Multiple Myeloma: An Overview
Multiple myeloma (MM) is a neoplastic proliferation of clonal plasma cell producing a monoclonal immunoglobulin. One of the most important discoveries in the past two years was the molecular subclones in almost all patients with MM, which are present at the time of diagnosis and derived from a common ancestral clone. These clonal plasma cells proliferate in the bone marrow and often result in extensive skeletal destruction with osteolytic lesions, osteopenia and or pathological fractures. Bone marrow localization is a fundamental characteristic of MM; the dissemination of MM cells in the other tissues and organs genetically occurs at a late stage of the disease. Tumoral microenvironment plays a pivotal role in tumour growth, survival, migration, evasion of immune system and drug resistance of MM cells. Cells from the bone marrow microenvironment (BMMe) secrete the chemokine stromal cell-derived factor 1α, which allows the homing of MM cells through their (CXCR) receptor. Disease related complications include hypercalcemia, renal insufficiency, anaemia and infections. Unlike MGUS and Smouldering multiple myeloma, all patients with a confirmed diagnosis of MM require treatment. Initial evaluation of patients with MM must establish the extent and sites of disease, the patients’ performance status and comorbid conditions. In addition, specific tests are performed for risk stratification and to determine eligibility for autologous hematopoietic cell transplantation. Amongst the high-risk chromosomal abnormalities, the most powerful ones are del(17p), t(4;14), and del(1p32). Identification of good risk patients is essentially based on the absence of high-risk genetic features, associated with a low b2-microglobulin level. Patients should be evaluated before each treatment cycle to determine how the disease at a late stage is responding to therapy and to assess for potential treatment-related and disease-related complications. Almost all patients with MM who survive initial treatment will eventually relapse and require further therapy. Therapy for relapsed disease is indicated if there is a clinical relapse or a rapid rise in paraproteins. Treatment options for patients with relapsed or refractory MM include hematopoietic cell transplantation or a trial of a new regimen. In MM, prognosis can be markedly different in patients with similar staging and host factors. These disparities are driven primarily by differences in underlying disease biology. These factors can greatly influence the aggressiveness of the clinical course. Some of the most important markers of disease biology include cytogenetic abnormalities, bone marrow plasma cell Immunophenotyping, plasma cell proliferative rate and circulating plasma cells. Achievement of immunofixation negative complete remission is a crucial step for long lasting response and survival in MM, either in the transplantation setting or in elderly patients. In standard response criteria major amendments was the incorporation of stringent complete remission (sCR). Minimum residual disease in MM by multipara metric Flow Cytometry is the most used method for monitoring of MRD presence in the bone marrow of MM patients; however, detection of molecular changes can be used as well. MRD refers to myeloma cells that are present in the bone marrow after a clinical response has been measured and the patient is in remission. These residual myeloma cells are clinically relevant, as they may lead to disease progression and relapse.
Correspondence: Professor M. A. Khan, Department of Haematology, Dhaka Medical College & Hospital. email: firstname.lastname@example.org
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