Survival studies comparing mobilized study patients to the non-mobilized patients and to an autologous historical bone marrow transplant group showed no differences in median survival time.

Autologous Bone Marrow Transplantation⁷

Following a dose-ranging Phase I/II trial in patients undergoing autologous BMT for lymphoid malignancies,^8,9 three single-center, randomized, placebo-controlled and double-blinded studies were conducted to evaluate the safety and efficacy of Leukine for promoting hematopoietic reconstitution following autologous BMT. A total of 128 patients (65 Leukine, 63 placebo) were enrolled in these 3 studies. The majority of the patients had lymphoid malignancy (87 NHL, 17 ALL), 23 patients had Hodgkin's disease, and 1 patient had acute myeloblastic leukemia (AML). In 72 patients with NHL or ALL, the bone marrow harvest was purged prior to storage with one of several monoclonal antibodies. No chemical agent was used for in vitro treatment of the bone marrow. Preparative regimens in the 3 studies included cyclophosphamide (total dose 120-150 mg/kg) and total body irradiation (total dose 1,200-1,575 rads). Other regimens used in patients with Hodgkin's disease and NHL without radiotherapy consisted of 3 or more of the following in combination (expressed as total dose): cytosine arabinoside (400 mg/m²) and carmustine (300 mg/m²), cyclophosphamide (140-150 mg/kg), hydroxyurea (4.5 gm/m²) and etoposide (375-450 mg/m²).

Compared to placebo, administration of Leukine in 2 studies (n=44 and 47) significantly improved the following hematologic and clinical endpoints: time to neutrophil engraftment, duration of hospitalization and infection experience or antibacterial usage. In the third study (n=37) there was a positive trend toward earlier myeloid engraftment in favor of Leukine. This latter study differed from the other 2 in having enrolled a large number of patients with Hodgkin's disease who had also received extensive radiation and chemotherapy prior to harvest of autologous bone marrow. A subgroup analysis of the data from all 3 studies revealed that the median time to engraftment for patients with Hodgkin's disease, regardless of treatment, was 6 days longer when compared to patients with NHL and ALL, but that the overall beneficial Leukine treatment effect was the same. In the following combined analysis of the 3 studies, these 2 subgroups (NHL and ALL vs. Hodgkin's disease) are presented separately.

Patients with Lymphoid Malignancy (Non-Hodgkin's Lymphoma and Acute Lymphoblastic Leukemia): Myeloid engraftment (absolute neutrophil count [ANC] 3500 cells/mm³) in 54 patients receiving Leukine was observed 6 days earlier than in 50 patients treated with placebo (see table below). Accelerated myeloid engraftment was associated with significant clinical benefits. The median duration of hospitalization was 6 days shorter for the Leukine group than for the placebo group. Median duration of infectious episodes (defined as fever and neutropenia; or 2 positive cultures of the same organism; or fever >38­C and 1 positive blood culture; or clinical evidence of infection) was 3 days less in the group treated with Leukine. The median duration of antibacterial administration in the post-transplantation period was 4 days shorter for the patients treated with Leukine than for placebo-treated patients. The study was unable to detect a significant difference between the treatment groups in rate of disease relapse 24 months post-transplantation. As a group, leukemic subjects receiving Leukine derived less benefit than NHL subjects. However, both the leukemic and NHL groups receiving Leukine engrafted earlier than controls. 

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