Responses and Outcome Following Immunosuppressive Therapy in Large Granular Lymphocyte Leukemia-Associated Pure Red Cell Aplasia: A Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group.

Background: Large granular lymphocyte (LGL) leukemia accounts for a significant part of secondary PRCA. Cyclophosphamide (CPA) therapy has been reported as being useful in the literature. However, because of its rarity, the long-term response and relapse rate after immunosuppressive therapy including CPA in LGL leukemia-associated PRCA are largely unknown, and optimal management of this disorder remains unclear.

Objectives: We conducted a nationwide survey of immunosuppressive therapy for PRCA in Japan to elucidate the long-term response and overall survival (OS) of this disorder. This report is a summary focusing on CPA therapy for LGL leukemia-associated PRCA.

Methods: The questionnaires were sent to 109 medical institutions in Japan to estimate the number of patients with newly diagnosed acquired PRCA. From a total of 185 patients consisting of 73 idiopathic and 112 secondary PRCA cases, we evaluated 14 patients with LGL leukemia for this report. Endpoints of this study were the response rate and the duration of the response to immunosuppressive therapy and overall survival.

Results. Efficacy of the first remission induction therapy was seen in 6 out of 8 patients treated with CPA (75%), 1 out of 4 patients with cyclosporine (CsA) (25%), and 0 of 2 with corticosteroid (0%), respectively. The median initial dose of CPA for the responding patients (n=6) was 100 mg. The initial dose of CsA for the responding patient was 3.7 mg/kg. Two patients, who failed to respond to the initial CPA therapy, received CsA therapy resulting in the response in one patient. Three patients, who failed to respond to the initial CsA therapy, received CPA therapy resulting in the response in all of three patients. Two patients, who failed to respond to the initial prednisolone therapy, received CsA therapy resulting in the response in one patient. We classified the patients with LGL-associated PRCA into the CPA-group (n=9) and the CsA-group (n=3) according to the response to initial or salvage therapy. Relapse was seen in two CPA-responders following discontinuation of maintenance therapy (23, 45 months), whereas no patients relapsed on maintenance CPA therapy. The estimated median duration of the response to CPA was 125 months. The median OS has yet been reached with the median observation period of 89 months.

Conclusion: CPA showed an excellent response in LGL leukemia-associated PRCA and CPA-containing regimens were effective to prevent relapse of anemia. However, most patients are still receiving CPA for maintenance therapy, and it remains uncertain whether CPA can induce maintenance-free hematological response.