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What the Intensivist Needs to Know About Hematopoietic Stem Cell Transplantation?

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… The two most common preparative regimens for autologous HSCT are single-agent melphalan (primarily used for plasma cell disorders) and the combination of BCNU/carmustine, etoposide, Ara-C/cytarabine, and melphalan (BEAM) (primarily used for lymphomas). …

Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study.

BackgroundPatients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited.MethodsWe investigated the feasibility and clinical impact of multiparametric, single-cell, drug-respo

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… Roughly 60% of patients typically respond with complete remission to induction therapy, 31 which consists of cytarabine combined with daunorubicin and etoposide. 32 , 33 Each patient sample was screened through a drug combination matrix of all three first-line drugs, consisting of 125 unique drug concentration …

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Adults.

The nutritional status of patients submitted to hematopoietic stem cell transplant is considered an independent risk factor, which may influence on quality of life and tolerance to the proposed treatment. The impairment of nutritional status during hematopoietic stem cell transplant occurs mainly due to the adverse effects resulting from conditioning to which the patient is subjected. Therefore, adequate nutritional evaluation and follow-up during hematopoietic stem cell transplant are essential. To emphasize the importance of nutritional status and body composition during treatment, as well a

Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).

Cisplatin resistance remains a primary obstacle in oncology, leading to therapeutic failure and disease recurrence. While resistance mechanisms are multifactorial, metabolic reprogramming has emerged as a critical adaptive strategy for cancer cells to evade cisplatin-induced cytotoxicity. This review synthesizes current evidence on how altered metabolism drives cisplatin resistance, with a particular emphasis on the pivotal role of pyruvate dehydrogenase kinases (PDKs). PDKs act as metabolic gatekeepers by inhibiting the pyruvate dehydrogenase complex (PDHC), diverting glucose flux away from m

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… Liu Y Huang Q Tian L Zheng X Chen G Xu H Neoadjuvant adebrelimab combined with chemotherapy (cisplatin/carboplatin and etoposide) for limited-stage small-cell lung cancer: a study protocol of phase 2 trial (NIUS) BMJ Open 2025 15 1 e087302 10.1136/bmjopen-2024-087302 39800398 PMC11752003 Liu Y, Huang … Neoadjuvant adebrelimab combined with chemotherapy (cisplatin/carboplatin and etoposide) for limited-stage small-cell lung cancer: a study protocol of phase 2 trial (NIUS). BMJ Open. 2025;15(1):e087302. 10.1136/bmjopen-2024-087302. 39800398 10.1136/bmjopen-2024-087302 PMC11752003 8. …

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies.

Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic a

Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients.

Brain cancer and leukemia are the most common cancers diagnosed in the pediatric population and are often treated with lifesaving chemotherapy. However, chemotherapy causes severe adverse effects and chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and debilitating side effect. CIPN can greatly impair quality of life and increases morbidity of pediatric patients with cancer, with the accompanying symptoms frequently remaining underdiagnosed. Little is known about the incidence of CIPN, its impact on the pediatric population, and the underlying pathophysiological mecha

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progress

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… BVZ in combination with other cytotoxic drugs like carboplatin and etoposide also showed therapeutic benefit in clinical trials but is yet to be approved by FDA. …

Targeting Oncoproteins for Molecular Cancer Therapy

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… Bauer KS Karp JE Garimella TS A phase I and pharmacologic study of idarubicin, cytarabine, etoposide, and the multidrug resistance protein (MDR1/Pgp) inhibitor PSC-833 in patients with refractory leukemia Leuk Res 2005 29 263 71 10.1016/j.leukres.2004.07.002 15661261 18. … Kolitz JE George SL Dodge RK Dose escalation studies of cytarabine, daunorubicin, and etoposide with and without multidrug resistance modulation with PSC-833 in untreated adults with acute myeloid leukemia younger than 60 years: final induction results of Cancer and Leukemia Group B Study 9621 J Clin …

Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation.

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2

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… He received re-irradiation and second-line oral chemotherapy with trofosfamide and etoposide. Two months after the initiation of the second-line treatment, further tumor progression combined with blood–brain-barrier dysfunction was detected. …

Looking for the Holy Grail-Drug Candidates for Glioblastoma Multiforme Chemotherapy.

Glioblastoma multiforme (GBM) is the deadliest and the most heterogeneous brain cancer. The median survival time of GBM patients is approximately 8 to 15 months after initial diagnosis. GBM development is determined by numerous signaling pathways and is considered one of the most challenging and complicated-to-treat cancer types. Standard GBM therapy consist of surgery followed by radiotherapy or chemotherapy, and combined treatment. Current standard of care (SOC) does not offer a significant chance for GBM patients to combat cancer, and the selection of available drugs is limited. For almost

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… For example, lomustine (60 mg/m 2 on days 8–21/56), vincristine (1.4 mg/m 2 on days 8 and 29/56), cisplatin (60–100 mg/m 2 once every 3–4 weeks), etoposide (50 mg daily), and procarbazine (110 mg/m 2 day 1/56) [ 20 ] are used in GBM treatment. …

Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation.

The age of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has increased during the last decades, mainly due to improved reduced-intensity/toxicity conditioning protocols. A reduced-intensity conditioning based on fludarabin, carmustin/BCNU and melphalan (FBM) has been previously developed at our institution. Since we observed detrimental effects in individual patients with compromised lung function, efforts have been made in order to replace BCNU by thiotepa (FTM) to reduce toxicity. In this study, we retrospectively analyzed the outcome, GvHD incidence, lung func

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… Jagannath S Dicke KA Armitage JO Cabanillas FF Horwitz LJ Vellekoop L High-dose cyclophosphamide, carmustine, and etoposide and autologous bone marrow transplantation for relapsed Hodgkin’s disease Ann Intern Med 1986 104 163 8 10.7326/0003-4819-104-2-163 3511811 4. …

Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia.

Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduce

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… These regimens included a high intensity treatment group (mitoxantrone/etoposide/cytarabine and FLAG-IDA) and a low intensity group (low-dose cytarabine and azacitidine) [ 47 ]. …

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors.

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, b

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… dexamethasone, Pd = pomalidomide + dexamethasone, PI = proteasome inhibitor, RRMM = relapsed refractory multiple myeloma, Sd = selinexor + dexamethasone, SVd = selinexor + bortezomib + dexamethasone, VdT-PACE = bortezomib + dexamethasone + thalidomide + cisplatin + doxorubicin + cyclophosphamide + Etoposide …

Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation.

Antimicrobial resistance is an important issue for global health; in immunocompromised patients, such as solid organ and hematological transplant recipients, it poses an even bigger threat. Colonization by multidrug-resistant (MDR) bacteria was acknowledged as a strong risk factor to subsequent infections, especially in individuals with a compromised immune system. A growing pile of studies has linked the imbalance caused by the dominance of certain taxa populating the gut, also known as intestinal microbiota dysbiosis, to an increased risk of MDR bacteria colonization. Several attempts were p

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… Their patient, a 14-year-old girl with a recent diagnosis of hemophagocytic lymphohistiocytosis treated with corticosteroids and etoposide, developed fever, and KPC-Kp was isolated through blood culture. …

New directions for emerging therapies in acute myeloid leukemia: the next chapter.

Conventional therapy for acute myeloid leukemia is composed of remission induction with cytarabine- and anthracycline-containing regimens, followed by consolidation therapy, including allogeneic stem cell transplantation, to prolong remission. In recent years, there has been a significant shift toward the use of novel and effective, target-directed therapies, including inhibitors of mutant FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase (IDH), the B-cell lymphoma 2 inhibitor venetoclax, and the hedgehog pathway inhibitor glasdegib. In older patients the combination of a hypometh

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… second-generation FLT3 inhibitors quizartinib and gilteritinib as single agents improved marrow remission rates and OS compared with traditional salvage chemotherapies (investigator’s choice of high-intensity therapies such as fludarabine–Ara-C–granulocyte colony-stimulating factor–idarubicin or mitoxantrone-etoposide-cytarabine …

Skeletal Metastases of Unknown Primary: Biological Landscape and Clinical Overview.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge in dealing with patients diagnosed with bone metastases. Management of these patients has improved significantly in the past few years. however, it is fraught with a lack of evidence. While some patients have achieved impressive gains, a more systematic and tailored treatment is required. Nevertheless, in real-life practice, the outlook at the beginning of treatment for SMUP is decidedly somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisf

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… Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: A randomized, phase III Sarah Cannon Oncology Research Consortium Trial Cancer J. 2010 16 70 75 10.1097/PPO.0b013e3181c6aa89 20164695 87. Culine S. …

Stem Cells as Potential Candidates for Psoriasis Cell-Replacement Therapy.

Recent years have seen considerable progress in explaining the mechanisms of the pathogenesis of psoriasis, with a significant role played in it by the hyper-reactivity of Th1 and Th17 cells, Treg function disorder, as well as complex relationships between immune cells, keratinocytes, and vascular endothelium. The effect of stem cells in the epidermis and stem cells on T cells has been identified and the dysfunction of various types of stem cells may be a prime cause of dysregulation of the inflammatory response in psoriasis. However, exploring these mechanisms in detail could provide a chance

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… ; ATG, antithymocyte globulin; AA, aplastic anemia; ASCT, autologous stem cell transplantation; PPP, plantopalmar psoriasis pustulosa; DRB, doxorubicin; 6-MP, 6-mercaptopurine; BH-AC; AML, acute myeloid leukemia; BH-AC, behenoyl cytosine arabinoside; BCNU1,3-bis (2-chloroethyl)-1-nitroso-urea; ETO, etoposide …

The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

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… Moreover, FI-sufficient cells exhibits significant resistance to programmed cell death via etoposide and they create larger colonies than FI-deficient ones [ 111 ]. 5.15. …

Canine Multicentric Lymphoma: Diagnostic, Treatment, and Prognostic Insights.

Lymphoma accounts for 24% of all documented canine neoplasms and 85% of hematological malignancies, while multicentric lymphoma corresponds to 84% of all canine lymphomas. Canine lymphomas of B-cell origin account for 60% to 80% of lymphomas. Similar to humans, the histologic grade, architecture, as well as immunophenotype determination, are crucial. These lesions are the most prevalent spontaneous tumors in dogs and this species may be a valuable animal model for the study of human non-Hodgkin's lymphoma. Therefore, it is important to investigate and assess therapeutic responses and to seek p

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… The most common drugs used are actinomycin D, mitoxantrone, doxorubicin (if not used in the original induction protocol), dacarbazine (DTIC), temozolomide, CCNU, L-asparaginase, mechlorethamine, vincristine, vinblastine, procarbazine, prednisone, and etoposide ( Table 4 ). …

Leptomeningeal carcinomatosis in gastric cancer: A Review.

Gastric cancer is the fifth most common cancer worldwide and leptomeningeal carcinomatosis (LM) occurs in 0.06% of gastric cancers. As such, trials are difficult to power and quantitative analyses difficult to standardize. We composed a review and analysis of 47 recent cases to be used as a comprehensive resource for an oncologist faced with managing this highly morbid, rapidly fatal disease. Gold-standard of diagnosis of LM is through cerebral spinal fluid (CSF) cytology; MRI is the preferred imaging modality to identify LM. However, repeated lumbar punctures and imaging studies are often req

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… NCCN guidelines recommend systemic therapy specific to the primary cancer type and intrathecal chemotherapy with thiotepa, topotecan, etoposide, cytarabine, or methotrexate – doses and duration of treatment are not included [ 34 ]. …