Future Prospects
Tariq I Mughal, John M Goldman, Sabena T Mughal in Understanding Leukemias, Lymphomas, and Myelomas, 2017
The dominant effect of the microenvironment on the prognosis of a cancer probably reflects the importance of the immune cells in the biology and pathogenesis of hematologic cancers. Such observations lend support to the notion that the growth of some hematologic cancers is not always autonomous. A good example is the gastric mucosa-associated lymphoid tissue lymphomas associated with infection by the Helicobacter pylori bacterium; many patients with this lymphoma can be cured in their early stages by use of antibiotics which eradicate the infection. In some patients with B-cell chronic lymphocytic leukemia (B-CLL), there is evidence that suggests activation by antigens, which are likely to play a decisive role in the pathogenesis in these patients. If the critical components of the microenvironment in B-CLL or follicular lymphoma can be identified, we can anticipate new treatment options.
Polyphenols and Cancer Immunology
Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri in Plants That Fight Cancer, 2019
Another natural polyphenol which can directly or indirectly influence tumor microenvironment functions is ellagic acid along with its derivatives found in high amounts in Epilobium hirsitum L. (EH), Terminalia ferdinandiana, and Reaumuria vermiculata. It has been found that this polyphenol induces apoptosis and decreases MMP release in the tumor mass. It has been observed to exert toxic effects on B-lymphocytes isolated from chronic lymphocytic leukemia (CCL) patients, at the same time having limited influence on normal B-cells. Therefore, this compound may be considered as a potential anticancer molecule whose mode of action is targeted mainly at mitochondrial pathways (Salimi et al. 2015, Karakurt et al. 2016).
The use of ibrutinib before and after allogeneic stem cell transplantation
Published in Expert Opinion on Orphan Drugs, 2019
Massimo Martino, Anna Ferreri, Virginia Naso, Tiziana Moscato, Barbara Loteta, Massimo Gentile, Antonella Morabito, Fabio Provenzano, Michele Cimminiello, Angelo Michele Carella, Giuseppe Console, Anna Grazia Recchia
The B-cell receptor (BCR) is essential for normal B-cell development and maturation and it is implicated, as a pivotal pathway, in tumorigenesis in an increasing number of B-cell malignancies [1,2]. Mechanisms of BCR activation are quite diverse and range from chronic antigenic drive by microbial or viral antigens to autostimulation of B-cells by self-antigens to activating mutations in intracellular components of the BCR pathway. Chronic lymphocytic leukemia (CLL) has been recognized for decades as a malignancy of auto-reactive B-cells and its clinical course is in part determined by the differential response of the malignant cells to BCR activation [3]. Initial antigen selection during transformation or continued antigenic drive appears to play a role in additional B-cell malignancies, including mantle cell lymphoma (MCL) and follicular lymphoma (FL), resulting in activation of the NF-kB pathway [4].
Current therapies for chronic lymphocytic leukemia: risk and prophylaxis strategies for secondary/opportunistic infections
Published in Expert Review of Hematology, 2023
Lucia Diella, Davide Fiore Bavaro, Giacomo Loseto, Crescenza Pasciolla, Carla Minoia, Daniela Di Gennaro, Alessandra Belati, Maria Stella De Candia, Francesco Di Gennaro, Annalisa Saracino, Attilio Guarini
Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation. CLL accounts for about one-quarter of the new cases of leukemia. It is the most common adult leukemia in Western populations and comprises 25 to 30% of leukemias in the United States. According to the American Cancer Society, there will be approximately 21,250 new CLL cases and about 4,320 deaths in the year of 2021. Worldwide, 191,000 cases and 61,000 deaths are attributed to CLL every year. The average risk of a person over their lifetime of getting CLL is about 1 in 175 (0.57%). The risk is slightly higher in men than in women. Elderly are the population mainly affected by CLL. The average age of people when they are diagnosed is around 70 years. It is rare to see in people under age 40 and is extremely rare in children [1] [2].
Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor (CAR) T cell therapy
Published in Expert Review of Hematology, 2019
Utkarsh H. Acharya, Tejaswini Dhawale, Seongseok Yun, Caron A. Jacobson, Julio C. Chavez, Jorge D. Ramos, Jacob Appelbaum, David G. Maloney
While effective in treating a variety of CD19-expressing B-cell neoplasms, CAR T cells can cause potentially serious adverse events. The signature toxicities of CAR T cell therapy are cytokine release syndrome (CRS) and neurotoxicity. Both toxicities can range in severity from mild to life-threating [15–19] and were observed following treatment of patients with B-ALL, B-cell chronic lymphocytic leukemia (CLL), and B-cell non-Hodgkin lymphoma with a trend of increased frequency and severity in B-ALL. These toxicities are also observed, though less frequently, in diseases treated with CAR T cells targeting other antigens. For example, 63% of refractory multiple myeloma patients treated with the anti-BCMA CAR T cell product, bb2121, experienced any grade of CRS. Importantly, only 5% was grade 3 CRS or worse [20]. Furthermore, the anti-CD3/CD19 bispecific T cell-engager (BiTE), blinatumomab, that redirects T cells against CD19+ neoplasms also leads to CRS [21,22], reinforcing that T cell activation is indeed a trigger of CRS. CRS is a systemic inflammatory response that correlates with high serum cytokine levels associated with the activity of the infused CAR T cells [23,24]. The pathogenesis of neurotoxicity is not as well characterized [25]. Recent non-human primate models describe a picture of lymphocytic infiltration of the brain by a combination of CAR T and endogenous T cells leading to a combination of damage to the blood-brain barrier and cytokine release [26]. CRS and neurotoxicity can be part of the same clinical scenario or can occur independently, indicating different pathogenic mechanisms of the two toxicities.