Secondary Myelodysplastic Syndrome after Hydroxychloroquine Therapy.

Introduction: The myelodysplastic syndromes (MDSs) include a group of marrow disorders united by the common feature of ineffective hematopoiesis. Primary MDS is defined as occurring in the absence of exposure to ionizing radiation, chemotherapeutic agents or myelotoxic drugs. Secondary MDS occurs in the presence of such exposure. The reported hematological side effects of hydroxychloroquine include aplastic anemia, agranulocytosis, thrombocytopenia, and hemolytic anemia in individuals with G-6-PD deficiency. However the frequency of secondary MDS after treatment with hydroxychloroquine is unknown. We report four patients who developed MDS after hydroxychloroquine therapy, a previously unrecognized association.

Methods: We did a retrospective chart analysis of 217 patients on hydroxychloroquine for rhematological conditions in 2005. None of these patients had exposure to myelosuppressive drugs including methotrexate, radiation, chemotherapeutic agents, or benzene. Amongst these patients, 4 had been diagnosed with MDS in 2005. The demographics, type of MDS, karyotypic abnormalities, dose and duration of treatment with hydroxychloroquine were reviewed.

Results: Two patients were male (M) and two female (F); the median age was 69.75 years, (range 65–76). There was no personal or family history of hematopoietic cancer. The dose of hydroxychloroquine for all patients was 400 mg daily, with median treatment duration of 10.5 years and a range of 6–16. All patients had bone marrow biopsy confirmation of the diagnosis of MDS, and two had karyotype abnormalities.

Conclusion: The incidence of MDS in a group older than 70 years ranges from 15 to 50/100,000 persons/year. The diagnosis of four cases of MDS among 217 patients in one year is approximately 123–37 fold higher than the risk of MDS in the general population aged more than 70 years (P < 0.001) and suggest that long-term treatment with hydroxychloroquine is associated with an increased risk of developing secondary MDS.