SummaryTo reducing chemotherapy‐related toxicity, the chemo‐free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty‐one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow‐up of 15.4 months, 2‐year disease‐free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2‐year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2‐year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo‐free induction and early consolidation regimen was efficacious and well‐tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo‐free induction.
Objective. The aim of this study was to explore the relationship between the Hedgehog signaling pathway and drug resistance in multiple myeloma. Methods. The human myeloma cell line RPMI 8266 was taken as the research object. An azithromycin (AZM)-resistant cell line RPMI 8226/R was constructed, and GENT61 was used to block the Hedgehog signaling pathway. Cells were rolled into RPMI 8226/S (S group), RPMI 8226/R (R group), GENT61+RPMI 8226/S (GENT61+S group), and GENT61+RPMI 8226/R (GENT61+R group). The proliferation of cells in each group was assessed, and the expression of patched homolog 1 (PTCH1), zinc finger-containing transcription factors 1 (GLI1), GLI2, hair-division associated enhancer 1 (Hes1), and sonic hedgehog factor (SHH) in each group was detected. Interleukin (IL)-6 and vascular endothelial growth factor (VEGF) were measured. Results. Compared with the S group, the expression levels of PTCH1, GLI2, Hes1, and SHH and the contents of IL-6 and VEGF in the R group were greatly increased, while the expression level of GLI1 was notably decreased ( P < 0.05 ). Compared with the R group, the GENT61+R group greatly increased cell proliferation inhibition. However, the expression levels of PTCH1, GLI2, Hes1, and SHH, and the contents of IL-6 and VEGF were notably decreased, while GLI1 expression levels were greatly increased ( P < 0.05 ). Conclusion. AZM-resistant multiple myeloma was closely associated with the Hedgehog signaling pathway activation, and blocking the Hedgehog signaling pathway can be used as a therapeutic target to improve drug resistance in multiple myeloma.
Background:Traditional chemotherapy regimens are not ideal for the treatment of peripheral T-cell lymphoma(PTCL). Recent clinical data have shown Chidamide,a type of histone deacetylase inhibitors, as a new type of anti-tumor drug, have achieved remarkable results in the treatment of PTCL.Therefore, we performed a systematic literature review and meta-analysis to objectively assess the efficacy and safety for peripheral T-cell lymphoma treated with Chidamide alone or Chidamide combination with chemotherapy. Methods:We searched systematically for studies from the databases of PubMed, Embase, and the Cochrane Library published were searched without language restriction from inception until June 2022.using the following combination of free-text terms linked by Boolean operators: “peripheral T-cell lymphoma”OR“PTCL”OR“angioimmunoblastic lymphoma”OR“anaplastic large cell lymphoma”OR“NK/T-cell lymphoma”AND“Chidamide”. The primary end points were complete remission and overall response rates, adverse events were the secondary end points. Results: A total of 7 clinical trials including newly-diagnosed and relapsed or refractory PTCL patients were analyzed.The overall CR rate was 35.2%(95% CI, 24.2-48%, Figure 2). And the ORR was 65.8%(95% CI, 54.4-75.6%). Thrombocytopenia, anemia, neutropenia were the most common grade 3 and 4 AEs. Conclusion: Chidamide is effective for PTCL, and its efficacy can be increased with the combination traditional chemotherapy.
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