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*

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 evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10(9)/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions: RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.
Danazol ; Drug Combinations ; Humans ; Nitriles ; Pilot Projects ; Prednisone ; Primary Myelofibrosis/drug therapy* ; Pyrazoles/therapeutic use* ; Pyrimidines ; Thalidomide/therapeutic use* ; Treatment Outcome

Objective: To explore the effect of combination regimen of interferon alpha-1b, interleukin-2 and thalidomide (ITI regimen) on minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) who were in hematologic remission but MRD-positive. Methods: Eighteen patients (17 from Tumor Hospital of Zhengzhou University and 1 from the First People's Hospital of Pingdingshan City) with AML admitted from July 2016 to June 2018, who were in hematologic remission but MRD-positive were treated with different doses of ITI regimen, and the MRD levels were monitored. Results: Among 18 patients who received a conventional dose of ITI regimen for 1 to 2 months, 7 patients had undetectable MRD, 3 had significant decrease in MRD levels, 3 had elevated MRD level and had hematologic recurrence. Three patients with elevated MRD level received a higher dose of ITI regimen, 2 of them turned to MRD negative and the other 1 patient had decreased MRD level. The total response rate was 72.2%, and the response rate in patients with MRD > 1.0% was 57.1% (4/7) , and that of patients with MRD < 1.0% was 81.8% (9/11) , respectively. Conclusion: The ITI regimen can reduce the MRD level of patient with AML who are in hematologic remission but MRD-positive. The therapeutic effect could be improved by a higher dose administration of ITI regimen, and therapeutic effect may be negatively correlated with MRD level before treatment.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Flow Cytometry ; Humans ; Interferon-alpha ; Interleukin-2 ; Leukemia, Myeloid, Acute/drug therapy* ; Neoplasm, Residual ; Prognosis ; Remission Induction ; Thalidomide

Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.
Animals ; Chloroquine ; toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Etanercept ; therapeutic use ; Ganglia, Spinal ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pruritus ; chemically induced ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Receptors, Tumor Necrosis Factor, Type I ; deficiency ; genetics ; Receptors, Tumor Necrosis Factor, Type II ; deficiency ; genetics ; Signal Transduction ; drug effects ; Skin ; drug effects ; metabolism ; Spinal Cord ; drug effects ; metabolism ; Thalidomide ; therapeutic use ; Time Factors ; Tumor Necrosis Factor-alpha ; adverse effects ; genetics ; metabolism ; p-Methoxy-N-methylphenethylamine ; toxicity

OBJECTIVE: To evaluate the therapeutic effect and adverse reactions of the maintenance therapies with Thalidomine or Bortezomib in the patients with newly diagnosed multiple myeloma (MM), so as to provide a reference for clinical treatment. METHODS: A retrospective analysis was conducted to compare the progression-free survival (PFS), overall survival (OS) and adverse reaction rate of 23 MM patients received the maintenance therapies of Bortezomib and of 68 MM patients received maintenance therapy of Thalidomine. RESULTS: The maintenance therapy with Bortezomib could extend the PFS of MM patients as compared with Thalidomine (PFS rate of patients on the maintenance therapy of Bortezomib in 12th, and 24th month was 100%, 88.89%, and that of Thalidomine-treated group was 72.31%, 47.54%). What's more, some specific patients could get better 2-year PFS rate in Bortezomib group than that in Thalidomine group, such as older than 65 years old, after autologous hematopoietic stem cell transplantation(ASCT), having genetic changes, extramedullary lesions, poor renal function, low serum free light chain ratio, high β2-MG, anemia, high LDH, VGPR of induction and consolidation therapy. The OS rate of Bortezomib on 18th, 24th and 30th month was 100%, 88.89%, 80% verus 91.52%,83.63%,72.90% of the group with thalidemide at the same time. As for 2-year OS rate, the Bortezomib group was higher than Thalidomine without statistical differences. However, the patients such as older than 65 years old, poor renal function and with extramedullary lesions, would also get higher 2-year OS rate from Bortezomi. Bortezomib and thalidomide could cause bone marrow suppression, peripheral neuritis and other adverse reactions. CONCLUSION The efficacy of maintenance therapy with Bortezomib is superior to thalidomide. As a conclusion, bortezomib is a better option for maintenance therapy of MM patient.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; Bortezomib ; administration & dosage ; Disease-Free Survival ; Humans ; Multiple Myeloma ; drug therapy ; Pyrazines ; Retrospective Studies ; Thalidomide ; administration & dosage ; Transplantation, Autologous ; Treatment Outcome

Myelofibrosis, a clonal stem-cell disorder which is difficult to cure, The treatment for most of patients is conservative treatment, but the treatment effect is not ideal. Lenalidomide as a novel immunomodulator in the treatment of blood diseases showed good results in recent years, Its studies have shown that lenalidomide in myelofibrosis also showed a certain effect. As companed with single drug lenalidomide, the thalidomide has a higher response rate, clinical symptoms improved significantly. Ruxolitinib, JAK2 inhibitor, combined with lenalidomide not only can improve the quality of life of patients, but also extend the survival of patients. In addition, lenalidomide combined with prednisone for the treatment of bone marrow fibrosis is more effective and more safe, lenalidomide can significantly improve the clinical symptoms of patients, especially anemia, and prednisone can reduce the hematologic toxicity of lenalidomids. The purpose of this review is to evaluate the efficacy and safety of lenalidomide in the treatment of myelofibrosis, and focuses on the newest clinical research and application progress of lenalidomide for myelofibrosis.
Humans ; Lenalidomide ; therapeutic use ; Prednisone ; Primary Myelofibrosis ; drug therapy ; Quality of Life ; Thalidomide

Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Interferons ; therapeutic use ; Interleukin-2 ; therapeutic use ; Leukemia, Myeloid, Acute ; drug therapy ; Recurrence ; Remission Induction ; Thalidomide ; therapeutic use