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Одиссей моноколональных гаммопатий: сосредоточен на прекурсорах и переходе от MGUS и SMM к нескольким Myeloma, с кратким обзором новых терапевтических стратегий.

Моноклональные гаммопатии охватывают континуум от моноклональной гаммопатии неопределенного значения (MMUS) и заморозки нескольких миелом (SMM) до открытой множественной миеломы (MM). Эта постепенная клональная эволюция обусловлена первичными цитогенетическими повреждениями, вторичными геномными явлениями и эпигенетической реконструкцией в допустимой микроокружающей среде костного мозга. Традиционные биомаркеры (коэффициенты сыворотки М-протеина и свободных световых цепей) обеспечивают полезную, но неполную прогнозную информацию, поскольку они не отражают пространственной неоднородности или вр

The Role of NLRP3, a Star of Excellence in Myeloproliferative Neoplasms.

Nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) is the most widely investigated inflammasome member whose overactivation can be a driver of several carcinomas. It is activated in response to different signals and plays an important role in metabolic disorders and inflammatory and autoimmune diseases. NLRP3 belongs to the pattern recognition receptors (PRRs) family, expressed in numerous immune cells, and it plays its primary function in myeloid cells. NLRP3 has a crucial role in myeloproliferative neoplasms (MPNs), considered to be the diseases best studied in the inflammasome

First pediatric experience of SL-401, a CD123-targeted therapy, in patients with blastic plasmacytoid dendritic cell neoplasm: report of three cases.

BackgroundBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematological malignancy with extremely poor outcome. The median overall survival for adult patients is 9-13 months. Pediatric patients are exceedingly rare with an unclear clinical course. Currently, no standardized therapy has been established, although an acute lymphoblastic leukemia type of treatment appears to be more effective in those patients who are able to tolerate aggressive chemotherapy. SL-401 is a targeted therapy directed to CD123, a protein ubiquitously expressed at high level on the surface o

Pre-transplant depression decreased overall survival of patients receiving allogeneic hematopoietic stem cell transplantation: a nationwide cohort study.

Studies investigating association of depression with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) yielded conflicting results. A nationwide cohort study, which included all adult patients [n = 7,170; depression group, 13.3% (N = 956); non-depression group, 86.7% (N = 6,214)] who received allo-HSCT from 2002 to 2018 in South Korea, analyzed risk of pre-transplant depression in OS of allo-HSCT. Subjects were followed from the day they received allo-HSCT, to occurrence of death, or last follow-up day (December 31, 2018). Median age at allo-HSCT for de

Clonal Hematopoiesis and CAR T Cell Therapy: From Biological Crosstalk to Clinical Implications.

Clonal hematopoiesis (CH) is increasingly recognized as a significant biological phenomenon in aging and cancer, marked by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations in genes associated with myeloid neoplasms. While CH is strongly linked to a spectrum of inflammatory diseases and hematologic malignancies, its role in shaping responses to cancer immunotherapy-especially chimeric antigen receptor (CAR) T cell therapy-has only recently begun to emerge. This review explores the interplay between CH and CAR T cell therapy, highlighting CH prevalence in trea

Plasma Cell Disorders

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The impact of gut microbial signals on hematopoietic stem cells and the bone marrow microenvironment.

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiation in the bone marrow, which is tightly regulated by cues from the microenvironment. The gut microbiota, a dynamic community residing on the mucosal surface of vertebrates, plays a crucial role in maintaining host health. Recent evidence suggests that the gut microbiota influences HSCs differentiation by modulating the bone marrow microenvironment through microbial products. This paper comprehensively analyzes the impact of the gut microbiota on hematopoiesis and its effect on HSCs fate and differentiation by modifying the b

Венецоклакс в сочетании с азаситидином в лечении вторичного миэлодипластического синдрома после нескольких миелом: доклад о деле и обзор литературы.

Мы провели ретроспективный анализ клинических данных пациента с миелодипластическим синдромом (MDS) вторичной и стабильной миеломой (MM), который лечился вместе с венетоклаксом и азаситидином в Пятом народном госпитале Ченду. Кроме того, мы изучили соответствующую литературу. Пациентка, 74-year-old Мужчина был первоначально диагностирован миеломой (IgA-__, DS IIIA, ISS III, R-ISS II) и получил очень хороший частичный ответ (VGPR) после последовательного лечения в рамках режимов BCTD, RVD и PVD, которые впоследствии получали алидомидную терапию. Несмотря на постоянную ремиссию, у пациента появи

Therapy-related myeloid neoplasms in 39 Korean patients: a single institution experience.

BackgroundTherapy-related myeloid neoplasms (t-MN) occur as late complications of cytotoxic therapy. This study reviewed clinical and cytogenetic characteristics of patients with t-MN at a single institution in Korea.MethodsThe study subjects included 39 consecutive patients diagnosed with t-MN. Each subject's clinical history of previous diseases, treatments, and laboratory data was reviewed, including cytogenetics. The primary diagnosis was hematologic malignancy in 14 patients and solid tumor in 25 patients.ResultsTherapy-related acute myeloid leukemia (t-AML, 66.7%) was found to be more co

The Calcium Conundrum: Hypercalcemia of Unknown Etiology.

Hypercalcemia is a common clinical finding with a wide variety of clinical presentations and etiologies. The differential is broad and includes hyperparathyroidism, malignancy, medication adverse effects, endocrinopathies, and a variety of granulomatous diseases. We present the case of an 84-year-old woman with severe parathyroid hormone-independent hypercalcemia and elevated 1,25-OH Vitamin D. Non-necrotizing granulomas were identified on bone marrow biopsy. After an exhaustive workup for granulomatous disease, the patient was felt to have sarcoidosis isolated to the bone marrow and started o

MASTering systemic mastocytosis: Lessons learned from a large patient cohort.

BACKGROUND: Systemic mastocytosis (SM), a rare condition affecting about 32,000 individuals in the United States, is often misdiagnosed or underdiagnosed owing to its nonspecific symptoms and the need for invasive biopsies. OBJECTIVE: Our aim was to identify, classify, and characterize the natural history of patients with SM. METHODS: In a retrospective cohort study, administrative data from a large managed care organization was used to identify patients with confirmed SM, based on World Health Organization criteria. Demographic data, delay to diagnosis, disease progression, and health care

Apical lung mass-A rare presentation of multiple myeloma.

Multiple myeloma is a neoplastic proliferation of immunoglobulin-producing plasma cells with clinical features resulting from infiltration of plasma cells into bones and other organs. Multiple myeloma manifesting as an apical lung mass is less common and very few cases have been reported. We report the case of a 50-year-old female who presented with an apical lung mass which happened to be multiple myeloma arising from the upper ribs into the lung. At the time of diagnosis, patient had axillary lymph node metastasis with extensive bony involvement. This case report and literature review provid

Emerging burden of post-cancer therapy complications on unplanned hospitalisation and costs among Australian cancer patients: a retrospective cohort study over 14 years.

Cancer treatment using systemic therapy and radiotherapy may cause post-therapy complications, resulting in increased unplanned hospitalisation. The evidence on such complications, their impact on unplanned hospitalisations, and associated costs is scant in Australia. We aimed to estimate the prevalence of post-therapy complications, evaluate their impact on unplanned hospitalisation, length of stay (LOS) and investigate the associated medical costs. A retrospective cohort study was conducted among 8,633 cancer patients (1.03 million emergency hospital admissions) in Victoria, Australia from J

Pathology Competencies in Medical Education and Educational Cases: Update 2023.

Pathology is a core component of medical school curricula because understanding the pathogenesis of the disease is foundational both for diagnostic efficiency and optimal use of ancillary resources in patient care. The Pathology Competencies for Medical Education (PCME) were developed as a national resource of expectations of pathology knowledge for medical students. The PCME are composed of three competencies: disease mechanisms and processes, organ system pathology, and diagnostic pathology and therapeutic pathology. The learning goals and learning objectives of the PCME that were first publ

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… Objective HWC4.1: Clinical Features of Bone Marrow Neoplasms . Identify the tumors of bone marrow most likely to present with anemia, leukopenia, or thrombocytopenia and discuss the presenting clinical features most likely to be associated with each. …

Solitary osseous plasmacytomas in dogs: 13 cases (2004-2019).

ObjectivesTo further characterise solitary osseous plasmacytoma in dogs, an extremely rare disease. To describe diagnosis, disease progression and treatment outcomes in dogs with solitary osseous plasmacytoma.Materials and methodsRetrospective review of dogs with solitary osseous plasmacytomas that were diagnosed and treated at a single institution from 2005 to 2019. Kaplan-Meier single group survival analysis was used to estimate median survival time and progression-free interval.ResultsThirteen dogs met the inclusion criteria for the study, and of those, 11 were treated. The median age at di

Hematopoietic stem cell transplantation in Zagreb: the first 40 years.

Hematopoietic stem cell transplantation is the most effective treatment for acute leukemia, severe aplastic anemia, and some hereditary hematological disorders. The principal source of stem cells in this procedure are bone marrow and peripheral blood cells. In recent years, the transplantation outcome has significantly improved. The availability of the donor no longer poses a problem, as transplantation has been performed routinely from related, unrelated, and haploidentical donors. A high success rate has been reported in elderly patients transplanted with reduced-intensity conditioning. Impr

Clonal hematopoiesis and its progression to myeloid neoplasms: insights into risk, biology, and therapeutic strategies.

Clonal hematopoiesis (CH) is defined by the clonal expansion of hematopoietic stem and progenitor cells harboring somatic mutations that confer a fitness advantage. CH is common with advancing age and becomes nearly ubiquitous in middle age. Although typically asymptomatic, CH is associated with an increased risk of hematologic malignancies particularly myeloid neoplasms (MN), diverse non-malignant conditions, and all-cause mortality. Over the past decade, research has provided major insights into the origins of CH. In addition to aging, CH is promoted by environmental exposures, inherited gen

Acute myeloid leukemia with plasmacytoid dendritic cell proliferation: A case report and literature review.

The present study describes a rare case of plasmacytoid dendritic cell-associated acute myeloid leukemia (pDC-AML). A 70-year-old male patient was diagnosed with pDC-AML and underwent induction chemotherapy using the venetoclax + azacitidine (VA) regimen. After 3 weeks of treatment, bone marrow examination indicated a morphologic leukemia-free state (MLFS); however, the patient experienced persistent cytopenia, which was further complicated by severe pneumonia and gastrointestinal bleeding, both of which improved following treatment. After 3 weeks in MLFS, bone marrow morphology and minimal re

Evolving Therapeutic Strategies for the Classic Philadelphia-Negative Myeloproliferative Neoplasms.

Despite the emergence of JAK inhibitors, there is a need for disease-modifying treatments for Philadelphia-negative myeloproliferative neoplasms (MPNs). JAK inhibitors ameliorate symptoms and address splenomegaly, but because of the heterogeneous contributors to the disease process, JAK inhibitor monotherapy incompletely addresses the burden of disease. The ever-growing understanding of MPN pathogenesis has provided the rationale for testing novel and targeted therapeutic agents, as monotherapies or in combination, in preclinical and clinical settings. A number of intriguing options have emerg

Hematopoietic Tumors

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