Distinguishing myelodysplastic syndromes (MDS) from idiopathic cytopenia of undetermined significance (ICUS): HUMARA unravels clonality in a subgroup of patients.
BACKGROUND
Patients not fulfilling minimal criteria for myelodysplastic syndromes (MDS) but presenting with persisting cytopenia(s) not attributable to a haematological or non-haematological disease are defined as 'idiopathic cytopenia of undetermined significance' (ICUS).


METHODS
We retrospectively analysed 67 of 3504 patients from our MDS Registry fulfilling the criteria for ICUS. Furthermore, we used the human androgen receptor gene-based assay (HUMARA) to look for clonality.


RESULTS
Of all 67 patients, 66% had unilineage, 18% bilineage and 12% trilineage cytopenias. The majority of patients (67%) presented with anaemia. Median overall survival was 44 months (range: 1-199 months). In the entire group, eight patients (12%) developed acute myeloid leukaemia (AML). Of the 23 patients eligible for HUMARA, 17 had non-clonal X-chromosome inactivation patterns, while 6 patients showed clonal patterns. Two of these six patients developed AML indicating that a clonal stem cell disorder was the reason for the anteceding cytopenia, while there was no AML observed among the 17 patients with non-clonal patterns (P = 0.013).


CONCLUSIONS
Since some of the ICUS patients had a clonal bone marrow disease when presenting with cytopenia(s) and 8 of 67 patients with ICUS later developed AML, we recommend to follow these patients thoroughly. As demonstrated here, HUMARA can facilitate the discrimination between ICUS and a 'manifest' MDS.
Schroeder
T
T
Department of Haematology, Oncology and Clinical Immunology. Electronic address: thomas.schroeder@med.uni-duesseldorf.de.
Ruf
L
L
Department of Haematology, Oncology and Clinical Immunology.
Bernhardt
A
A
Department of Haematology, Oncology and Clinical Immunology.
Hildebrandt
B
B
Institute of Human Genetics and Anthropology, Heinrich-Heine University, Düsseldorf, Germany.
Aivado
M
M
Department of Haematology, Oncology and Clinical Immunology; Global Clinical Development Oncology GlaxoSmithKline, Collegeville, PA, USA.
Aul
C
C
Department of Haematology, Oncology and Clinical Immunology, St Johannes Hospital, Duisburg, Germany.
Gattermann
N
N
Department of Haematology, Oncology and Clinical Immunology.
Haas
R
R
Department of Haematology, Oncology and Clinical Immunology.
Germing
U
U
Department of Haematology, Oncology and Clinical Immunology.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001855:Bone Marrow Diseases / Q000175:diagnosis* / Q000235:genetics; D002999:Clone Cells; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011944:Receptors, Androgen / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
C410798:AR protein, human; D011944:Receptors, Androgen