NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2019

Featured Updates to the NCCN Guidelines

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Survival outcomes for older adults with acute lymphoblastic leukemia (ALL) are poor and optimal management is challenging due to higher-risk leukemia genetics, comorbidities, and lower tolerance to intensive therapy. A critical understanding of these factors guides the selection of frontline therapies and subsequent treatment strategies. In addition, there have been recent developments in minimal/measurable residual disease (MRD) testing and blinatumomab use in the context of MRD-positive disease after therapy. These NCCN Guidelines Insights discuss recent updates to the NCCN Guidelines for ALL regarding upfront therapy in older adults and MRD monitoring/testing in response to ALL treatment.

  • 1.

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    Wermann WK, Viardot A, Kayser S, . Comorbidities are frequent in older patients with de novo acute lymphoblastic leukemia (ALL) and correlate with induction mortality: analysis of more than 1200 patients from GMALL data bases [abstract]. Blood 2018;132(Suppl 1):Abstract 660.

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  • 4.

    Foà R, Vitale A, Vignetti M, . Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 2011;118:6521–6528.

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    Jabbour E, Kantarjian H, Ravandi F, . Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. Lancet Oncol 2015;16:1547–1555.

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    Martinelli G, Piciocchi A, Papayannidis C, . First report of the Gimema LAL1811 phase II prospective study of the combination of steroids with ponatinib as frontline therapy of elderly or unfit patients with Philadelphia chromosome-positive acute lymphoblastic leukemia [abstract]. Blood 2017;130(Suppl 1):Abstract 99.

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  • 7.

    Ottmann OG, Pfeifer H, Cayuela JM, . Nilotinib (Tasigna) and low intensity chemotherapy for first-line treatment of elderly patients with BCR-ABL1- positive acute lymphoblastic leukemia: final results of a prospective multicenter trial (EWALL-PH02) [abstract]. Blood 2018;132(Suppl 1):Abstract 31.

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    Rousselot P, Coudé MM, Gokbuget N, . Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood 2016;128:774–782.

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  • 9.

    Thomas DA, O’Brien SM, Faderl S, . Long-term outcome after hyper-CVAD and imatinib (IM) for de novo or minimally treated Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) [abstract]. J Clin Oncol 2010;28(Suppl):Abstract 6506.

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  • 10.

    Wieduwilt MJ, Yin J, Wetzler M, . A phase II study of dasatinib and dexamethasone as primary therapy followed by transplantation for adults with newly diagnosed Ph/BCR-ABL1-positive acute lymphoblastic leukemia (Ph+ ALL): final results of Alliance/CALGB Study 10701 [abstract]. Blood 2018;132(Suppl 1):Abstract 309.

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    Stengel A, Schnittger S, Weissmann S, . TP53 mutations occur in 15.7% of ALL and are associated with MYC-rearrangement, low hypodiploidy, and a poor prognosis. Blood 2014;124:251–258.

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    Jabo B, Morgan JW, Martinez ME, . Sociodemographic disparities in chemotherapy and hematopoietic cell transplantation utilization among adult acute lymphoblastic and acute myeloid leukemia patients. PLoS One 2017;12:e0174760.

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    Kim C, Molony JT, Chia VM, . Patient characteristics, treatment patterns, and mortality in elderly patients newly diagnosed with ALL. Leuk Lymphoma 2018:1–7.

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    Kozlowski P, Lennmyr E, Ahlberg L, . Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden. Eur J Haematol 2017;99:141–149.

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    Berry DA, Zhou S, Higley H, . Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA Oncol 2017;3:e170580.

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  • 25.

    Gökbuget N, Dombret H, Bonifacio M, . Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood 2018;131:1522–1531.

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  • 26.

    Topp MS, Gökbuget N, Zugmaier G, . Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 2012;120:5185–5187.

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  • 27.

    Topp MS, Kufer P, Gökbuget N, . Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 2011;29:2493–2498.

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  • 31.

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  • 32.

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  • 34.

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  • 37.

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  • 51.

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    Topp MS, Gökbuget N, Zugmaier G, . Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol 2014;32:4134–4140.

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