Leukine in Autologous Bone Marrow Transplantation (AuBMT)
Leukine is indicated for acceleration of myeloid recovery in patients with non-Hodgkin’s lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin’s disease undergoing autologous bone marrow transplantation (BMT). After autologous BMT in patients with NHL, ALL, or Hodgkin’s disease, Leukine has been found to be safe and effective in accelerating myeloid engraftment, decreasing median duration of antibiotic administration, reducing the median duration of infectious episodes and shortening the median duration of hospitalization. Hematologic response to Leukine can be detected by complete blood count (CBC) with differential cell counts performed twice per week.
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 three studies. The majority of the patients had lymphoid malignancy (87 NHL, 17 ALL), 23 patients had Hodgkin’s disease, and one 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 three 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 three 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 grams/m2) and etoposide (375-450 mg/m2).
In patients undergoing AuBMT, Leukine was well tolerated and effective in reducing neutropenia after transplantation, thus decreasing morbidity5:
Hematopoietic Cell Recovery
Nemunaitis J, et al. N Engl. J Med. 1991.
- Adverse events occurring in >10% of Autologous BMT patients receiving Leukine in controlled clinical trials and reported in a higher frequency than placebo were asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
- Neutrophil recovery occurred significantly earlier in the Leukine group than in the placebo group
- Absolute neutrophil count (ANC) ≥500/mm3 (p<0.05) was reached in 19 days with Leukine vs. 26 days with placebo
- ANC ≥1000/mm3 (p<0.05) was reached approximately in 26 days with Leukine vs. 33 days with placebo*
- The duration of IV antibiotic therapy was significantly shorter (21 days for Leukine and 26 days for placebo) in the Leukine group than in the placebo group (P =.009)
- The median duration of initial hospitalization was significantly shorter (25 days for Leukine and 31 days for placebo) in the Leukine group (P =.01)
- Median duration of infectious episodes was less in the Leukine group
*The data shown are from the Leukine package insert. These data differ from those reported in the study by Nemunaitis et al and are the result of different calculation methods.
|Percent of AuBMT Patients Reporting Events|
|Events by Body System||LEUKINE (n=79)||Placebo (n=77)||Events by Body System||LEUKINE (n=79)||Placebo (n=77)|
|Body, General||Metabolic, Nutritional Disorder|
|Mucous membrane disorder||75||78||Peripheral edema||11||7|
|Digestive System||Hemic and Lymphatic System|
|GI disorder||37||47||Urinary tract disorder||14||13|
|GI hemorrhage||27||33||Kidney function abnormal||8||10|
|Liver damage||13||14||CNS disorder||11||16|
|Skin and Appendages|
- LEUKINE® (sargramostim) [package insert]. Genzyme Corporation 2009.
- Rowe JM, Rubin A, Mazza JJ, et al. Incidence of infections in adult patients (> 55 years) with acute myeloid leukemia treated with yeast-derived GM-CSF (sargramostim): results of a double-blind prospective study by the Eastern Cooperative Oncology Group. In: Hiddemann W, et al, eds. Acute Leukemias V: Experimental Approaches and Management of Refractory Diseases. Berlin, Germany: Springer-Verlag; 1996:178-184.
- Rowe JM. Treatment of acute myeloid leukemia with cytokines: effect on duration of neutropenia and response to infections. Clin Infect Dis. 1998;26:1290-1294.
- Rowe JM, Anderson JW, Mazza JJ, et al. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (>55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995;86:457-462.
- Nemunaitis J, Rabinowe S, Singer JW, et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med. 1991;324:1773-1778.
- Nemunaitis J, Rosenfeld CS, Ash R, et al. Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation.Bone Marrow Transplant. 1995;15:949-954.
- Data on file. Genzyme Corporation.