Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

OBJECTIVE: To explore the predictors of hematologic responses of non-transfusion-dependent β-thalassemia (NTDT) to thalidomide. METHODS: 33 patients with NTDT who treated with thalidomide in the 923rd Hospital of the Joint Logistics Support Force of the People's Liberation Army from May 2016 to June 2019 were included in the study. The basic data, hematological indexes, degree of treatment response and genetic background of the patients were analyzed. RESULTS: The baseline fetal hemoglobin (HbF) level of main responders (MaR) was significantly higher than that of minor responders (MiR) and no responders (NR) (P=0.001). And the baseline HbF level was positively correlated with hemoglobin increment after treatment (r=0.601). Genetic background analysis showed that the frequencies of the genotype CT of HBG2 rs7482144 (P=0.031), the genotypes CT/CC (P=0.030) and the minor allele C (P=0.015) of HBS1L-MYB rs9399137, the genotypes AT/TT (P=0.030) and the minor allele T (P=0.028) of HBS1L-MYB rs4895440, the genotypes AG/GG (P=0.030) and the minor allele G (P=0.028) of HBS1L-MYB rs4895441 (P=0.030) in MaR group were significantly higher than those in MiR and NR groups. Comparing the area under the ROC curve (AUC) of the above indicators to predict the main response, the results demonstrated that the predictive value of baseline HbF level was significantly better than rs7482144 (0.91 vs 0.72, P=0.003), rs9399137 (0.91 vs 0.74, P=0.022), rs4895440 (0.91 vs 0.74, P=0.023) and rs4895441 (0.91 vs 0.74, P=0.023), but there was no significant difference in the predictive value between combined single nucleotide polymorphisms (SNPs) (0.91 vs 0.88, P=0.658）and baseline HbF combined SNPs (0.91 vs 0.97, P=0.132). The AUC value of baseline HbF predicting the efficacy of thalidomide as the main response was 0.91, the cut-off value was 27.4%, the sensitivity was 100%, and the specificity was 58.3% (P=0.001). CONCLUSION The hematologic response of NTDT to thalidomide is variable and complex. Compared to genetic background, baseline HbF may be a simpler and more efficient tool to predict efficacy response.
Fetal Hemoglobin/genetics* ; Humans ; MicroRNAs ; Polymorphism, Single Nucleotide ; Repressor Proteins/genetics* ; Thalidomide/therapeutic use* ; beta-Thalassemia/genetics*

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4 CONCLUSION The ITI regimen can raise the ratio of CD4
CD8-Positive T-Lymphocytes ; Humans ; Interferon-alpha ; Interleukin-2 ; Leukemia, Myeloid, Acute/drug therapy* ; Perforin ; Thalidomide

China ; Humans ; Lenalidomide/therapeutic use* ; Multiple Myeloma/drug therapy* ; Thalidomide ; Therapeutic Equivalency

Thalidomide and its derivatives have been used in the treatment of myelodysplastic syndrome (MDS) because of their anti-angiogenic and immunomodulatory effects. In recent years, some studies have found that thalidomide and its derivatives not only showed significant efficacy in lower-risk MDS patients with del (5q), but also showed advantages in non-del (5q) MDS patients. In addition, the discovery of its molecular targets and new substrates makes it possible to develop a new generation of immunomodulatory drugs (IMiDs) and to design IMiDs-based proteolysis-targeting chimeras. In this review, the new progress in mechanism and clinical application of thalidomide and its derivatives were summarized briefly, so as to provide a more scientific, reasonable and effective scheme to the treatment of MDS.
Humans ; Immunomodulating Agents ; Myelodysplastic Syndromes/drug therapy* ; Thalidomide/therapeutic use*

OBJECTIVE: To investigate the efficacy of disease control, survival time and safely in treatment of newly diagnosed multiple mycloma patients with different dose of tenalidomide regimens. METHODS: The clinical data of 116 patients with multiple myeloma from June 2011 to June 2015 were collected and analyzed retrospectively. According to doses of used lenalidomide based on dexamethasone plus lenalidomide regimen 116 patients were divided into 2 groups: conventional dose group (58 cases) and low dose group (58 cases). The ORR, PFS rate and OS rate during followed-up for 3 years, KPS score, RNS score and immunophenotypic index before and after treatment and drug toxicity incidence were compared between 2 groups. RESULTS: The ORR for 2 treatment courses of low dose group was significantly lower than that in conventienal dose group (P＜0.05). The ORR for 4 and 6 treatment courses was not significantly different between 2 groups (P＞0.05). The PFS rate and OS rate during followed-up for 3 years was no significantly different between 2 groups (P＞0.05). The KPS score and RNS score after treatment of low dose group were significantly better than those in conventional dose group and before treatment (P＜0.05). The levels of immunophenotypic index after treatment of both groups were significantly better than those before treatment (P＜0.05). The incidence of III-IV grade hematological toxicity, pulmonary infection and herpes were not significantly different between 2 groups (P＞0.05). The incidence of peripheral neuropathy and gastrointestinal reactions in the low dose group were significantly lower than that in conventional dose group (P＜0.05). CONCLUSION Conventional and low doses of lenalidomide possess the same control effects and survival time for treatment of newly dingnosed patients with multiple myeloma; Despite, the initiation of effects from the low dose lenalidomide is relatively slower, it contributes to raise the overall quality of life and reduce the risk of drug toxicity.
Antineoplastic Combined Chemotherapy Protocols ; Blood Coagulation ; Child ; Dexamethasone ; Humans ; Multiple Myeloma ; Purpura, Schoenlein-Henoch ; Quality of Life ; Retrospective Studies ; Thalidomide ; Thrombelastography ; Treatment Outcome

OBJECTIVE: To evaluate the prognostic value of R-ISS staging system in patients with newly diagnosed multiple myeloma (NDMM). METHODS: The Chinical data of 412 patients with NDMM in our hospital from May 2010 to May 2016 were retrospectively analyzed. All the patients received conventional chemotherapy or thalidomide or bortezomib-based chemotherapy. All the patients with NDMM were divided into R-ISS-Ⅰ, R-ISS-Ⅱ and R-ISS-Ⅲ groups according to R-ISS staging system on the basis of ISS staging system, cytogenetics and LDH level. The progression-free survival (PFS) time and overall survival(OS) of different groups were compared. RESULTS: Among all 412 patients, 76 were rated as R-ISS-Ⅰ, 259 as R-ISS-Ⅱ and 77 as R-ISS-Ⅲ. The median PFS time in 3 groups were 44, 25 and 14 months respectively (P<0.01). The median OS time of the 3 groups were not reached 54 and 25 months respectively (P<0.01). Further analysis also found that statistically different survival associated with different R-ISS groups in the conventional chemotherapy group (P<0.05), bortezomib-based chemotherapy group (P<0.01), thalidomide-based chemotherapy group (P<0.01), transplantation group (P<0.05), different-age stratified group (≤65y P<0.01, 66-75y P<0.01,≥76y P<0.01), damaged renal function group (P<0.01) and extramedullary infiltration group (P<0.01). CONCLUSION PFS and OS in the patients with multiple myeloma were different among three distrinct R-ISS stages. The R-ISS staging system has important clinical significance for the prognosis evaluation of multiple myeloma.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib ; Humans ; Multiple Myeloma ; diagnosis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Thalidomide ; Treatment Outcome

OBJECTIVE: To evaluate the quality of life (QOL) on patients with multiple myeloma(MM) during maintenance therapy and to explore the related factors important for QOL. METHODS: The demography, clinical and laboratorial data of 66 MM patients during maintenance therapy were collected and explored by using a cross-sectional question naire(EORTC QLQ C30 V 3.0). The statistical analysis was performed using Nowegram normal mode(NM) and reference values(RV) of MM patients which were used as control. RESULTS: In comparison with Nowegran normal mode, the scores of general health status, physical function, role function and social function of patients during maintenance therapy were lower than those of normal mode (61.3, 73.9, 65.4 and 65.2 vs 75.3, 89.9, 83.3 and 85.8 respectively), while the scores of constipation and financial difficulty were higher than those of normal mode(16.7 and 44.4 vs 10.7 and 9.7 respectively) (P<0.05). In comparison with reference values, the scores of general health status, emotional and coguitive functions of patients during maintenance therapy were significantly higher than those of reference values(61.3, 81.7 and 84.3 vs 55.7, 71.3 and 78.1 respectively) (P<0.05). In addition, the maintenance therapy yet decreasd the scores of fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss and constipation of patients, but increased the score of financial difficulty of patients (P<0.05). The age of initial diagnosis, serum LDH level, peripheral neuropathy, high ratio of own expense and underlying diseases were main factors affecting the general health status of patients (P<0.05), while the decrease of Hb level, increase of blood Ca level and accompanied genetic changes negatively influence the QOL (P<0.05), while the high culture level showed positive effect on QOL (P<0.05). The choise of drugs for maintenace (therapy thalidomide and bortezomib) not had significant effect on QOL of patients. CONCLUSION The maintenance therapy can improve the QOL of MM patients, the age at initial diagnses, serum LDH level, peripheral neuropathy and high ratio of own expence are the main factors affecting the QOL of MM patients.
Cross-Sectional Studies ; Humans ; Multiple Myeloma ; therapy ; Quality of Life ; Thalidomide

OBJECTIVE: To study the effects of clinicopathological features, laboratory parameters and treatment regimens on the prognosis of patients with multiple myeloma. METHODS: The clinical data of 97 patients with multiple myeloma treated with chemotherapy in Department of Hematology, the 1st Hospital of Hainan Medical College were analyzed retrospectively. The clinicopathological features (age, sex, severe anemia, light chain type, hypoproteinemia, paraplegia, renal injury, amyloidosis, complex karyotype, bone disease classification, Eastern Cooperative Oncology Group (ECOG) physical status score, complete remission, etc.), laboratory parameters (C-reactive protein, lactate dehydrogenase, blood calcium, serum β2 microglobulin, etc.), and treatment schemes (thalidomide maintenance treatment) were recorded. The patients were followed up for 1-60 months, and their total survival time were recorded. A single factor and multiple factors were used to analyze the factors affecting the total and early mortality of the patients. The survival curves were plotted by the Kaplan-Meier method and the survival analysis was carried out by Log-rank test. RESULTS: Among 97 patients, 29 cases (29.90%) achieved complete remission, and 56 cases (57.73%) achineved partial remission. The total effective rate was 87.63% (85/97). At the end of the follow-up, 19 cases (19.59%) died, and 1, 3 and 5 year survival rates were 80.41%, 71.13% and 37.11% respectively. The median overall survival time was 29 (1-60) months. The results of single factor analysis showed that age, hypoproteinemia, severe anemia, paraplegia, renal injury, amyloidosis, complex karyotype, complete remission and thalidomide maintenance therapy were the factors affecting the prognosis of the patients (all P＜0.05). Further multiple factor Logistic regression analysis showed that age and hypoproteinemia, severe anemia, paraplegia, amyloidosis, complex karyotype and thalidomide maintenance treatment were factors affecting the prognosis (P＜0.05). Of the 97 patients, 8 cases died early. The results of single factor analysis showed that amyloidosis and severe anemia were risk factors for early death (all P＜0.05), and further multivariate Logistic regression analysis showed that amyloidosis was an independent risk factor for early death (P＜0.05). CONCLUSION There are many adverse factors affecting the prognosis of patients with multiple myeloma, such as age, hypoproteinemia, severe anemia, paraplegia, amyloidosis, complex karyotype and so on. The risk of early death in the patients with amyloidosis is higher, and salidomide maintenance therapy can help to prolong the life span of the patient.
Amyloidosis ; Humans ; Multiple Myeloma ; Prognosis ; Retrospective Studies ; Thalidomide

OBJECTIVE: To explore the effects of different concentration of pomalidomide on human multiple myeloma cell line MM1.S and the expression of CRBN. METHODS: CCK-8 method was used for detecting inhibition effect of promalidomide on proliferation of MM1.S cells. Apoptosis rate of MM1.S cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Real-time quantitative PCR was used to determine CRBN gene expression level. Western blot was used to detect the effect of pomalidomide on the protein expression of CRBN in MM1.S cells. RESULTS: Pomalidomide has an inhibitory effect on MM1.S cells with time-and dose-dependent manners. Pomalidomide induced apoptosis in MM1.S cells. When the concentration of pomalidomide was 0, 40 and 80 μmol/L, the expression of CRBN gene after the treatment of MM1.S cells for 72 hours was 1.487±0.340, 0.211±0.054 and 0.055±0.005, by using actin as internal refereme. Pomalidomide significantly reduced CRBN protein expression in MM1.S cells. CONCLUSION Pomalidomide can inhibit the proliferation of MM1.S cells and promote its apoptosis. A certain concentration of pomalidomide can reduce the expression of CRBN gene and down-regulate its protein expression in MM1.S cells.
Adaptor Proteins, Signal Transducing ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma ; Thalidomide ; analogs & derivatives