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NCCN Guidelines and Compendium Updated

NCCN Flash Update sent March 25, 2013

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.

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