Disease Overview
Multiple myeloma accounts for approximately 10% of hematologic malignancies.
Diagnosis
The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy‐proven plasmacytoma ...plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥ 100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging.
Risk Stratification
The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high‐risk multiple myeloma. The presence of any two high risk factors is considered double‐hit myeloma, and three or more high risk factors is triple‐hit myeloma.
Risk‐Adapted Initial Therapy
In patients who are candidates for autologous stem cell transplantation, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3–4 cycles followed by autologous stem cell transplantation (ASCT). In high‐risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara‐VRd) is an alternative to VRd. Selected standard‐risk patients can collect stem cells, get additional cycles of induction therapy, and delay transplant until first relapse. Patients who are not candidates for transplant are treated with VRd for approximately 8–12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression.
Maintenance Therapy
Standard‐risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high‐risk myeloma.
Management of Relapsed Disease
A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse.
Approach to treatment of newly diagnosed myeloma in transplant eligible patients.
Disease overview
Multiple myeloma accounts for approximately 10% of hematologic malignancies.
Diagnosis
The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma ...plus evidence of one or more multiple myeloma defining events (MDE) namely CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging (MRI).
Risk stratification
The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high‐risk multiple myeloma. Presence of any two high risk factors is considered double‐hit myeloma; three or more high risk factors is triple‐hit myeloma.
Risk‐adapted initial therapy
In transplant eligible patients, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3‐4 cycles followed by autologous stem cell transplantation (ASCT). In high‐risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara‐VRd) is an alternative to VRd. Selected standard risk patients can get additional cycles of induction, and delay transplant until first relapse. Patients not candidates for transplant are typically treated with VRd for approximately 8‐12 cycles followed by lenalidomide; alternatively these patients can be treated with daratumumab, lenalidomide, dexamethasone (DRd).
Maintenance therapy
After ASCT, standard risk patients need lenalidomide maintenance, while bortezomib‐based maintenance is needed for patients with high‐risk myeloma.
Management of refractory disease
Most patients require a triplet regimen at relapse, with the choice of regimen varying with each successive relapse.
Multiple myeloma accounts for approximately 10% of hematologic malignancies. The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more ...multiple myeloma defining events: CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. Patients with del(17p), t(14;16), and t(14;20) have high‐risk multiple myeloma. Patients with t(4;14) translocation and gain(1q) have intermediate‐risk. All others are considered standard‐risk. Initial treatment consists of bortezomib, lenalidomide, dexamethasone (VRd). In high‐risk patients, carfilzomib, lenalidomide, dexamethasone (KRd) is an alternative to VRd. In eligible patients, initial therapy is given for approximately 3‐4 cycles followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT at first relapse. Patients not candidates for transplant are treated with VRd for approximately 8‐12 cycles followed by lenalidomide or lenalidomide plus dexamethasone. After ASCT, lenalidomide maintenance is recommended for standard risk patients, while maintenance with a bortezomib‐based regimen is needed for patients with intermediate or high‐risk disease. Most patients require a triplet regimen at relapse, with the choice of regimen varying with each successive relapse. Aggressive relapse with extramedullary plasmacytomas or plasma cell leukemia may require anthracycline containing combination chemotherapy regimens.
Direct injection diesel engines are more popular in the automotive sector than spark ignition (SI) engines due to its fuel lean operation. However, the demand of fossil fuel is rising day by day and ...hence the major fuel source of diesel engine, the petroleum based fuel, is depleting rapidly. Many countries depend mainly on imported fossil fuels due to lack of fuel reserves and it has great impact on the economy. In addition to this, the major concerns of diesel engine are its oxides of nitrogen and smoke emissions. Therefore, for the past several decades extensive efforts are being made to search for alternate fuels to overcome the dependence on fossil fuel and environment pollution. In this regard, several alternate fuels namely hydrogen, oxygenated fuels like alcohol fuels, dimethyl ether and biodiesel fuels etc., have been extensively analysed. Recent studies show that biodiesel is one of the most promising alternate fuels for diesel engines because of its biodegradable, oxygenated, sulphur free and renewable characteristics. Hence, it is getting the attention of researchers all over the world. The blends of biodiesel with fossil diesel have many benefits like reduction in emissions, lower engine wear, lesser engine oil consumption and comparable thermal efficiency vis-a-vis diesel fuel. Exhaustive experimental works have been carried out to analyse the suitability of biodiesel fuel as alternate fuel and to explore their advantages in diesel engines. Hence, this paper is attempted to present a comprehensive review on the performance, combustion and emission characteristics of some important biodiesel fuels on diesel engines. This comprehensive review on the published literature will be helpful to the researchers to understand the state-of-the-art technology of the biodiesel fuelled compression ignition engine.
The diagnosis and treatment of multiple myeloma has changed dramatically in the past decade. The disease definition has been updated to include highly specific biomarkers in addition to established ...markers of end-organ damage. The staging system has been revised to combine both measures of tumor burden and disease biology. Advances in therapy have resulted in a marked improvement in overall survival. New drugs introduced in the past few years include carfilzomib, pomalidomide, panobinostat, ixazomib, elotuzumab, and daratumumab. In this review, we outline the current approach to the diagnosis, prognosis, and management of multiple myeloma.
PDF
