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

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.     

Spontaneous remission in pure red cell aplasia associated with thymoma.

A 57-year-old woman with thymoma-associated pure red cell aplasia (PRCA) manifested spontaneous recovery of erythropoiesis. Anemia recurred before the surgical removal of her thymoma, however, and the second anemic remission following surgery did not occur promptly. In this report, we describe a rare occurrence of spontaneous remission in PRCA.     

Steroid-responsive pure red cell aplasia associated with natural killer cell lymphocytosis

A patient with pure red cell aplasia and expansion of the peripheral blood natural killer (NK) cell population is described. Despite normal absolute and differential leukocyte counts, NK cells were increased at diagnosis and at relapse. Furthermore, these cells were not morphologically recognizable on the peripheral blood smear examination. A favorable clinical response to glucocorticoid therapy was accompanied by a decrease in NK cells.     

Chronic T-cell lymphoproliferative disorder associated with pure red cell aplasia

A 42-year-old woman was admitted to our hospital because of easy fatigability in Jan. 1976. Laboratory examination revealed severe macrocytic anemia and slight lymphocytosis. She was diagnosed as having pure red cell aplasia (PRCA). She went into hematological remission 6 weeks following 40 mg/day treatment with prednisolone, but the anemia relapsed frequently when the dosage was lessened. She was then treated with 50 mg/day of cyclophosphamide, 50 mg/day of azathioprine, splenectomy, and methylprednisolone pulse therapy, but the recovery from anemia was temporary after each treatment. Since 1984, peripheral lymphocyte counts were 1-30,000/microliters, and reticulocyte counts were 0. She died of sepsis of Listeria in Sep. 1986. Peripheral lymphocytes had large azurophilic granules and an immunophenotype of OKT3+8+11+Ia1+Leu7+.     

Intrahepatic cholestasis and pure red cell aplasia associated with ticlopidine

A 77-year-old woman developed jaundice and anemia 3 and 8 weeks, respectively, after starting ticlopidine (100 mg daily) for cerebral infarction. From the laboratory findings, including histological study of the liver and bone marrow specimen, ticlopidine-induced intrahepatic cholestasis and pure red cell aplasia were highly suspected. Jaundice slowly improved after the withdrawal of ticlopidine. Anemia immediately improved with steroid therapy. These are very rare adverse effects of ticlopidine; nevertheless, periodic laboratory examinations are recommended.     

Lamivudine-induced pure red cell aplasia

The aim of this report is to describe five patients with lamivudine-induced pure red cell aplasia, an association not previously described. We describe patients with unresponsive anemia in whom a complete study including blood cell counts, reticulocyte counts, hemolysis tests, and bone marrow aspiration was performed. Pure red cell aplasia was considered when anemia was associated with normal leukocyte and platelet counts with a corrected reticulocyte count below 1% and less than 5% bone marrow erythroid progenitors in the absence of positive hemolysis tests. Complete remission was considered when bone marrow erythroid progenitors were at least 16%. Five male patients had pure red cell aplasia with a median age of 32 years (range 29 to 37 years). Before lamivudine, they had hemoglobin >11.8 g/dl without transfusion requirements. After receiving the drug, hemoglobin dropped to 5.2 g/dl (4.3 to 6.1 g/dl) with high transfusion requirements and mean bone marrow erythroid progenitors of 1.84% (0 to 4%). Withdrawal of lamivudine was attempted to confirm the diagnosis. Seven weeks after stopping lamivudine, hemoglobin rose up to 12.8 g/dl (11 .3 to 13.8 g/dl) and bone marrow erythroid progenitors increased up to 25.6% (21 to 40%) without transfusion requirements. Lamivudine-induced pure red cell aplasia may be a cause of anemia unresponsive to conventional treatment in AIDS. Since lamivudine use in Mexico has been relatively short, we expect more cases to appear in the future.     

Monoclonal gammopathy‐associated pure red cell aplasia

Pure red cell aplasia (PRCA) is a rare disorder characterized by inhibition of erythroid precursors in the bone marrow and normochromic, normocytic anaemia with reticulocytopenia. Among 51 PRCA patients, we identified 12 (24%) patients having monoclonal gammopathy, monoclonal gammopathy of undetermined significance or smouldering multiple myeloma, with presence of monoclonal protein or abnormal serum free light chains and atypical bone marrow features of clonal plasmacytosis, hypercellularity and fibrosis. Thus far, three patients treated with anti‐myeloma based therapeutics have responded with reticulocyte recovery and clinical transfusion independence, suggesting plasma cells play a key role in the pathogenesis of this specific monoclonal gammopathy‐associated PRCA.     

Azathioprine-associated pure red cell aplasia

Abstract. Azathioprine-associated pure red cell aplasia in patients with a renal allograft is a rare complication. Although immunological inhibition of erythroid progenitor cell has been suggested, the cause of this phenomenon remains unclear. The patient we describe showed a decrease in the number of erythroid progenitor cells and no evidence for the presence of a serum inhibitor of these precursor cells. Discontinuation of azathioprine was associated with a complete recovery from anaemia as well, with an increase in the number of erythroid progenitor cells.     

Remission of pure red cell aplasia following oxymetholone therapy

A 53-year-old male with a long-standing idiopathic pure red cell aplasia, refractory to testosterone cypionate, fluoxymesterone, and corticosteroid, was successfully treated with oxymetholone. Blood count, bone marrow, reticuloendothelial bone marrow scan, and ferrokinetic studies showed a marked increase of erythropoiesis in response to oxymetholone. The patient became hematologically normal within 12 weeks and has required no further transfusions. This observation suggests possible difference of mechanisms in the action of various androgenic drugs. It also suggests that failure of response to one androgenic agent does not necessarily mean the other androgenic agents will not be effective in cases of refractory idiopathic pure red cell aplasia.     

Isoniazid-induced pure red cell aplasia

Pure red blood cell aplasia (PRCA) is an extremely rare side effect of isoniazid (INH). We have encountered 2 patients who developed anemia caused by PRCA. One was receiving INH preventive therapy and the other was being treated with INH and rifampin. On withdrawal of INH, the anemia responded rapidly. For unexplained anemia during INH therapy, PRCA should be considered as a cause.