1,721,358 research outputs found
Steps towards a multiple myeloma cure?
Full text linkMultiple myeloma survival has increased in last 20 years because of new treatments, better clinical management due to novel diagnostic tools such as imaging, and better understanding of the disease, biologically and genetically. Novel drugs have been introduced that act with different therapeutic mechanisms, but so have novel therapeutic strategies such as consolidation and maintenance after autologous stem cell transplant. Imaging (such as PET-CT and MRI) has been applied at diagnosis and after therapy for minimal residual disease monitoring. Multiparametric flow and molecular NGS may detect, with high-sensitivity, residual monoclonal plasma cells in the bone marrow. With this novel therapeutic and biological approach, a considerable fraction of multiple myeloma patients can achieve durable remission or even MGUS-like regression, which can ultimately lead to disease disappearance. The big dogma, “Myeloma is an incurable disease”, is hopefully fading
Immunotherapy in Chronic Myeloid Leukemia
No full textImatinib has become standard therapy for all phases of chronic myeloid leukemia (CML). However, data generated by monitoring several thousands of patients worldwide suggest that although imatinib is highly active against the differentiated mass of CML cells, it probably fails to eradicate all residual leukemia cells, even in the best responders. This is supported by several lines of evidence: (i) despite the fact that more than 80% of previously untreated patients achieve a complete cytogenetic remission (CCgR), only a minority of patients remain durably negative when tested by real-time quantitative polymerase chain reaction (RT-PCR) for BCR-ABL transcripts (1); (ii) even patients treated with imatinib who achieve a complete molecular response (CMolR) usually return to Philadelphia (Ph)-positivity if the drug is stopped (2); and (iii) studies performed in vitro suggest that primitive Ph-positive progenitors or stem cells are relatively insensitive to imatinib (3) and the persistence of BCR-ABL-positive precursors in complete cytogenetic response (CCyR) patients, despite continued imatinib therapy, has been recently documented (4). At least theoretically, any amount of residual disease under imatinib treatment could provide the basis for the emergence of Ph-positive sub-clones bearing mutations in the BCR-ABL kinase domain, which are associated with various degrees of resistance to this agent (5). For all these reasons recent CML guidelines recommend that alternative strategies should be considered in early chronic phase (CP) patients with suboptimal response or failure to adequate imatinib (6). Less straightforward is the management of residual “molecular” disease found in a great majority of patients. At present, these patients usually continue to receive standard doses of imatinib, and their response is monitored by RT-PCR and cytogenetics. Although we do not yet know the impact on survival of such minimal residual disease (MRD) (7), it appears prudent to develop specific additional therapies that could complete the excellent work of imatinib. The ultimate and ambitious aim of a supplementary treatment would be the attainment of a “true cure” of CML (eradication of all leukemia cells) instead of an “operational cure” (persistence of minimal amount of leukemia cells), which may be achieved with imatinib alone. One such strategy is to exploit the fact that CML is a disease known to be susceptible to immune attack. The most striking proof of this is the fact that until now, a “cure” (defined as continuous negativity for BCR-ABL by PCR) for CML patients is probably achieved only by the graft-versus-leukemia (GvL) effect following allogeneic stem cell transplantation or donor lymphocytes infusion (8), although it remains formally unproven that undetectability of BCR-ABL is equivalent to eradication of the malignant clone. Although the GvL effect is to a great extent due to major and minor HLA mismatches between donors and recipients, some experimental data suggest that CML-specific donor T lymphocytes could be the key to long-term control or even eradication of residual leukemia cells (9). Additionally, the activity of interferon-α (IFN-α), a biological modifier widely used for CML in the pre-imatinib era, could be partly due to an immune-mediated effect, and a possible role of this agent in the context of MRD surviving imatinib will be discussed. CML offers a unique opportunity to test the efficacy and feasibility of immunotherapeutic strategies, as currently most patients achieve very pronounced responses furnishing an ideal situation for immunotherapy in a disease known to be responsive in principle to immune attack. Immunotherapy approaches currently under evaluation include active specific immunotherapies (vaccines) and nonspecific immunotherapies [IFN-α, interleukin-2 (IL-2), granulocyte-macrophage colony stimulating factor (GM-CSF), and other immunostimulators]
Cutaneous myeloma and bortezumib
No full textWe read with great interest the recent paper by Siniscalchi et al. [1] in which they described a 69-year-old woman with a cutaneous relapse of multiple myeloma (MM) after six cycles of MPT regimen (melphalan, prednisone, and thalidomide) and thalidomide maintenance therapy. They reported a complete response after four cycles of bortezomib (B) and dexamethasone, suggesting a possible employment in cutaneous plasmacytomas
CD26/DPP-4 in Chronic Myeloid Leukemia
No full textCD26 expression is altered in many solid tumors and hematological malignancies. Recently, it has been demonstrated that it is a specific marker expressed on LSCs of CML, both in BM and PB samples, and absent on CD34+/CD38− stem cells in normal subjects or on LSCs of other myeloid neoplasms. CD26+ LSCs have been detected by flow-cytometry assays in all PB samples of Chronic-Phase CML patients evaluated at diagnosis. Additionally, it has been demonstrated that most CML patients undergoing Tyrosine Kinase Inhibitors (TKIs) treatment still harbored circulating measurable residual CD26+ LSCs, even when displaying a consistent deep molecular response without any significant association among the amounts of BCR-ABL transcript and CD26+ LSCs. Preliminary data of our Italian prospective multicenter study showed that CML patients with a poorer response presented with a higher number of CD26+ LSCs at diagnosis. These data confirmed that CD26 is a specific marker of CML and suggest that it could be considered for the monitoring of therapeutic responses
Is there any role left for p210-derived peptide vaccines in chronic myeloid leukemia?
No full textDespite the fact that the idea of educating the immune system against tumor-specific antigens by using an active immunotherapy such as a vaccine has been pursued by many researchers, consistent clinical data on the effectiveness of anticancer vaccines have not yet been produced. Lack of tumor specific targets, low immunogenicity of the tumorassociated antigens, inappropriate vaccine formulation and large tumor burdens of the vaccinated patients are some of the most frequent reasons accounting for the current disappointing results
with anticancer vaccines
Is bendamustine plus rituximab a suitable option for rituximab-refractory duodenal-type follicular lymphoma?
Full text linkDuodenal follicular lymphoma (DFL) is a specific variant of FL, predominantly localized in the second portion of the duodenum and often represents an incidental finding, even if some cases can present with abdominal pain. Overall prognosis is excellent, with high progression-free survival (PFS) and overall survival (OS) (1). Watch&wait, rituximab or radiotherapy (RT) should represent a suitable first-line therapy with long-term efficacy (1-4). However, a small proportion of rituximab- refractory patients exists. Here we would like to report a rituximab-refractory DFL successfully treated with rituximab and bendamustine (BR)
Hyperlipidemia in a myeloma patient after bortezomib treatment
No full textWe read with great interest the article by Gotoh et al. [1], inwhich they reported about a multiple myeloma patient refractory to VAD therapy who developed hyperlipidemia (total cholesterol, TC, 388 mg/dl and triglycerides, TG, 411 mg/dl) and multiple lipoma after two courses of Bortezomib, dexamethasone. We would like to share some experience and raise few questions about it
Tp53 disruptions: Is there a marker of poor prognosis in chronic lymphoproliferative disorders?
Full text linkTherapeutic advancements in multiple myeloma
Full text linkCentral nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM. Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease. © 2014 Bentham Science Publishers
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