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Treatment of Acute Lymphoblastic Leukemia

Treatment Plan

Treatment is based on the Hammersmith 82 regimen, which in recent updates provides successful results for total survival. For rare variants of the disease, documentation of this regimen is uncertain, therefore other alternatives are available.

Patients with acute lymphoblastic leukemia are usually not candidates for an allogeneic stem cell transplantation in the first remission because results from chemotherapy are usually good. The most important exception is for patients with detected Philadelphia chromosome and/or BCR-ABL fusion transcription in the leukemia cells. For these patients, an imatinib regimen and allogeneic stem cell transplantation are recommended in the first remission. There are also other prognostic factors.

Surveillance of minimal residual disease (MRD) in bone marrow is recommended in patients < 60 years where an allogeneic stem cell transplantation may be appropriate, but where the indication is uncertain based on traditional risk factors.

Hammersmith 82

Treatment for acute lymphoblastic leukemia consists of an induction phase of 16 weeks followed by maintenance treatment for three years.

Induction treatment

  • Vincristine 2 mg intravenously day 1 for weeks 1–5
  • Doxorubicin 30 mg/m2 intravenously day 1 weeks 2, 3 and 4
  • Asparginase 10000 µg/m2 intravenously every other day in weeks 2 and 3
  • Metotrexate intrathecal 15 mg day 1 in weeks 3, 5, 7, 10, 12, 14 and 16
  • Cyclophosphamide 750 mg/ m2 intravenously day 1 in weeks 3 and 5
  • Prednisolone 40 mg/m2 orally daily in weeks 1–4, gradually reducing until discontinuation in week 5
  • DTC:
    • Daunorubicin 50 mg/m2 intravenously days 1, 3 and 5 in week 7
    • Cytosar 200 mg/ m2/ 24 hours, on days 1–5 in week 7
    • Thioguanin 150 mg/m2 orally on days 1–5 in week 7
  • Metotrexate 1500 mg/m2 intravenously with calcium folinate in weeks 10 and 12
  • Mercaptopurine 35 mg/m2 orally daily in weeks 10–16

An examination of bone marrow is performed in week 4-5 before starting DTC and with the MRD examination in week 16. Modification of dosage intensity is often necessary due to serious side effects.

Maintenance treatment (x 13)

  • Dexamethazone 6 mg/m2 orally daily in weeks 1–3
  • Vincristine 2 mg intravenously day 1 weeks 1–3
  • Doxorubicin 30 mg/m2 intravenously day 1 in week 2
  • Cyclophosphamide 600 mg/m2 intravenously day 1 in week 3
  • Methotrexate 15 mg/m2 orally daily for 3–5 days in week 4
  • Mercaptopurin 70 mg/m2 orally daily in weeks 5–8
  • Methotrexate 15 mg/m2 for 3–5 days in week 8
  • Mercaptopurine 80 mg/m2 orally daily in weeks 9–11
  • Methotrexate 15 mg/m2, 3–5 days in week 12 

In the first two maintenance cycles, monthly intrathecal methotrexate (15 mg) is administered for a total of 13 intrathecal injections.

Vincristine can often not be given in full because of polyneuropathy.

During maintenance treatment, moderate bone marrow suppression is striven for (neutrophiles and granulocytes are held between 0.5–1.5 x 109/l.

During the last three maintenance cycles, doxorubicin is replaced with cytarabine to avoid too high accumulation of anthracycline dosage.

If infections due to treatment occur as a result of bone marrow suppression, the treatment intensity should be reduced. 

Treatment of elderly patients (~60+)

Older patients with acute lymphoblastic leukemia usually suffer more from side effects than benefit from the most intense chemotherapies. The goal of treatment is palliative for most of these patients.

If assessing whether it is possible to complete intensive chemotherapy: normal ALL-protocol (Hammersmith) can be used as a framework with reduction of dosage and shortening. Stop vincristine if there is neuropathy. Asparaginase can be omitted in some. High-dose methotrexate is not tolerated well in elderly; maximum dosage is 500 mg/m2.

When remission is reached after induction, direct transition to simplified maintenance (6 mercaptopurine + methotrexate (if possible)) should be considered, without consolidation.

Patients over 60 often do not tolerate intense chemotherapy well, but may benefit from taking imatinib for a period, for Ph+ (BCR-ABL+) acute lymphoblastic leukemia.

The OPAL or VAD regimen is used by some as a palliative induction regimen for acute lymphoblastic leukemia in elderly patients with reduced function status.

Acute lymphoblastic leukemia in the central nervous system

For blasts in spinal fluid, intrathecal methotrexate is administered (15 mg twice per week) until the spinal fluid is free of blasts. Thereafter, weekly four times, for example.

The CNS prophylaxis is resumed according to protocol if the response has been successful.

Systemic treatment is continued according to protocol.

At least 8 intrathecal injections should be administered with not more than a 1 month interval after the spinal fluid is free of blasts.

If the brain is involved, CNS radiation of 24 Gy may be considered when remission is reached.

In a palliative situation, cytarabine with depot properties can be considered to reduce the number of injections.

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