Important Safety Considerations

Leukine® (sargramostim) is indicated for the following uses: (i) following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery; (ii) for mobilization and following transplantation of autologous peripheral blood progenitor cells; (iii) for myeloid reconstitution after autologous or allogeneic bone marrow transplantation (BMT); (iv) for use in bone marrow transplantation failure or engraftment delay.
Click here for additional Important Safety Information.
Click here for Indications.

Leukine in Allogeneic Bone Marrow Transplantation (AlloBMT)

Leukine®(sargramostim) is indicated for acceleration of myeloid recovery in patients undergoing allogeneic BMT from HLA-matched related donors. Leukine has been found to be safe and effective in accelerating myeloid engraftment, reducing the incidence of bacteremia and other culture positive infections, and shortening the median duration of hospitalization.

Multi-center, randomized, placebo-controlled, and double-blinded study was conducted to evaluate the safety and efficacy of Leukine for promoting hematopoietic reconstitution following allogeneic BMT. A total of 109 patients (53 LEUKINE, 56 placebo) were enrolled in the study. Twenty-three patients (11 LEUKINE, 12 placebo) were 18 years old or younger. Sixty-seven patients had myeloid malignancies (33 AML, 34 CML), 17 had lymphoid malignancies (12 ALL, 5 NHL), three patients had Hodgkin’s disease, six had multiple myeloma, nine had myelodysplastic disease, and seven patients had aplastic anemia. In 22 patients at one of the seven study sites, bone marrow harvests were depleted of T cells. Preparative regimens included cyclophosphamide, busulfan, cytosine arabinoside, etoposide, methotrexate, corticosteroids, and asparaginase. Some patients also received total body, splenic, or testicular irradiation. Primary graft-versus-host disease (GVHD) prophylaxis was cyclosporine A and a corticosteroid. Adverse events occurring in >10% of Allogeneic BMT patients receiving Leukine in controlled clinical trials and reported in a higher frequency than placebo abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high BUN, and high cholesterol).

Neutrophil recovery occurred significantly earlier in the Leukine group1,6

Hematopoietic Cell Recovery

Leukine in Allogenic Bone Marrow Transplantation

Nemunaitis J, et al. Bone Marrow Transplant. 1995.

  • Leukine patients reached an ANC of ≥500/mm3 4 days earlier than patients in the placebo group: 13 days versus 17 days, respectively (P <.05)
  • Leukine patients reached an ANC of ≥1000 /mm3 5 days earlier than patients in the placebo group: 14 days versus 19 days, respectively (P<.05)*

Summary of Infection

Leukine in Allogenic Bone Marrow Transplantation

Nemunaitis J, et al. Bone Marrow Transplant. 1995.

Leukine decreased the incidence of bacteremias by 50%1

  • 9 patients in the Leukine group developed bacteremia versus 19 in the placebo group (P =.043)

Leukine decreased duration of hospitalization1

  • 25 days of hospitalization in the Leukine group versus 26 days in the placebo group (P =.02)
  • Leukine should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or CHF; respiratory symptoms or disease; cardiac symptoms or disease; and renal or hepatic dysfunction.
Use in Mobilization and Following Transplantation of Autologous Peripheral Blood Progenitor Cells
Percent of Allogeneic BMT Reporting Events
Events by Body System LEUKINE (n=53) Placebo (n=56) Events by Body System LEUKINE (n=53) Placebo (n=56)
Body, General     Metabolic, Nutritional Disorder    
Fever 77 80 Bilirubinemia 30 27
Abdominal pain 38 23 Hyperglycemia 25 23
Headache 36 36 Peripheral edema 15 21
Chills 25 21 Increased creatinine 15 14
Pain 17 36 Hypomagnesemia 15 9
Asthemia 17 20 Increased SGPT 13 16
Chest pain 15 9 Edema 13 11
Back pain 9 18 Increased alk. phosphatase 8 14
Digestive System     Respiratory System    
Diarrhea 81 66 Pharyngitis 23 13
Nausea 70 60 Epistaxis 17 16
Vomiting 70 57 Dyspnea 15 14
Stomatitis 62 63 Rhinitis 11 14
Anorexia 51 57 Hemic and Lymphatic System    
Dyspensia 17 20 Thrombocytopenia 19 34
Hematamesis 13 7 Leukopenia 17 29
Dysphagia 11 7 Petechia 6 11
GI hemorrhage 11 5 Agranulocytosis 6 11
Constipation 8 11 Urogenital System    
Skin and Appendages     Hematuria 9 21
Rash 70 73 Nervous System    
Alopecia 45 45 Paresthesia 11 13
Pruritis 23 13 Insomnia 6 11
Musculo-skeletal System     Anxiety 11 2
Bone pain 21 5 Laboratory Abnormalities*    
Arthralgia 11 4 High glucose 41 49
Special Senses     Low albumin    
Eye hemorrhage 11 0 High BUN 23 17
Cardiovascular System     Low calcium 2 17
Hypertension 34 32 High cholesterol 17 8
Tachycardia 11 9      
*Grade 3 and 4 laboratory abnormalities only. Denominators may vary due to missing laboratory measurements.
Leukine in Allogenic Bone Marrow Transplantation


References:

  1. LEUKINE® (sargramostim) [package insert]. Genzyme Corporation 2009.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Data on file. Genzyme Corporation.

Leukine Resources

Indication

Leukine® (sargramostim) is indicated for the following uses: (i) following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery; (ii) for mobilization and following transplantation of autologous peripheral blood progenitor cells; (iii) for myeloid reconstitution after autologous or allogeneic bone marrow transplantation (BMT); (iv) for use in bone marrow transplantation failure or engraftment delay.

Important Safety Information for Leukine® (sargramostim)

  • Leukine is contraindicated in patients with excessive leukemic myeloid blasts in bone marrow or peripheral blood (≥10%); in patients with known hypersensitivity to GM-CSF, yeast-derived products, orany component of Leukine; and for concomitant use with chemotherapy and radiotherapy.
  • Serious allergic or anaphylactic reactions have been reported with Leukine. If any serious allergic or anaphylactic reactions occur, Leukine therapy should be immediately discontinued and appropriate therapy initiated.
  • Liquid solutions containing benzyl alcohol (including liquid Leukine) or lyophilized Leukine reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates.
  • Leukine should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure, respiratory symptoms or disease; cardiac symptoms or disease; and renal or hepatic dysfunction.
  • Edema, capillary leak syndrome, pleural and/or pericardial effusion, sequestration of granulocytes in the pulmonary circulation, and dyspnea have been reported in patients after Leukine administration. Occasional transient supraventricular arrhythmia has been reported during Leukine administration. Leukine has induced the elevation of serum creatinine or bilirubin and hepatic enzymes in some patients. Monitoring of renal and hepatic function in patients with preexisting renal or hepatic dysfunction is recommended at least every other week during Leukine administration.
  • Adverse events occurring in >10% of patients receiving Leukine in controlled clinical trials and reported in a higher frequency than placebo were: in AML patients – (fever, skin reactions, metabolic disturbances, nausea, vomiting, weight-loss, edema, anorexia); in Autologous BMT patients – (asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder); and in Allogeneic BMT patients – (abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high BUN, and high cholesterol).
  • If ANC > 20,000 cells/mm3 or if platelet counts > 500,000/mm3, Leukine administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
  • Leukine therapy should be discontinued if disease progression is detected during treatment.
  • Drugs that can increase WBCs, such as lithium and corticosteroids, should be used with caution while receiving Leukine. Interactions between Leukine and other drugs have not been fully evaluated.

Please see full Prescribing Information.