Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience.

BACKGROUND: Hairy cell leukemia (HCL) is a rare mature B-cell malignancy that is primarily treated with purine analogues. However, relapse remains a significant challenge, prompting the search for alternative therapies. The BRAF V600E mutation prevalent in HCL patients provides a target for treatment with vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study included nine patients with relapsed/refractory (R/R) HCL from six different centers. Patient data included demographics, prior treatments, clinical outcomes, and adverse events. RESULTS: Patients received different treatment regimens between centers, including vemurafenib alone or in combination with rituximab. Despite the differences in protocols, all patients achieved at least a partial response, with seven patients achieving a complete response. Adverse events were generally mild with manageable side effects. The absence of myelotoxic effects and manageable side effects make BRAF inhibitors attractive, especially for patients ineligible for purine analogues or those with severe neutropenia. CONCLUSION: Single agent vemurafenib or in combination with rituximab appears to be a promising therapeutic option for R/R HCL. Further research is needed to establish standardized treatment protocols and to investigate long-term outcomes.

Relapsed refractory multiple myeloma with CNS involvement successfully treated with Elranatamab: first reported case.

Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare and challenging complication associated with poor prognosis and limited treatment options. Emerging T-cell directing therapies, such as bispecific antibodies (bsAbs) and chimeric antigen receptor T cells (CAR-T), have shown remarkable success in treating MM, but their efficacy in CNS involvement remains unclear. Elranatamab, a humanized bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3-expressing T cells, has demonstrated promising results in relapsed refractory MM. However, its efficacy in treating CNS-MM has not been reported. We present a case of a 37-year-old male MM patient with CNS involvement who has been successfully treated with Elranatamab.

Plerixafor in autologous stem cell transplantation: Does it affect engraftment kinetics?

Plerixafor increases stem cell mobilization by reversibly binding to the chemokine receptor CXCR4. In our study, we examined the results of mobilization with plerixafor and granulocyte colony-stimulating factor (G-CSF) and revealed their effects on autologous stem cell transplantation (ASCT) engraftment kinetics. The study included all cases of ASCT performed in the Adult Bone Marrow Transplantation Unit of xxx University between January 2014 and January 2022. It included a total of 300 patients. The total number of CD34 + cells collected was 7.44 ± 4.19 in patients with plerixafor and 9.53 ± 6.09 in patients without plerixafor. The mean neutrophil and platelet engraftment took longer in plerixafor-mobilized patients (neutrophil: 12 ± 4.1 vs. 10.2 ± 2.7 days; platelet: 21.6 ± 13.9 vs. 14.2 ± 5.9 days; p = 0.008 and p = 0.002). The number of febrile neutropenia attacks was significantly higher in plerixafor-mobilized patients (p = 0.04). In the chemo-mobilized patient subgroup, plerixafor-mobilized patients experienced more febrile neutropenia attacks (p = 0.04). The mean time to both neutrophil and platelet engraftment was longer in patients mobilized with plerixafor. In the subgroup of patients with MM, the mean time to platelet engraftment was longer in patients mobilized with plerixafor. Plerixafor and its effect on engraftment kinetics should be evaluated with further studies in a larger population with survival analysis.

A preliminary study: is fibulin 1 a friend or an enemy that needs to be silenced with siRNAs for mesothelioma?

INTRODUCTION: The impaired balance between cell proliferation and cell death, followed the inability to receive the death signals, cells push towards the neoplasia pathway. Fibulin 1 (FBLN1) plays a role as a co-factor in the mechanism of action of a protease such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), which has important roles in angiogenesis, can also act as both tumor suppressor gene (TSG) and an oncogene in the main constituent of the extra-cellular matrix. This preliminary study has investigated the effects of silencing FBLN1 with siRNA on autophagy, proliferation, apoptosis pathways in the MSM cell line. MATERIAL AND METHODS: It was transfected siRNA specific to FBLN1 incubated MSM SPC212 cells, and compared with negative control siRNAs by a real-time polymerase chain reaction. It was determined apoptosis, proliferation, autophagy-related genes in mRNA levels. RESULTS: It was observed that increased anti-apoptosis genes, such as CASP2, CASP7, DDFA, and BCL2, anti-apoptotic gene, reduced APAF1, CASP8. Proliferation induced through while increased ADAMTS1, CDH1, CDH6, CLDN7, CSF3, MMP7, MMP13 genes. Autophagy increased via increasing MAP1LC3B, ATG-16L1 genes while decreased via suppressed ULK1, and ATG7 genes by silencing FBLN1 with siRNAs (p < 0.05). CONCLUSIONS: Proliferation can be induction with silencing of FBLN1 with siRNA in processing mechanism MSM. It was concluded that FBLN1 could be act as pleiotropic on autophagy, and apoptosis pathways in proliferation processing for MSM. Therefore we think that FBLN1 acts like a TSG. FBLN1 can be considered as a targeted treatment option in advanced stage MSM.