Management of chemotherapy-induced neutropenia in cancer patients

Chemotherapy is widely used as a successful treatment option for cancer patients, showing a higher success rate in hematological cancers than solid tumours. Chemotherapy-induced neutropenia (CIN), defined as “a reduction in the number of circulating neutrophils due to administration of myelotoxic chemotherapy”, is one of the major side effects of chemotherapy. As chemotherapy targets, all the rapidly dividing cells of the body along with cancerous cells such as bone marrow cells and all blood cells including red blood cells, platelets, and neutrophils are compromised. It also disrupts the mucosal lining of the gut which prevents entry of normal flora into the bloodstream. Neutrophils are the first line of defence against infections and the most abundant leukocytes in peripheral circulation, and when they are decreased, cancer patients are left unprotected. On the other hand, when the mucosal lining is destroyed and normal gut floral gets access to the bloodstream, these cancer patients on chemotherapy develop infections along with fever known as febrile neutropenia. Major risk factors of febrile neutropenia (FN) include old age, comorbid conditions, and the type of cancer, the type and number of myelosuppressive chemotherapy agents used. The treatment options available to date for FN are the administration of antibiotics and growth factors. While these treatments may shorten the period of neutropenia, infection - especially fungal infections - remains the major cause of septic death in the cancer patient. Cancer patients on chemotherapy are diagnosed as high risk or low risk on basis of MASCC score and high risk patients are given G-CSFs which per dose can cost about $3000-$4000, along with antibiotics to prevent infection. Still, these options do not improve the overall survival of these cancer patients. The other major issue faced by cancer patients on chemotherapy is that to date there is no method to detect neutropenia prior to the onset of infection. FN is diagnosed when patients develop fever and come to A&E at a point that is already too late to prevent infection onset. Timely detection and neutrophil transfusion can prevent neutropenic sepsis in cancer patients on chemotherapy. This project aims: • To provide proof-of-concept that dielectric spectroscopy can be used to detect early onset of neutropenia in cancer patients on chemotherapy. • To identify the effects of chemotherapy on the liver and renal functions from the analysis of blood biochemistry reports of neutropenic patients. • To develop a strategy for the generation of mature neutrophils from human umbilical cord blood-derived hematopoietic stem cells (UCB-HSC) to manage CIN in cancer patients. Objectives: 1. To detect the change in the number of neutrophils of cancer patients on chemotherapy/post-chemo by measuring the permittivity and identifying any variation in dielectric properties at optimum microwave frequency by using dielectric spectroscopy. 2. To identify the effects of chemotherapy on the liver and renal functions from the analysis of blood biochemistry reports of neutropenic patients. 3. To isolate CD34+ HSCs from UCB, ex vivo expansion and differentiation of these ex vivo expanded HSCs in to mature neutrophils.

Publisher

NUI Galway

Collections

University of Galway Theses (PhD Theses)