Suboptimal Duration of Granulocyte Colony–stimulating Factor Use and Chemotherapy-induced Neutropenia in Women Diagnosed With Breast Cancer

Purpose

Prophylactic use of granulocyte colony–stimulating factor (G-CSF) is recommended for cancer patients who are at high risk of neutropenic events. However, whether the clinical effectiveness of G-CSF from randomized controlled trials translates into “real-world” clinical practice is questionable. The goal of this retrospective cohort study was to examine the impact of G-CSF prophylaxis and other potential risk factors of severe neutropenia in women with breast cancer.

Methods

Our study subjects were women who were diagnosed with breast cancer and who received a new course of chemotherapy between January 1, 2010, and December 31, 2010, at a cancer center in Taiwan. Generalized estimating equations were applied to examine the association between G-CSF prophylaxis and neutropenic events.

Findings

We identified 353 women with breast cancer who received a total of 2776 cycles of chemotherapy. G-CSF was used as primary prophylaxis in 7% (n = 202) of cycles and as secondary prophylaxis in 11% (n = 319) of cycles. The mean duration of G-CSF for primary and secondary prophylaxis was 4.9 and 3.7 days, respectively. A chemotherapy regimen with high risk of febrile neutropenia was found to be a risk factor for severe neutropenic events (odds ratio, 3.22 [95% CI, 1.97–5.27]). Prophylactic use of G-CSF was not statistically significantly associated with febrile neutropenia.

Implications

The major determinants of neutropenic events among patients with breast cancer were the content and intensity of chemotherapy regimens. Suboptimal use of G-CSF may not be effective in preventing neutropenic events among women with breast cancer.     

急性淋巴细胞白血病患儿粒细胞缺乏并革兰阴性杆菌感染时血清内源性二氧化硫水平变化及其意义

目的 探讨内源性二氧化硫(SO2)在急性淋巴细胞白血病(ALL)患儿大剂量阿糖胞苷(HD-AraC)化疗后粒细胞缺乏期并革兰阴性杆菌感染时的水平变化及其病理生理学意义.方法 2010年1-12月在本院儿童血液肿瘤科住院的ALL患儿共31例,均行HD-AraC化疗,均出现骨髓抑制期并革兰阴性杆菌感染.分别测定患儿化疗前(WBC>3.0×109 L-1)、化疗后骨髓抑制期未感染时(WBC<1.0×109 L-1)、化疗后骨髓抑制期并革兰阴性杆菌感染时(WBC<1.0×109 L-1)及感染控制后粒细胞恢复期(WBC>2.0×109 L-1)血清SO2、CRP、IL-6和IL-8水平变化,分析其变化趋势.结果 ALL患儿化疗后,骨髓抑制期未合并感染时其血清SO2水平[(8.91±3.80) μmol·L-1]较化疗前[(6.15±3.16) μmol·L-1]明显升高(P<0.05);并革兰阴性杆菌感染后其血清SO2水平[(24.39±7.84) μmol·L-1]较未合并感染时进一步升高,差异有统计学意义(P<0.01);而感染控制后患儿血清SO2水平[(5.09±3.02) μmol·L-1]较感染组显著下降(P<0.01).与恢复期比较,骨髓抑制期粒细胞缺乏并革兰阴性杆菌感染后患儿血清CRP[(35.72±14.97) mg·L-1 vs (2.39±1.66) mg·L-1]、IL-6[(152.24±20.42) ng·L-1 vs (121.26±15.50) ng·L-1]和IL-8[(222.35±39.79) ng·L-1 vs (124.36±13.28) ng·L-1]水平均显著升高(Pa<0.01).结论 内源性SO2可以作为一种生物活性分子,参与ALL患儿粒细胞缺乏时革兰阴性杆菌感染的调节过程.     

Four novel ELANE mutations in patients with congenital neutropenia

Congenital neutropenia is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoesis at the promyelocyte/myelocyte stage. Cyclic neutropenia (CyN) and severe congenital neutropenia (SCN) are two main forms of congenital neutropenia. Genetic analysis has shown that heterozygous mutations in the ELANE gene encoding the neutrophil elastase are the major cause of these disorders. We investigated the prevalence of ELANE mutations in a group of 16 patients from 14 families with congenital neutropenia. Five patients had typical manifestations of CyN, and 11 patients had SCN. Seven different heterozygous ELANE mutations were found, including four novel mutations.     

The importance of dental care for a child with severe congenital neutropenia: a case report

Congenital neutropenia is characterized by a decrease in the absolute number of circulating neutrophils and an increased susceptibility to infections. This paper describes the case history of a child with severe congenital neutropenia who had aggressive periodontitis associated with generalized carious lesions. She had Kostmann syndrome, which is associated with recessive mutation of the HAX‐1 gene. She had extensive dental caries, which is not common in patients with Kostmann syndrome. The caries caused oral pain and loss of weight and could have been avoided if the parents had received early oral hygiene instructions, and if the child had received regular, professional dental care.     

Defective natural killer cell activity of peripheral blood lymphocytes correlates with the degree of neutropenia in patients with chronic idiopathic neutropenia of adults

 Natural killer cell activity (Nka) of peripheral blood mononuclear cells (PBMCs) against K562 cell targets was assessed in 66 patients with chronic idiopathic neutropenia of adults (CINA) using the 16-h ⁵¹Cr-release assay. It was found that CINA patients exhibited significantly lower Nkr than normal subjects, which strongly correlated with the degree of neutropenia and the numbers of circulating neutrophils. Patients' NKa was increased by recombinant human interleukin-2 (rhIL-2) or recombinant human interferon-α (rhIFN-α), but the values obtained did not reach the respective NKa values found in normals. However, percentages of cytokine-induced rises of NKa did not differ statistically between patients and normal subjects. No serum inhibitors of NKa were demonstrated in our patients. CINA patients had low numbers of circulating NK cells as defined by the expression of NK-cell-related surface markers CD16, CD56, and CD57. CD16⁺ and CD56⁺, but not CD57⁺, cells correlated with the values of baseline NKa. The numbers of all these cell subsets correlated with the degree of neutropenia and the numbers of circulating neutrophils. Using CD56⁺-enriched PBL suspensions, it was shown that patients' NK cells displayed normal tumor cell binding capacity and produced in vitro normal amounts of natural killer cytotoxic factor(s) against K562 cell targets upon activation with rhIFN-α. Finally, percentages of perforin-expressing and granzyme B-expressing CD16⁺ cells did not differ statistically between patients and normal controls. Based on all these observations, we concluded that CINA patients display low NKa probably because they have low numbers of circulating NK cells. No functional abnormalities of NK cells were demonstrated. The cause and the underlying mechanisms leading to NK-cell depletion in these patients remain to be clarified. Received: 21 August 1997 / Accepted: 3 February 1998     

Patients with non‐immune chronic idiopathic neutropenia syndrome have increased splenic volume on ultrasonography

Clinically detectable splenomegaly is rarely seen in patients with non‐immune chronic idiopathic neutropenia syndrome (NI‐CINS). Using ultrasound, we estimated splenic volume in 52 NI‐CINS patients and 14 age‐ and sex‐matched normal controls by determining the ‘corrected splenic index’ (CSI) from the product of length, width and thickness of the organ expressed in cm³/m² body surface area. We found that CSI was significantly higher in the group of patients compared to controls (202.8 ± 82.0 vs. 133.8 ± 28.1 cm³/m², P=0.003), and that individual CSI values was inversely correlated with the number of circulating neutrophils (r=–0.5097, P < 0.0001). About 48.1% of the patients had CSI above 190 cm³/m² body surface, representing the upper 95% confidence limit of values found in the controls. Patients also had increased serum concentrations of pro‐inflammatory cytokines and chemokines mainly produced by activated macrophages (IL‐1β, TNF‐α, RANTES and IL‐8), as well as increased serum levels of soluble cell adhesion molecules derived from activated endothelium (sE‐Selectin, sICAM and sVCAM). We hypothesize that the increased splenic volume in NI‐CINS patients may be due to the accumulation of activated macrophages inside the spleen, possibly as the result of an unrecognized low‐grade chronic inflammatory process. The nature of such an inflammation is unknown. A study was designed to search for viral or bacterial genomic material in patients’ bone marrow stromal macrophages in which the unknown causal agent might be located.     

The Quality of Care in the Emergency Management of Cancer Patients With Febrile Neutropenia: A Records-Based Cohort

IntroductionFebrile neutropenia is one of the most severe oncological emergencies associated with the treatment of cancer. Patients with febrile neutropenia are at grave risk of developing life-threatening sepsis unless there is rapid initiation of treatment. The aim of this study was to evaluate the quality of ED care of patients with febrile neutropenia using the 3 quality dimensions of safety, effectiveness, and timeliness of care.MethodsA retrospective review of all available records of adult cancer patients with febrile neutropenia who presented to 1 urban emergency department in Atlantic Canada was conducted over 5 years.ResultsExamining the 9 quality indicators of the 431 patients included in the study identified areas for improvement in each of the 3 dimensions. More than one third of the participants were unsafely discharged from the emergency department despite the severity of their conditions. Patients in the study were not seen promptly by the physician and did not receive timely treatment during different phases of their visit. Most importantly, the delay in antibiotic administration presented a major risk for this population.DiscussionAspects of care provided to this cohort of febrile neutropenia patients were inconsistent with the recommended evidence. Strengthening ED care is necessary to reduce the gap between evidence-based and actual care. Quality initiatives can be implemented to improve care to become safer, effective, and timely. Nurses who are in direct contact with the patients and who are actively involved in every single process of the health care system are well positioned to lead this change.