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Biomarkers for the Immune Checkpoint Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Weijie Ma, Sixi Wei, Eddie C. Tian, Tianhong Li
Several recent studies showed that ICIs could increase the absolute number of lymphocytes, restore the function in exhausted CD8+ T cells, and induce phenotypic and functional changes of effector immune cells. PD-L1 expressed on the surface of TILs may be correlated to the efficacy of anti-PD-1 immunotherapy in NSCLC [113]. Examination of blood-derived parameters, including absolute neutrophil counts (ANC) and derived neutrophil-to-lymphocyte ratio (dNLR), could identify responders to immune checkpoint inhibition. A prospective study of 720 patients with metastatic MM shows that elevated ANC levels are associated with a significant decrease in the OS and PFS of the patients treated with ipilimumab. High absolute lymphocyte counts (ALC) measured before and during ipilimumab treatment are linked to prolonged PFS [51, 52]. High dNLR, defined as the ratio of pretreatment neutrophils/(leukocytes minus neutrophils), and lactate dehydrogenase (LDH) levels were associated with resistance to ICI treatment. A lung immune prognostic index (LIPI) based on a dNLR greater than 3 and LDH greater than the upper limit of normal was correlated with worse outcomes for immunotherapy. Median OS for poor, intermediate, and good LIPI was 3 months, 10 months, and 34 months, respectively [53]. In a subgroup analysis of patients treated with ipilimumab in a phase II trial, higher baseline C-reaction protein (CRP) levels were associated with significantly improved freedom from relapse and a marginally significant improvement in relapse-free survival [54].
Breast cancer
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Sarah J Vinnicombe, Alexandra Athanasiou
The ACOSOG Z0011 study has fundamentally changed management of the axilla in ESBC. It concluded that patients with T1/2 tumours, clinically negative axillae, and up to 2 positive SLN could be spared ANC, provided systemic treatment and whole-breast radiotherapy were given (107). Ten-year results show no significant difference in disease-free and overall survival in patients treated only with SLNB (108). However, the results cannot be generalized to patients undergoing mastectomy or with ILC. Subsequently, the question has arisen whether US is excluding patients from the potential benefits of avoiding ANC by identifying small volume nodal disease. However, US is critical in identification of impalpable N2/N3 disease, which affects therapy planning (109). It can exclude a heavy nodal burden with NPVs approaching 96% and 83% for IDC and ILC, respectively (110), and is crucial before NAC. The ongoing SOUND trial is comparing SLNB vs. observation in patients with small breast cancers and a negative axillary US (111), and the POSNOC trial of women with 1–2 macrometastases at SLNB is comparing the results of adjuvant therapy plus axillary intervention (ANC or axillary radiotherapy) with adjuvant therapy alone (112).
Acute Leukemia and Myelodysplastic Syndromes
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Mark D. Brissette, James D. Cotelingam
M5 is monocytic leukemia and comprises 10% of AML. Monoblasts, promonocytes, and monocytes constitute 80% or more of ANC in bone marrow. There are two subtypes determined by the percentage of monoblasts: M5a and M5b (Figs. 10 and 11, Tables 6 and 7). Monocyte differentiation is shown by positivity for A-EST and/or B-EST.
Pregnant women’s perceptions of antenatal care and utilisation of digital health tools in Magu District, Tanzania: a qualitative study
Published in Sexual and Reproductive Health Matters, 2023
Sandra van Pelt, Marit van der Pijl, Robert A.C. Ruiter, Pendo M. Ndaki, Rehema Kilimba, Laura Shields-Zeeman, John B.F. de Wit, Karlijn Massar
Although women did not explicitly state that the quality of care they received was poor, the current study also found that participants did express some concerns about the quality of care, specifically in relation to their experiences of receiving ANC (Theme 1), the perceived barriers to attending ANC (Theme 3), and their views on healthcare workers’ behaviours and responsibilities (Theme 4). Specifically, they noted poor availability of diagnostic tests, as well as the low motivation of healthcare workers. This is in line with the findings of other studies on ANC.1,3,5,16,18,20,55 Previous research on healthcare workers’ perceptions of the quality of ANC in Magu District indicated a lack of motivated healthcare workers providing ANC,50,56 which is in line with the experiences of our participants. Furthermore, participants mentioned they were often obliged to buy medication, despite the policy of the Ministry of Health to provide free medication. Healthcare workers obliging women to buy their medication is a well-known issue in Tanzania, as also identified in other studies.1,7,16,18
Real-world experience of treatment with thrombopoietin receptor agonists in anti-thymocyte globulin-naïve patients with aplastic anemia: an observational retrospective analysis in a single institution
Published in Hematology, 2022
Masaki Iino, Atsushi Jinguji, Tomoya Sato, Ayato Nakadate
AA and the severity of disease have been defined previously [8]. Platelet, erythroid, and neutrophil responses were defined as described previously [17]. Briefly, platelet response was defined as an increase to 20×109/L above baseline in non-transfused patients, or in transfused patients, stable platelet counts with transfusion independence for at least 8 weeks. Erythroid response was defined as an increase in hemoglobin by 1.5 g/dL in non-transfused patients, or in transfused patients, an absolute reduction of at least 4 units of packed red blood cell transfusions for 8 consecutive weeks, compared with the number of transfusions in the 8 weeks prior to treatment. Neutrophil response was defined as a two-fold increase in absolute neutrophil counts (ANC) from a baseline level of <0.5 × 109/L, or an increase in ANC ≥ 0.5 × 109/L from baseline. In patients with platelet counts ≥100 × 109/L, hemoglobin levels ≥9 g/dL, and ANC ≥ 1.0 × 109/L at enrollment, increases in these parameters were not considered for response assessment. Time to hematologic response was defined as the interval from eltrombopag initiation to any hematologic response. OS was defined as the duration from the first day of eltrombopag administration to death from any cause. AEs during TPO-RA treatment were evaluated in accordance with the National Cancer Institute’s Common Terminology Criteria, version 5.0 [18].
Colony stimulating factors for prophylaxis of chemotherapy-induced neutropenia in children
Published in Expert Review of Clinical Pharmacology, 2022
Neutropenia is the absolute neutrophil count (ANC) less than 500 cells/mm3 or an ANC that is expected to decrease to less than 500 cells/mm3 during the next 48 hours. Profound neutropenia is ANC of 100 cells/mm3 or less. Fever where temperature of 38.3°C or greater during chemotherapy-induced neutropenia may be the indication for severe infection. It is possible for neutropenic or other immunocompromised patients to have an infection without a presence of fever [2]. High-risk patients are those with anticipated prolonged (more than 7 days) and profound neutropenia and/or significant comorbidities such as hypotension, pneumonia, new onset abdominal pain, or neurological changes. These patients need to be initially admitted to a hospital for empirical therapy [2].