TY - JOUR
T1 - NPM1 mutations define a specific subgroup of MDS and MDS/MPN patients with favorable outcomes with intensive chemotherapy
AU - Montalban-Bravo, Guillermo
AU - Kanagal-Shamanna, Rashmi
AU - Sasaki, Koji
AU - Patel, Keyur
AU - Ganan-Gomez, Irene
AU - Jabbour, Elias
AU - Kadia, Tapan
AU - Ravandi, Farhad
AU - DiNardo, Courtney
AU - Borthakur, Gautham
AU - Takahashi, Koichi
AU - Konopleva, Marina
AU - Komrokji, Rami S.
AU - DeZern, Amy
AU - Kuzmanovic, Teodora
AU - Maciejewski, Jaroslaw
AU - Pierce, Sherry
AU - Colla, Simona
AU - Sekeres, Mikkael A.
AU - Kantarjian, Hagop
AU - Bueso-Ramos, Carlos
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology
PY - 2019/3/26
Y1 - 2019/3/26
N2 - Nucleophosmin (NPM1) mutations are common in acute myeloid leukemia and are associated with high remission rates and prolonged survival with intensive chemotherapy. NPM1 mutations are rare in myelodysplastic syndromes (MDS) or myelodysplastic/ myeloproliferative neoplasm (MDS/MPN), and the clinical outcomes of these patients, when treated with intensive chemotherapy, are unknown. We retrospectively evaluated the clinicopathologic characteristics and the impact of therapy in 31 patients with MDS or MDS/MPN and NPM1 mutations. Next-generation sequencing was performed at diagnosis in 22 patients. Median age was 62 years (range, 19-86). Twenty-four patients (77%) had normal karyotype, and all had multilineage dysplasia. Most patients could be classified as MDS with excess blasts (19/31, 61%). NPM1 mutations were detected at a median allele frequency of 0.38 (range, 0.09-0.49). Mutation burden did not correlate with bone marrow blast frequency, and its clearance seemed to be associated with decreased morphologic dysplasia. Ten of the 31 patients (32%) received cytotoxic chemotherapy, 20 (65%) hypomethylating agents, and 1 (4%) lenalidomide. Sequential sequencing was available in 16 (52%) patients, and mutation burden correlated with disease status and response to therapy. Patients treated with chemotherapy had higher complete response rates (90% vs 28%, P 5 .004), longer median progression-free survival (not reached vs 7.5 months, P 5 .023), and overall survival (not reached vs 16 months, P 5 .047). Intensive chemotherapy and allogeneic stem cell transplantation (SCT) may be associated with improved clinical outcomes in patients with NPM1-mutated MDS or MDS/MPN who are candidates for this form of therapy.
AB - Nucleophosmin (NPM1) mutations are common in acute myeloid leukemia and are associated with high remission rates and prolonged survival with intensive chemotherapy. NPM1 mutations are rare in myelodysplastic syndromes (MDS) or myelodysplastic/ myeloproliferative neoplasm (MDS/MPN), and the clinical outcomes of these patients, when treated with intensive chemotherapy, are unknown. We retrospectively evaluated the clinicopathologic characteristics and the impact of therapy in 31 patients with MDS or MDS/MPN and NPM1 mutations. Next-generation sequencing was performed at diagnosis in 22 patients. Median age was 62 years (range, 19-86). Twenty-four patients (77%) had normal karyotype, and all had multilineage dysplasia. Most patients could be classified as MDS with excess blasts (19/31, 61%). NPM1 mutations were detected at a median allele frequency of 0.38 (range, 0.09-0.49). Mutation burden did not correlate with bone marrow blast frequency, and its clearance seemed to be associated with decreased morphologic dysplasia. Ten of the 31 patients (32%) received cytotoxic chemotherapy, 20 (65%) hypomethylating agents, and 1 (4%) lenalidomide. Sequential sequencing was available in 16 (52%) patients, and mutation burden correlated with disease status and response to therapy. Patients treated with chemotherapy had higher complete response rates (90% vs 28%, P 5 .004), longer median progression-free survival (not reached vs 7.5 months, P 5 .023), and overall survival (not reached vs 16 months, P 5 .047). Intensive chemotherapy and allogeneic stem cell transplantation (SCT) may be associated with improved clinical outcomes in patients with NPM1-mutated MDS or MDS/MPN who are candidates for this form of therapy.
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U2 - 10.1182/bloodadvances.2018026989
DO - 10.1182/bloodadvances.2018026989
M3 - Article
C2 - 30902805
AN - SCOPUS:85069973765
SN - 2473-9529
VL - 3
SP - 922
EP - 933
JO - Blood Advances
JF - Blood Advances
IS - 6
ER -