Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG)

Agnieszka Wierzbowska; Ewa Wawrzyniak; Monika Siemieniuk-Rys; Aleksandra Kotkowska; Agnieszka Pluta; Aleksandra Golos; Tadeusz Robak; Marta Szarawarska; Anna Jaskowiec; Ewa Duszenko; Justyna Rybka; Jadwiga Holojda; Sebastian Grosicki; Barbara Pienkowska-Grela; Renata Woroniecka; Anna Ejduk; Marzena Watek; Malgorzata Wach; Barbara Mucha; Katarzyna Skonieczka; Maria Czyzewska; Anna Jachalska; Agnieszka Klonowska; Mariola Iliszko; Wanda Knopinska-Posluszny; Malgorzata Jarmuz-Szymczak; Anna Przybylowicz-Chalecka; Lidia Gil; Agnieszka Kopacz; Jerzy Holowiecki; Olga Haus

doi:10.1080/10428194.2016.1219901

Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG)

Leuk Lymphoma. 2017 Apr;58(4):889-897. doi: 10.1080/10428194.2016.1219901. Epub 2016 Aug 26.

Authors

Agnieszka Wierzbowska¹, Ewa Wawrzyniak¹, Monika Siemieniuk-Rys², Aleksandra Kotkowska², Agnieszka Pluta¹, Aleksandra Golos², Tadeusz Robak¹, Marta Szarawarska³, Anna Jaskowiec³, Ewa Duszenko³, Justyna Rybka³, Jadwiga Holojda⁴, Sebastian Grosicki⁵, Barbara Pienkowska-Grela⁶, Renata Woroniecka⁶, Anna Ejduk⁷, Marzena Watek⁸, Malgorzata Wach⁹, Barbara Mucha¹⁰, Katarzyna Skonieczka¹⁰, Maria Czyzewska¹¹, Anna Jachalska¹², Agnieszka Klonowska¹³, Mariola Iliszko¹³, Wanda Knopinska-Posluszny¹⁴, Malgorzata Jarmuz-Szymczak^{15

16}, Anna Przybylowicz-Chalecka¹⁶, Lidia Gil¹⁶, Agnieszka Kopacz¹⁷, Jerzy Holowiecki¹⁸, Olga Haus^{3

10}

Affiliations

¹ a Department of Hematology , Medical University of Lodz , Lodz , Poland.
² b Department of Hematology , Copernicus Memorial Hospital , Lodz , Poland.
³ c Department of Hematology , Blood Malignancies and Bone Marrow Transplantation, Medical University of Wroclaw , Wroclaw , Poland.
⁴ d Department of Hematology , WSS , Legnica , Poland.
⁵ e Department of Hematology , ZSM of Chorzow , Chorzow , Poland.
⁶ f Cancer Genetics Laboratory of Pathology Department , M Sklodowska-Curie Memorial Cancer Center and Institute , Warsaw , Poland.
⁷ g Department of Hematology , Institute of Hematology and Blood Transfusion , Warsaw , Poland.
⁸ h Department of Hematology , Holycross Cancer Center , Kielce , Poland.
⁹ i Department of Hematooncology and Bone Marrow Transplantation , Medical University of Lublin , Lublin , Poland.
¹⁰ j Department of Clinical Genetics , Collegium Medicum of Nicolaus Copernicus University , Bydgoszcz , Poland.
¹¹ k Department of Hematology , Nicolaus Copernicus Municipal Specialist Hospital , Torun , Poland.
¹² l Department of Hematology , Medical University of Bydgoszcz , Bydgoszcz , Poland.
¹³ m Department of Biology and Genetics , Medical University of Gdansk , Gdansk , Poland.
¹⁴ n Department of Hematology , SP ZOZ WMCO Oncology Center , Olsztyn , Poland.
¹⁵ o Institute of Human Genetics, PAN , Poznan , Poland.
¹⁶ p Department of Hematology and Bone Marrow Transplantation , University of Medical Sciences , Poznan , Poland.
¹⁷ q Department of Hematology , Oncology Center, Municipal Hospital , Rzeszow , Poland.
¹⁸ r Department of Bone Marrow Transplantation , M. Sklodowska-Curie Institute of Oncology , Gliwice , Poland.

PMID: 27561449
DOI: 10.1080/10428194.2016.1219901

Abstract

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK⁺ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK⁺ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK⁺ MK^- and CK⁺ MK⁺ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK^- but not in MK⁺ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK⁺.

Keywords: Acute myeloid leukemia; cladribine; complex karyotype; monosomal karyotype; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Biomarkers
Chromosome Aberrations*
Combined Modality Therapy
Female
Hematopoietic Stem Cell Transplantation
Humans
Karyotype*
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / mortality*
Leukemia, Myeloid, Acute / therapy
Male
Middle Aged
Monosomy*
Poland
Prognosis
Retrospective Studies
Survival Analysis
Transplantation, Homologous
Treatment Outcome
Young Adult

Substances

Biomarkers