- A randomized placebo-controlled phase II study of clarithromycin or placebo combined with VCD induction therapy prior to high-dose melphalan with stem cell support in patients with newly diagnosed multiple myeloma. [Journal Article]
- EHExp Hematol Oncol 2018; 7:18
- CONCLUSIONS: The study was prematurely stopped due to serious adverse events, in particular serious gastrointestinal complications and septicemia. The response data do not suggest any effect of clarithromycin when added to the VCD regimen. The combination of clarithromycin and bortezomib containing regimens is toxic and do not seem to offer extra anti-myeloma efficacy.Trial registration EudraCT (no. 2014-002187-32, registered 7 October 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002187-32/DK) and ClinicalTrials.gov (no NCT02573935, retrospectively registered 12 October 2015, https://www.clinicaltrials.gov/ct2/show/NCT02573935?term=Gregersen&cntry=DK&rank=9).
- Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14. [Journal Article]
- CPCell Physiol Biochem 2018 Aug 17; 48(6):2517-2527
- CONCLUSIONS: Linc00515 enhanced autophagy and chemoresistance of melphalan-resistant myeloma by directly inhibiting miR-140-5p, which elevated ATG14 level.
- Graft-versus-leukaemia effect post fludarabine, melphalan and alemtuzumab reduced intensity allogeneic stem cell transplantat in HIV-infected patient with acute myeloid leukaemia. [Journal Article]
- BMBone Marrow Transplant 2018 Aug 16
- Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite the advent of highly active antiretroviral treatment, HIV-infected patients ...
Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite the advent of highly active antiretroviral treatment, HIV-infected patients display a remarkable risk for haematological neoplasms such as non-Hodgkin lymphomas, Hodgkin lymphoma and acute leukaemia. Several case series have confirmed the efficacy of the autologous stem cell transplantation for the treatment of non-Hodgkin lymphomas in the HIV setting. Nonetheless, there is a paucity of data for the role of the Allo-HSCT in HIV-infected individuals with haematological malignancies. Herein, we presented the successful long-term outcome of a HIV-infected patient who received reduced intensity conditioned, matched unrelated donor transplant with alemtuzumab as graft-versus-host disease prophylaxis for therapy-related acute myeloid leukaemia. We propose that Allo-HSCT in HIV patients is safe and that alemtuzumab-based conditioning could further work to eradicate HIV in those whose donor is not CCR5 homozygous.
- Comparable outcomes using propylene glycol-free melphalan for autologous stem cell transplantation in multiple myeloma. [Journal Article]
- BMBone Marrow Transplant 2018 Aug 16
- Autologous stem cell transplantation (ASCT) remains a mainstay in the treatment of multiple myeloma (MM). While the procedure is generally safe, toxicities associated with high-dose melphalan conditi...
Autologous stem cell transplantation (ASCT) remains a mainstay in the treatment of multiple myeloma (MM). While the procedure is generally safe, toxicities associated with high-dose melphalan conditioning are common and significantly affect patient quality of life. Recently, a propylene glycol-free melphalan formulation (PG-free MEL; Evomela®) was approved by the United States Food and Drug Administration as an ASCT-conditioning regimen for MM. PG-free MEL is more soluble and stable than propylene glycol-solubilized melphalan (PG-solubilized MEL; Alkeran®). As such, there is speculation that it could decrease toxicities and increase the efficacy of ASCT. We compared the outcomes of patients conditioned with PG-free MEL (n = 216) to PG-solubilized MEL (n = 200) at our institution. The baseline characteristics were similar between the two groups. After Day +0, there were no differences in terms of hospitalizations, neutropenic fevers, intravenous granisetron requirement, World Health Organization grade ≥ 2 oral/esophageal mucositis, intravenous fluid requirement, or narcotic requirement. However, PG-free MEL patients had a higher incidence of diarrhea, which was mostly C. difficile-negative (82% vs. 71%, P = 0.015*). Day + 100 hematologic responses and progression-free survival after ASCT were comparable. In summary, we demonstrate that switching to PG-free MEL did not significantly reduce short-term complications of ASCT or improve outcomes in MM.
- Dose-intensified bendamustine and melphalan (BenMel) conditioning before second autologous transplantation in myeloma patients. [Journal Article]
- HOHematol Oncol 2018 Aug 15
- Consolidation in myeloma patients with high-dose melphalan chemotherapy (Mel HDCT) and autologous transplantation (ASCT) is standard of care since more than two decades. However, definite cure remain...
Consolidation in myeloma patients with high-dose melphalan chemotherapy (Mel HDCT) and autologous transplantation (ASCT) is standard of care since more than two decades. However, definite cure remains exceptional despite intensive treatment, and improving effectiveness of HDCT remains an unmet clinical need. Combining intensified bendamustine with melphalan may represent an option. We analyzed safety and efficacy of combining dose-intensified bendamustine (200 mg/m2 on days -4/-3) with high-dose melphalan (100 mg/m2 on days -2/-1) before a 2nd (tandem) ASCT in adverse risk myeloma patients after Mel HDCT/ASCT1. Twelve patients received BenMel conditioning before ASCT2 because of high-risk cytogenetics and/or failure to achieve complete remission (CR) after Mel HDCT/ASCT1. Comparing Mel HDCT/ASCT1 and BenMel HDCT/ASCT2, we observed no differences in hematologic recovery and tolerance. Acute renal injury after BenMel conditioning occurred in three (25%) patients, but was reversible in all patients, and there were no treatment related deaths. CR rates were increasing from 42% after Mel/ASCT1 to 75% after BenMel/ASCT2. PFS one year after ASCT2 was 67% and OS was 83%. These data suggest that dose-intensified bendamustine with melphalan conditioning is safe and warrants a prospective randomized comparison to standard melphalan HDCT in myeloma patients.
- Trifascicular block as primary presentation of the cardiac amyloidosis; A rare case report. [Journal Article]
- AAARYA Atheroscler 2018; 14(2):101-104
- CONCLUSIONS: It shows that rapid diagnosis of AL amyloidosis can enhance the prognosis. Applying an optimal strategy for the treatment leads to effective therapy, too.
- New role of hypoxia in pathophysiology of multiple myeloma through miR-210. [Journal Article]
- EJEXCLI J 2018; 17:647-662
- Bone is one of the most common sites of complication in multiple myeloma (MM) progression and bone remodeling gets definitively perturbed during disease progression. Hypoxia and miR-210 play an impor...
Bone is one of the most common sites of complication in multiple myeloma (MM) progression and bone remodeling gets definitively perturbed during disease progression. Hypoxia and miR-210 play an important role in hematological malignancies. In an attempt to elucidate the specificity of the pathways of hypoxia and miR-210 in suppression of osteoblastic differentiation in MM patients, we examined the effect of miR-210 and hypoxia on expression of important cytokines and genes of myeloma cells. Differentiation of BM-MSCs towards osteoblastic cells in response to microvesicles (MVs) was also investigated. Finally, we proposed a molecular model on how HIF-1α may promote bone lesions in MM patients. To validate the effect of miR-210 and HIF-1α on targeted genes, the shRNA of HIF-1α and off-hsa-miR-210 were transfected into RPMI-8226 cells. BM-MSCs were cultured in osteoblastic inducer and 50 µg/mL of MVs derived from both hypoxic and normoxic myeloma cells. We designed an in vitro study to establish the effects of HIF-1α and miR-210 on the crosstalk between MM and osteoblasts. We here showed that hypoxia-induced miR-210 increased the mRNA expression of VLA-4, CXCR4, IL-6 and TGF-β in myeloma cells. MiR-210 is mandatory for the hypoxia-increased resistance of MM cells to melphalan. Moreover, MVs derived from hypoxic myeloma cells substantially decreased osteoblast differentiation. Considered comprehensively, our findings explain one of the reasons of bone loss that occurs at the sites of MM and a nascent crosstalk model in MM pathogenesis.
- Cryopreserved versus non-cryopreserved peripheral blood stem cells for autologous transplantation after high-dose Melphalan in multiple myeloma: comparative analysis. [Letter]
- BMBone Marrow Transplant 2018 Aug 14
- Combined high-dose intra-arterial and intrathecal chemotherapy for the treatment of a case of extraocular retinoblastoma. [Journal Article]
- PBPediatr Blood Cancer 2018 Aug 13; :e27385
- Patients with retinoblastoma and central nervous system (CNS) involvement are rarely curable with available treatments. We designed a high-dose intra-arterial regimen targeting the ophthalmic artery ...
Patients with retinoblastoma and central nervous system (CNS) involvement are rarely curable with available treatments. We designed a high-dose intra-arterial regimen targeting the ophthalmic artery and chiasm combined with intrathecal chemotherapy to treat a 4-year-old patient with retinoblastoma metastasized to the CNS. After three cycles of this regimen, including carboplatin, melphalan, and intrathecal topotecan, a partial response of the orbital tumor mass and chiasmatic lesion, and complete response in the cerebrospinal fluid and bone marrow were achieved. This new treatment strategy may be explored as a treatment component for patients with overt extraocular retinoblastoma and CNS dissemination.
New Search Next
- High-dose melphalan and stem cell transplantation in systemic AL amyloidosis in the era of novel anti-plasma cell therapy: a comprehensive review. [Journal Article]
- BMBone Marrow Transplant 2018 Aug 08
- The application of high-dose melphalan and autologous stem cell transplant (SCT) to systemic AL amyloidosis (AL) has evolved over the past two decades and remains an important component of therapy fo...
The application of high-dose melphalan and autologous stem cell transplant (SCT) to systemic AL amyloidosis (AL) has evolved over the past two decades and remains an important component of therapy for patients with AL. The era of novel agents created the opportunity to provide well -tolerated induction and post-SCT consolidation to AL patients eligible for SCT and the current availability of new monoclonal antibody therapies will likely provide additional opportunities to enhance the outcomes with SCT. In this review, we touch on the history of SCT for AL and examine the data on eligibility, mobilization, induction, risk-adapted melphalan dosing, engraftment, consolidation and maintenance, and long-term outcomes with SCT. We note that induction therapy may deprive some patients of the opportunity to proceed to SCT but is likely needed if the marrow plasmacytosis is > 10%, that risk-adapted melphalan dosing continues to be relevant, and that post-SCT consolidation improves the complete response rate as well as long-term overall survival. The importance of baseline cytogenetics is also highlighted, particularly for patients whose clonal plasma cells are ≤ 10% but harbor the t(11;14), because they may have improved survival with SCT.