Median time to myeloid engraftment (ANC 3500 cells/mm³) in 53 patients receiving Leukine (Sargramostim) was 4 days less than in 56 patients treated with placebo (see table below). The number of patients with bacteremia and infection was significantly lower in the Leukine group compared to the placebo group (9/53 versus 19/56 and 30/53 versus 42/56, respectively). There were a number of secondary laboratory and clinical endpoints. Of these, only the incidence of severe (grade 3/4) mucositis was significantly improved in the Leukine group (4/53) compared to the placebo group (16/56) at p<0.05. Leukine treated patients also had a shorter median duration of post-transplant IV antibiotic infusions, and shorter median number of days to last platelet and RBC transfusions compared to placebo patients, but none of these differences reached statistical significance.

Allogeneic BMT: Analysis of Data from Placebo-Controlled Clinical Trial Median Values (days or number of patients)  

* p <0.05 generalized Wilcoxon test
** p <0.05 simple Chi-square test

Bone Marrow Transplantation Failure or Engraftment Delay 

A historically-controlled study was conducted in patients experiencing graft failure following allogeneic or autologous BMT to determine whether Leukine improved survival after BMT failure.

Three categories of patients were eligible for this study:

1) patients displaying a delay in engraftment (ANC £ 100 cells/mm³ by day 28 post-transplantation);

2) patients displaying a delay in engraftment (ANC £ 100 cells/mm³ by day 21 post-transplantation) and who had evidence of an active infection; and

3) patients who lost their marrow graft after a transient engraftment (manifested by an average of ANC ³ 500 cells/mm³ for at least one week followed by loss of engraftment with ANC < 500 cells/mm³ for at least one week beyond day 21 post-transplantation).

A total of 140 eligible patients from 35 institutions were treated with Leukine and evaluated in comparison to 103 historical control patients from a single institution. One hundred sixty-three patients had lymphoid or myeloid leukemia, 24 patients had non-Hodgkin's lymphoma, 19 patients had Hodgkin's disease and 37 patients had other diseases, such as aplastic anemia, myelodysplasia or non-hematologic malignancy. The majority of patients (223 out of 243) had received prior chemotherapy with or without radiotherapy and/or immunotherapy prior to preparation for transplantation.

One hundred day survival was improved in favor of the patients treated with Leukine after graft failure following either autologous or allogeneic BMT. In addition, the median survival was improved by greater than 2-fold. The median survival of patients treated with Leukine after autologous failure was 474 days versus 161 days for the historical patients. Similarly, after allogeneic failure, the median survival was 97 days with Leukine treatment and 35 days for the historical controls. Improvement in survival was better in patients with fewer impaired organs.

Median Survival by Multiple Organ Failure (MOF) Category Median Survival (days)  

The MOF score is a simple clinical and laboratory assessment of 7 major organ systems: cardiovascular, respiratory, gastrointestinal, hematologic, renal, hepatic and neurologic.¹⁰ Assessment of the MOF score is recommended as an additional method of determining the need to initiate treatment with Leukine in patients with graft failure or delay in engraftment following autologous or allogeneic BMT.

Factors that Contribute to Survival: The probability of survival was relatively greater for patients with any one of the following characteristics: autologous BMT failure or delay in engraftment, exclusion of total body irradiation from the preparative regimen, a non-leukemic malignancy or MOF score < 2 (0, 1 or 2 dysfunctional organ systems). Leukemic subjects derived less benefit than other subjects.

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