Important Safety Considerations
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 or any component of Leukine, and for concomitant use with chemotherapy and radiotherapy. View additional Important Safety Information. View Indications.

What Cancer Does

This section of Leukine.com discusses the effect that cancer treatments have on immune system cells, the resulting infection risks, and the role Leukine® (sargramostim) may play in helping to rebuild the immune system following cancer treatment.

The Immune System and Cancer Treatments

Cancer treatments can temporarily weaken your immune system. Chemotherapy and radiation therapy, which target and destroy fast-growing cancerous cells, can also kill healthy cells. Because some infection-fighting white blood cells (WBCs) are also fast-growing, they may be affected by chemotherapy and radiation therapy.

Stem cell transplantation (from bone marrow or peripheral blood) is another type of cancer treatment that can compromise your immune system. A transplant may be performed if your bone marrow has been damaged and cannot make some or all of the blood cells your body needs. Damage to the bone marrow may be a result of disease that affects the bone marrow itself, or it may result from intense anticancer therapies.

During stem cell transplantation, healthy pluripotent stem cells are harvested (from a donor or from the patient) and then infused into the patient. It takes time for these new or reinfused cells to repopulate the body and establish normal immune system functions. During this time your body is at greater risk for infection.

Cancer Treatments and the Risk of infection

After chemotherapy, radiation therapy, or stem cell transplantation, your healthcare team will closely monitor your immune system, using blood tests that measure the levels of various cell types. As part of this process, they will monitor your absolute neutrophil count (ANC), which is an important marker that can indicate your risk of infection. Your ANC refers to the number of neutrophils in your blood. Neutrophils are monitored because they are the most abundant type of WBC, and are the first to rush to the site of an infection and attack foreign antigens. If the number of neutrophils in your body is abnormally low (a condition called neutropenia), it is an indication that your body may be unable to successfully defend itself against infection. An increased risk of infection occurs once the number of neutrophils drops below 1000 and especially below 500. Following cancer therapy, your doctor will monitor the number of white blood cells (WBCs) in your blood with regular blood tests to determine when the WBCs reach a level that is high enough to help fight infections. Generally, that is the point at which Leukine® therapy is stopped.

Other cells of the immune system, such as macrophages and dendritic cells, are also very important in regard to infection risk. However, they are not measured and used as markers because they are not nearly as abundant as neutrophils.

As your healthcare team monitors your immune system following cancer treatment, remember that it is important for you to do everything possible to reduce your risk of infection. An infection of any kind can disrupt your cancer treatment and, in severe cases, may require hospitalization.

Absolute Neutrophil Count (ANC)

In order to offer adequate protection from infection, your ANC should be around 1500 cells per mm3.1 Risk of infection increases when your ANC drops below 1000 cells per mm3 and especially below 500 cells per mm3.

Treatments to Help Boost the Immune System and Fight Infection

Antibiotics are used to treat an infection once it occurs and are sometimes given to prevent infections. In addition, there are other types of drugs available that can help your immune system recover more quickly from cancer treatment, thereby reducing the risk of infection. One of these drugs is Leukine, which is frequently prescribed in certain instances described below to help raise your ANC above the critical level of 1500 cells per mm3.

Leukine is approved for use following induction chemotherapy in older adults with acute myelogenous leukemia, after bone marrow transplantation, before and/or after peripheral blood stem cell transplantation, and for bone marrow transplantation failure or engraftment delay.2 Some doctors may choose to prescribe Leukine for other uses as well.

Patients who take Leukine may experience fewer and less severe infections. For example, clinical studies have shown that Leukine significantly reduced the incidence and severity of infections in older patients who received Leukine following induction chemotherapy for acute myelogenous leukemia.3,4 Clinical studies have also shown that Leukine reduced the incidence of infections in patients who received autologous (cells from the patient) and allogeneic (cells from a donor) bone marrow transplantation.2,5,6

About Leukine

As part of your cancer treatment, Leukine may be prescribed by your doctor to help your body's immune system recover and return to normal function. Leukine is a man-made form of a colony-stimulating factor (CSF). A CSF is a type of protein also known as a growth factor. Your body makes this protein when it is functioning normally to help increase the number and function of your WBCs.

Because Leukine increases your body's production of three types of WBCs (neutrophils, monocytes/macrophages, and myeloid-derived dendritic cells), it may help activate your body's natural defenses against multiple types of infectious organisms, including bacteria, fungi, and viruses.4,5,7

Patients who take Leukine may experience side effects, most of which are mild to moderate. Some common side effects include bone pain; a slight temperature elevation (usually less than 100.5°F or 38°C) for one to four hours after injection; and swelling, redness, and/or discomfort at the injection site. Skin reactions may occur because cells of the immune system, such as macrophages, are drawn to the injection site. You may also feel tired or weak, experience muscle aches, have diarrhea, experience stomach upset, or feel like you have the flu.

Immune Cells Stimulated by Leukine

Immune Cells Stimulated by Leukine<sup>®</sup>

Leukine provides enhanced protection against infection by stimulating cells that activate additional immune system responses.

 

Indication

Leukine® 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 Considerations

  • 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, or any 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.

Please see full Prescribing Information.

To report suspected adverse events, contact Genzyme Corporation at 1-888-4RX-LEUKINE or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. Bodey GP, Buckley M, Sathe YS, et al. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64:328-340.

  2. LEUKINE® (sargramostim) [package insert]. Genzyme Corporation 2009.

  3. Rowe JM, Andersen 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.

  4. 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: Hiddeman W, ed. Acute Leukemias V: Experimental Approaches and Management of Refractory Diseases. Berlin, Germany: Springer-Verlag; 1996.

  5. 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.

  6. Nemunaitis J, Rabinowe SN, Singer JW, et al. Recombinant granulocytemacrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med. 1991;324:1773-1778.

  7. Nemunaitis J. Granulocyte-macrophage colony-stimulating factor: a review from preclinical development to clinical applications. Transfusion. 1993;33:70-83.