THE USE OF HEMATOPOIETIC GROWTH FACTORS IN CHILDREN WITH CANCER: RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE-COLONY-STIMULATING FACTOR (RHGM-CSF)

I. INDICATIONS AND CONTRAINDICATIONS

A.     Proven indications

To accelerate myeloid recovery in patients who have just received an autologous bone marrow transplant secondary to non-Hodgkin lymphoma, Hodgkin disease, or acute lymphoblastic leukemia after conditioning drugs have been given

To accelerate myeloid recovery when delayed or failure of engraftment after autologous or allogeneic bone marrow transplant

To accelerate myeloid recovery after peripheral blood stem cell transplantation

B.     Controversial indications

To accelerate myeloid recovery in patients who have undergone allogeneic bone marrow transplantation for any malignancy and in patients with myeloid malignancy undergoing autologous bone marrow transplantation

When the planned chemotherapy for a nonmyeloid malignancy is likely to result in an ANC < 500 cells/uL for 7 or more days

To treat myelodysplastic syndrome

C.     Inappropriate indications

To mature or cycle myeloid blasts for better chemotherapeu-tic response to therapy.

D.     Contraindications

Excessive myeloid blasts (> 10%) in bone marrow or peripheral blood

Juvenile chronic myeloid leukemia or monosomy 7 syndrome.

History of hypersensitivity to rhGM-CSF or yeast-derived proteins

II. ADMINISTRATION (rhGM-CSF, sargamostim, Leukine)

A.     Dosage

Starting dose is 250 ug/m2/day IV over 2-4 hours for both the prevention and the treatment of engraftment delay. rhGM-CSF can be administered subcutaneously if indicated.

If a severe adverse reaction occurs, reduce or discontinue the dose.

B.     Duration

When given to prevent engraftment delay, the first dose should be given within 2-4 hours after the bone marrow transplant, then once a day for 21 days or until the ANC > 10,000 cells/pL.

rhGM-CSF should not be given within 24 hours of last chemotherapy or within 12 hours of last dose of radiation therapy.

In case of engraftment delay or failure of bone marrow transplant, 14 or more days of treatment may be necessary.

C.     Monitoring

CBC with differential and platelet counts shuld be monitored at least twice weekly and rhGM-CSF should be discontinued when ANC > 10,000 cells/pL; avoid white blood cell count (WBC) >50,000 cells/pL.

More frequent monitoring of WBC might be needed to avoid excessive leukocytosis.

If blasts appear or disease progresses, discontinue rhGM-CSF.

Monitor renal and hepatic function twice a week and more often for patients with organ dysfunction.

Due to possible fluid retention syndrome, monitor patients for weight gain, respiratory distress, and pleural or pericardial effusions.

D.     Formulation and preparation

1. Sterile, white, preservative-free, lyophilized powder in vials containing 250 or 500 pg of rhGM-CSF with 40 mg of mannitol, 10 mg of sucrose, and 1.2 mg of tromethamine in 1 mL of water

a.     Reconstitute rhGM-CSF in 1 mL of sterile or bacterio-

static water. Avoid shaking.

b.     Administer product reconstituted with sterile water

within 6 hours of preparation; product reconstituted

with bacteriostatic water may be stored for up to 20

days at 2-8° C.

2. Sterile, preserved (1.1% benzyl alcohol), injectable solution in multiple-dose vials containing 500 ug of rhGM-CSF with 40 mg of mannitol, 10 mg of sucrose, and 1.2 mg of tromethamine in 1 mL of water

Since this product is preserved, once the vial is entered, the drug may be stored for up to 20 days at 2-8° C. Discard any remaining solution after 20 days.

E.     Dilution

Dilute with 0.9% NaCl and administer as a 2 to 4 hour infusion.

If the concentration of rhGM-CSF is <1 0 ug/mL, to prevent absorption to the drug delivery system, add albumin to the saline to make a 0.1% albumin solution before adding rhGM-CSF.

F.     Storage

Store all preparations at 2-8° C. Do not freeze.

Prepared or diluted rhGM-CSF is stable for 6 hours after reconstitution. Since the diluted solution is preservative-free, practice caution to maintain sterility.

III. ADVERSE EFFECTS

A.     Occasional

Bone pain, leukocytosis, diarrhea, asthenia, rash, malaise, headache, fever, chills, arthralgias, chest pain, thrombocytopenia, dyspnea, and thrombophlebitis

B.     Uncommon

Fluid retention: peripheral edema, pleural effusion, pericardial effusion, dyspnea, respiratory distress syndrome, weight gain, renal failure, thrombosis of vena cava, hypotension, facial flushing, bundle branch block, supraventricular arrhythmias, and elevation of LDH, alkaline phosphatase, and liver function tests

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Cancer