5q-syndrome in Japan

Abstract

5q-syndrome is a form of refractory anemia that occurs predominantly in females and is characterized by pronounced macrocytosis, frequent erythroblastopenia, absent or mild leukopenia, normal or elevated platelet counts, abnormal large monolobulate megakaryocytes with eccentric nuclei, typically normal bone marrow blast percentage, isolated deletion of the long arm of chromosome 5, rare progression to acute myeloid leukemia (AML), and prolonged survival [1]. Patients with 5q-syndrome are severely anemic, and show transfusion dependency at presentation; therefore, iron overload is an important prognostic factor for 5q-syndrome. 5q-syndrome patients demonstrate clear geographic, racial, ethnic, age, and gender variation in both incidence and mortality [2, 3]. 5q-syndrome is rare among Japanese MDS patients, and to our knowledge no study of Japanese 5q-syndrome patient series has been reported. To this end, we sought to characterize Japanese 5q-syndrome patients with, on the verge of the lenalidomide era in Japan, an emphasis on iron overload. Data from 21 5q-syndrome patients were obtained from a previous study [2]. Four patients were newly diagnosed, and were recruited into this study from the Japanese Cooperative Study Group for Intractable Bone Marrow Diseases. 5q-syndrome patients were assessed by (1) the international prognostic scoring system (IPSS), World Health Organization (WHO) classification-based prognostic scoring system (WPSS) [4, 5], and (2) degree of cytopenia, transfusion dependency, and iron overload. The median age of patients with 5q-syndrome was 67 years, and the male-to-female ratio was 11/14, which was in agreement with the well-known female predominance of 5q-syndrome. All cases had anemia, with median red blood cell count and hemoglobin level of 2.25 9 10/ll and 7.5 g/dl, respectively. Median neutrophil and platelet counts were 1624/ll and 25.2 9 10/ll, respectively. All cases were diagnosed as having refractory anemia (RA), according to the FAB classification. Thirteen patients were classified as low-risk, and 12 were classified as Int-1, following the IPSS scale. Eight patients were sorted to very low risk and 17 were classified as low-risk of WPSS classification. Seventeen patients (68%) required red blood cell transfusion more than once in the 8-week period, indicating transfusion dependency. In contrast, none of the patients required platelet transfusion. The degree of iron overload was estimated by serum ferritin concentration. Serum ferritin concentration at diagnosis ranged from 64.3 to 9114.5 ng/ml (median 252.7 ng/ml; Table 1). Additional data were obtained from 14 patients concerning maximum ferritin concentrations during their clinical courses, which ranged from 511 to 16470 ng/ml (median 1291 ng/ml; Table 1). UPN 1 and 14 showed ECG abnormality, heart failure and hepatic insufficiency. Five patients (20%) received iron chelating agents. UPN 1, 9, 14 and 18 died, and the causes of death were as follows: cardiac failure owing to hemochromatosis (UPN1 and UPN14), severe infection (UPN9) and neurogenic tumor (UPN18). None of the patients progressed to acute leukemia. On behalf of the Japanese Cooperative Study Group for Intractable Bone Marrow Diseases.