The Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML) : A representative and useful real-life data source for further biomedical research

Abstract

In the Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML) clinicolaboratory real-life data have been captured from 606 CMML patients from 14 different hospitals over the last 30 years. It is the only large biodatabase worldwide in which functional methods such as semisolid in vitro cultures complement modern molecular methods such as next generation sequencing. This provides the possibility to comprehensively study the biology of CMML. The aim of this study was to compare patient characteristics with published CMML cohorts and to validate established prognostic parameters in order to examine if this real-life database can serve as a representative and useful data source for further research. After exclusion of patients in transformation characteristics of 531 patients were compared with published CMML cohorts. Median values for age, leukocytes, hemoglobin, platelets, lactate dehydrogenase (LDH) and circulating blasts were within the ranges of reported CMML series. Established prognostic parameters including leukocytes, hemoglobin, blasts and adverse cytogenetics were able to discriminate patients with different outcome. Myeloproliferative (MP) as compared to myelodysplastic (MD)-CMML patients had higher values for circulating blasts, LDH, RAS-pathway mutations and for spontaneous myelomonocytic colony growth in vitro as well as more often splenomegaly. This study demonstrates that the patient cohort of the ABCMML shares clinicolaboratory characteristics with reported CMML cohorts from other countries and confirms phenotypic and genotypic differences between MP-CMML and MD-CMML. Therefore, results obtained from molecular and biological analyses using material from the national cohort will also be applicable to other CMML series and thus may have a more general significance.

Keywords: CFU-GM; CMML; In vitro culture; NGS; RAS.

Fig. 1

Summary of patients and samples collected in the Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML). The discrepancy between the number of samples and patients is due to the fact that serial samples were taken in a proportion of patients. ^aPatients with transformation before inclusion into the biodatabase. NGS next generation sequencing, AML acute myeloid leukemia

Fig. 2

Kaplan-Meier survival analysis and median overall survival of four established prognostic variables such as leukocytes (a), haemoglobin (b), peripheral blood blasts (c) and adverse cytogenetic features (d). The cytogenetic risk classification was performed as described in Materials and Methods. WBC White blood cells, Hb hemoglobin, PB peripheral blood

Fig. 3

Violin plot of growth factor independent myeloid colony growth in patients with MD-CMML and MP-CMML. Cultures were performed as described in Materials and Methods. The number of CFU-GM per 10⁵ PBMNC is given