E.A. Jones, A.A. Boylard, D.C. Dale, "The Journal of the American Medical Association, 1993", volume 270..

Objective - To evaluate the impact of long-term granulocyte colony-stimulating factor (GCSF) treatment on quality of life of patients with congenital, cyclic, or idiopathic neutropenia.

Study Design, Intervention, and Outcome Measures - Twenty-one patients receiving daily subcutaneous GCSF responded to retrospective questions about disease-related symptoms and physical, psychological, and social functioning before and with GCSF therapy.

Results - Statistically significant improvement occurred in energy, emotional reactions, social isolation, functional ability, life satisfaction, decreased hospital admissions, and school attendance.

Conclusion - GCSF greatly improves quality of life in patients with severe chronic neutropenia.

NEUTROPENIA, defined as an absolute neutrophil count less than 0.5 x 109 /L, is a frequent problem in patients with hematological malignancies, following cancer chemotherapy, with idiosyncratic drug reactions, and in some viral infections and autoimmune disorders. Severe chronic neutropenia as a primary hematological problem is far less common; most patients with this condition are categorized with congenital, cyclic, or chronic idiopathic neutropenia. They suffer recurrent fevers, infections, and mucosal ulcerations. The chronic nature of the disease leads to anticipation of relapse even when patients are feeling well and has a profound impact on patients’ livelihood, schooling, and self-perceptions.

Until recently, there has been no specific treatment for neutropenia except antibiotics for infectious episodes. The development of the colony-stimulating factors was a major advance in neutropenia treatment. The initial trials of recombinant human GCSF for severe chronic neutropenia showed a clinical benefit in neutropenic patients taking these drugs. Also, it became apparent that these patients’ lives were changing in several ways. We therefore undertook a formal quality-of-life study to evaluate their perceptions of the value of this new therapy.


Subjects consisted of 21 of 22 patients (10 males and 11 females; mean age, 24 years, range, 4 to 68 years) enrolled in long-term trials of GCSF for congenital, cyclic, or idiopathic neutropenia (7, 9, and 5 patients respectively) at the University of Washington. Before enrollment all were neutropenic and had significant problems with infections.

GCSF (0.3 to 24 mg/kg per day, Amgen, Thousand Oaks, Calif) was administered subcutaneously to maintain a mean absolute neutrophil count between 1.5 and 10.0 x 109 /L.

Two questionnaires were developed. Questionnaire A asked patients to recall factual data, feelings, and perceptions about their health the year prior to taking GCSF. Questionnaire B contained similar questions for the treatment period. Both were mailed to patients after a mean treatment duration of 31.4 months (range 19.9 to 49.7 months), with instructions to complete both questionnaires at one sitting, first A, then B, and not modify any answers after completing them. Children younger than 10 years were assisted by a parent.

Subjective health status was evaluated with the Nottingham Health Profile. Patients were also asked about their health satisfaction: "How satisfied were (are) you with your health?" (7 possible responses) and to rate their overall health (excellent, good, fair, or poor). Happiness was measured by asking: "Taking all things together, how would you say things were (are)?Would you say you were (are) very happy, fairly happy, or not too happy?" The Index of Overall Life Satisfaction was based on bipolar responses to the question: "How satisfied were (are) you before (since) beginning GCSF treatment?" Responses were scored from 1.0 ("completely dissatisfied) to 7.0 ("completely satisfied").

To evaluate interactions with the health care system, they reported patients’ hospital admissions, total hospital days, total "out of pocket" expenses, and physician visits for the year preceding GCSF treatment and the year prior to completing the questionnaires.

To evaluate disease symptoms, patients estimated number of days per year with mouth ulcers, number of ulcers per year, and average duration of ulcers. Functional ability was assessed with the Karnofsky score.

To evaluate the impact of disease on school or employment, patients reported number of days per month missed from school or work because of symptoms and the extent to which disease impaired their performance. School or employment status was determined by standard questions in each questionnaire.

The Wilcoxon signed rank test was used for continuous variables; the McNemar test was used for categorical data.


The Nottingham Health Profile showed improvement in most quality-of-life indicators (Table). Health satisfaction also improved. For example, 14% of patients responded that they were "satisfied" with their health before GCSF, whereas 86% reported they were "satisfied" on treatment (P<.01; n=21).

Similarly, the percentage of patients reporting "excellent" or "good" health increased from 24% to 86% (P<.01; n=21). The life satisfaction index improved from 4.2 to 5.5 (P=.002, n=21).

Health care utilization, an indirect measure of health status, also decreased with GCSF treatment. Hospital admissions, hospital days, yearly out-of-pocket expenses, and physician visits decreased significantly (P<.05).

The number of days per year with mouth ulcers, absolute numbers of ulcers per year, and median duration of mouth ulcers decreased significantly. Functional status (Karnofsky score) demonstrated a significant improvement (mean index pre-GCSF, 3.7 ± 1.8, mean index with GCSF 2.2± 1.4) (P=.004). Prior to treatment, 29% reported being relatively free of limitations; on treatment, this number increased to 81% (P<.02; n=21).

Patients reported an improved ability to work and attend school. Before treatment, patients missed an average of 2.7 days of work per month which dropped to 0.36 days per month with treatment (n=7). Health problems limiting job performance decreased from 25% (n=8) to 0% with treatment (n=7). School absences decreased from a mean of 4.3 days per month to 1.3 days per month after treatment (P=.006; n=12). Prior to treatment, 77% of students reported that disease impaired their performance; this number dropped to 15% with treatment (P<.01; n=12).

Table. - Nottingham Health Profile



Post -Rx










Emotional Reactions








Social Isolation













Job or work








Social Life




Personal Relations




Sex life













*Wilcoxen signed ranks test between pre and posttreatment questionnaires.

**All values in this table represent arithmetic means for 21 respondents.

*** McNemar test between pre and posttreatment questionnaires.


Quality of life is an important component of overall health. This study shows that quality of life is enhanced in patients with severe chronic neutropenia receiving long-term treatment with GCSF. These results correlate well with previous work by Fazio and Glaspy who demonstrated similar benefits in 10 patients after shorter term GCSF therapy. Using the Ferrans and Powers Quality of Life Index, they showed improvement in four subscales: health and functioning, socioeconomic, psychological/spiritual, and family. Our study used a number of different instruments to show changes is a larger and more diverse group of patients over a substantially longer period. Unlike previous studies, this study combined a general measure of health status with disease-specific quality-of-life parameters (oral symptoms, missed work/school). The magnitude of improvement in oral symptoms, in terms of patient days with ulcers, is comparable to that obtained in prospective randomized studies of these patients, lending credibility to our retrospectively collected data.

This study relies on a few basic assumptions. First, we assumed that all patients can reliably recall factual data, personal feelings, and perceptions about their life with a chronic illness prior to a new long-term treatment. It is our impression that patients tended to minimize the magnitude of improvement they experienced; however, one cannot refute the advantage of prospectively collected data. Second, the instruments we used were designed for an adult population and we assumed that they can be reliably applied to younger patients with the aid of a parent, but this has not been formally validated.

From a broader perspective, biotechnology is providing an increasing number of new therapies but few have been evaluated in quality-of-life studies. Future clinical trials should include quality-of-life data to complement biologic endpoints. Patients’ perspectives provide an important dimension for assessing the value of costly new treatments.

This study was supported by a National Institutes of Health grant #M01RR0003. The authors are indebted to Ronald O. Ling and the Clinical Research Center at the University of Washington Medical Center for computational assistance.