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BMC Cancer Jun 2024Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best...
PURPOSE
Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG.
METHODS
A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis.
RESULTS
The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction.
CONCLUSIONS
Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.
Topics: Humans; Temozolomide; Female; Male; Adult; Pyridines; Glioma; Adolescent; Retrospective Studies; Child; Brain Neoplasms; Young Adult; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Middle Aged; Treatment Outcome
PubMed: 38907215
DOI: 10.1186/s12885-024-12373-9 -
Phytomedicine : International Journal... Jun 2024Myelosuppression is a serious and common complication of radiotherapy and chemotherapy in cancer patients and is characterized by a reduction of peripheral blood cells.... (Review)
Review
BACKGROUND
Myelosuppression is a serious and common complication of radiotherapy and chemotherapy in cancer patients and is characterized by a reduction of peripheral blood cells. This condition not only compromises the efficacy of treatment but also increases the risk of patient death. Natural products are emerging as promising adjuvant therapies due to their antioxidant properties, ability to modulate immune responses, and capacity to stimulate haematopoietic stem cell proliferation. These therapies demonstrate significant potential in ameliorating myelosuppression.
METHODS
A systematic review of the literature was performed utilizing the search terms "natural products," "traditional Chinese medicine," and "myelosuppression" across prominent databases, including Google Scholar, PubMed, and Web of Science. All pertinent literature was meticulously analysed and summarized. The objective of this study was to perform a pertinent analysis to elucidate the mechanisms underlying myelosuppression and to categorize and synthesize information on natural products and traditional Chinese medicines employed for the therapeutic management of myelosuppression.
RESULTS
Myelosuppression resulting from drug and radiation exposure, viral infections, and exosomes is characterized by multiple underlying mechanisms involving immune factors, target genes, and the activation of diverse signalling pathways, including the (TGF-β)/Smad pathway. Recently, traditional Chinese medicine monomers and compounds, including more than twenty natural products, such as Astragalus and Angelica, have shown promising potential as therapeutics for ameliorating myelosuppression. These natural products exert their effects by modulating haematopoietic stem cells, immune factors, and critical signalling pathways.
CONCLUSIONS
Understanding the various mechanisms of myelosuppression facilitates the exploration of natural product therapies and biological target identification for evaluating herbal medicine efficacy. This study aimed to establish a foundation for the clinical application of natural products and provide methodologies and technical support for exploring additional treatments for myelosuppression.
PubMed: 38905848
DOI: 10.1016/j.phymed.2024.155810 -
Scientific Reports Jun 2024This study aimed to investigate impacts of Omicron infection on cancer patients in China. A retrospective study was conducted, including 347 cancer patients undergoing...
Completion rates and myelosuppression degrees of cancer patients receiving radiotherapy or chemoradiotherapy unchanged regardless of delay duration after Omicron infection.
This study aimed to investigate impacts of Omicron infection on cancer patients in China. A retrospective study was conducted, including 347 cancer patients undergoing radiotherapy or chemoradiotherapy between July 2022 and March 2023. Three groups involved: 108 patients without SARS-CoV-2 infection (non-COVID-19 group), 102 patients beginning treatment 10 days after first SARS-CoV-2 infection (≥ 10 days COVID-19 group), and 137 patients beginning treatment less than 10 days after first SARS-CoV-2 infection (< 10 days COVID-19 group). SAA, hsCRP, ALT, etc., were used to assess COVID-19 infection. Serum levels of SAA, hsCRP and IL-6 were all raised in two COVID-19-infected groups (SAA < 0.01, hsCRP < 0.01, IL-6 < 0.05), but PCT, ALT, LDH and HBDH levels were only elevated in ≥ 10 days COVID-19 group (PCT = 0.0478, ALT = 0.0022, LDH = 0.0313, HBDH = 0.0077). Moreover, moderate and severe infected cases were higher in ≥ 10 days COVID-19 group than < 10 days COVID-19 group (12/102 vs 5/137, p = 0.0211), but no significance in myelosuppression and completion rates among three groups. Omicron infection led to inflammation, liver and cardiovascular injury on cancer patients, but delay duration of radiotherapy or chemoradiotherapy after infection did not affect the completion rates and myelosuppression of current therapy. Besides, severity of Omicron infection was even worse among cancer patients who received delayed treatment.
Topics: Humans; COVID-19; Female; Male; Middle Aged; Neoplasms; Chemoradiotherapy; Retrospective Studies; Aged; SARS-CoV-2; Adult; China
PubMed: 38902401
DOI: 10.1038/s41598-024-65019-y -
BioRxiv : the Preprint Server For... Jun 2024Treatment strategies for Crohn's disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous hematopoietic stem cell...
BACKGROUND
Treatment strategies for Crohn's disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous hematopoietic stem cell transplantation (SCT) has emerged as a therapy for medically refractory CD. SCT was developed to rescue cancer patients from myelosuppressive chemotherapy but its use for CD and other immune diseases necessitates reimagining SCT as a cellular therapy that restores appropriately responsive immune cell populations from hematopoietic progenitors in the stem cell autograft (i.e. immune "reset"). Here we present a paradigm to understand SCT as a cellular therapy for immune diseases and reveal how SCT re-establishes cellular immunity utilizing high-dimensional cellular phenotyping and functional studies of the stem cell grafts.
METHODS
Immunophenotyping using CyTOF, single cell RNA sequencing (scRNA-seq) and T cell receptor (TCR) sequencing was performed on peripheral blood and intestinal tissue samples from refractory CD patients who underwent SCT. The stem cell graft from these patients was analyzed using flow cytometry and functionally interrogated using a murine model for engraftment.
RESULTS
Our study revealed a remodeling of intestinal macrophages capable of supporting mucosal healing that was independently validated using multimodal studies of immune reconstitution events including CyTOF and scRNA-seq. Functional interrogation of hematopoietic stem cells (HSCs) using a xenograft model demonstrated that HSCs shape the timing of immune reconstitution, the selected reconstitution of specific cell lineages and potentially the clinical efficacy of SCT.
CONCLUSIONS
These studies indicate that SCT serves as a myeloid-directed cellular therapy re-establishing homeostatic intestinal macrophages that support intestinal healing and suggest refractory CD evolves from impairment of restorative functions in myeloid cells. Furthermore, we report heterogeneity among HSCs from CD patients which may drive SCT outcomes and suggests an unrecognized impact of CD pathophysiology on HSC in the marrow niche.
PubMed: 38895305
DOI: 10.1101/2024.05.30.596699 -
International Journal of Molecular... May 2024Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA)...
Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [At]PSMA-5 was administered to both normal male ICR mice ( = 85) and cynomolgus monkeys ( = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( = 10 per group) and 14 days ( = 5 per group). Monkeys were observed 24 h post-administration of [At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of At using a cyclotron supports its applicability for clinical use.
Topics: Animals; Male; Prostatic Neoplasms; Mice; Tissue Distribution; Mice, Inbred ICR; Astatine; Alpha Particles; Humans; Macaca fascicularis; Glutamate Carboxypeptidase II; Radiopharmaceuticals
PubMed: 38891856
DOI: 10.3390/ijms25115667 -
Gan To Kagaku Ryoho. Cancer &... May 2024A 73-year-old woman was referred to our hospital with a chief complaint of black stools and abdominal distention. She was diagnosed with advanced gastric cancer with...
A 73-year-old woman was referred to our hospital with a chief complaint of black stools and abdominal distention. She was diagnosed with advanced gastric cancer with pyloric stenosis and multiple lymph node metastasis(cT4aN3M0, cStage Ⅲ)and was administered preoperative chemotherapy after laparoscopy and gastric jejunal bypass surgery. The surgical diagnosis was sT4aN3M0P0CY0. After surgery, 2 courses of DS therapy were administered. However, a new liver metastatic lesion was found, and XELOX therapy was selected as the second-line of treatment. Subsequently, enlarged hepatic hilar lymph nodes were found; microsatellite instability testing confirmed MSI-High cancer. Nivolumab was selected as the third- line therapy. After 15 courses, a new liver metastatic lesion appeared. Although Ram+nab-PTX therapy was chosen as the fourth-line therapy, the patient developed myelosuppression after 3 courses. Two years and 4 months after the initial treatment, the patient was considered to have achieved CR. Because drug-induced liver injury had occurred, the Ram therapy was discontinued. The patient has remained in CR for 1 year without receiving any anticancer drugs. This case suggests that for MSI-high patients with gastric cancer, the consideration of treatment strategy should be based on the molecular biological background.
Topics: Humans; Stomach Neoplasms; Aged; Female; Antineoplastic Combined Chemotherapy Protocols; Microsatellite Instability
PubMed: 38881067
DOI: No ID Found -
Cancer Treatment and Research... May 2024Myelosuppression, a challenge in cancer treatment, often results in severe complications. Prophylactic granulocyte colony-stimulating factors, particularly... (Review)
Review
INTRODUCTION
Myelosuppression, a challenge in cancer treatment, often results in severe complications. Prophylactic granulocyte colony-stimulating factors, particularly pegfilgrastim, mitigate chemotherapy-induced neutropenia. This narrative review evaluates the role of on-body injector (OBI) devices for pegfilgrastim administration. A comprehensive search strategy of PubMed and AI-powered intuitive search tools, complemented by authors' contributions, yielded a body of papers presenting evidence on OBI devices, their effectiveness and safety, the benefits and challenges of OBI versus pre-filled syringe administration, patient preferences for pegfilgrastim administration, and economic considerations.
DISCUSSION
OBI devices prove effective and safe, with advantages such as reduced clinic visits and enhanced adherence. Studies highlight cost-efficiency and expanded access, emphasizing the socioeconomic context. Patient and provider preferences underscore the potential of OBI devices in cancer care, with implications for healthcare resource utilization and pharmacoeconomics.
CONCLUSION
The value proposition of OBI devices lies in improving patient outcomes, convenience, resource optimization, and enhancing the overall cancer care experience. As biosimilar OBIs enter the market, they may offer cost savings, further influencing their adoption and their positioning as a cost-efficient alternative in cancer care. Ongoing research and technological advancements are expected to contribute to the broader acceptance of OBI devices in cancer care delivery.
PubMed: 38865836
DOI: 10.1016/j.ctarc.2024.100824 -
Clinical Lymphoma, Myeloma & Leukemia May 2024Outcomes are dismal for patients with myelofibrosis (MF) who are no longer responsive to JAK2 inhibitors (JAKi) and/or have increasing blast cell numbers. Although prior...
BACKGROUND
Outcomes are dismal for patients with myelofibrosis (MF) who are no longer responsive to JAK2 inhibitors (JAKi) and/or have increasing blast cell numbers. Although prior reports have suggested the benefits of intravenous decitabine (DAC) combined with ruxolitinib for patients with Myeloproliferative Neoplasm (MPN) accelerated/blast phase (AP/BP), decitabine-cedazuridine (DEC-C), an oral fixed-dose combination providing equivalent pharmacokinetic exposure, has not been evaluated in MF.
METHODS
We conducted a retrospective analysis of 14 patients with high-risk MF refractory to ruxolitinib or MPN-AP (10-19% blasts) treated with DEC-C +/- JAKi at Mount Sinai Hospital from 2021 to 2024.
RESULTS
The cohort was elderly (median age,76 years) and almost uniformly possessed high risk mutations with 13 of the 14 patients progressing on JAKi therapy. With a median follow-up of 9.4 months, the median overall survival (OS) was 29 months for the entire cohort. Median OS was 10.8 months for MPN-AP and was not reached for ruxolitinib refractory MF patients. All patients (n = 9) receiving > 4 cycles of DEC-C had clinical benefit exemplified by a reduction in blast cell numbers, spleen size, and lack of progression to MPN-BP (78%). Furthermore, 3/14 patients proceeded to allogeneic stem cell transplant. Myelosuppression was a common adverse event which was managed by reducing the number of days of administration of DEC-C from 5 to 3 per cycle.
CONCLUSIONS
This report demonstrates the feasibility, tolerability, and clinical benefit of an exclusively ambulatory regimen for high-risk, elderly patients with advanced MF which warrants further evaluation in a prospective clinical trial.
PubMed: 38839448
DOI: 10.1016/j.clml.2024.05.012 -
Frontiers in Immunology 2024This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and...
PD-1 inhibitor combined with paclitaxel and cisplatin in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma: efficacy and survival outcomes.
OBJECTIVE
This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC).
METHODS
Patients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3-4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism.
CONCLUSION
In the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.
Topics: Humans; Paclitaxel; Male; Female; Middle Aged; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Aged; Hypopharyngeal Neoplasms; Retrospective Studies; Adult; Neoplasm Recurrence, Local; Immune Checkpoint Inhibitors; Laryngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome; Programmed Cell Death 1 Receptor; Neoplasm Metastasis
PubMed: 38827739
DOI: 10.3389/fimmu.2024.1353435