National Comprehensive Cancer Network

NCCN has published updates for the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Acute Lymphoblastic Leukemia (ALL). These NCCN Guidelines^® are currently available as Version 1.2013.

Ph-negative ALL (ALL-5 and ALL-6)
- For consolidation options in AYA patients and Adults (age <65 years), factors to consider for allogeneic HSCT modified to include poor-risk cytogenetics and to remove WBC counts (except as a footnote for the latter).
Relapsed/Refractory ALL (ALL-7)
- The treatment recommendations for AYA and Adult patients consolidated.
- The following footnote added for allogeneic HSCT: For patients relapsing after allogeneic HSCT, a second allogeneic HSCT and/or donor lymphocyte infusion (DLI) can be considered.
- Donor lymphocyte infusion (DLI) removed as a treatment option for Ph+ ALL (except as a footnote, as mentioned above).
Supportive Care (ALL-B)
- Prophylactic anti-infectives (ALL-B 1 of 4)
  - The following added: VZV prophylaxis (eg, acyclovir) for at least 1 year after HSCT in transplant patients; and HBV prophylaxis (eg, adefovir, entecavir, lamivudine) for at least 6-12 months after HSCT depending on HBV serology.
- Steroid management (ALL-B 1 of 4)
  - The following added: Consider dose reduction for steroid-induced psychosis and mood alteration.
- Asparaginase Toxicity Management (ALL-B 3 of 4)
  - Toxicity grade clarified as CTCAE.
  - Toxicity grades changed from 2, 3, 4 to 1, 2, 3-4.
  - Systemic allergic reaction/anaphylaxis: recommendations for dosing substitutions removed.
  - Pancreatitis; Grade 1 and 2 recommendations combined: Continue asparaginase for asymptomatic amylase or lipase elevation > 3.0 x ULN (chemical pancreatitis) or only radiologic abnormalities; observe closely for rising amylase or lipase levels. Continue pegaspargase for nonsymptomatic chemical pancreatitis but observe patient closely for development of symptomatic pancreatitis for early treatment. Grade 3 and 4 recommendations combined: Permanently discontinue all asparaginase for clinical pancreatitis (vomiting, severe abdominal pain) with amylase or lipase elevation >3 x ULN for >3 days and/or development of pancreatic pseudocyst.
- Asparaginase Toxicity Management (ALL-B 4 of 4)
  - Non-CNS hemorrhage; Grade 2 to 4 recommendations combined: For bleeding in conjunction with hypofibrinogenemia, withhold asparaginase until bleeding ≤ grade 1, until acute toxicity and clinical signs resolve, and coagulant replacement therapy stable or completed.
  - CNS hemorrhage; Grade 1 and 2 recommendations combined: Discontinue all asparaginase; if CNS symptoms and signs are fully resolved and significant asparaginase remains to be administered, may resume asparaginase therapy at a lower dose and/or longer intervals between doses.
  - CNS thrombosis; Grade 2 recommendation modified with the addition of "with closely monitored anticoagulation."
Evaluation and Treatment of Extramedullary Involvement (ALL-C)
- CNS leukemia clarified as having CNS-3 and/or cranial nerve involvement.
Principles of Chemotherapy (ALL-D)
- Induction regimens for Ph-positive ALL (ALL-D 1 of 4)
  - Adult patients aged ³40 years; the following treatment option added: TKIs + vincristine + dexamethasone.
  - Protocols for AYA patients aged 15-39 years; the following treatment options added:
    TKIs + hyper-CVAD: imatinib or dasatinib; and hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose methotrexate, and cytarabine.
    TKIs + multiagent chemotherapy: imatinib; and daunorubicin, vincristine, prednisone, and cyclophosphamide.
- Maintenance regimens (ALL-D 1 of 4)
  - Modified to: Monthly vincristine/prednisone pulses (for 2-3 years). May include weekly methotrexate + daily mercaptopurine (6-MP) as tolerated. The following footnote added: May be necessary to reduce dose/eliminate antimetabolite in the setting of myelosuppression and/or hepatotoxicity.
- Salvage regimens for relapsed/refractory ALL (ALL-D 3 of 4)
  - Ph-positive ALL; Ponatinib added as a treatment option.
Treatment Options Based on BCR-ABL Kinase Domain Mutation Status (ALL-G)
- This table was updated to include Ponatinib.
The Discussion section was updated to reflect all changes within the algorithm.

For the complete updated versions of the NCCN Guidelines, the NCCN Compendium^®, and the NCCN Chemotherapy Order Templates (NCCN Templates^®), please visit NCCN.org.

To view the NCCN Guidelines for Patients^®, please visit NCCN.com.

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