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.
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Transplantation of Peripheral Blood Progenitor Cells (PBPCs)

Leukine® (sargramostim) is indicated for the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis. Mobilization allows for the collection of increased numbers of progenitor cells capable of engraftment as compared with collection without mobilization. After myeloablative chemotherapy, the transplantation of an increased number of progenitor cells can lead to more rapid engraftment, which may result in a decreased need for supportive care. Myeloid reconstitution is further accelerated by administration of Leukine following peripheral blood progenitor cell transplantation.

A retrospective review was conducted of data from patients with cancer undergoing collection of peripheral blood progenitor cells (PBPC) at a single transplant center. Mobilization of PBPC and myeloid reconstitution post-transplant were compared between four groups of patients (n=196) receiving Leukine for mobilization and a historical control group who did not receive any mobilization treatment [progenitor cells collected by leukapheresis without mobilization (n=100)]. The cohorts differed by dose (125 or 250 mcg/m2/day), route (IV over 24 hours or SC) and use of Leukine post-transplant.

Leukine was effective for mobilization of PBPCs before and during leukapheresis of cells for transplantation. Leukine increased the number of progenitor cells and myeloid recovery after PBPC transplantation. Leukine decreased days to neutrophil recovery, days to last red blood cell (RBC) transfusion, days to last platelet transfusion, days to engraftment, and days of hospitalization. Leukine did not adversely affect relapse rate or survival. The detailed results are provided below.

ANC and Platelet Recovery After PBPC Transplant1


Route for
Mobilization
Post-Transplant
Leukine
ENGRAFTMENT
(Median Value in Days)
ANC > 500/mm3 Last Platelet Transfusion
No Mobilization No 29 28
Leukine
(250 mcg/mm3)
IV
IV
SC
No
Yes
Yes
21
12
12
24
19
17
Transplantation of Peripheral Blood Progenitor Cells

The most marked mobilization and post-transplant effects were seen in patients administered the higher dose of Leukine1:

  • Mobilized patients had fewer days to the last platelet transfusion and last RBC transfusion, and a shorter duration of hospitalization, than did non-mobilized patients
  • 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
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    
Fever 95 96 Edema 34 35
Mucous membrane disorder 75 78 Peripheral edema 11 7
Asthenia 66 51 Respiratory System    
Malaise 57 51 Dyspnea 28 31
Sepsis 11 14 Lung disorder 20 23
Digestive System     Hemic and Lymphatic System    
Nausea 90 96 Blood dyscrasia 25 27
Diarrhea 89 82 Cardiovascular System    
Vomiting 85 90 Hemorrhage 23 30
Anorexia 54 58 Urogenital System    
GI disorder 37 47 Urinary tract disorder 14 13
GI hemorrhage 27 33 Kidney function abnormal 8 10
Stomatitis 24 29 Nervous System    
Liver damage 13 14 CNS disorder 11 16
Skin and Appendages          
Alopecia 73 74      
Rash 44 38      
Transplantation of Peripheral Blood Progenitor Cells
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.

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