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.

Bone Marrow Transplant Information

A bone marrow transplant is a procedure for replacing blood-forming cells in the bone marrow that have been destroyed by chemotherapy with healthy bone marrow, while a peripheral blood stem cell transplantation is a method of replacing blood-forming cells destroyed by cancer treatment (also called peripheral stem cell support). In a peripheral blood stem cell transplant, immature blood cells in the circulating blood that are similar to those in the bone marrow are given to the patient after treatment to help the bone marrow recover and continue producing healthy blood cells.

There are three categories of bone marrow and peripheral blood stem cell transplantation — autologous, allogeneic, and syngeneic. Two of these transplantation types — autologous and allogeneic — are described in detail below.

What is a stem cell?

A stem cell is an immature cell found in the bone marrow and sometimes in the blood. It is the mother cell that is involved in the production of various types of cells in the blood. New blood cells are produced in the bone marrow.

What is a Stem Cell

What is a Stem Cell click here to view full graphic


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Autologous bone marrow and peripheral blood stem cell transplantation

An autologous transplant is when a patient receives his or her own stem cells that were removed and stored before treatment rather than receiving cells from a donor (allogeneic transplant) or from an identical twin (syngeneic transplant).

The autologous transplant process

  • Collection — Stem cells are collected from the patient's bone marrow or blood.
  • Processing — Bone marrow or peripheral blood is processed in the laboratory to purify and concentrate the stem cells.
  • Cryopreservation— Bone marrow or blood is preserved by freezing (cryopreservation) to keep stem cells alive until they are reinfused into the patient's bloodstream.
  • Chemotherapy — High-dose chemotherapy and/or radiation therapy is given to the patient.
  • Reinfusion — Thawed stem cells are reinfused into the patient's bloodstream.

The Autologous Transplant Process

The Autologous Transplant Process

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Collecting stem cells from bone marrow

A needle is used to harvest or collect bone marrow from several areas of the pelvis.

  • The procedure is usually performed in a hospital room under general anesthesia
  • There is usually soreness in the collection area for several days to a couple of weeks

Collecting stem cells from blood (Peripheral Blood Stem Cells)

A procedure called mobilization moves stem cells from the bone marrow into the bloodstream. Your physician may also administer chemotherapy or other medications to help increase the number of stem cells in the blood. A process called apheresis is used to collect the patient's blood. The blood is taken through a thin, flexible plastic tube called a catheter. The catheter is inserted into the chest or the arm.

Common side effects from PBSC collection include:

  • Slight dizziness
  • Tingling sensation in hands and feet

Less common side effects are tremors, chills, and muscle cramps.

Processing stem cells

Processing stem cells lowers the risk that some tumor cells will be reinfused back into the patient. Bone marrow or peripheral blood is taken to the processing laboratory where the stem cells are concentrated and prepared for the freezing process.

Processing Stem Cells

Processing Stem Cells

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Freezing stem cells
Bone marrow or blood is preserved by freezing (cryopreserving) to keep stem cells alive until they are reinfused into the patient's bloodstream. DMSO (dimethyl sulfoxide) is mixed with the blood or bone marrow to keep water in the cells from forming crystals that would damage the cells.

High-dose chemotherapy and/or radiation therapy

High-dose chemotherapy (sometimes combined with radiation therapy) destroys cancer cells more effectively than standard chemotherapy because patients receive higher doses of anticancer medications. Treatment can last several weeks or several months with rest periods between cycles of treatment.

Common side effects of high-dose chemotherapy include:

  • Nausea, vomiting, and diarrhea
  • Loss of hair
  • Skin rash, mouth sores

Reinfusion of stem cells into the patient

After high-dose chemotherapy is completed, the frozen bone marrow or blood cells are thawed and injected into the bloodstream through a catheter. Infusion of stem cells usually takes 2 to 4 hours.

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Allogeneic bone marrow and peripheral blood stem cell transplantation

An allogeneic transplant is when the patient receives stem cells from someone other than the patient (autologous transplant) or identical twin (syngeneic transplant). The donor may be the patient's sister, brother, or sometimes a person not related to the patient.

  • Allogeneic transplantation success depends to a large extent on how well the human leukocyte antigens (HLA) of the donor's bone marrow match the HLA of the patient's marrow. The higher the number of matching HLA, the greater the chance of success. HLA is identified by a special blood test
  • Close relatives (especially brothers and sisters) usually have a greater chance of having HLA-matched bone marrow than unrelated donors

The allogeneic transplant process

  1. Collection — Stem cells are collected from the donor's bone marrow or blood.
  2. Processing — Bone marrow or peripheral blood is taken to the processing laboratory where the stem cells are concentrated and prepared for the freezing process.
  3. Cryopreservation — Bone marrow or blood is preserved by freezing (cryopreservation) to keep stem cells alive until they are infused into the patient's bloodstream.
  4. Chemotherapy — High-dose chemotherapy and/or radiation therapy is given to the patient.
  5. Infusion — Thawed stem cells are infused into the patient's bloodstream.

The Allogeneic Transplant Process

The Allogeneic Transplant Process

click here to view full graphic

Collecting stem cells from donor's bone marrow
A needle is used to harvest or collect bone marrow from several areas of the donor's pelvic (hip) bone or breast bone.

  • The procedure is usually performed in a hospital room under general anesthesia
  • There is usually soreness in the collection area for several days to a couple of weeks
  • Within a few weeks, the donor's body will have replaced the donated marrow

Collecting stem cells from donor's blood (Peripheral Blood Stem Cells)

A process called apheresis is used to collect or harvest peripheral blood stem cells for transplantation. The donor may be given a medication to increase the number of stem cells for 4 or 5 days before apheresis. The blood is removed through a thin, flexible plastic tube called a catheter. The catheter is placed in the chest or arm. No general anesthesia is required and the procedure is usually done on an outpatient basis.

Freezing stem cells

Bone marrow or blood is preserved by freezing (cryopreserving) to keep stem cells alive until they are infused into the patient's bloodstream. DMSO (dimethyl sulfoxide) is mixed with the blood or bone marrow to keep water in the cells from forming crystals that would damage the cells.

alive until they are infused into the patient's bloodstream. DMSO (dimethyl sulfoxide) is mixed with the blood or to keep water in the cells from forming crystals that would damage the cells. alive until they are infused into the patient's bloodstream. DMSO (dimethyl sulfoxide) is mixed with the blood or to keep water in the cells from forming crystals that would damage the cells. or blood is preserved by freezing (cryopreserving) to keep alive until they are infused into the patient's bloodstream. DMSO (dimethyl sulfoxide) is mixed with the blood or to keep water in the cells from forming crystals that would damage the cells.

High-dose chemotherapy and/or radiation therapy

High-dose chemotherapy (sometimes combined with radiation therapy) destroys cancer cells more effectively than standard chemotherapy because patients receive higher doses of anticancer medications. Treatment can last several weeks or several months with rest periods between cycles of treatment.

Common side effects of high-dose chemotherapy include:

  • Nausea, vomiting, and diarrhea
  • Loss of hair
  • Skin rash, mouth sores

Infusion of stem cells into the patient

After high-dose chemotherapy is completed, the frozen bone marrow or blood cells are thawed and injected into the patient's bloodstream through a catheter. Infusion of stem cells usually takes 2 to 4 hours.

Graft Versus Host Disease (GVHD)

A complication called graft-versus-host disease (GVHD) sometimes occurs with allogeneic bone marrow transplantation. White blood cells (WBCs) from the donor marrow (the graft) attack the cells of the patient's body (the host) because they identify the patient's body as foreign. GVHD can usually be treated with steroids or other immunosuppressive agents.

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Non-myeloblative transplant

A non-myeloblative transplant, which may be called a mini-transplant, is a type of allogeneic transplant that is being studied in clinical trials for certain types of cancer. Mini-transplants use lower doses of chemotherapy and/or radiation therapy to the entire body that are less toxic. This eliminates some, but not all, of the patient's bone marrow and reduces the number of cancer cells and suppresses the patient's immune system to prevent rejection of the transplant.

Once the bone marrow cells from the donor begin to graft, they may cause a "graft-verses-tumor effect" and may work to destroy the cancer cells that were not eliminated by the chemotherapy drugs. To boost the graft-versus-tumor effect, the patient may be given an injection of their donor's WBCs. This procedure is called a "donor lymphocyte infusion."

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Common side effects of infusion, engraftment and recovery, and preventing infection

Common side effects of infusion (allogeneic) and reinfusion (autologous):

  • Nausea, vomiting, and cramping
  • Chills
  • Unusual odor, taste of garlic
  • In rare cases DMSO (an agent used to protect cells during the freezing process) may cause side effects such as low blood pressure, fast heart rate, or shortness of breath

Engraftment and recovery

  • During the process called engraftment, the stem cells that have been reinfused make their way to the bone marrow and begin producing replacement blood cells. This process lasts for several weeks
  • Patients will be required to report for frequent check-ups and tests. Outpatients will need to stay close to the hospital during recovery. Some patients will be admitted to the hospital during recovery
  • Patients are very susceptible to developing infections until the engraftment process is completed. Even common colds can cause serious problems for the body's weakened immune system. Preventing infections is a high priority during the engraftment and recovery process

Preventing infection

  • Patients may have transfusions of red blood cells and platelets to prevent anemia and bleeding
  • Patients often receive antibiotics to help prevent infection
  • Visitors are usually asked to wear masks and gloves
  • Flowers, fresh fruit, and fresh vegetables may be prohibited from the patient's room
  • Avoid small children, pets, and people who are ill
  • If infection and fever occur, patients may receive antibiotics in the hospital

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Colony-stimulating factors and Leukine (sargramostim) in transplantation

Shortly after your stem cell infusion, you may begin to receive infusions of a colony-stimulating factor (CSF). CSFs are also known as hematopoietic growth factors, which means they stimulate the production of blood cells in the bone marrow. In addition to their use in mobilization of stem cells, CSFs are capable of simulating certain WBCs in the bone marrow to multiply more quickly, thereby shortening the time necessary for the stem cell transplant to engraft. In particular, CSFs help your body replenish WBCs that play an important role in fighting infection. Use of these agents may help reduce the incidence of infection and fever, lessen the need for antibiotics, and/or shorten the duration of hospitalization.

Leukine, a CSF, is approved for use after bone marrow transplantation (BMT), before and/or after peripheral blood stem cell transplantation, and in cases where BMT has failed or engraftment is delayed. In clinical trials of Leukine in patients undergoing autologous bone marrow transplantation (AuBMT) and allogeneic bone marrow transplantation (AlloBMT), Leukine provided benefit.

In AuBMT, treatment with Leukine resulted in faster times to neutrophil recovery (compared with a placebo), less use of antibiotics, and shorter hospital stays.1 In AlloBMT, treatment with Leukine resulted in earlier and more rapid transplantation (BMT) recovery, fewer infections, a reduction in cases of severe chemotherapy, and shorter hospital stays.2

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.

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).

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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. Nemunaitis J, Rabinowe S, Singer J, et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. New Engl J Med. 1991;324:1773-1778.

  2. 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.