In three studies of patients with prior exposure to chemotherapy‚ the median CFU-GM yield in the leukapheresis product ranged from 20.9 to 32.7 x 10⁴/kg body weight (n = 105). In two of these studies where CD34+ yields in the leukapheresis product were also determined‚ the median CD34⁺ yields were 3.11 and 2.80 x 10⁶/kg, respectively (n = 56). In an additional study of 18 chemotherapy-naive patients‚ the median CFU-GM yield was 123.4 x 10⁴/kg.

Engraftment: Engraftment following NEUPOGEN®-mobilized PBPC is summarized for 101 patients in the following table. In all studies, a Cox regression model showed that the total number of CFU-GM and/or CD34⁺ cells collected was a significant predictor of time to platelet recovery.

In a randomized, unblinded study of patients with HD or NHL undergoing myeloablative chemotherapy (Amgen study 3)‚ 27 patients received NEUPOGEN®-mobilized PBPC followed by NEUPOGEN® and 31 patients received ABMT followed by NEUPOGEN®. Patients randomized to the NEUPOGEN®-mobilized PBPC group compared to the ABMT group had significantly fewer days of platelet transfusions (median 6 vs 10 days)‚ a significantly shorter time to a sustained platelet count > 20‚000/mm³ (median 16 vs 23 days)‚ a significantly shorter time to recovery of a sustained ANC ≥ 500/mm³ (median 11 vs 14 days)‚ significantly fewer days of red blood cell transfusions (median 2 vs 3 days) and a significantly shorter duration of posttransplant hospitalization.

Three of the 101 patients (3%) did not achieve the criteria for engraftment as defined by a platelet count ≥ 20‚000/mm³ by day 28. In clinical trials of NEUPOGEN® for the mobilization of PBPC‚ NEUPOGEN® was administered to patients at 5 to 24 mcg/kg/day after reinfusion of the collected cells until a sustainable ANC ( ≥ 500/mm³) was reached. The rate of engraftment of these cells in the absence of NEUPOGEN® posttransplantation has not been studied.

Patients With Severe Chronic Neutropenia

Severe chronic neutropenia (SCN) (idiopathic‚ cyclic‚ and congenital) is characterized by a selective decrease in the number of circulating neutrophils and an enhanced susceptibility to bacterial infections.

The daily administration of NEUPOGEN® has been shown to be safe and effective in causing a sustained increase in the neutrophil count and a decrease in infectious morbidity in children and adults with the clinical syndrome of SCN.16 In the phase 3 trial‚ summarized in the following table‚ daily treatment with NEUPOGEN® resulted in significant beneficial changes in the incidence and duration of infection‚ fever‚ antibiotic use‚ and oropharyngeal ulcers. In this trial‚ 120 patients with a median age of 12 years (range 1 to 76 years) were treated.

Overall Significant Changes in Clinical Endpoints Median Incidence^a (events) or Duration (days) per 28-day Period

The incidence for each of these 5 clinical parameters was lower in the NEUPOGEN® arm compared to the control arm for cohorts in each of the 3 major diagnostic categories. All 3 diagnostic groups showed favorable trends in favor of treatment. An analysis of variance showed no significant interaction between treatment and diagnosis‚ suggesting that efficacy did not differ substantially in the different diseases. Although NEUPOGEN® substantially reduced neutropenia in all patient groups‚ in patients with cyclic neutropenia‚ cycling persisted but the period of neutropenia was shortened to 1 day.

As a result of the lower incidence and duration of infections‚ there was also a lower number of episodes of hospitalization (28 hospitalizations in 62 patients in the treated group vs 44 hospitalizations in 60 patients in the control group over a 4-month period [p = 0.0034]). Patients treated with NEUPOGEN® also reported a lower number of episodes of diarrhea‚ nausea‚ fatigue‚ and sore throat.

In the phase 3 trial‚ untreated patients had a median ANC of 210/mm³ (range 0 to 1550/mm³). NEUPOGEN® therapy was adjusted to maintain the median ANC between 1500 and 10‚000/mm³. Overall‚ the response to NEUPOGEN® was observed in 1 to 2 weeks. The median ANC after 5 months of NEUPOGEN® therapy for all patients was 7460/mm³ (range 30 to 30‚880/mm³). NEUPOGEN® dosing requirements were generally higher for patients with congenital neutropenia (2.3 to 40 mcg/kg/day) than for patients with idiopathic (0.6 to 11.5 mcg/kg/day) or cyclic (0.5 to 6 mcg/kg/day) neutropenia.

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