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. 2025 Jan 1;131(1):e35696.
doi: 10.1002/cncr.35696.

Treatment patterns and outcomes in secondary acute myeloid leukemia arising after hypomethylating agents: PETHEMA registry study

Pilar Lloret-Madrid  1 , Blanca Boluda  1   2 , Joaquín Martínez-López  3 , Juan Bergua  4 , Eduardo Rodriguez Arboli  5 , Jorge Labrador  6 , Claudia Sossa  7 , Cristina Gil  8 , Lorenzo Algarra  9 , Esperanza Lavilla-Rubira  10 , Josefina Serrano  11 , Beatriz de Rueda  12 , Francisco Ibañez  13 , Bernardo J González González  14 , María Luz Amigo  15 , Daniel García Belmonte  16 , Carlos Rodríguez-Medina  17 , María I Gómez-Roncero  18 , Mercedes Colorado  19 , José L López Lorenzo  20 , Mar Tormo  21 , Olga Arce Fernández  22 , Isabel Cano-Ferri  1   2 , Antonio Solana-Altabella  2   23 , Maria-Angeles Foncillas  24 , Ana Alfonso Pierola  25 , Susana Vives  26 , Marta Valero Núñez  27 , Hernán López-Vidal  28 , Esther Pérez-Santaolalla  29 , Lourdes Hermosín Ramos  30 , Raimundo García Boyero  31 , Laura Llorente González  32 , Alicia Roldán  33 , Soledad Casado Calderón  34 , Joana Brioso Infante  35 , Teresa Olave  36 , Julio García-Suárez  37 , Almudena de Laiglesia  38 , Rebeca Rodríguez-Veiga  1   2 , Fernanda Trigo  39 , David Martínez-Cuadrón  1   2 , Pau Montesinos  1   2
Affiliations

Treatment patterns and outcomes in secondary acute myeloid leukemia arising after hypomethylating agents: PETHEMA registry study

Pilar Lloret-Madrid et al. Cancer. .

Abstract

Background: Patients with secondary acute myeloid leukemia who previously received hypomethylating agents for prior myeloid neoplasms (HMA-sAML) face a dismal prognosis.

Methods: The authors analyze the characteristics, therapeutic approaches, and outcomes of patients with HMA-sAML from the Programa Español para el Tratamiento de Hemopatías Malignas (PETHEMA) registry.

Results: A total of 479 patients were included, mostly from prior myelodysplastic syndrome (84%). Frontline therapy consisted of intensive chemotherapy (IC) in 31%, low-dose cytarabine-based in 19%, supportive care and clinical trial 17% each, and HMA-based therapy in 12% and 4% in venetoclax-based regimen. Complete remission was achieved in 95 patients (27%), with higher rate among IC and venetoclax-based groups (44% and 41%, respectively). The median overall survival (OS) was 4.93 months, with 7.68 months for IC patients, 7.82 months after HMA monotherapy, and 4.66 months after venetoclax-based regimens. Patients who underwent allogeneic hematopoietic stem cell transplantation in first remission (n = 33, 9%) had a better survival outcome (median OS not reached). Multivariate analyses identified age (≥65 years), Eastern Cooperative Oncology Group >2, higher white blood cell count, and adverse risk cytogenetic as adverse prognostic factors, whereas NPM1 mutation was a favorable factor.

Conclusions: Patients with HMA-sAML have a poor prognosis and suboptimal outcomes with conventional treatments, including BCL2 inhibitors, highlighting the need for clinical trials targeting this population.

Keywords: acute myeloid leukemia; hypomethylating agents; myelodysplastic syndrome; outcomes; secondary AML.

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References

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