Proliferation Of Plasma Cells Research Articles

A Rare Case of Castleman Variant of POEMS Syndrome

Abstract POEMS syndrome is a rare multisystemic disease, characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. The presence of polyneuropathy and monoclonal plasma cell proliferation is mandatory for the diagnosis of typical POEMS syndrome. However, some patients lack one of the mandatory features and are classified as the variants of POEMS syndrome. A 61-year-old male presented with the clinical picture of progressive numbness in both lower extremities and weakness in all four extremities for a 6-month duration associated with bilateral axillary lymphadenopathies, pedal edema, clubbing, and unintentional weight loss of 15 kg in 6 months. A nerve conduction study showed severe sensorimotor polyneuropathy of demyelinating type in all four extremities. A lymph node biopsy showed Castleman disease, and the computed tomography scan was suggestive of multiple osteosclerotic lesions. A diagnosis of the Castleman variant of POEMS syndrome was made, and the patient was treated with Bortezomib-based therapy with improvement in his symptoms on follow-up at 1 year. Due to the lack of definite treatment guidelines for this disease, the information provided through case reports and case series becomes very important for the treatment of such patients leading to the resolution of polyneuropathy and the maintenance of functionality in patients.

Monoclonal gammopathy of clinical signifi cance with osteosclerotic lesions - a case report and a literature review.

Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding. In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma. Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.

Anti-tumor effect of dandelion flavone on multiple myeloma cells and its mechanism

BackgroundMultiple myeloma (MM) is a prevalent hematologic malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow and excessive monoclonal immunoglobulin production, leading to organ damage. Despite therapeutic advancements, recurrence and drug resistance remain significant challenges.ObjectiveThis study investigates the effects of dandelion flavone (DF) on MM cell proliferation, migration, and invasion, aiming to elucidate the mechanisms involved in MM metastasis and to explore the potential of traditional Chinese medicine in MM therapy.MethodsDF's impact on myeloma cell viability was evaluated using the CCK-8 and colony formation assays. Cell mobility and invasiveness were assessed through wound healing and transwell assays, respectively. RT-PCR was employed to quantify mRNA levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Apoptotic rates and molecular markers were analyzed via flow cytometry and RT-PCR. The PI3K/AKT signaling pathway was studied using Western blot and ELISA, with IGF-1 and the PI3K inhibitor LY294002 used to validate the findings.ResultsDF demonstrated dose-dependent inhibitory effects on MM cell proliferation, migration, and invasion. It reduced mRNA levels of MMP-2 and MMP-9 while increasing those of TIMP-1 and TIMP-2. Furthermore, DF enhanced the expression of pro-apoptotic proteins and inhibited M2 macrophage polarization by targeting key molecules and enzymes. The anti-myeloma activity of DF was mediated through the inhibition of the PI3K/AKT pathway, as evidenced by diminished phosphorylation and differential effects in the presence of IGF-1 and LY294002.ConclusionBy modulating the PI3K/AKT pathway, DF effectively inhibits MM cell proliferation, migration, and invasion, and induces apoptosis, establishing a novel therapeutic strategy for MM based on traditional Chinese medicine.

Novel method for the detection of circulating tumor plasma cells in multiple myeloma.

e19520 Background: Multiple Myeloma (MM) is characterized by the proliferation of abnormal plasma cells within the bone marrow. A bone marrow examination is essential for the diagnosis of multiple myeloma. This is a test that causes great pain to patients because it requires collecting and analyzing the bone marrow fluid inside the bone. In addition, there is a disadvantage that it cannot be carried out frequently due to cost issues. Therefore, the development of new diagnostic methods is absolutely necessary. The aim of this study is to access the potential of circulating tumor plasma cells (CTPC) for the diagnosis of MM using CytoGen's Smart Biopsy platform. Methods: Spiking tests using MM cell line (RPMI8226) was conducted with the purpose of making an environment similar to the MM patient's blood. RPMI8226 cells (200 cells) stained with CellTracker were spiked into human blood sample (5mL, healthy donor). Then, spiked cells were isolated by CytoGen’s Smart Biopsy isolator, subsequently recovery rate was accessed by counting of isolated RPMI8226 or immunofluorescence (IF) staining with multiple myeloma-specific marker, CD138. Then, clinical evaluation was performed with bone marrow (3mL) and peripheral blood (5mL) samples of MM patients (n=20). The presence of CTPC in patient samples was tested by IF staining with anti-CD138 antibody. Results: In in vitro experiments to test recovery rate of CTPC using CytoGen's Smart Biopsy isolator, MM cell line’s recovery rate was validated to over 80%. CD138 expression was clearly detected by IF staining of spiking samples of multiple myeloma cell line and was not detected at all in the negative controls. In clinical evaluation study, CTPC was successfully observed after the isolation from bone marrow and peripheral blood using CytoGen's Smart Biopsy isolator by IF staining with CD138. Conclusions: This study shows a novel method for the detection of MM with liquid biopsy. CTPC from liquid biopsy of MM could be isolated using CytoGen's Smart Biopsy isolator with high recovery rate and can clearly be detected with specific marker of MM, CD138 by IF staining. These results suggested that CytoGen's Smart Biopsy platform might be an effective diagnostic tool for the detection of MM. Expanded clinical study will be performed with more MM samples for clinical validation. Clinical trial information: 2013-09-009 .

Comprehensive assessment of adverse event profiles associated with bispecific T cell engagers in multiple myeloma.

e19527 Background: Multiple myeloma (MM) is a hematologic malignancy caused by the uncontrolled proliferation of malignant plasma cells. Bispecific T Cell engagers (BiTEs) are a novel class of drugs currently assessed in the setting of relapsed/refractory MM. BiTEs are designed to target specific antigenic epitopes on the surface of plasma cells and CD3 on T cells. The plasma cell targets include B cell maturation antigen (BCMA), G protein coupled receptor, class C, group 5, member D (GPRC5D) and Fc receptor homolog 5 (FcRH5). Methods: We conducted a comprehensive review of the available literature including abstracts and full publications using PubMed/Scopus through Dec 31, 2023. We found 23 studies which include BCMA agents: teclistamab (Tec), elranatamab, linvoseltamab, pavurutamab, and alnuctamab; and non-BCMA targets including: GPRC5D, talquetamab (Tal) and FcRH5, cevostamab, as well as combination therapies including a BiTE, specifically Tec+Tal and Tal+daratumumab (Tal+D). A pooled analysis based on the Welch's test was then performed on all BiTEs to compare the safety profile of each agent. t-distributed stochastic neighbor embedding (t-SNE) was also applied to cluster 23 BiTEs based on their AEs. Results: We found a cohort of 1899 patients with MM across 23 studies. 1094 individuals underwent treatment involving BCMAs. 677 were subjected to non-BCMA anti-agents. 65 participants received Tec + Tal and 63 patients received Tal+D. The median follow-up duration for both BCMA BiTE and non-BCMA BiTE groups extended to 9 and 14 months. When analyzing hematological AEs of any grade, neutropenia and anemia affected 44% of patients and lymphopenia 40%. Respiratory infections manifested in 44%. CRS (Cytokine Release Syndrome) was reported in 64%. Dysgeusia was reported in only non-BCMA at 53%. Grade 3+ AEs were as follows: neutropenia at 40%, infections at 18%, CRS at 2%, anemia at 28%, and lymphopenia at 45%. Upon conducting a comprehensive pooled analysis, subtle disparities emerged between BCMA and non-BCMA BiTEs. More instances of CRS and CRS with Tocilizumab occurred with BCMA BiTEs vs non-BCMA BiTes, P < 0.024. Friedman's findings emphasized substantial distinctions between BCMA and non-BCMA agents for both overall and severe G3+ AEs (p < 0.0001). t-SNE was applied to examine the clustering patterns among agents across all grades and grades 3+ AEs. The findings revealed that agents with all grades and grades 3+ showed similar clustering patterns except for one agent. Conclusions: The use of BiTEs in MM has demonstrated remarkable efficacy; however, these have been linked to a unique AE profile. Our results showed that non-BCMA were associated with less hematotoxicity (combined G3+ AEs and hypogammaglobulinemia), whereas BCMA BiTEs were associated with less CRS rates. This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes.

Assessing the prognostic value of transcriptomic data in multiple myeloma through machine learning methodologies.

7513 Background: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. Identifying the characteristics within transcriptomic data of MM patients could be imperative for elucidating long-term cancer prognosis. Prediction and bioinformatic evidence could be valuable for therapeutic intervention. Methods: To discover a precise collection of biomarkers, a large-scale disproportionality analysis of MM patients using the FDA Spontaneous Reporting System database is conducted. This analysis aims to provide pharmacovigilance evidence regarding severe adverse events (AEs) due to medications. Additionally, pharmacogenomic insights from OMIM and MM drug targets are integrated into the analysis to carefully select 84 essential biomarkers. Seven different machine learning (ML) algorithms, namely AdaBoost, K-Nearest Neighbors (KNN), Decision Tree (DT), Gaussian Naïve Bayes (GNB), Support Vector Machine (SVM), Random Forest (RF), and Multilayer Perceptron (MLP) were then employed to assess the classification of disease outcomes. Specifically, the focus was on distinguishing deceased patients (due to MM) from surviving patients in the MM Research Foundation (MMRF) dataset based on the identified essential biomarker. Results: The classification involved a total of 787 patients from MMRF (624 alive and 163 deceased). Four sampling strategies (original raw data, undersampling, oversampling, and simultaneous sampling) were included in the training and testing process on ML models to alleviate the influence of imbalanced data. SVM achieved the highest accuracy while RF achieved highest mean across four sampling methods (Table). We then performed the Kaplan-Meier survival analysis of the prognostic values of essential genes. The expression of two genes (BRAC1 and CTLA4) from MMRF data when comparing deceased to survival patients was associated with patient outcomes. Additionally, seven genes were potentially prognostic factors in MM (Positive prognostic: ATM, CYBA, NR3C1, PIK3CA, and PIK3CG; Negative prognostic: IFNG and NTRK2). Conclusions: This study successfully showcased a computational methodology that holds potential for optimizing future clinical trials in MM. The approach includes identifying the most suitable patient population for a particular MM regimen, thereby contributing to improved patient care. It also offers strategies for reducing AEs, lowering mortality rates, and ensuring the optimal allocation of healthcare resources. [Table: see text]

Characterization of the BCMA epitope bound by BCMA-CD3 T cell engager elranatamab.

7546 Background: Elranatamab is a BCMA-CD3 bispecific antibody with an accelerated approval in the US and EU for relapsed/refractory multiple myeloma (RRMM). Elranatamab binds to CD3 on T cells and BCMA on MM tumor cells; this dual binding results in T cell activation, cytokine release, and tumor cell killing. Engagement of the BCMA surface receptor by its ligands, APRIL and BAFF, mediates plasma cell proliferation and survival. Elevated BCMA, as well as BAFF and APRIL are present in MM patients, yet in vitro functional assays have shown physiologically relevant soluble APRIL or BAFF concentrations did not significantly impact elranatamab activity. Moreover, emerging clinical data from relapsed patients has identified novel, yet relatively rare BCMA protein mutations that may impact BCMA ligand or targeted modality binding. Here we characterized the BCMA binding affinity, evaluated the impact on BCMA binding to BAFF and APRIL interactions, and identified the BCMA binding epitope. We also generated a model from crystal structure data to map reported BCMA mutations identified in patients. Methods: Elranatamab binding affinity to recombinant human BCMA and characterization of BAFF and APRIL interactions with elranatamab-bound BCMA were calculated via SPR at 37˚C with a classical sandwich format. The elranatamab BCMA binding epitope was identified by a co-crystal structure with a parental anti-BCMA Fab that has identical CDR sequences to elranatamab. Alpha-fold modeling was used to map identified BCMA mutations on the antibody/BCMA interface. Results: Elranatamab binds to BCMA with higher affinity (~38 pM) compared to reported binding affinities of BAFF (μM range) and APRIL (nM range) ligands. The identified elranatamab epitope largely overlaps with known ligand epitopes, supporting that elranatamab higher affinity BCMA binding blocks ligand binding. Alpha fold modeling of four recently reported rare BCMA mutations shows that they lie along the binding interface. Conclusions: Due to its high affinity for BCMA, elranatamab potency is unlikely to be impacted by elevated levels of soluble BAFF or APRIL in RRMM patients. Future studies are needed to characterize the impact of emerging MM patient BCMA mutations on the binding and function of anti-BCMA targeting modalities, particularly given the small extracellular domain of BCMA available for therapeutic targeting and the highly overlapping binding epitopes reported for approved BCMA agents.

A case of multiple myeloma misdiagnosed as seronegative rheumatoid arthritis: a rare case report

Introduction: Multiple myeloma (MM) is a malignant plasma cell proliferation producing large numbers of monoclonal immunoglobulins. Typical MM symptoms include anemia, bone pain, hypercalcemia, and renal failure. Atypical presentations like joint involvement were rarely reported in the literature and may cause significant delays in treatment and adverse outcomes. Case presentation: The authors report a case of a 54-year-old female who presented with symmetrical polyarthritis and was misdiagnosed with rheumatoid arthritis. The diagnosis of MM was made after failing many treatments of rheumatoid arthritis and with further laboratory tests and procedures. Conclusion: This rare manifestation of MM carries a diagnostic challenge and causes a significant delay in treating such patients. Here, the authors report this unusual initial presentation with a review of several cases in the literature describing similar presentations.

Autoimmune Diseases and Plasma Cells Dyscrasias: Pathogenetic, Molecular and Prognostic Correlations.

Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part in the growth of immunotolerance conditions that make it easier for the development of neoplastic malignancies. Uncontrolled immune activation resulting in chronic inflammation is also known to be at the basis of the evolution toward neoplastic pathologies, as well as multiple myeloma. Another point is the impact that myeloma-specific therapies have on the course of concomitant autoimmune diseases. Indeed, cases have been observed of patients suffering from multiple myeloma treated with daratumumab and bortezomib who also benefited from their autoimmune condition or patients under treatment with immunomodulators in which there has been an arising or worsening of autoimmunity conditions. The role of bone marrow transplantation in the course of concomitant autoimmune diseases remains under analysis.

Enhancing diagnostic accuracy of multiple myeloma through ML-driven analysis of hematological slides: new dataset and identification model to support hematologists

Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Diagnosing MM presents considerable challenges, involving the identification of plasma cells in cytology examinations on hematological slides. At present, this is still a time-consuming manual task and has high labor costs. These challenges have adverse implications, which rely heavily on medical professionals’ expertise and experience. To tackle these challenges, we present an investigation using Artificial Intelligence, specifically a Machine Learning analysis of hematological slides with a Deep Neural Network (DNN), to support specialists during the process of diagnosing MM. In this sense, the contribution of this study is twofold: in addition to the trained model to diagnose MM, we also make available to the community a fully-curated hematological slide dataset with thousands of images of plasma cells. Taken together, the setup we established here is a framework that researchers and hospitals with limited resources can promptly use. Our contributions provide practical results that have been directly applied in the public health system in Brazil. Given the open-source nature of the project, we anticipate it will be used and extended to diagnose other malignancies.

Multiple punched out lesions: A case report of multiple myeloma

Multiple myeloma (MM) is a relatively uncommon malignant neoplasm, characterized by abnormal proliferation of plasma cell. It usually has a multicentric origin within the bone. It constitutes about 1% of all malignancies and 15% of all hematologic malignancies. We present a case of a 25-year-old male patient who presented with a gingival enlargement in the maxilla and mandible with punched-out radiolucencies in the skull and mandible.

Activated interferon response from DNA damage in multiple myeloma cells contributes to the chemotherapeutic effects of anthracyclines.

Multiple myeloma (MM) is a malignant plasma cell disease caused by abnormal proliferation of clonal plasma cells in bone marrow. Upfront identification of tumor subgroups with specific biological markers has the potential to improve biologically-driven therapy. Previously, we established a molecular classification by stratifying multiple myeloma into two subtypes with a different prognosis based on a gene module co-expressed with MCL-1 (MCL1-M). Gene Ontology (GO) analysis with differentially expressed genes was performed to identify signal pathway. Drug sensitivity was analyzed using the OncoPredict algorithm. Drug sensitivity of different myeloma cell lines was detected by CCK8 and flow cytometry. RNA-seq was performed on drug-sensitive cell lines before and after adriamycin treatment. RT-qPCR was used to further verify the sequencing results. The expression of γ-H2AX and dsDNA in sensitive and resistant cell lines was detected by immunofluorescence method. In our study, we demonstrated that MCL1-M low MM were more sensitive to anthracyclines. We treated different myeloma cell lines with doxorubicin in vitro and discovered the association of drug sensitivity with IFN signaling. Herein, we demonstrate that the doxorubicin-sensitive myeloma cell line showed significant DNA damage and up-regulated expression of genes related to the IFN response, which was not observed in drug-insensitive cell lines. Our results suggest that the active IFN signaling pathway may serve as a marker for predicting chemotherapy sensitivity in patients with myeloma. With our MCL1-M molecular classification system, we can screen patients with a potentially good response to the interferon signaling pathway and provide individualized treatment for MM. We propose IFN-a as adjuvant therapy for patients with myeloma sensitive to anthracyclines to further improve the therapeutic effect and prolong the survival of patients.

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

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

POEMS Syndrome

POEMS syndrome is a multisystem disorder associated with monoclonal plasma cell proliferation and the overproduction of vascular endothelial growth factors. The prognosis of POEMS syndrome has significantly improved owing to anti-myeloma treatments such as thalidomide and autologous stem cell transplantation. Therefore, early diagnosis and appropriate treatment are becoming increasingly important. A thorough and comprehensive evaluation of both systemic symptoms and laboratory abnormalities associated with the disease is essential for early diagnosis. The collaboration between neurology and hematology is indispensable to ensure proper treatment.

A young patient with cord compression diagnosed as a solitary sacral plasmacytoma: a case report

Plasmacytoma is a subgroup of plasma cell neoplasms characterized by localized proliferation of neoplastic plasma cells. It is a rare disease that accounts for only less than 5% of all plasma cell tumours and can present alone or with multiple myeloma. Here, we report a clinical case of unusual presentation, in which solitary sacral plasmacytoma of a previously well young woman presented with bilateral lower limb numbness. She was found to have a sacral-originated tumour, which was later diagnosed as a solitary sacral plasmacytoma with the help of imaging and histological evaluation, along with the absence of the end organ damage.

A Very Rare Relaps Type in Multiple Myeloma: Leptomenıngeal and Cranial Involvement

Multiple myeloma is a hematological malignancy that develops as a result of clonal proliferation of plasma cells and progresses with remissions and relapses. It is clinically characterized by many symptoms and signs such as osteolytic bone lesions, hypercalcemia, renal dysfunction, hypergammaglobulinemia and anemia. However, involvement of the central nervous system, especially the leptomeningeal/cranial region, is a rare and prognostically important form of relapse of the disease. This case report discusses this rare clinical presentation, diagnostic approach, and treatment strategies of extramedullary involvement of multiple myeloma.

Therapeutic potential of third-generation chimeric antigen receptor T cells targeting B cell maturation antigen for treating multiple myeloma

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the rapid proliferation of malignant plasma cells within the bone marrow. Standard therapies often fail due to patient resistance. The US FDA has approved second-generation chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (anti-BCMA-CAR2 T cells) for MM treatment. However, achieving enduring clinical responses remains a challenge in CAR T cell therapy. This study developed third-generation T cells with an anti-BCMA CAR (anti-BCMA-CAR3). The CAR incorporated a fully human scFv specific to BCMA, linked to the CD8 hinge region. The design included the CD28 transmembrane domain, two co-stimulatory domains (CD28 and 4-1BB), and the CD3ζ signaling domain (28BBζ). Lentiviral technology generated these modified T cells, which were compared against anti-BCMA-CAR2 T cells for efficacy against cancer. Anti-BCMA-CAR3 T cells exhibited significantly higher cytotoxic activity against BCMA-expressing cells (KMS-12-PE and NCI-H929) compared to anti-BCMA-CAR2 T cells. At an effector-to-target ratio of 10:1, anti-BCMA-CAR3 T cells induced lysis in 75.5 ± 3.8% of NCI-H929 cells, whereas anti-BCMA-CAR2 T cells achieved 56.7 ± 3.4% (p = 0.0023). Notably, after twelve days of cultivation, anti-BCMA-CAR3 T cells nearly eradicated BCMA-positive cells (4.1 ± 2.1%), while anti-BCMA-CAR2 T cells allowed 36.8 ± 20.1% to survive. This study highlights the superior efficacy of anti-BCMA-CAR3 T cells against both low and high BCMA-expressing MM cells, surpassing anti-BCMA-CAR2 T cells. These findings suggest potential for advancing anti-BCMA-CAR3 T cells in chimeric antigen receptor T (CAR-T) therapy for relapsed/refractory MM.

The numerous facets of 1q21+ in multiple myeloma: Pathogenesis, clinicopathological features, prognosis and clinical progress (Review).

Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal proliferation of abnormal plasma cells (PCs) in the bone marrow and recurrent cytogenetic abnormalities. The incidence of MM worldwide is on the rise. 1q21+ has been found in ~30-40% of newly diagnosed MM (NDMM) patients.1q21+ is associated with the pathophysiological mechanisms of disease progression and drug resistance in MM. In the present review, the pathogenesis and clinicopathological features of MM patients with 1q21+ were studied, the key data of 1q21+ on the prognosis of MM patients were summarized, and the clinical treatment significance of MM patients with 1q21+ was clarified, in order to provide reference for clinicians to develop treatment strategies targeting 1q21+.

Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the neoplastic proliferation of plasma cells, which produce monoclonal immunoglobulin that can cause vital organ damage, subsequently leading to significant morbidity and mortality. Autologous hematopoietic stem cell transplant (ASCT) is the standard-of-care management of eligible patients with newly diagnosed MM. Experts recommend collecting enough stem cells upfront to support a possible tandem transplant, salvage ASCT, or a stem cell "boost" to allow for the administration of multiagent cytotoxic chemotherapy in patients with relapsed/refractory disease. There is currently a paucity of data on the response rates and outcomes of patients with relapsed MM who undergo cytotoxic chemotherapy followed by a stem cell boost; this study examines the outcomes of patients treated with this approach. We conducted a retrospective chart review from two oncologic treatment centers in the United States of adult patients who underwent a first ASCT between 1999 and 2021 and subsequently received cytotoxic chemotherapy followed by stem cell boost further on in their disease course. Survival analysis was carried out using the Kaplan-Meier method, and the log-rank test was used to compare survival curves. We found that the majority (56.6%) of these patients responded to therapy and that 60.6% of these patients were able to receive at least one subsequent line of therapy post-boost. Furthermore, patients who responded to therapy had significantly longer median overall survival compared to those who did not respond (323 days vs 93 days, p=0.0045), and age did not affect response to therapy. This data allow clinicians to appropriately implement and inform patients of the therapeutic uses and clinical outcomes of stem cell boost in patients with multiply relapsed/refractory MM.

Epidemiological data, etiology, pathogenesis, risk factors, clinical manifestations, modern methods of diagnosis and treatment, prediction of the course of multiple myeloma (literature review)

Background. Multiple myeloma (MM) is a neoplastic disease with a multistage course characterized by uncontrolled, multifocal proliferation of monoclonal plasma cells in the bone marrow, which produce monoclonal immunoglobulin or only its fragments, which lead to destruction of bone tissue and organ damage. Quite high rates of both morbidity and mortality from MM require more careful attention and deeper scientific research of this problem. Objective of the article is to investigate the epidemiology, etiology, pathogenesis, risk factors, clinical manifestations, modern methods of diagnosis and treatment, and also prediction of the course of MM. Methods. The following research methods were used: search, extraction and processing of information; assessment of the quality of sources; systematic literature review; content analysis. Research materials are thematic publications of ukrainian and foreign scientists. Results. MM accounts for ~1% of all malignant neoplasms and ~14% of hematological neoplasms worldwide. Etiological factors of MM: genetic predisposition, bacterial or viral infections, ionizing radiation, carcinogenic toxins. The clinical syndrome of MM is characterized by hypergammaglobulinemia, hypercalcemia, susceptibility to infections, and pathological fractures. Diagnosis of MM includes: general analysis of peripheral blood; diagnosis of serum and urine proteins; aspiration biopsy and trepanobiopsy of bone marrow; cytogenetic and molecular diagnostics; other laboratory diagnostics; radiography, CT, MRT and PET-CT. The main methods of treatment of MM: radiation therapy, chemotherapy, combined CT with the inclusion of new drugs, HDCT + autologous THSC. Prediction of the course of MM depends on the R-ISS stage, LDH level and high-risk cytogenetics. Conclusion. During the last years of modern oncohematology, we observe scientific achievements in the diagnosis and treatment of MM. A thorough study of the epidemiology, etiology and pathogenesis, risk factors and clinical manifestations of MM contribute to effective diagnosis and selection of the optimal treatment strategy and tactics, as well as determining the prognosis of the course of MM.