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C. Cameron Yin, Nitin Jain, Meenakshi Mehrotra, Jianhua Zhagn, Alexei Protopopov, Zhuang Zuo, Naveen Pemmaraju, Courtney DiNardo, Cheryl Hirsch-Ginsberg, Sa A. Wang, L. Jeffrey Medeiros, Lynda Chin, Keyur P. Patel, Farhad Ravandi, Andrew Futreal, and Carlos E. Bueso-Ramos

Acute promyelocytic leukemia (APL) is characterized by the fusion of retinoic acid receptor alpha (RARA) with promyelocytic leukemia (PML) or, rarely, other gene partners. This report presents a patient with APL with a novel fusion between RARA and the interferon regulatory factor 2 binding protein 2 (IRF2BP2) genes. A bone marrow examination in a 19-year-old woman who presented with ecchymoses and epistaxis showed morphologic and immunophenotypic features consistent with APL. PML oncogenic domain antibody was positive. Results of fluorescence in situ hybridization, conventional cytogenetics, reverse transcription–polymerase chain reaction (RT-PCR), and oligonucleotide microarray for PML-RARA and common APL variant translocations were negative. Next-generation RNA-sequencing analysis followed by RT-PCR and direct sequencing revealed distinct breakpoints within IRF2BP2 exon 2 and RARA intron 2. The patient received all-trans retinoic acid, arsenic, and gemtuzumab ozogamicin, and achieved complete remission. However, the disease relapsed 10 months later, 2 months after consolidation therapy. This is the first report showing involvement of IRF2BP2 in APL, and it expands the list of novel RARA partners identified in APL.

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Sanjeev Kumar Gupta, Nitin Jain, Guilin Tang, Andrew Futreal, Sa A. Wang, Joseph D. Khoury, Richard K. Yang, Hong Fang, Keyur P. Patel, Rajyalakshmi Luthra, Mark Routbort, Bedia A. Barkoh, Wei Chen, Xizeng Mao, Jianhua Zhang, L. Jeffrey Medeiros, Carlos E. Bueso-Ramos, and Sanam Loghavi

RNA-seq was used to identify the partner gene and confirm the presence of a BCR-PDGFRB fusion. Identification of this fusion product resulted in successful treatment and long-term remission of this myeloid neoplasm. Based on our results, we suggest that despite current WHO recommendations, screening for PDGFRB rearrangement in cases of leukocytosis with eosinophilia and no other etiologic explanation is necessary, even if the karyotype is normal.

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Patrick A. Brown, Matthew Wieduwilt, Aaron Logan, Daniel J. DeAngelo, Eunice S. Wang, Amir Fathi, Ryan D. Cassaday, Mark Litzow, Anjali Advani, Patricia Aoun, Bhavana Bhatnagar, Michael W. Boyer, Teresa Bryan, Patrick W. Burke, Peter F. Coccia, Steven E. Coutre, Nitin Jain, Suzanne Kirby, Arthur Liu, Stephanie Massaro, Ryan J. Mattison, Olalekan Oluwole, Nikolaos Papadantonakis, Jae Park, Jeffrey E. Rubnitz, Geoffrey L. Uy, Kristina M. Gregory, Ndiya Ogba, and Bijal Shah

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.

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Patrick A. Brown, Bijal Shah, Anjali Advani, Patricia Aoun, Michael W. Boyer, Patrick W. Burke, Daniel J. DeAngelo, Shira Dinner, Amir T. Fathi, Jordan Gauthier, Nitin Jain, Suzanne Kirby, Michaela Liedtke, Mark Litzow, Aaron Logan, Selina Luger, Lori J. Maness, Stephanie Massaro, Ryan J. Mattison, William May, Olalekan Oluwole, Jae Park, Amanda Przespolewski, Sravanti Rangaraju, Jeffrey E. Rubnitz, Geoffrey L. Uy, Madhuri Vusirikala, Matthew Wieduwilt, Beth Lynn, Ryan A. Berardi, Deborah A. Freedman-Cass, and Mallory Campbell

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.