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Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma.

Molecular remission (MR) is associated with improved outcome in mantle cell lymphoma (MCL). If MR is not achieved, patients are at high risk of relapse. We retrospectively describe the molecular and clinical follow-ups of 4 patients with molecular relapses (M-rels) who were treated with rituximab. The 4 patients received rituximab-supplemented, high-dose sequential chemotherapy and autologous stem cell transplantation as induction treatment and achieved clinical remission and MR. M-rel was defined as polymerase chain reaction (PCR) positivity in 2 consecutive samples in the absence of clinical

Novel bicistronic retroviral vector expressing gamma-glutamylcysteine synthetase and the multidrug resistance protein 1 (MRP1) protects cells from MRP1-effluxed drugs and alkylating agents.

We have constructed two retroviral vectors, one expressing multidrug resistance protein 1 (MRP1) alone (SF91MRP) and the other expressing MRP1 and gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme of glutathione biosynthesis (SF91GCS-MRP). We have utilized the hybrid FMEV (Friend mink cell focus-forming/murine embryonic stem cell virus) backbone, previously shown to be efficient in early hematopoietic cells, even when coexpressing two distinct genes. In SF91GCS-MRP, the cDNAs were combined via an internal ribosomal entry site (IRES) sequence from poliovirus, resulting in

Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with transplant-ineligible multiple myeloma: a network meta-analysis.

BACKGROUND: Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-lin … myeloma. SELECTION CRITERIA: We included RCTs comparing combination therapies of V, R, and T, plus melphalan and prednisone (MP) or dexamethasone (D) for first-line treatment of adults with transplant-ineligible multiple myeloma. We excluded trials including adults with relapsed or refractory disease, trials comparing drug therapies to other types of thera …

Daratumumab and antineoplastic therapy versus antineoplastic therapy only for adults with newly diagnosed multiple myeloma ineligible for transplant.

BACKGROUND: Multiple myeloma (MM) is a haematological malignancy that is characterised by proliferation of malignant plasma cells in the bon … without daratumumab. In the ALCYONE and OCTANS trials, daratumumab was combined with bortezomib and melphalan-prednisone. In the AMaRC 03-16 study, it was combined with bortezomib, cyclophosphamide, and dexamethasone, and in the MAIA study, it was combined with lenalidomide and dexamethasone. None of the included studies was blinded (high risk of performanc …

Xanthoma-like Skin Changes in an Elderly Woman with a Normal Lipid Profile.

Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the perio … he rarity of the disease, the optimal therapy has not been not defined. Frequently, chlorambucil or melphalan have been used alone or in combination with prednisone (4). Treatment may result in remission of symptoms on the skin, but it does not provide a permanent cure (8). There are also single reports of the successful use of thalidomide, lenalidomide, cy …

Carfilzomib induction, consolidation, and maintenance with or without autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: pre-planned cytogenetic subgroup analysis of the randomised, phase 2 FORTE trial.

BACKGROUND: Patients with newly diagnosed multiple myeloma and high-risk cytogenetic abnormalities (HRCA) represent an unmet medical need. I … 1:1) to KRd plus autologous stem-cell transplantation (ASCT; four 28-day induction cycles with KRd, melphalan at 200 mg/m2 and ASCT [MEL200-ASCT], followed by four 28-day KRd consolidation cycles), 12 28-day KRd cycles, or KCd plus ASCT (four 28-day induction cycles with KCd, MEL200-ASCT, and four 28-day KCd consolidation cycles), using a web-based system ( …

15th Report on Carcinogens.

BACKGROUND: The Report on Carcinogens (RoC) is a congressionally mandated, science-based public health document that the National Toxicology … nds; Lindane, Hexachlorocyclohexane (Technical Grade), and Other Hexachlorocyclohexane Isomers. M: Melphalan; Merkel Cell Polyomavirus (see Viruses: Eight Listings); Methoxsalen with Ultraviolet A Therapy; 2-Methylaziridine; 5-Methylchrysene (see Polycyclic Aromatic Hydrocarbons: 15 Listings); 4,4'-Methylenebis(2-chloroaniline); 4,4'-Methylenebis(N,N-dimet …

Daratumumab (Darzalex SC): Therapeutic area: Multiple myeloma in patients ineligible for autologous stem cell transplant: Reimbursement Review

What is multiple myeloma?Multiple myeloma is a cancer of plasma cells (the white blood cells that make immunoglobulins) found in the bone ma … n with cyclophosphamide, bortezomib, and dexamethasone; daratumumab in combination with bortezomib, melphalan, and prednisone (DVMp); and isatuximab in combination with VRd (Isa-VRd). Among these, DRd is the standard of care in Canada, according to the clinical experts consulted by Canada’s Drug Agency (CDA-AMC).What is darzalex sc and why did cda-amc condu …

Treatment of Multiple Myeloma in Elderly Patients: A Review of Literature and Practice Guidelines.

Multiple myeloma (MM) is a clonal disorder of malignant plasma cells that comprises approximately 10% of hematologic malignancies. With median age of 66 at the time of presentation, multiple myeloma is predominantly a disease of the elderly. The availability of new combination regimens and the enhanced safety of autologous hematopoietic stem cell transplant has increased the treatment options for elderly patients with multiple myeloma. We provide a summary of data supporting the current management of elderly patients with newly diagnosed multiple myeloma.

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… Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. Mateos MV, Richardson PG, Schlag R, et al. … Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Palumbo A, Bringhen S, Bruno B, et al. Blood. 2010;115:1873–1879. doi: 10.1182/blood-2009-09-241737. 39. …

Custom-Made Mouthpiece-Assisted Oral Cryotherapy During Hematopoietic Stem Cell Transplantation in a Patient With Hemimaxillectomy-Related Oroantral Communication: A Case Report.

A custom-made mouthpiece enabled safe oral cryotherapy in a patient with extensive oroantral communication after hemimaxillectomy and may also be applicable to other patients with communication between the oral cavity and the maxillary sinus or nasal cavity.

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… Because melphalan is rapidly cleared from plasma, oral cryotherapy is considered a rational preventive intervention to reduce mucosal exposure to circulating melphalan [ 8 , 9 ]. … Myeloablative conditioning was then initiated with fludarabine at 30 mg/m 2 /day for 6 days, busulfan at 3.2 mg/kg/day for 4 days, and melphalan at 40 mg/m 2 /day for 2 days. Oral cryotherapy was performed on both days of melphalan administration. …

Current status of autologous stem cell transplantation for multiple myeloma.

More than 30 years after its introduction, autologous stem cell transplantation (ASCT) remains the standard of care for young patients with newly diagnosed multiple myeloma. Not only did the arrival of novel agents such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and monoclonal antibodies not replace ASCT, instead they solidified its central role as standard of care. Novel agent use is now inarguably essential in induction, maintenance, and possibly consolidation. In light of these new advancements, new challenges arise in deciding on optimal practice. Who is most suited to u

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… The effect of intravenous busulfan is being studied in a phase III trial whereby HDM is compared to busulfan-melphalan (Bu-Mel: busulfan 130 mg/m 2 daily for 4 days followed by two daily doses of melphalan at 70 mg/m 2 ) 73 . … Whether novel melphalan formulations such as FDA-approved propylene glycol-free melphalan have increased efficacy and decreased toxicity compared to melphalan is to be investigated. One study failed to demonstrate superiority of propylene glycol-free melphalan over melphalan 108 . …

Autologous Hematopoietic Cell Transplant as an Effective Treatment Modality for Systemic Sclerosis and Multiple Myeloma.

Systemic sclerosis (SSc) is a multi-system disease characterized by a dysregulated immune system. Autologous hematopoietic cell transplantation (AHCT) is the only treatment that has been shown to confer significant benefit in controlling disease and improving survival for patients with SSc. A diagnosis of multiple myeloma (MM) after the diagnosis of SSc is rare and optimal treatment in such cases remains unclear. We here report a case of a female patient who was diagnosed with MM while she was undergoing evaluation for AHCT due to SSc. A novel conditioning regimen for AHCT, with therapeutic ef

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… Melphalan, an alkylating agent, has been integral to the treatment of MM since its introduction in 1958. 33 The results of the Intergroupe Francophone du Myelome 9502 randomized trial established melphalan 200mg/m 2 as the conditioning regimen for MM as melphalan 200mg/m 2 resulted in superior PFS compared … It also suggests that melphalan may be an effective lymphodepleting alternative for patients with SSc. …

Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

ObjectivesControversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT.MethodsPubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were

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… with conditioning containing high-dose melphalan | Oral cryotherapy (placing ice chips in the mouth) started 30 minutes before and continued for 6 hours after high-dose melphalan. | Room temperature normal saline rinse Toro [ 21 ] | Patients with MM | Auto-HSCT with conditioning containing high-dose … melphalan | Oral cryotherapy plus saline solution | Saline solution Salvador [ 22 ] | Patients with MM | Auto-HSCT with conditioning containing high-dose melphalan | Oral cryotherapy (sucking on ice chips) started 5 minutes before, during, and after the administration of melphalan for a total of 60 …

Role of Stem Cell Transplantation in Multiple Myeloma.

Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs

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… Melphalan to date has been shown to be an effective conditioning regimen; thus, the question arises as to what the effective dose of melphalan in patients with RI is. … Attempts are being made for better outcomes by supplementing melphalan with other agents. …

Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice.

Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achiev

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… A third lenalidomide maintenance study compared melphalan, prednisone, and lenalidomide (MPR) vs. tandem ASCT with high-dose melphalan [ 36 ]. … Notably, risk increased when lenalidomide was paired with melphalan compared with melphalan alone (HR, 4.86; p < 0.0001), whereas exposure to lenalidomide plus cyclophosphamide (HR, 1.26; p = 0.75) or lenalidomide plus dexamethasone (HR, 0.86; p = 0.76) did not increase hematologic SPM risk versus melphalan …

Evolving treatment strategies for myeloma.

In this article, we will discuss how treatment strategies for myeloma have evolved and outline the challenges now faced following the introduction of a number of novel active agents. In particular, we will focus on how achieving a maximum response and maintaining such responses is becoming a key therapeutic strategy and how novel agents can be used to achieve this in the context of current strategies such as autologous transplantation.

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… as oral melphalan. … These cells are then used to support high-dose melphalan, which consolidates the responses obtained. …

Efficacy of palifermin in the hematopoietic stem cell transplant setting.

Palifermin is a recombinant human keratinocyte growth factor that stimulates proliferation and differentiation of epithelial cells. Palifermin's biological activity exerts cytoprotective and healing effects that decrease cell injury caused by chemotherapy and radiation therapy. In randomized, placebo-controlled trials, palifermin significantly reduced the incidence and duration of severe oral mucositis. Based on these findings, the US Food and Drug Administration approved palifermin for patients with hematologic malignancies undergoing myeloablative therapy followed by hematopoietic stem cell

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… Efficacy of Palifermin With High-Dose Melphalan as a Conditioning Regimen High-dose melphalan is the most common conditioning regimen used for treatment of multiple myeloma (MM) followed by autologous HSCT (Vogl et al., 2010). … A total of 281 patients were randomized to 3 arms: the pre/post arm (n = 115) received 3 doses of palifermin before and 3 doses after melphalan infusion; the pre arm (n = 109) received only 3 doses of palifermin before melphalan, and the placebo arm (n = 57). …

AL Amyloidosis: Current Chemotherapy and Immune Therapy Treatment Strategies: JACC: CardioOncology State-of-the-Art Review.

Immunoglobulin light chain (AL) amyloidosis is an incurable plasma cell disorder characterized by deposition of fibrils of misfolded immunoglobulin free light chains (FLC) in target organs, leading to failure. Cardiac involvement is common in AL amyloidosis and represents the single most adverse prognostic feature. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to arrest the process of amyloid deposition and preserve organ function. The clinical use of molecularly targeted drugs, such as protea

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… Melphalan flufenamide Melphalan flufenamide (melflufen) is a peptide-conjugated, melphalan derivative that has shown encouraging activity in MM, leading to its FDA approval in combination with dexamethasone in triple class relapsed/refractory MM. … High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis N Engl J Med 357 2007 1083 1093 17855669 10.1056/NEJMoa070484 42 D'Souza A. Dispenzieri A. Wirk B. …

Subcutaneous bortezomib for multiple myeloma treatment: patients' benefits.

The use of novel agents such as thalidomide, lenalidomide, and bortezomib has considerably improved the outcome of multiple myeloma patients. Besides greater biological activity, these drugs unfortunately have also been associated with greater toxicity. To evaluate the positive effect on the quality of life of patients, driven by both the tolerability and antimyeloma activity of bortezomib, we analyzed data that have been published concerning different strategies used to improve its tolerability as once weekly and/or subcutaneous administration.

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… Intergroupe Francophone du Myélome Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99–06): a randomized trial. … Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis. Leukemia. 2011;25(4):689–696. doi: 10.1038/leu.2010.313. 8. Mateos MV, Richardson PG, Schlag R, et al. …

The Progress of Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Multiple Myeloma (Review).

Multiple myeloma (MM) is a malignant hematological disease originating from plasma cells that remains incurable. Autologous stem cell transplantation (ASCT) is an important treatment method for MM. With the development of new drugs, the treatment of MM patients who meet the ASCT criteria has significantly improved, and the median survival time has increased by 8-10 years. The current treatment for MM patients who meet the ASCT criteria consists mainly of the following stages: induction therapy, stem cell collection, stem cell transplantation, and consolidation and maintenance therapy. Even tod

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… group or the group receiving melphalan alone at a 1:1 ratio. … The trial showed PFS was higher with the combination of intravenous busulfan with melphalan pretreatment than with melphalan alone. …