**12. Neutropenia and cancer type**

#### **12.1. Solid cancer**

**11.2. Age**

210 Updates on Cancer Treatment

**11.3. Ethnic group**

neutropenia [32, 52].

Neutropenia is more common among the elderly (i.e., 50 years of age or older). Indeed these individual are already less able to produce mature neutrophil cells [2, 8, 13, 17]. According to the National Cancer Registry of Malaysia (2003), cancer incidence, especially breast cancer incidence, is more predominant at the age of 50 years or more. Yip and Omar Hasan Kasule (2005) reported that neutropenia occurred mostly in people aged 50 - 59 years and 75% of the neutropenic patients in their study were diagnosed with breast cancer [48, 49]. In his study, Crawford (2007) investigated 282 lymphoma cancer patients treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP), and said that the incidence of neutropenia was predominant among individuals aged 65 years or more compared to younger than 65 years of age [50]. Moreover, in the United States, Voelker *et al.* (2004) carried out a retrospective study from 1991 to 1999 on 7,238 patients with non-Hodgkin lymphoma (NHL). The main objective was to find the major risk factors associated with initiation and duration of hospi‐ talization among neutropenic patients after chemotherapy. The median age was 75 years (range: 66 to 100 years). About 22% of patients needed hospitalization and half were first admitted within the first 42 days of treatment. The mean duration of hospitalization was 55.7 ± 1.43 days and the median was 34 days. The risk factors found to be associated with hospital admission were patients' age, gender, chemotherapy type, history, and disease stage. The risk of hospitalization due to neutropenia increased with age until the age of 80 years [51]. So the study by Voelker *et al*. (2004) demonstrated a significant association between neutropenia and patients' age and gender. At these advanced ages, chemotherapy doses usually reduced and

The ethnic group has been suggested to have a significant effect on ANC and therefore there is a relationship between these variables and neutropenia [13]. However, some specific types of cancers are highly associated with specific races. According to Kaur *et al*. (2007), breast cancer incidence in Penang mostly occurs among the Chinese (62.5%), followed by the Malays (26.7%), and the Indians (10.2%), and breast cancer is most highly associated with neutropenia (Wolf *et al*., 2005), which could indicate that the ethnic group does play a role in the incidence of

Moreover, in the United States, another study by Hershman *et al*. (2003) also showed that there is an association between ethnicity and neutropenia (WBC level) in breast cancer survivors. Their study was performed on African American and White American women with breast cancer (stage I and II) treated with chemotherapy. It showed that the WBC level in African American women was significantly lower than that of White American women. There was also a significant difference between the period of chemotherapy treatment of African American (19 women) versus White American women due to neutropenia. The explanation for the difference in period of treatment was said to be due to lower ANC. Besides that, neutropenia occurrence led to a delay in chemotherapy administration. Therefore, their study demonstrated a significant association between neutropenia occurrence and ethnicity [53].

the administration of G-CSF (Filgrastim) is increased [17, 36].

Neutropenia has been shown to be associated with solid tumors especially breast cancer, as about 25% of breast cancer patients develop neutropenia. Lyman and Wilmot (2006) and Wolf *et al.* (2005) found that among patients with solid cancer, breast cancer patients had the highest risk for developing severe neutropenia and febrile neutropenia during the first cycle of chemotherapy. Due to the neutropenia, 40% of the breast cancer patients had the chemotherapy delayed and about 25% had their chemotherapy treatment doses reduced. The possibility of breast cancer patients to develop neutropenia at point during chemotherapy was 78% [17, 32]. Patients with solid tumors usually have normal neutrophil cell function as compared to patients with hematological malignancies, whose neutrophil function is completely abnormal and thus would suffer from neutropenia. Patients with solid tumors are also not immuno‐ compromised as are those with hematological malignancies, and many centers now consider solid tumor patients to have a low risk of neutropenia [54, 55]. A significant association was also found between cancer type and neutropenia duration, but not between cancer type and neutropenia severity [56]. The study by AL-Ahwal (2005) also showed that the association between neutropenia severity and solid cancer was not significant, but that co-morbidity of chemotherapy with solid cancer was significant. Among breast cancer with neutropenia, more than 75% of cases seemed to be associated with the type of chemotherapy employed, which was CMF [17]. In a retrospective study on 117 solid cancer patients with neutropenia conducted by Bassam and colleagues in Penang, the type of solid cancer played an insignificant role in the incidence and/or neutropenia severity. The main explanation for this result was that patients with a solid tumor are different from those with hematological malignancy, in the sense that solid tumor patients usually have normal neutrophil cell function. While, in case of hematological malignant patients where by their neutrophil cells function is completely abnormal and thus they suffer from neutropenia. In contrast, neutropenia occurrence among solid cancer patients usually starts after chemotherapy, and severe neutropenia may last for 7 - 10 days. Thus the main cause of neutropenia is not the presence of cancer itself, but the chemotherapeutic agents or drugs used. For this reason solid tumor patients who developed neutropenia are considered to be at low risk for neutropenia [26].

#### **12.2. Hematological cancer**

Patients with hematological malignancies are necessarily immunocompromised, either as a result of the malignancy or due to the therapeutic interventions used to manage it. Some hematological malignancies are associated with specific immune defects that predispose to infections with particular pathogens. For example, patients with acute leukemia have an increased risk of severe gram-negative bacterial infections as a result of quantitative or functional neutropenia. Patients with chronic lymphocytic leukemia and multiple myeloma are susceptible to invasive bacterial infections from staphylococci, streptococci, and especially pneumococcus. Patients with lymphoma have abnormalities of the cellular immune system that result in an increased risk of viral (e.g., herpes simplex) and fungal infections (e.g., cryptococcus). Moreover, therapeutic interventions such as corticosteroids, chemotherapy, stem cell transplant, and radiation also produce deficiencies in the host immune defense [57].

Neutropenia due to chemotherapy is the most common risk factor for severe bacterial infections in hematological malignancies. Impaired T-cell function in patients undergoing allogenic stem cell transplant is associated with an increased susceptibility to invasive viral infections. It can also induce alterations in host colonization, such as disruption of natural skin and mucosal barriers, and can interfere with nutrition, which can cause an increase in the risk of infection. Therefore, the degree of neutropenia either as a consequence of the disease or the therapy, is directly related to the incidence of serious bacterial and fungal infection in patients with hematological malignancies. There is a significant increase in the incidence of serious infection once ANC falls below 500 cells/µl. Patients with ANC below 100 cells/µl are at the highest risk of infection. The duration of neutropenia also contributes significantly to the risk of serious infections. Qualitative defects in neutrophil function have been described in hematological malignancies. These include defects in chemotaxis, phagocytosis, bactericidal capacity, and the absence of respiratory burst that accompanies phagocytosis. Additionally, chemotherapeutic regimens used in association with corticosteroids can decrease phagocytosis and neutrophil migration [57].
