Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD

Laura Vilorio-Marqués; Christelle Castañón Fernández; Elvira Mora; Lorena Gutiérrez; Beatriz Rey Bua; Maria José Jiménez Lorenzo; Marina Díaz Beya; Miriam Vara Pampliega; Antonieta Molero; Joaquín Sánchez-García; Marisa Calabuig; Maria Teresa Cedena; Tzu Chen-Liang; Johana Alejandra Díaz Santa; Irene Padilla; Francisca Hernández; Rosana Díez; Pedro Asensi; Blanca Xicoy; Guillermo Sanz; David Valcárcel; María Diez-Campelo; Teresa Bernal

doi:10.1177/20406207221127547

Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD

Ther Adv Hematol. 2022 Sep 29:13:20406207221127547. doi: 10.1177/20406207221127547. eCollection 2022.

Authors

Laura Vilorio-Marqués¹, Christelle Castañón Fernández¹, Elvira Mora², Lorena Gutiérrez³, Beatriz Rey Bua⁴, Maria José Jiménez Lorenzo⁵, Marina Díaz Beya⁶, Miriam Vara Pampliega⁷, Antonieta Molero⁸, Joaquín Sánchez-García⁹, Marisa Calabuig¹⁰, Maria Teresa Cedena¹¹, Tzu Chen-Liang¹², Johana Alejandra Díaz Santa¹³, Irene Padilla¹⁴, Francisca Hernández¹⁵, Rosana Díez¹⁶, Pedro Asensi², Blanca Xicoy⁵, Guillermo Sanz², David Valcárcel⁸, María Diez-Campelo⁴, Teresa Bernal^{17

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Affiliations

¹ Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
² Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
³ Hematology Department, Hospital Universitario de Canarias, La Laguna, Spain.
⁴ Hematology Department, Hospital Clínico Universitario, Salamanca, Spain.
⁵ Hematology Department, Hospital Germans Trias i Pujol, Institut Català d'Oncologia-Josep Carreras, Leukemia Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁶ Hematology Department, Hospital Clínico Barcelona, Barcelona, Spain.
⁷ Hematology Department, Hospital Universitario Cruces, Barakaldo, Spain.
⁸ Hematology Department, Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
⁹ Hematology Department, Hospital Universitario Reina Sofía, Cordoba, Spain.
¹⁰ Hematology Department, Hospital Clínico de Valencia, Valencia, Spain.
¹¹ Hematology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
¹² Hematology Department, Hospital Universitario Morales Messeguer, Murcia, Spain.
¹³ Hematology Department, Institut Catalá de Oncología, Girona, Spain.
¹⁴ Hematology Department, Complejo Asistencial Universitario de León, Castilla y León, Spain.
¹⁵ Hematology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain.
¹⁶ Hematology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain.
¹⁷ Hematology Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias.
¹⁸ Instituto Universitario de Oncología del Principado de Asturias.
¹⁹ Departamento de Medicina, Universidad de Oviedo.
²⁰ CIBER enfermedades respiratorias, Madrid, Spain.

Abstract

Background: The consequences of infectious toxicity of hypomethylating agents (HMAs) on overall survival (OS) of patients diagnosed with high-risk myeloid neoplasms have not been thoroughly investigated.

Objectives: We aimed to evaluate whether infectious events (IEs) negatively influenced the results of HMA treatment in a real-world setting.

Design: Observational study.

Methods: We obtained data from 412 non-selected consecutive patients from 23 Spanish hospitals who were diagnosed with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia and were treated with HMA. HMAs received after chemotherapy or stem cell transplant were excluded. All IEs were recorded. Outcomes included OS, modifications to the pre-planned treatment, incidence and characteristics of IEs, hospitalization, red blood cell transfusions, and factors associated with infection.

Results: The rate of infection was 1.2 per patient/year. Next-cycle delay (p = 0.001) and hospitalizations (p = 0.001) were significantly influenced by IEs. Transfusion requirements during each cycle were significantly higher after infection compared with cycles without infection (coefficient = 1.55 [95% confidence interval (CI) = 1.26-1.84], p < 0.001). The median number of cycles was lower in patients experiencing any infection during the first four cycles (5 [3-8] versu 8 [5-16], p < 0.001). In the multivariable analysis, factors associated with lower OS were having any infection during the first four cycles (hazard ratio (HR) = 1.43 [95% CI = 1.09-1.88], p = 0.01), bone marrow blasts ⩾30% (HR = 2.13 [95% CI = 1.14-3.96], p = 0.01), adverse cytogenetics (HR = 1.70 [95% CI = 1.30-2.24], p < 0.001), and platelet count <50 × 10⁹/l (HR = 1.69 [95% CI = 1.3-2.2], p < 0.001). BM blasts >20% (HR = 1.57 [95% CI = 1.19-2.01], p < 0.001) and adverse cytogenetics (HR = 1.7 [95% CI = 1.35-2.14], p < 0.001) were associated with infection, whereas hemoglobin >9 g/dl (HR = 0.65 [95% CI = 0.51-0.82], p < 0.001) and higher platelet count (HR = 0.997 [95% CI = 0.996-0.998], p = 0.016) protected from it.

Conclusion: HMA infectious toxicity worsens OS, hinders the adherence to antineoplastic treatment and results in significant morbidity. Preventive strategies are fundamental in vulnerable patients.

Keywords: acute myeloid leukemia; hypomethylating agent; infection; myelodysplastic syndrome; treatment outcome.