Long-term responses and outcomes 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

Abstract

Large granular lymphocyte leukemia-associated pure red cell aplasia accounts for a significant portion of secondary pure red cell aplasia cases. However, because of its rarity, long-term responses and relapse rates after immunosuppressive therapy are largely unknown. We conducted a nationwide survey in Japan and collected 185 evaluable patients. Fourteen patients with large granular lymphocyte leukemia-associated pure red cell aplasia were evaluated. Cyclophosphamide, cyclosporine A and prednisolone produced remissions in 6/8, 1/4 and 0/2 patients respectively. Seven and 5 patients were maintained on cyclophosphamide or cyclosporine A respectively. Two patients relapsed after stopping cyclophosphamide, and 2 patients relapsed during maintenance therapy with cyclosporine A. The median relapse-free survival in the cyclophosphamide -and the cyclosporine A groups was 53 and 123 months respectively. Large granular lymphocyte leukemia-associated pure red cell aplasia showed a good response to either cyclophosphamide or cyclosporine A. Most patients continued to receive maintenance therapy and it remains uncertain whether cyclophosphamide or cyclosporine A can induce a maintenance-free hematologic response in large granular lymphocyte leukemia-associated pure red cell aplasia.

How I treat LGL leukemia

“…The cyclophosphamide response rate compares favorably with that of MTX, with an ORR of 66% and 55%, respectively, in the French series. 13,59,65,71,72 Time to response ranges from one to 4 months in our experience. Importantly, we have reported that 11 of 15 patients responded to cyclophosphamide after having failed to respond to MTX.…”

“…12,13,[65][66][67]69,[72][73][74][75] Response rates vary from one study to another and are usually better in the small series. Patients with pure red cell aplasia appear to have a good response.…”

Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches

“…The cytopenias are usually corrected without the clone being eradicated, since this is often resistant to treatment. Immunomodulatory drugs, such as methotrexate (10 mg/m 2 /week), cyclosporine A (5-10 mg/kg/day) or low dose cyclophosphamide (50 to 100 mg/day) [37][38][39][40] are commonly used. Corticosteroids may be useful as a part of the initial treatment to accelerate response and growth factors are often used.…”

Guest editorial: the seven wonders of erythropoiesis

“…In this symposium, based on a nationwide survey in Japan, current strategies for the treatment of PRCA were introduced in a presidential lecture. Although this issue is not reviewed in this PIH series, relevant articles can be found elsewhere [21,22] as can focused articles on idiopathic [23], thymoma-associated [24], large granular lymphocyte leukemia-associated [25] and lymphoma-associated PRCA [26]. Oligodeoxynucleotides (ODN) are another deserving wonder that does not appear in this PIH series.…”