RESUMO
The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD. The current study involved 74 subjects (41 NDMM patients, 33 controls). MBD was assessed by whole-body low-dose computed tomography. sRANKL, periostin, and osteopontin were assayed by commercial ELISA kits. At diagnosis, all tested parameters were significantly higher in NDMM patients compared to the controls (p < 0.0001), correlating with disease stage, MBD grade, and BM infiltration by MPCs. During therapy, the serum levels of all tested proteins decrease, most prominently after autologous stem cell transplantation (p < 0.0001). A significant reduction was established in patients achieving complete and very-good partial response compared to all others (p < 0.05). In conclusion, sRANKL, periostin, and osteopontin reflect MBD severity and could be promising markers for MBD monitoring and the effect of myeloma treatment.
RESUMO
Dickkopf-1 (DKK-1) and sclerostin are essential Wnt/ß-catenin pathway inhibitors, playing an important role in multiple myeloma bone disease (MBD). We aimed to examine the serum DKK-1 and sclerostin variations in newly diagnosed multiple myeloma (NDMM) patients at diagnosis and in the course of therapy, including autologous stem cell transplantation (ASCT). This study included 41 NDMM-patients and 33 controls. MBD was assessed by whole-body low-dose computed tomography. DKK-1 and sclerostin were assayed by commercial ELISA kits. At diagnosis, NDMM-patients revealed significantly higher DKK-1 and sclerostin values (p < 0.0001), showing dependence on disease stage (lowest in ISS-I and highest in ISS-III: p < 0.0012 and p < 0.025, respectively, for both proteins). Bone lesions revealed significant positive correlation with both DKK-1 (p < 0.05) and sclerostin (p < 0.0001). In the course of therapy, significant reduction, more prominent after ASCT, was observed for both parameters in each treatment point compared to the baseline (p < 0.0001). Markedly lower sclerostin (p < 0.01) and DKK-1 (p < 0.05) values were observed in patients with complete and very good partial response compared to those with partial response, stable, or progressive disease. Sclerostin and DKK-1 in NDMM patients reflect the MBD severity and the effect of therapy. Both proteins could represent a novel tool for better disease monitoring and effectiveness of therapy.
RESUMO
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is an aggressive disease with poor outcomes. Despite the incorporation of tyrosine kinase inhibitors (TKIs) in the therapeutic strategies, patients who relapse after chemotherapy plus TKI have poor overall survival (OS) and less chance to proceed to hematopoietic stem cell transplantation (HSCT) which remains the only curative approach. Therefore, new drugs, such as antibody-targeted therapies alone or in combination with TKIs, offer new therapeutic options for those patients. However, the combination of inotuzumab plus ponatinib has limited application. We present a case of a patient affected by Ph + ALL with T315I mutation successfully treated after early relapse with inotuzumab plus ponatinib, followed by allogeneic HSCT and ponatinib maintenance.
