Cyclophosphamide therapy for pure red cell aplasia associated with granular lymphocyte‐proliferative disorders

Abstract

Granular lymphocytes have been characterized as cells with azurophilic granules in the cytoplasm. Patients with increased numbers of granular lymphocytes are designated as granular lymphocyte‐proliferative disorders (GLPDs). A variety of haematological abnormalities are associated with T‐cell‐lineage GLPD. Among these, pure red cell aplasia is frequent, and adequate therapy is required. Seven patients with pure red cell aplasia, or a related condition complicating T‐cell‐lineage GLPD, were entered into this study. Cyclophosphamide was initiated at a daily oral dose of 100 mg. After 2 weeks the dose was reduced to 50 mg/d, and maintained at that dose. Cyclophosphamide was administered until the lymphocyte count was <1 ×109 l and T‐cell receptor‐β gene analysis was used to monitor the response to treatment. All the patients were successfully treated, irrespective of their former treatment. Clinical remission was associated with the disappearance of the abnormal granular lymphocyte clone, as detected by Southern blot hybridization analysis. Therapeutic responses began after 8 weeks, and clinical complete remissions were obtained after 6 months. Oral cyclophosphamide monotherapy can successfully treat the pure red cell aplasia associated with T‐cell‐lineage GLPD.

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

“…8,9 LGL leukemia-associated PRCA has been primarily treated with chemotherapy, such as oral cyclophosphamide (CY) with or without prednisolone (PSL), cyclosporine A (CsA), or methotrexate. 5,9,10,11 The combination of CY and PSL is associated with a longer duration of response than PSL alone. 1,10,12 The overall response to initial CY therapy has been reported to be 66-100% 5,11 and the median duration of response is 32 months.…”

“…5,9,10,11 The combination of CY and PSL is associated with a longer duration of response than PSL alone. 1,10,12 The overall response to initial CY therapy has been reported to be 66-100% 5,11 and the median duration of response is 32 months. 11 However, optimal management of LGL leukemia-associated PRCA and long-term outcome after immunosuppressive therapy are largely unknown because of the rarity of this disorder.…”

“…[1][2][3] LGL leukemia is also referred to as granular lymphocyte-proliferative disorders (GLPD) or lymphoproliferative disease of granular lymphocytes. 1,2,[4][5][6] LGL leukemia is a heterogeneous disorder characterized by a persistent increase in the number of peripheral blood LGLs, and the majority of patients have a clonal rearrangement of T-cell receptors. 4,6,7 Clonal disorders of LGLs may arise from natural killer cells, and may be indolent or behave as an aggressive disease.…”

T-.GAMMA. .DELTA. Large Granular Lymphocyte Leukemia Preceded by Pure Red Cell Aplasia and Complicated with Hemophagocytic Syndrome Caused by Epstein-Barr Virus Infection

“…In patients with LDGL, cytopenia is usually manifested as anemia or neutropenia, and much less frequently, thrombocytopenia and pancytopenia (4)(5)(6)(7)(8)(9)(10). These are diagnosed as PRCA,myelodysplastic syndrome or aplastic anemia (4)(5)(6)(7)(8)(9)(10).…”

“…Granular lymphocytes of these patients have been shown to selectively inhibit erythroid progeitors but not myeloid progenitors (4)(5)(6)(7)(8)(9)(10). (11)(12)(13)(14)(15).…”