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Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application.

JAK-STAT (Janus associated kinase-signal transducer and activator of transcription) pathway plays a critical role in transduction of extracellular signals from cytokines and growth factors involved in hematopoiesis, immune regulation, fertility, lactation, growth and embryogenesis. JAK family contains four cytoplasmic tyrosine kinases, JAK1-3 and Tyk2. Seven STAT proteins have been identified in human cells, STAT1-6, including STAT5a and STAT5b. Negative regulators of JAK-STAT pathways include tyrosine phosphatases (SHP1 and 2, CD45), protein inhibitors of activated STATs (PIAS), suppressors o

The Bloody Crossroads: Interactions between Periodontitis and Hematologic Diseases.

Periodontitis is a common oral condition that can have a significant impact on the overall health of the body. In recent years, attention has been paid to potential relationships between periodontitis and various hematological disorders. This publication aims to present information available in the literature on this relationship, focusing on examples of red blood cell disorders (such as aplastic anemia and sickle cell anemia) and white blood cell disorders (such as cyclic neutropenia, maladaptive trained immunity, clonal hematopoiesis, leukemia, and multiple myeloma). Understanding these asso

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… Proposed Protocol for Treatment of Severe Periodontitis without Platelet Transfusion in Patients with Aplastic Anemia: A Case Report. J. Med. Case Rep. 2021;15:581. doi: 10.1186/s13256-021-03170-0. 30. Roberts M., Jimson S., Srinivasan M. …

Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report.

Castleman disease (CD) is a relatively rare lymphoproliferative disorder. Lesions predominantly originate on the chest and neck and rarely occur on the abdomen. A 34-year-old female presented to our hospital with an unexplained 10-year history of anemia. A pathological diagnosis of plasma cell-type CD was established. One cycle of chemotherapy (thalidomide, cyclophosphamide, and prednisolone) improved her anemia significantly. Prompt etiological diagnosis and early intervention are essential to address systemic manifestations in patients with CD, and it is crucial to consider CD as a different

A Focus on Special Populations in Relapsed Multiple Myeloma.

The overall care of patients with multiple myeloma can present similar challenges. However, disparities in health care require that providers consider each individual's unique circumstances. Disparities based on ethnic/racial group, religion, socioeconomic status, age, sexual orientation or gender identity, or other characteristics can lead to patients receiving less than optimal care and therefore poorer outcomes. Patients who have received more than two lines of therapy can acquire new genetic changes, accelerated cadence of relapse, and suffer from disease sequelae such as pain from prior o

Chimeric antigen receptor therapy for hematological malignancies: a pediatric perspective from leukapheresis to infusion.

Immunotherapy, particularly chimeric antigen receptor T cells (CAR T)s, has changed the landscape of B-cell malignancy treatment and represents a promising approach to cancer therapy. The use of CAR T-based therapy in pediatric patients presents several critical issues such as the quality of the leukapheresis process and the treatment-related toxicity. Nevertheless, the experience with anti-CD19 CAR Ts in treating pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) demonstrated its feasibility and efficacy with a complete response rate greater than 80%. Although CAR T therapy is

Safety and efficacy of daratumumab in immune thrombocytopenia.

AbstractResistance to B-cell-targeted therapies in immune thrombocytopenia (ITP) has been linked to persistence of autoantibody-producing CD38+ long-lived plasma cells. CD38 antibody daratumumab has been proposed as a potential therapy for ITP. This multicenter, open-label, phase 2 study evaluated safety and efficacy of daratumumab in 21 patients with previously treated ITP. Following a safety run-in, 2 dosing cohorts received 8 and 10 subcutaneous injections of 1800 mg daratumumab weekly, respectively. Primary end points were safety and response (2 consecutive platelet counts ≥50 × 109/L at w

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… Rescue therapy (IV immunoglobulin, corticosteroids, anti-D and platelet transfusions) was allowed until the day of the administration of the last injection of study treatment; its use after that qualified the patient as a nonresponder. …

Anti-IL-6R Ab tocilizumab to treat paraneoplastic inflammatory syndrome of solid cancers.

BACKGROUND: Paraneoplastic inflammatory syndrome (PIS) with fever and biological inflammation is a rare but severe condition often caused by the systemic production of interleukin 6 (IL-6) by cancer cells. We report on the efficacy of tocilizumab, an anti-IL-6 receptor antibody, in 35 patients with severe PIS. PATIENTS AND METHODS: All 35 patients with solid cancers (sarcomas, lung carcinoma, and breast carcinoma) diagnosed with a PIS from 2019 to 2024 treated with tocilizumab were analyzed in this single-center study (health authorities' approval R201-004-478). Patients' characteristics and

Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention.

Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis,

Targeted antineoplastic therapy in critically ill cancer patients: a multicenter analysis of the iCHOP registry.

Approximately 20% of intensive care unit (ICU) patients have cancer, and their prognosis has markedly improved in recent years. In addition to improved treatment in the ICU, this is a result of advancements in cancer therapies, including the use of targeted therapies (TTs), such as antibodies and small-molecule kinase inhibitors. Despite the increasing use of TT, there are currently no comprehensive studies examining critically ill cancer patients receiving TT in the ICU. We studied the clinical characteristics of a multicenter cohort of cancer patients who received TT in the ICU. To this end,

Intensive Care Outcomes of Patients after High Dose Chemotherapy and Subsequent Autologous Stem Cell Transplantation: A Retrospective, Single Centre Analysis.

High dose chemotherapy (HDT) followed by autologous peripheral blood stem cell transplantation (ASCT) is standard of care including a curative treatment option for several cancers. While much is known about the management of patients with allogenic SCT at the intensive care unit (ICU), data regarding incidence, clinical impact, and outcome of critical illness following ASCT are less reported. This study included 256 patients with different cancer entities. Median age was 56 years (interquartile ranges (IQR): 45-64), and 67% were male. One-year survival was 89%; 15 patients (6%) required treatm

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… However, neutropenia is expected to be severe, and patients often need red blood cell and platelet transfusion as well as intravenous antibiotic treatment. Overall, the predominant complications of HDT are infections [ 8 ]. …

Myeloablative fractionated busulfan for allogeneic stem cell transplant in older patients or patients with comorbidities.

Traditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce nonrelapse mortality (NRM) while retaining antileukemic effects. Here, we performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m2 as outpatients on days -20 and -13 before transplant.

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… Platelet engraftment was defined as a platelet count of ≥20 × 10 9 cells per L for 7 consecutive days without platelet transfusion. …

Acute Respiratory Failure After Hematopoietic Stem Cell Transplantation

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… Platelet transfusion is of limited value. Mortality is commonly due to superimposed multiorgan system failure or sepsis. …

High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration.

The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m(-2)), etoposide (900 mg m(-2)) and melphalan (100 mg m(-2)) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological tox

Pharmacovigilance in Cell and Gene Therapy: Evolving Challenges in Risk Management and Long-Term Follow-Up.

Cell and gene therapies, including CAR T-cells, CRISPR-based genome editing, and next-generation viral and non-viral delivery platforms, are transforming treatment paradigms across cancer, rare genetic disorders, immune dysregulation, and neurodegenerative disease. These therapies offer curative potential but also present safety challenges owing to prolonged biological activity, systemic immune engagement, and lasting genomic alterations. This review examines the range of related toxicities, including immune complications, genotoxicity, and organ-specific effects, with attention to atypical pr

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… Management is mainly supportive and includes red blood cell and platelet transfusions, the use of growth factors such as G-CSF or thrombopoietin receptor agonists to stimulate blood cell production, and antimicrobial prophylaxis to reduce the risk of infection. … Proactive supportive measures, including G-CSF for neutropenia, red cell and platelet transfusions, intravenous immunoglobulin (IVIG) for hypogammaglobulinemia, and tailored antimicrobial prophylaxis, are critical to reducing infection-related nonrelapse mortality, which accounts for over half of all …

Синдром PEEMS: 2026 Обновленная информация по диагностике, статистике рисков и управлению.

Синдром PEMS — это угрожающий жизни синдром, вызванный плазменной неоплазмой. Основными критериями для этого синдрома являются полиномропатическое расстройство клональных клеток (ПХД), склеротические повреждения костей, повышенный сосудистый эндотелиальный фактор роста и наличие болезни Каслмана. Незначительные особенности включают в себя органомегалию, эндокринопатию, характерные изменения кожи, папилледему, вневаскулярную перегрузку объема и тромбоцитоз. Диагноз синдрома POEMS three основных критериев, two в том числе полиномропаты и клональные плазменные клетки, и по крайней мере one незнач

Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study.

Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) - a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end-organ damage. To date, carfilzomib-associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance single-agent carfilzomib, two occurred at induction with carfilzo

Indications for haematopoietic cell transplantation and CAR-T for haematological diseases, solid tumours and immune disorders: 2025 EBMT practice recommendations.

For over two decades, the EBMT has updated recommendations on indications for haematopoietic cell transplantation (HCT) practice based on clinical and scientific developments in the field. This is the ninth special EBMT report on indications for HCT for haematological diseases, solid tumours and immune disorders. Our aim is to provide guidance on HCT indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered with the risk of the disease, risk of HCT procedure and non-HCT strategies, includi

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… Hb <80 g/L, ANC < 0.8 × 10 9 /L, platelets <50 × 10 9 /L), or severe BM fibrosis. d e.g. extramedullary involvement, significant B symptoms, (hyper)leukocytosis, iron overload, red blood cell transfusion dependence (≥2 per month), platelet transfusion dependence (≥1 per week) splenomegaly, PB or BM blasts …

Clinical Outcomes and Treatment Strategies of Adult Transplant-Associated Thrombotic Microangiopathy: External Validation of Harmonizing Definitions and High-Risk Criteria.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high-risk features on the clinical outcomes of adult patients meeting the updated TA-TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA-TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34-283 days). The development of TA-TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97

7-day longitudinal proteomics of critically ill patients: a pilot study.

An adult's health, indicated by measurable parameters, is stable over time. With the exception of circadian rhythms, variability in these parameters typically does not exceed 20%. In this pilot study, we looked into the stability of proteome in intensive care unit (ICU) patients. This was a single-center, prospective, observational pilot study of blood plasma from adult ICU patients with statistically heterogeneous patterns of clinically observed parameters. Eight week-long batches from seven patients (one patient participated twice) were analyzed by means of bottom-up proteomics. The data wer

Parvovirus B19-induced hemophagocytic lymphohistiocytosis: Case report and review of the literature.

HLH is a catastrophic and likely underdiagnosed pathology with multiple triggers including infection. PVB19 can cause persistent marrow infection leading to HLH despite negative acute serologic markers making timely diagnosis difficult. Increased awareness of PVB19-HLH is warranted given its potentially lethal nature and the careful interpretation required with serologic markers.