,OR=1.256, 95%CI=1.004-1.572, P=0.046; TT,OR=1.773, 95% CI=1.131-2.778, P=0.013; NFKBIA -881 AG,OR=1.277, 95% CI=1.023-1.599, P=0.031; GG,OR=1.801, 95% CI=1.169-2.775, P=0.008]. Several genotypic combinations of the three polymorphisms also showed significant association with lung cancer risk. The risk association of NFKB1 polymorphism remained significant when analyses were done according to gender and smoking status [P<0.05]. The significance of NFKBIA risk association was not observed when gender-specific analyses were made [P>0.05], while only NFKBIA -881 GG genotype showed significant risk association among smokers when analyzed according to smoking status [P=0.032]

Conclusions: Polymorphisms in NFKB1 and NFKBIAgenes were associated with risk of lung cancer

Prognostic factors analysis for R-CHOP regimen therapy in diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To reassess the prognostic factors of diffuse large B cell lymphoma (DLBCL) treated with R-CHOP therapy.</p><p><b>METHODS</b>One hundred and twenty five patients were enrolled in this study from Feb. 2000 to Sep. 2006. They received 6 courses of R-CHOP regimen consisting of rituximab 375 mg/ m2, intravenously, d 1; cyclophosphamide 750 mg/m2, bolus intravenously, d 2; doxorubicin 50 mg/m2, bolus intravenously, d 2; vincristine 1.4 mg/m2, bolus intravenously, d 2 and prednisone 60 mg, orally, d 2 - 6. All the patients were evaluated and followed up after the treatment.</p><p><b>RESULTS</b>Eighty six patients (68.8%) achieved complete response (CR), 16 (12.8%) partial response (PR), 11 (12.8%) stable disease (SD) and 12 (9.6%) progressive disease (PD). In univariate analysis, performance status (PS), clinical stage, LDH level, extranodal disease, international prognostic index (IPI) and bulky disease were statistically significantly correlated with the induction of CR; however, only PS, clinical stage and bulky disease remained significant in multi-variate analysis (P = 0.0098, 0.000 and 0.004, respectively). Twenty four month for time to treatment failure (TTF) rate, overall survival (OS) rate, and disease free survival (DFS) rate was (59.7 +/- 5. 3)%, (67.1 +/- 5.6)% and (77.6 +/- 5.8)%, respectively. In univariate analysis, LDH, clinical stage and PS exerted significant effect on TTF and OS rate, but not on DFS rate; age and extranodal disease was not related with TTF, OS and DFS rate. In multi-variate analysis, achieved CR was the only prognostic factor for TTF (P =0.001) and bulky disease had influence on DFS rate. LDH level, PS, and achieved CR was correlated with the OS rate in multi-variate setting (P = 0.002, 0.009 and 0.001 respectively).</p><p><b>CONCLUSION</b>IPI score has its limitation in predicting the prognosis in the R-CHOP era in DLBCL. Other two relevant prognostic factors are bulky disease and achieved CR after 6 courses of treatment.</p>

Present status in studying immunotherapy for acute leukemia and its perspective--Editorial / 中国实验血液学杂志

One of the important approaches for further prolonging remission duration and eradicating minimal residual disease in acute leukemia is immunotherapy. Four kinds of immunotherapy for acute leukemia are under investigation: (1) monoclonal antibodies, among them, Mylotarg (cytotoxic antibiotic calicheamicin linked to CD33 Mab) is given for the treatment of refractory or relapsed acute myeloid leukemia and molecular relapse in acute promyelocytic leukemia with good results, Campath-1H (antiCD52 Mab) is administered in the treatment of prolymphocytic leukemia and Rituximab (anti-CD20 Mab) in B-PLL with high complete remission rates. Other Mabs under preclinical and clinical trials include anti-IL-2 receptor Mab for the treatment of acute T lymphocytic leukemia, anti-220 kD Mab-6G7 for acute leukemias, recombinant immune toxin BL22 (anti-CD22) for hairy cell leukemia and Mabs labeled with radio-isotopes for different types of acute leukemias; (2) adoptive cellular immunotherapy using cytokine-induced killer cell, alloreactive NK cells, allogeneic or autologous leukemic-specific CD8(+) cytotoxic T lymphocytes, and other immune effector cells; (3) cytokines and other immune modulators comprising IL-2, IL-12, GM-CSF, CD40L, FLT-3L and thalidomide and its derivatives; (4) leukemia vaccines of several different formulations including antigen-specific, leukemia cell-based, leukemia antigen-pulsed dendritic cell (DC) and leukemia-derived DC vaccines, the latter two formulations are more attractive. In conclusion, up to now, the most effective example of immunotherapy in acute leukemia is provided by the administration of Mabs, and the majority of other approaches in immunotherapy for acute leukemia although promising, need further studies.

Studies on the effects of lead on the growth and differentiation of hippocampal neural cells as well as the expression of Oct-2 / 中华预防医学杂志

<p><b>OBJECTIVE</b>In order to explore the effects of lead on the growth and development of cultured hippocampal neural cells and on the expression of Oct-2, the II subtype POU domain protein.</p><p><b>METHODS</b>Experiment cell model was established using primary culture of hippocampal neural cells from SD rat embryos. Target cells were exposed to lead acetate in the different concentrations, i.e. 10(-1), 10(0), 10(1), 10(2), 10(3) micromol/L, while the control group was given the same quantity of the culture medium. The immunohistochemistry method was utilized to detect the expressions of Neurofilament (NF) and Glial Fibrillary Acidic Protein (GFAP), the markers for neuron and astrocyte, respectively, and the expression of Oct-2 as well.</p><p><b>RESULTS</b>The results showed that 10 micromol/L lead acetate treatment caused diminishing of neuronal cell body and the decreases of both axon lengths and inter-cellular connections. In addition, 1 micromol/L lead acetate significantly increased the number of GFAP-positive cells compared with the control group (P < 0.05). By image analysis system, 1 micromol/L lead acetate treatment was found to induce a statistically significant increase of the positive area rate concerning Oct-2 expression in hippocampal neurons and astrocytes, while both positive area rate and integral density of light of Oct-2 expression were found to increase markedly in the groups treated by 10 micromol/L lead acetate (P < 0.01).</p><p><b>CONCLUSIONS</b>Lead acetate treatment may contribute to the inhibitions of both growth and differentiation of hippocampus neurons, and to the stimulation of glial cell hyperplasia simultaneously. In addition, the CNS impairments caused by lead is partly correlated with the enhancement of Oct-2 expression.</p>