Canterbury DHB

Modified OPAL Protocol

Refer to Lister, T. A., J. M. Whitehouse, et al BMJ 1978:199 - 203.

• This is suitable for patients with ALL who do not satisfy entry criteria for UKALL 14 or the COG Trials and who do not have Burkitt-like ALL. This protocol is one of several which may be appropriate for an older or frailer patient who is not suitable for the more intensive UKALL 14-type protocol.
• Investigations - see investigations required for New Patients. Not all these investigations will be required. Discuss with Consultant.

Initial Therapy and Prescription Sheets

Caution: Intrathecal chemotherapy should not be given on the same day as intravenous chemotherapy.

Note: A copy of the prescription sheet for the Modified OPAL induction protocol is available. You must print this out and use it for the prescription to be sent to Pharmacy.

Caution: L-asparaginase

This drug has a number of serious, potentially life threatening complications. Refer to L-Asparaginase Administration and Toxicity before prescribing this drug. L-asparaginase should be given before CR and before cranial irradiation and the last 5 doses of IT MTX are given. The four injections of L–Asparaginase 10,000 iu/m² IM in the OPAL protocol should be given the week before remission induction treatment is completed provided the patient is in, or near, CR. They are given every other day.

In general 4 injections of vincristine and 5 of adriamycin should be given during remission induction. With the exception of the 2nd dose of adriamycin, which is given on Day 2, these 2 drugs are given on the same day by IV bolus. If given peripherally they should be given into a fast running drip. The first injection of IT MTX is usually given at diagnosis. Sometimes if the peripheral blast count is very high a decision may be made to delay it until blasts have cleared from the blood. Avoid giving intrathecal chemotherapy on the same day as intravenous therapy. A further dose of intrathecal MTX is given at the end of the asparaginase injections. A further 5 doses of IT Methotrexate are given during the cranial radiotherapy.

Difficulty may arise on day 14,21 or 28 if the patient is cytopenic. If the neutrophil count is <0.5 x 10⁹/L and falling, and the platelets <50 x 10⁹/L and falling a bone marrow aspirate should be performed and chemotherapy withheld if it is hypoplastic. If the marrow is infiltrated and this is causing the cytopenias then further chemotherapy should be given.

A bone marrow should be done around day 35 to confirm CR.

Consolidation Treatment

When a complete remission is documented and when the induction therapy is completed cranial irradiation and further intrathecal methotrexate therapy is started. Cranial irradiation may be given in a dose of between 1800–2400 hr and usually takes 2–3 weeks to complete and coincides with the last 5 intrathecal injections. During this period oral 6 mercaptopurine should be started.

Remission Maintenance

The OPAL protocol uses 6MP / methotrexate orally as shown below. Re–induction therapy, either with vincristine or prednisone every 3 months, or vincristine, prednisone, adriamycin every 3 months. If the latter is given the number of doses is usually limited to four since one will be getting near the maximum dose of adriamycin. The decision with regard to 3 monthly re–induction therapy is made by the Consultant. Maintenance treatment is continued for 2 to 3 years.

Oral Maintenance Therapy

If not tolerated 6MP 50 mg/m² PO daily and MTX 20 mg/m² PO once weekly may be tried). Aim to keep the WBC between 3.0–3.5. If WBC is higher escalate the dose of MTX.

Topic Code: 4418