Leucomax (Novartis)

Use Following Induction Chemotherapy in Acute Myelogenous Leukemia

Leucomax (Novartis) (Leucomax (Novartis)) is indicated for use following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death. The safety and efficacy of Leucomax (Novartis) (Leucomax (Novartis)) have not been assessed in patients with AML under 55 years of age.

The term acute myelogenous leukemia, also referred to as acute non-lymphocytic leukemia (ANLL), encompasses a heterogeneous group of leukemias arising from various non-lymphoid cell lines which have been defined morphologically by the French-American- British (FAB) system of classification.

Use in Mobilization and Following Transplantation of Autologous Peripheral Blood Progenitor Cells

Leucomax (Novartis) (Leucomax (Novartis)) 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 Leucomax (Novartis) (Leucomax (Novartis)) following peripheral blood progenitor cell transplantation.

Use in Myeloid Reconstitution After Autologous Bone Marrow Transplantation

Leucomax (Novartis) (Leucomax (Novartis)) is indicated for acceleration of myeloid recovery in patients with non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin's disease undergoing autologous bone marrow transplantation (BMT). After autologous BMT in patients with NHL, ALL, or Hodgkin's disease, Leucomax (Novartis) (Leucomax (Novartis)) has been found to be safe and effective in accelerating myeloid engraftment, decreasing median duration of antibiotic administration, reducing the median duration of infectious episodes and shortening the median duration of hospitalization. Hematologic response to Leucomax (Novartis) (Leucomax (Novartis)) can be detected by complete blood count (CBC) with differential cell counts performed twice per week.

Use in Myeloid Reconstitution After Allogeneic Bone Marrow Transplantation

Leucomax (Novartis) (Leucomax (Novartis)) is indicated for acceleration of myeloid recovery in patients undergoing allogeneic BMT from HLAmatched related donors. Leucomax (Novartis) (Leucomax (Novartis)) 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.

Use in Bone Marrow Transplantation Failure or Engraftment Delay

Leucomax (Novartis) (Leucomax (Novartis)) is indicated in patients who have undergone allogeneic or autologous bone marrow transplantation (BMT) in whom engraftment is delayed or has failed. Leucomax (Novartis) (Leucomax (Novartis)) has been found to be safe and effective in prolonging survival of patients who are experiencing graft failure or engraftment delay, in the presence or absence of infection, following autologous or allogeneic BMT. Survival benefit may be relatively greater in those patients who demonstrate one or more of the following characteristics: autologous BMT failure or engraftment delay, no previous total body irradiation, malignancy other than leukemia or a multiple organ failure (MOF) score ≤ two. Hematologic response to Leucomax (Novartis) (Leucomax (Novartis)) can be detected by complete blood count (CBC) with differential performed twice per week.

Leucomax (Novartis) is a synthetic (man-made) version of a substance that is naturally produced in your body called a colony stimulating factor. It helps the bone marrow to make new white blood cells.

When certain cancer medicines are used to fight cancer cells, they also affect the white blood cells that fight infections. Leucomax (Novartis) is used to prevent or reduce the risk of infection while you are being treated with cancer medicines. Leucomax (Novartis) is also used to help the bone marrow recover after a bone marrow transplantation, and for a process called peripheral blood progenitor cell collection in cancer patients.

Leucomax (Novartis) is available only with your doctor's prescription.

Neutrophil Recovery Following Chemotherapy in Acute Myelogenous Leukemia

The recommended dose is 250mcg/m²/day administered intravenously over a 4 hour period starting approximately on day 11 or four days following the completion of induction chemotherapy, if the day 10 bone marrow is hypoplastic with < 5% blasts. If a second cycle of induction chemotherapy is necessary, Leucomax (Novartis) (Leucomax (Novartis)) should be administered approximately four days after the completion of chemotherapy if the bone marrow is hypoplastic with < 5% blasts. Leucomax (Novartis) (Leucomax (Novartis)) should be continued until an ANC > 1500 cells/mm³ for 3 consecutive days or a maximum of 42 days. Leucomax (Novartis) (Leucomax (Novartis)) should be discontinued immediately if leukemic regrowth occurs. If a severe adverse reaction occurs, the dose can be reduced by 50% or temporarily discontinued until the reaction abates.

In order to avoid potential complications of excessive leukocytosis (WBC > 50,000 cells/mm³ or ANC > 20,000 cells/mm³) a CBC with differential is recommended twice per week during Leucomax (Novartis) (Leucomax (Novartis)) therapy. Leucomax (Novartis) (Leucomax (Novartis)) treatment should be interrupted or the dose reduced by half if the ANC exceeds 20,000 cells/mm³.

Mobilization of Peripheral Blood Progenitor Cells

The recommended dose is 250 mcg/m²/day administered IV over 24 hours or SC once daily. Dosing should continue at the same dose through the period of PBPC collection. The optimal schedule for PBPC collection has not been established. In clinical studies, collection of PBPC was usually begun by day 5 and performed daily until protocol specified targets were achieved. If WBC > 50,000 cells/mm³, the Leucomax (Novartis) (Leucomax (Novartis)) dose should be reduced by 50%. If adequate numbers of progenitor cells are not collected, other mobilization therapy should be considered.

Post Peripheral Blood Progenitor Cell Transplantation

The recommended dose is 250 mcg/m²/day administered IV over 24 hours or SC once daily beginning immediately following infusion of progenitor cells and continuing until an ANC > 1500 cells/mm³ for three consecutive days is attained.

Myeloid Reconstitution After Autologous or Allogeneic Bone MarrowTransplantation

The recommended dose is 250mcg/m²/day administered IV over a 2-hour period beginning two to four hours after bone marrow infusion, and not less than 24 hours after the last dose of chemotherapy or radiotherapy. Patients should not receive Leucomax (Novartis) (Leucomax (Novartis)) until the post marrow infusion ANC is less than 500 cells/mm³. Leucomax (Novartis) (Leucomax (Novartis)) should be continued until an ANC > 1500 cells/mm³ for three consecutive days is attained. If a severe adverse reaction occurs, the dose can be reduced by 50% or temporarily discontinued until the reaction abates. Leucomax (Novartis) (Leucomax (Novartis)) should be discontinued immediately if blast cells appear or disease progression occurs.

In order to avoid potential complications of excessive leukocytosis (WBC > 50,000 cells/mm³, ANC > 20,000 cells/mm³) a CBC with differential is recommended twice per week during Leucomax (Novartis) (Leucomax (Novartis)) therapy. Leucomax (Novartis) (Leucomax (Novartis)) treatment should be interrupted or the dose reduced by 50% if the ANC exceeds 20,000 cells/mm³.

Bone Marrow Transplantation Failure or Engraftment Delay

The recommended dose is 250 mcg/m²/day for 14 days as a 2-hour IV infusion. The dose can be repeated after 7 days off therapy if engraftment has not occurred. If engraftment still has not occurred, a third course of 500 mcg/m²/day for 14 days may be tried after another 7 days off therapy. If there is still no improvement, it is unlikely that further dose escalation will be beneficial. If a severe adverse reaction occurs, the dose can be reduced by 50% or temporarily discontinued until the reaction abates. Leucomax (Novartis) (Leucomax (Novartis)) should be discontinued immediately if blast cells appear or disease progression occurs.

In order to avoid potential complications of excessive leukocytosis (WBC > 50,000 cells/mm³, ANC > 20,000 cells/mm³) a CBC with differential is recommended twice per week during Leucomax (Novartis) (Leucomax (Novartis)) therapy. Leucomax (Novartis) (Leucomax (Novartis)) treatment should be interrupted or the dose reduced by half if the ANC exceeds 20,000 cells/mm³.

Preparation of Leucomax (Novartis) (Leucomax (Novartis))

1. Liquid Leucomax (Novartis) (Leucomax (Novartis)) is formulated as a sterile, preserved (1.1% benzyl alcohol), injectable solution (500 mcg/mL) in a vial. Lyophilized Leucomax (Novartis) (Leucomax (Novartis)) is a sterile, white, preservative-free powder (250mcg) that requires reconstitution with 1mL SterileWater for Injection, USP, or 1 mL Bacteriostatic Water for Injection, USP.
2. Liquid Leucomax (Novartis) (Leucomax (Novartis)) may be stored for up to 20 days at 2-8°C once the vial has been entered. Discard any remaining solution after 20 days.
3. Lyophilized Leucomax (Novartis) (Leucomax (Novartis)) (250 mcg) should be reconstituted aseptically with 1.0 mL of diluent. The contents of vials reconstituted with different diluents should not be mixed together.

   Sterile Water for Injection, USP (without preservative): Lyophilized Leucomax (Novartis) (Leucomax (Novartis)) vials contain no antibacterial preservative, and therefore solutions prepared with Sterile Water for Injection, USP should be administered as soon as possible, and within 6 hours following reconstitution and/or dilution for IV infusion. The vial should not be re-entered or reused. Do not save any unused portion for administration more than 6 hours following reconstitution.

   Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol): Reconstituted solutions prepared with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) may be stored for up to 20 days at 2-8°C prior to use. Discard reconstituted solution after 20 days. Previously reconstituted solutions mixed with freshly reconstituted solutions must be administered within 6 hours following mixing. Preparations containing benzyl alcohol (including liquid Leucomax (Novartis) (Leucomax (Novartis)) and lyophilized Leucomax (Novartis) (Leucomax (Novartis)) reconstituted with Bacteriostatic Water for Injection) should not be used in neonates .

4. During reconstitution of lyophilized Leucomax (Novartis) (Leucomax (Novartis)) the diluent should be directed at the side of the vial and the contents gently swirled to avoid foaming during dissolution. Avoid excessive or vigorous agitation; do not shake.
5. Leucomax (Novartis) (Leucomax (Novartis)) should be used for SC injection without further dilution. Dilution for IV infusion should be performed in 0.9% Sodium Chloride Injection, USP. If the final concentration of Leucomax (Novartis) (Leucomax (Novartis)) is below 10 mcg/mL, Albumin (Human) at a final concentration of 0.1% should be added to the saline prior to addition of Leucomax (Novartis) (Leucomax (Novartis)) to prevent adsorption to the components of the drug delivery system. To obtain a final concentration of 0.1% Albumin (Human), add 1 mg Albumin (Human) per 1 Ml 0.9%SodiumChloride Injection, USP (e.g., use 1mL 5%Albumin [Human] in 50 mL 0.9% Sodium Chloride Injection, USP).
6. An in-line membrane filter should NOT be used for intravenous infusion of Leucomax (Novartis) (Leucomax (Novartis)).
7. Store liquid Leucomax (Novartis) (Leucomax (Novartis)) and reconstituted lyophilized Leucomax (Novartis) (Leucomax (Novartis)) solutions under refrigeration at 2-8°C (36-46°F); DO NOT FREEZE.
8. In the absence of compatibility and stability information, no other medication should be added to infusion solutions containing Leucomax (Novartis) (Leucomax (Novartis)). Use only 0.9% Sodium Chloride Injection, USP to prepare IV infusion solutions.
9. Aseptic technique should be employed in the preparation of all Leucomax (Novartis) (Leucomax (Novartis)) solutions. To assure correct concentration following reconstitution, care should be exercised to eliminate any air bubbles from the needle hub of the syringe used to prepare the diluent.

   Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter is present or the solution is discolored, the vial should not be used.

How supplied

Liquid Leucomax (Novartis) (Leucomax (Novartis)) is available in vials containing 500 mcg/mL (2.8 x 10 IU/vial) Leucomax (Novartis).

Each dosage form is supplied as follows:

Lyophilized Leucomax (Novartis) (Leucomax (Novartis))

Carton of five vials of lyophilized Leucomax (Novartis) (Leucomax (Novartis)) 250 mcg (NDC 50419-002-33)

Liquid Leucomax (Novartis) (Leucomax (Novartis))

Carton of one multiple-use vial; each vial contains 1 mL of preserved 500 mcg/mL liquid Leucomax (Novartis) (Leucomax (Novartis)) (NDC 50419-050-14)

Carton of five multiple-use vials; each vial contains 1 mL of preserved 500 mcg/mL liquid Leucomax (Novartis) (Leucomax (Novartis)). (NDC 50419-050-30)

Storage

Leucomax (Novartis) (Leucomax (Novartis)) should be refrigerated at 2-8°C (36-46°F). Do not freeze or shake. Do not use beyond the expiration date printed on the vial.

Manufactured by: Bayer HealthCare Pharmaceuticals, LLC., Seattle, WA 98101. Revised April 2008. FDA rev date: 03/05/91

See also:
What is the most important information I should know about Leucomax (Novartis)?

Leucomax (Novartis) (Leucomax (Novartis)) is contraindicated:

1. in patients with excessive leukemic myeloid blasts in the bone marrow or peripheral blood ( ≥ 10%);
2. in patients with known hypersensitivity to GM-CSF, yeast derived products or any component of the product;
3. for concomitant use with chemotherapy and radiotherapy.

Due to the potential sensitivity of rapidly dividing hematopoietic progenitor cells, Leucomax (Novartis) (Leucomax (Novartis)) should not be administered simultaneously with cytotoxic chemotherapy or radiotherapy or within 24 hours preceding or following chemotherapy or radiotherapy. In one controlled study, patients with small cell lung cancer received Leucomax (Novartis) (Leucomax (Novartis)) and concurrent thoracic radiotherapy and chemotherapy or the identical radiotherapy and chemotherapy without Leucomax (Novartis) (Leucomax (Novartis)). The patients randomized to Leucomax (Novartis) (Leucomax (Novartis)) had significantly higher incidence of adverse events, including higher mortality and a higher incidence of grade 3 and 4 infections and grade 3 and 4 thrombocytopenia.

REFERENCES

11. Bunn P, Crowley J, Kelly K, et al. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the southwest oncology group. JCO 1995; 13(7):1632-1641.

Use Leucomax (Novartis) exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Leucomax (Novartis) should not be used within 24 hours before or after you receive chemotherapy or radiation.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Leucomax (Novartis) is injected into a vein or under the skin. You may be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, syringes, IV tubing, and other items used to inject the medicine.

When injected into a vein, Leucomax (Novartis) must be given slowly. The IV infusion can take up to 24 hours to complete.

Use a different place on your stomach, thigh, or upper arm each time you give the injection under the skin. Just before you give the injection, apply an ice pack to the skin for one minute. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row.

Leucomax (Novartis) powder must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medication.

Do not shake the mixed medicine or it may foam. Do not use the medication if it has changed colors or has particles in it. Call your doctor for a new prescription.

To be sure Leucomax (Novartis) is helping your condition, your blood may need to be tested often. This will help your doctor determine how long to treat you with Leucomax (Novartis). Your liver function will also need to be tested. Visit your doctor regularly.

Store the liquid medicine in the refrigerator, do not freeze. Protect from light. You may take the medicine out and allow it to reach room temperature before measuring your dose in a syringe. Then return the medicine to the refrigerator. Throw away any unused liquid after 20 days. After mixing Leucomax (Novartis) powder with a diluent, store in the refrigerator and use it within 6 hours. Do not freeze. Protect from light. If you have mixed the powder with bacteriostatic water, you may store this mixture in the refrigerator for up to 20 days.

Leucomax (Novartis) is a man-made version of a certain natural substance made in your body. It is used to help your body make more white blood cells. White blood cells are important to help you fight off infections. Leucomax (Novartis) is given to people whose ability to make white blood cells is reduced (for instance, due to chemotherapy). It is also used in certain treatment procedures (such as bone marrow/stem cell transplant).

How to use Leucomax (Novartis) injection

Read the Patient Information Leaflet if available from your pharmacist before you start using Leucomax (Novartis) and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

This medication is given by injection under the skin or into a vein as directed by your doctor, usually once a day. The dosage is based on your medical condition, body size, lab tests, and response to treatment.

If you are using this medication at home, learn all preparation and usage instructions from your health care professional and the product package. Take the medication out of the refrigerator at least 30 minutes before you inject it to allow it to reach room temperature. Do not shake the medication. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid.

If you are injecting this drug under the skin, first clean the injection site with rubbing alcohol. Change the injection site each time to lessen injury under the skin. Do not inject Leucomax (Novartis) into skin that is bruised, tender, red, hard, or that has scars or stretch marks.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time each day.

This medication may cause a reaction after the first dose of each treatment period. Tell your doctor or nurse right away if you have any signs of a serious reaction, including: flushing, shortness of breath, dizziness, fainting, or fast heartbeat.

Learn how to store and discard medical supplies safely.

If you are receiving cancer chemotherapy or radiation treatment, you should not use this medication within 24 hours before or 24 hours after chemotherapy or radiation treatment. Ask your doctor for specific directions about when to use this medication.

See also:
What other drugs will affect Leucomax (Novartis)?

Belotecan: Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan. Consider therapy modification

Bleomycin: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of bleomycin. Consider therapy modification

Corticosteroids (Systemic): May enhance the therapeutic effect of Leucomax (Novartis). Specifically, corticosteroids may enhance the myeloproliferative effects of Leucomax (Novartis). Monitor therapy

Cyclophosphamide: May enhance the adverse/toxic effect of Leucomax (Novartis). Specifically, the risk of pulmonary toxicity may be enhanced. Monitor therapy

Lithium: Leucomax (Novartis) may enhance the adverse/toxic effect of Lithium. Specifically, the myeloproliferative effects may be increased. Monitor therapy

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Monitor therapy

Tisagenlecleucel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Tisagenlecleucel. Avoid combination

Topotecan: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination. Consider therapy modification

See also:
What are the possible side effects of Leucomax (Novartis)?

Autologous and Allogeneic Bone Marrow Transplantation

Leucomax (Novartis) (Leucomax (Novartis)) is generally well tolerated. In three placebo-controlled studies enrolling a total of 156 patients after autologous BMT or peripheral blood progenitor cell transplantation, events reported in at least 10% of patients who received IV Leucomax (Novartis) (Leucomax (Novartis)) or placebo were as reported in Table 6.

Table 6: Percent of AuBMT Patients Reporting Events

No significant differences were observed between Leucomax (Novartis) (Leucomax (Novartis)) and placebo-treated patients in the type or frequency of laboratory abnormalities, including renal and hepatic parameters. In some patients with preexisting renal or hepatic dysfunction enrolled in uncontrolled clinical trials, administration of Leucomax (Novartis) (Leucomax (Novartis)) has induced elevation of serum creatinine or bilirubin and hepatic enzymes. In addition, there was no significant difference in relapse rate and 24 month survival between the Leucomax (Novartis) (Leucomax (Novartis)) and placebo-treated patients.

In the placebo-controlled trial of 109 patients after allogeneic BMT, events reported in at least 10% of patients who received IV Leucomax (Novartis) (Leucomax (Novartis)) or placebo were as reported in Table 7.

Table 7: Percent of Allogeneic BMT Patients Reporting Events

There were no significant differences in the incidence or severity of GVHD, relapse rates and survival between the Leucomax (Novartis) (Leucomax (Novartis)) and placebo-treated patients.

Adverse events observed for the patients treated with Leucomax (Novartis) (Leucomax (Novartis)) in the historically-controlled BMT failure study were similar to those reported in the placebo-controlled studies. In addition, headache (26%), pericardial effusion (25%), arthralgia (21%) and myalgia (18%) were also reported in patients treated with Leucomax (Novartis) (Leucomax (Novartis)) in the graft failure study.

In uncontrolled Phase I/II studies with Leucomax (Novartis) (Leucomax (Novartis)) in 215 patients, the most frequent adverse events were fever, asthenia, headache, bone pain, chills and myalgia. These systemic events were generally mild or moderate and were usually prevented or reversed by the administration of analgesics and antipyretics such as acetaminophen. In these uncontrolled trials, other infrequent events reported were dyspnea, peripheral edema, and rash.

Reports of events occurring with marketed Leucomax (Novartis) (Leucomax (Novartis)) include arrhythmia, fainting, eosinophilia, dizziness, hypotension, injection site reactions, pain (including abdominal, back, chest, and joint pain), tachycardia, thrombosis, and transient liver function abnormalities.

In patients with preexisting edema, capillary leak syndrome, pleural and/or pericardial effusion, administration of Leucomax (Novartis) may aggravate fluid retention. Body weight and hydration status should be carefully monitored during Leucomax (Novartis) (Leucomax (Novartis)) administration.

Adverse events observed in pediatric patients in controlled studies were comparable to those observed in adult patients.

Acute Myelogenous Leukemia

Adverse events reported in at least 10% of patients who received Leucomax (Novartis) (Leucomax (Novartis)) or placebo were as reported in Table 8.

Table 8: Percent of AML Patients Reporting Events

Nearly all patients reported leukopenia, thrombocytopenia and anemia. The frequency and type of adverse events observed following induction were similar between Leucomax (Novartis) (Leucomax (Novartis)) and placebo groups. The only significant difference in the rates of these adverse events was an increase in skin associated events in the Leucomax (Novartis) (Leucomax (Novartis)) group (p=0.002). No significant differences were observed in laboratory results, renal or hepatic toxicity. No significant differences were observed between the Leucomax (Novartis) (Leucomax (Novartis)) and placebo-treated patients for adverse events following consolidation. There was no significant difference in response rate or relapse rate.

In a historically-controlled study of 86 patients with acute myelogenous leukemia (AML), the Leucomax (Novartis) (Leucomax (Novartis)) treated group exhibited an increased incidence of weight gain (p=0.007), low serum proteins and prolonged prothrombin time (p=0.02) when compared to the control group. Two Leucomax (Novartis) (Leucomax (Novartis)) treated patients had progressive increase in circulating monocytes and promonocytes and blasts in the marrow which reversed when Leucomax (Novartis) (Leucomax (Novartis)) was discontinued. The historical control group exhibited an increased incidence of cardiac events (p=0.018), liver function abnormalities (p=0.008), and neurocortical hemorrhagic events (p=0.025).

Antibody Formation

Serum samples collected before and after Leucomax (Novartis) (Leucomax (Novartis)) treatment from 214 patients with a variety of underlying diseases have been examined for immunogenicity based on the presence of antibodies. Neutralizing antibodies were detected in five of 214 patients (2.3%) after receiving Leucomax (Novartis) (Leucomax (Novartis)) by continuous IV infusion (three patients) or subcutaneous injection (SC)(two patients) for 28 to 84 days in multiple courses. All five patients had impaired hematopoiesis before the administration of Leucomax (Novartis) (Leucomax (Novartis)) and consequently the effect of the development of anti-GM-CSF antibodies on normal hematopoiesis could not be assessed. Antibody studies of 75 patients with Crohn's disease receiving Leucomax (Novartis) (Leucomax (Novartis)) by subcutaneous injection with normal hematopoiesis and no other immunosuppressive drugs showed one patient (1.3%) with detectable neutralizing antibodies. The clinical relevance of the presence of these antibodies are unknown. Drug-induced neutropenia, neutralization of endogenous GM-CSF activity and diminution of the therapeutic effect of Leucomax (Novartis) (Leucomax (Novartis)) secondary to formation of neutralizing antibody remain a theoretical possibility. Serious allergic and anaphylactoid reactions have been reported with Leucomax (Novartis) (Leucomax (Novartis)) but the rate of occurrence of antibodies in such patients has not been assessed.

Human, recombinant GM-CSF, expressed in yeast. Glycoprotein that is 127 residues. Substitution of Leu23 leads to a difference from native protein.