Deletions of the long arm of chromosome 20 have conventionally been associated with myeloid neoplasms. The frequency of chromosome 20q deletion (del(20q)) is 1–10% in myeloid diseases and associated with good prognosis in patients with myelodysplastic syndromes (MDS) and poor response to treatment in patients with acute myeloid leukemia (Greenberg 1997; Campel 1994). Previously chromosome 20q deletions were thought to be pathognomonic for myelodysplastic syndrome. Due to the observation that del(20q) may be present in non-malignant clones in patients with non-myeloid cancers, the 2008 WHO Classification (Swerdlow ed.) stated that MDS could not be diagnosed solely on the basis of isolated del(20q). The significance of isolated del(20q) in non-myeloid disorders have yet to be defined. When this chromosomal abnormality is found incidentally in marrows of patients for non-myeloid cancers, some oncologist may consider altering plans for cytotoxic chemotherapy out of concern for developing MDS. The aim of this study was to determine if isolated del(20q) in non-myeloid disorders implies an impending myeloid disease and if treatment should be altered for such patients.
We conducted a retrospective, single institution cohort study among patients who between January 2005 and July 2012 were found to have 20q deletions without other chromosomal alterations per conventional cytogenetics and non-myeloid disorders per clinical history or bone marrow biopsies. Patients with isolated 20q deletion were identified from the clinical cytogenetic laboratory database and results were reviewed per cytogeneticist for accuracy. Pathology reviewed initial and subsequent bone marrow biopsies for histopathologic or immunophenotypic evidence of a myeloid disease. If a subsequent bone marrow exam was not available, the patient's complete blood counts were reviewed to determine if they developed clinical evidence of a myeloid disorder. We defined clinical suspicion for MDS as the development of transfusion dependence (≥1 unit red blood cell transfusion every 8 weeks over 4 months), any grade = 2 anemia with either grade = 2 thrombocytopenia or grade = 2 neutropenia not related to chemotherapy or immunotherapy, or any grade = 3 cytopenia without known etiology. For patients undergoing chemotherapy, MDS was suspected if there was evidence of poor bone marrow reserve as manifest by dose modifications or delays for hematologic toxicity.
Thirty nine patients with isolated del(20q) were identified in the cytogenetic database from January 2005 to July 2012. Twelve out of thirty nine (31%) patients were found to have non-myeloid disorders. Three patients with multiple myeloma (25%), two patients with chronic lymphocytic leukemia (17%), two patients with autoimmune disorders (17%) and five others with breast cancer, diffuse large B cell lymphoma, monoclonal gammopathy of undetermined significance, Crohn's disease and melanoma. There were an equal number of men and woman with median age of 60 years (range 30–83 years) at the time of isolated del(20q) detection. Six patients were found to have del(20q) at the initial presentation of their disease and six developed del(20q) after undergoing treatment. Nine patients were treated with standard first line systemic therapies. Six of the nine patients were treated with chemotherapy and four of them did not have to undergo any dose modifications due to myelosuppression. In the patients with chronic lymphocytic leukemia, FCR (Fludarabine,Cyclophosphamide and Rituximab) was dose modified and later discontinued due to persistent neutropenia and thrombocytopenia. After a median follow up of twenty two months (range 2 – 64 months) no patients developed evidence of a myeloid disorder by bone marrow pathology or clinical evidence.
Isolated deletion of the long arm of chromosome 20 in patients with non-myeloid disorders does not result in bone marrow failure or myeloid disease, therefore physicians should not alter their treatment plans. Further patient follow up is necessary to provide more insight on the prognosis and treatment of non-myeloid disorders with isolated chromosome 20q deletion.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.