The presence or absence of cytogenetic and molecular abnormalities present at the time of diagnosis of acute myeloid leukemia (AML) not only provides important prognostic information, but also directs decisions regarding postremission therapy. In no other group has molecular analysis been more important than for the 40% to 50% of newly diagnosed patients in whom clonal chromosomal aberrations are not detected. Patients with cytogenetically normal (CN) AML were once considered a homogenous group, but are now classified into molecularly defined subgroups with distinct clinical outcomes. Evaluating FLT3, NPM1, and CEBPA mutational status is a routine component of the diagnostic evaluation for all patients with CN-AML and is used to determine outcome risk. However, in patients with FLT3 wild-type/NPM1 wild-type/CEBPA wild-type CN-AML, the optimal postremission therapy has not been well defined. This article reviews treatment outcomes for this group of patients after chemotherapy and autologous and allogeneic stem cell transplantation. New recurrent somatic mutations and their prognostic significance in patients with FLT3 wild-type/NPM1 wild-type CN-AML are also addressed.
Alison R. Walker and Guido Marcucci
Sandipkumar H. Patel, Sumithira Vasu, Ling Guo, Olivia Lemaster, John C. Byrd and Alison Walker
Acute undifferentiated leukemia (AUL) is a subtype of acute leukemias of ambiguous lineage. There is no standard treatment approach for AUL, although acute lymphoblastic leukemia–like regimens for induction therapy have been used. Additional data suggest that AUL may be better treated as acute myeloid leukemia (AML), given their similarities in genetic, cytogenetic, and gene expression patterns. Somatic mutations of IDH1 are found in 7% to 14% of patients with AML; however, the patient in this study was the first patient with IDH1-mutated AUL treated with ivosidenib. In this case, a woman aged 39 years was found to have anemia and thrombocytopenia after presenting to her primary care physician with fatigue, weight loss, and persistent infections. During further workup of the cytopenia, she was diagnosed with AUL and received 7+3 (daunorubicin, 60 mg/m2/d intravenously on days 1–3, and cytarabine, 100 mg/m2 24-hour continuous intravenous infusion on days 1–7) due to the presence of the IDH1 mutation. Bone marrow biopsy performed on day 14 of 7+3 showed persistent disease, and ivosidenib was initiated due to severe HLA alloimmunization (panel-reactive antibody, 100%) and significant bleeding complications. The patient achieved a complete morphologic and molecular remission on ivosidenib monotherapy despite critical bleeding complications during induction. Targeted therapy using ivosidenib may represent an encouraging therapeutic option in patients with AUL and IDH1 mutations. Additional evaluation of ivosidenib in this subgroup of patients with AUL is needed.
Peter L. Greenberg, Richard M. Stone, Aref Al-Kali, Stefan K. Barta, Rafael Bejar, John M. Bennett, Hetty Carraway, Carlos M. De Castro, H. Joachim Deeg, Amy E. DeZern, Amir T. Fathi, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Elizabeth A. Griffiths, David Head, Ruth Horsfall, Robert A. Johnson, Mark Juckett, Virginia M. Klimek, Rami Komrokji, Lisa A. Kujawski, Lori J. Maness, Margaret R. O'Donnell, Daniel A. Pollyea, Paul J. Shami, Brady L. Stein, Alison R. Walker, Peter Westervelt, Amer Zeidan, Dorothy A. Shead and Courtney Smith
The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low-intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches.