Hairy Cell Leukemia
Dongyou Liu in Tumors and Cancers, 2017
Patients with HCL may be asymptomatic, and the disease is discovered on a routine checkup. Alternatively, patients manifest symptoms associated with cytopenias such as opportunistic infections, fatigue, bleeding, and/or abdominal discomfort due to the spleen enlargement. Other rare manifestations are cutaneous and bone lytic lesions, gastrointestinal or central nervous system involvement, and/or autoimmune disorders. Peripheral lymphadenopathy is very rare, but around 10%–15% of patients may have abdominal lymphadenopathy. Therefore, CT scan is recommended in the diagnostic and staging workup. The blood counts show variable degrees of anemia, thrombocytopenia, and neutropenia. Macrocytosis is frequent, and monocytopenia is characteristic in active HCL. Most cases have a few circulating lymphocytes with the morphology of hairy cells. Liver function tests may show a raised alkaline phosphatase that often correlates with liver involvement by the disease. In addition to the diagnostic tests on blood and bone marrow, the European Society for Medical Oncology (ESMO) guidelines recommend the following investigations for a staging workup: full blood counts with differential and reticulocytes, liver and renal biochemistry, serum immunoglobulins, B2 microglobulin, direct antiglobulin test (DAT), hepatitis B and C serology, and CT scan of the chest, abdomen, and pelvis [5].
Macrophage Heterogeneity
Gloria H. Heppner, Amy M. Fulton in Macrophages and Cancer, 2019
Tumor-induced alterations in MP populations obviously may affect host resistance, possibly increasing susceptibility to infection in cancer patients.9 In this regard, it is interesting that considerable monocytopenia can occur in mice or in clinical situations without necessarily impairing host resistance,211,283 suggesting an important role for tissue MOs in such resistance. How the tumor burden ultimately affects tissue MOs remains to be defined; both enhancement and inhibition of MP functions have been observed.9 Tumors, as demonstrated for many viral infections,212 may also affect MP physiologic functions so that levels of biologically potent secretory products (complement components, tumor necrosis factor, interleukin-1 (IL-1), and neutral proteases) are altered. Such changes can have profound effects on the normal physiology of cancer patients.
The Origin of Kupffer Cells and Their Anatomic Relationship to Hepatocytes
Timothy R. Billiar, Ronald D. Curran in Hepatocyte and Kupffer Cell Interactions, 2017
Other investigators reported extensively on the local proliferative capacity of resident macrophages or Kupffer cells. Interesting data were obtained in the early fetal rat liver where, from the 11th day of gestation on, phagocytosing and dividing macrophages were observed which had the characteristic peroxidase pattern of mature Kupffer cells. At this ontogenic stage, no monocytic cells were observed since they arise only from the 17th day of gestation on.29-32 In adult life, proliferating Kupffer cells were demonstrated either by the observation of metaphases or by autoradiographic detection of cells that had incorporated tritiated thymidine. Dividing Kupffer cells were reported at low frequency during the normal steady state.8,17,33 A much higher frequency of locally proliferating Kupffer cells is observed after partial hepatectomy and in inflammatory conditions (Figures 6, 9, and 10).8,33-36In vitro, growth and even clonal expansion of Kupffer cells has been reported.37,38 Recently, Ya-mada et al.39 investigated the population kinetics of Kupffer cells in severely monocytopenic mice. A prolonged monocytopenia was obtained by local bone marrow irradiation using the 89Sr isotope combined with or without splenectomy. Kupffer cells were characterized unequivocally by immunohistochem-istry with the anti-mouse macrophage monoclonal antibody F4/80, electron microscopy, and endogenous peroxidase cytochemistry. Local proliferation in the liver was analyzed by cell counting and by tritiated thymidine autoradiography. The authors could conclude from their experiments that, in their model, Kupffer cells were self-renewing through local cell division and could even increase in number and form granulomas during inflammation.
Deciphering the genotype and phenotype of hairy cell leukemia: clues for diagnosis and treatment
Published in Expert Review of Clinical Immunology, 2019
Margot C.E. Polderdijk, Michiel Heron, Saskia Kuipers, Ger T. Rijkers
Less attention has been given lately to the monocytopenia characteristic of HCL. So far it is unclear what would cause this monocytopenia. Zuzel and Cawley [33] have suggested that it could be caused by a growth factor deficiency or the production of suppression factors; either way, a compound that is secreted by the hairy cells could be the culprit. It should be noted that already in 1996, Schwarzmeier et al. [92] looked into the secretion of several growth factors (G-CSF, GM-CSF, IL-3, IL-6, and TNF-α) by peripheral blood mononuclear cells of HCL patients. They found a deficiency for every one of these growth factors and cytokines, which was corrected by autologous monocyte enrichment, as also seen in the case presented by Hersh et al. [35]. Furthermore, they showed that in vitro treatment of hairy cells with IFN-α, which was the standard treatment for HCL at the time, leads to an increase in IL-6 expression.
Mavrilimumab: a unique insight and update on the current status in the treatment of rheumatoid arthritis
Published in Expert Opinion on Investigational Drugs, 2019
Chiara Crotti, Martina Biggioggero, Andrea Becciolini, Elena Agape, Ennio Giulio Favalli
During the open-label long-term extension of both phase IIb studies [56], AEs were for the majority mild or moderate, whereas only 10.0% of the overall as-treated patients reported a treatment-emergent AE of grade ≥3 severity. Nasopharyngitis (n = 69; 7.68 per 100 patient-years) and bronchitis (n = 51; 5.68 per 100 patient-years) were the most common treatment-emergent AEs. No cases of monocytopenia were observed, neutropenia was reported in four patients, and 14 patients showed serious infections (1.56 per 100 patient-years). Furthermore, despite the concerns related to the effects of GM-CSF on the pulmonary mucosa, mavrilimumab was not associated with substantial negative effects on pulmonary safety (no cases of PAP nor pulmonary-related deaths) [56].
Normal Absolute Monocyte Count in Combination with Normal/High Absolute Lymphocyte Count at the Time of Relapse is Associated with Improved Survival in Patients with Early Relapsed Acute Myeloid Leukemia
Published in Cancer Investigation, 2021
Yu Zhang, Kanchun Dai, Qianying Zhang, Yisha Huang, Yiyun Feng, Deeksha Bhardwaj, Kang Yu, Jianhua Feng
Peripheral monocytes are a key component of the innate immunity system, and play a key role in restoration of tissue integrity and control of immunoinflammatory responses (16). Previous studies have shown monocytopenia to be associated with increased risk of infections and decreased survival in patients with hematological malignancies receiving intensive induction chemotherapy or allo-HSCT (17–21). On the other hand, peripheral monocytes, which reflect the tumor microenvironment, have been reported to promote tumorigenesis and angiogenesis and contribute to systemic immunosuppression (22–24). Recent studies have reinforced the belief that increased absolute monocyte count (AMC) are associated with poor survival in patients with hematological malignancies (25–28). Furthermore, low absolute lymphocyte count (ALC), as a surrogate marker of host immune status, has also been shown to be linked to adverse outcomes in patients with hematological malignancies (29–32). However, no studies regarding the prognostic impact of peripheral AMC and ALC in early relapsed AML are available. Moreover, either AMC or ALC, as a single parameter, is not enough to accurately reflect the in vivo immune status. Therefore, in the present study, we combined AMC with ALC, to obtain a host immunity-related index, which was then used to evaluate the prognostic significance in 57 patients with early relapsed AML.
Related Knowledge Centers
- Aplastic Anemia
- Bone Marrow Suppression
- Glucocorticoid
- Lymphocytopenia
- Stress
- Neutropenia
- Monocyte
- Leukopenia
- Hairy Cell Leukemia
- Acute Myeloid Leukemia