Pure red cell aplasia associated with thymoma

A case of thymoma with mixed spindle and lymphocytic variety along with acquired, secondary, chronic pure red cell aplasia is an uncommon entity. The presented case is a case of anterior mediastinal tumour with marked anemia. On histopathologic and hematological examinations, it proved to be a case of thymoma along with pure red cell aplasia. High index of suspicion, bone marrow examination, radiological including CT scan examination, total thymectomy after preparation with repeated blood transfusion remains the mainstay of treatment. Prolonged corticosteroid therapy leads to remission for upto ten months after operative intervention.     

Successful corticosteroid therapy of a recurrent thymoma with pure red cell aplasia]

A 71-year-old man underwent extended thymomectomy with partial resection of the upper lobe of the left lung and pericardium for stage III invasive thymoma in March, 2000. Postoperative chemotherapy and radiation therapy were carried out. The patient did well until June 2005, when a mediastinal mass and pleural dissemination were detected. The recurrence of the thymoma was strongly suspected radiographically. Combination chemotherapy of carboplatin and paclitaxel achieved partial remission. About three months after the last chemotherapy, the patient had a severe anemia in February 2006. Based on the blood data and the bone marrow examination, pure red cell aplasia was diagnosed. Prednisolone treatment (50 mg daily) resulted in dramatic regression of recurrent mediastinal and pleural tumors, as well as improvement of pure red cell aplasia.     

Thymoma associated with pure red-cell aplasia: clinical features and prognosis

As information on the clinical features and prognosis of thymoma complicated by pure red-cell aplasia is limited, follow-up data on thymoma patients who had a thymectomy between 1954 and 1999 were analyzed retrospectively. Six of 166 cases were complicated by pure red-cell aplasia. In 3 of these, the pure red-cell aplasia appeared after surgical intervention. Remission was observed in 2 patients who underwent extended thymectomy. The other 4 patients subsequently died from pure red-cell aplasia. The outcome in patients with pure red-cell aplasia was poorer than that in the entire group of patients with thymoma and in those with thymoma complicated by myasthenia gravis. The possible onset of pure red-cell aplasia after thymectomy should be kept in mind during follow-up.     

Successful treatment of thymoma-associated pure red cell aplasia with intravenous immunoglobulins

Repeated cycles of intravenous immunoglobulins (IVIG) have been reported to be successful in a few patients with idiopathic pure red cell aplasia (PRCA) or associated with another pathology. The efficacy of this treatment for PRCA with thymoma has not been reported previously. We describe here the case of a 75-yr-old man who presented with PRCA associated with a benign thymoma. After failure of thymectomy, corticosteroids and octreotide, a complete durable remission was obtained after a single 5-d cycle of IVIG.     

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.     

Efficacy of danazol in pure red cell aplasia

Twenty-one unselected patients with refractory chronic anemias of various etiologies were treated with danazol, a synthetic attenuated androgen. All had previously failed treatment with hematinics, androgens, corticosteroids, high-dose intravenous immunoglobulin, antithymocyte globulin, cytotoxic immunosuppressive agents, and/or plasmapheresis. Three patients with pure red cell aplasia and one with aplastic anemia responded. No responses were observed in 11 patients with myelodysplastic syndromes, two patients with myelofibrosis, and two with paroxysmal nocturnal hemoglobinuria. Remission in pure red cell aplasia was maintained with danazol alone in one patient and required combined low-dose prednisone in two. Objective responses occurred in 2 to 3 weeks and therapy generally was well tolerated. To date, one patient with pure red cell aplasia remains in complete remission at 9 months on low-dose danazol alone. We conclude that danazol alone or combined with prednisone may induce and maintain remission in severe refractory pure red cell aplasia and possibly other chronic cytopenias characterized by immunologic marrow suppression. Further trials of danazol in treating these disorders are indicated.     

Deferasirox treatment improved hematopoiesis and led to complete remission in a patient with pure red cell aplasia

A 64-year-old woman developed pure red cell aplasia (PRCA) 4 years after thymectomy for thymoma. During anti-thymocyte globulin treatment, the patient developed cytomegalovirus pneumonia and was thus unable to continue immunosuppressive therapy and became transfusion dependent. Deferasirox was started for treatment with iron overload when serum ferritin increased to >1000 ng/mL. Seven months after initiation of deferasirox treatment, serum ferritin level decreased the normal range and the patient has remained transfusion independent thereafter. Deferasirox was discontinued when serum ferritin level decreased below 500 ng/mL, and she has maintained in complete remission over the last 15 months. Hypotheses have been raised regarding the improvement of hematopoiesis by deferasirox treatment, but the mechanism whereby this might be achieved remains unclear. Deferasirox treatment may be clinically beneficial both by reducing iron overload and by improving hematopoiesis in patients with PRCA.     

Relapse of autoimmune hemolytic anemia in Evans syndrome after thymectomy for pure red cell aplasia

A 81-year-old woman was referred to our hospital with pure red cell aplasia (PRCA) associated with a thymoma in May 2005. She had previously suffered from Evans syndrome which had been improved by prednisolone in 1999. She underwent a thymectomy, however her anemia subsequently got worse. Reticulocytopenia was noted and a marrow erythroid series was aplastic. Furthermore, both direct and indirect Coombs tests were positive, and the serum haptoglobin level was low. Based on these findings, the patient was diagnosed as having PRCA complicated with relapsed autoimmune hemolytic anemia (AIHA). The PRCA and AIHA were successfully treated with prednisolone and cyclosporine. To our knowledge, only one case of the PRCA complicated with AIHA after thymectomy has been reported. FoxP3 positive regulatory T-cells (Treg), which maintain immunological self-tolerance, were readily detectable in the excised thymoma. Thus, thymectomy resulted in removal of the Treg pool and might explain the autoimmune activation, believed to be one of the mechanisms of the post-thymectomy recurrence of the AIHA in this case.     

Membrane Bound IgG on Erythroblasts in Pure Red Cell Aplasia following Thymectomy

A case of pure red cell aplasia appearing 6 months following thymectomy is reported in a 43-year-old man. Immunofluorescence studies of the patient's bone marrow have demonstrated the presence of membrane-bound IgG on the majority of erythroblasts and some mature erythrocytes. It is suggested that the IgG represents anti-erythroid autoantibodies. The number of Ig-bearing lymphocytes in peripheral blood was decreased as was the level of immunoglobulins indicating a B-lymphocyte deficiency. T-lymphocyte functions were without remarks. The patient was initially treated with corticosteroids and oxymetholone. He responded well to this therapy but relapsed 9 month later. Cyclophosphamide treatment was started and followed by a complete haematologic remission.     

Pure red cell aplasia and thymoma: demonstration of persisting inhibition of erythropoiesis after thymectomy and resolution after immune suppressive treatment

A 61 year-old woman presented with general malaise, hair loss, pure red cell aplasia (PRCA) and thymoma: no growth of erythropoietic colonies in vitro (BFU-E) was observed in the presence of her own serum. The thymoma was removed: after the operation no improvement of her anaemic condition was observed and colony growth was very poor, although T-depleted narrow preparations showed a modest BFU-E formation in autologous serum. Following treatment with azathioprine, a complete recovery was seen, associated with normal BFU-E formation in vitro. This observation suggests that a complex inhibition of erythropoiesis may operate in PRCA involving both humoral and cellular factors; thymectomy alone may not be sufficient to restore haemopoiesis, but has to be followed by immune suppressive treatment.     

Clonal rearrangement of intratumoral T-cell receptor beta-chain gene in two patients with thymoma accompanied by pure red cell aplasia]

We encountered two cases of thymoma accompanied by pure red cell aplasia and demonstrating clonal rearrangement of the T-cell receptor beta-chain gene (TCR-beta) in lymphocytes. Patient 1 was a 55-year-old man and Patient 2 was a 43-year-old woman. Both had severe anemia and mediastinal tumors. Bone marrow aspiration was performed and pure red cell aplasia diagnosed. Thymoma was the presumptive diagnosis for the mediastinal tumors, and extended thymectomy was performed. The post-operative diagnosis was invasive thymoma (spindle-cell type) in Patient 1 and non-invasive thymoma (mixed lympho-epithelial type) in Patient 2. The cell compositions (%) obtained with T-cell surface marker analysis were as follows: [table: see text] Southern blot analysis disclosed clonal rearrangement of TCR-beta genes in thymoma thymocytes from both patients.     

Long-term remission of pure red cell aplasia after plasma exchange and lymphocytapheresis

A 57-year-old man with idiopathic pure red cell aplasia went into remission after plasma exchange. He relapsed after 5 months and then failed to respond to treatment with intensive plasma exchange and immunosuppressive agents. Because of a high proportion of T-suppressor cells in the peripheral blood he was treated with lymphocytapheresis in addition to the previous treatment. The patient achieved a long-term haematological remission which has now persisted for more than 3 yr.     

Thymoma-associated systemic lupus erythematosus, exacerbating after thymectomy. A case report and review of the literature

SIR, Myasthenia gravis (MG), pure red cell aplasia and acquiredhypogammaglobulinaemia are well recognized to be associatedwith thymoma, but systemic lupus erythematosus (SLE) can alsobe a manifestation of thymoma. The literature on the featuresof thymoma-associated SLE and the effect of thymectomy on SLEdisease activity is conflicting. A 76-yr-old Caucasian woman presented with malaise and weightloss of 10 kg over the past 6 months. Clinical examination atthat time revealed a low body weight of 46 kg and a body lengthof 160 cm. Laboratory examination showed     

Acquired amegakaryocytic thrombocytopenia and red cell aplasia in a patient with thymoma progressing to aplastic anemia successfully treated with allogenic stem cell transplantation

Association of pure red-cell aplasia with thymoma is well documented. However, acquired amegakaryocytic thrombocytopenia (AAMT) has been rarely associated with thymoma with only five reported cases in literature. We report a patient with thymoma complicated by pure red cell aplasia (PRCA) and AAMT who progressed to develop aplastic anemia (AA). The patient was refractory to 10-months of immunosuppressive therapy with cyclosporine, prednisone, and antithymocyte globulin. She was eventually treated with allogeneic stem cell transplantation (allo-SCT). On Day +323 the patient continues to be transfusion-independent. This case illustrates how in patients with thymoma and AAMT may herald development of AA. This is also the first report of a patient with AAMT progressing to thymoma-associated AA being successfully treated with allo-SCT. The successful outcome suggests allo-SCT as a feasible option similar to other AA patients.     

Successful treatment of pure red cell aplasia with autologous stem cell transplantation

We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was intolerant of conventional immunosuppressive therapies but achieved a complete long-term remission following autologous hematologic stem cell transplant (HSCT). The patient was initially treated with high-dose prednisone, cyclophosphamide, cyclosporine, antithymocyte globulin, and then rituximab. With the exception of rituximab, all of the above regimens achieved a transient response. However, because of the persistent requirement for red blood cell transfusions and intolerance to the multiple immunosuppressive therapies, autologous HSCT was eventually performed. The patient remains in complete remission and on no other therapy for 36 months following the autologous HSCT.     

Treatment of pure red cell aplasia and autoimmune haemolytic anaemia in chronic lymphocytic leukaemia with Campath-1H

A patient with chronic lymphocytic leukaemia (CLL) progressive on fludarabine therapy and life-threatening anaemia related to immune haemolysis and pure red cell aplasia was treated with Campath-1H. The patient had sustained complete remission of both CLL and anaemia, but died of recurrent sepsis and cachexia 10 months after completion of the treatment. Campath-1H (alemtuzumab), a humanised anti-CD52 monoclonal antibody, is a potent therapeutic agent against advanced CLL and immune cytopenias. It could be indicated in the treatment of severe immune complications of CLL unresponsive to corticosteroids. Prolonged immunosuppression is a serious side-effect leading to severe infectious complication.     

Treatment of Pure Red Cell Anaemia with Antilymphocytic Globulin

2 patients with pure red cell anaemia (PRCA) have been treated with antilymphocytic globulin (ALG). An 18-year-old man with PRCA refractory to corticosteroides and cyclaphosphamide was treated with 16 g of ALG and obtained a complete remission. 3 years later, he was still in complete remission. A 46-year-old man with PRCA appearing 6 months following thymectomy was treated with ALG in his third relapse of PRCA. ALG alone had no significant therapeutic effect, but a combination of corticosteroides and ALG induced a remission lasting for 6 months. A second remission was induced when ALG and corticosteroide again were instituted.     

Cyclosporin improved pure red cell aplasia associated with thymoma and tended to decrease thymoma size: a case report]

The case was a 56-year-old man who underwent extended thymothymectomy in 1993 because of an invasive thymoma classified as Masaoka IIa. The tumor was disseminated through the right thoracic cavity in 1994. Although the chemotherapy was repeated, the disseminated thymoma tended to increase in size. The patient was suffering from severe anemia, and pure red cell aplasia was diagnosed in September 2002. The administration of cyclosporin was initiated, and not only brought about improvement of pure red cell aplasia but also tended to shrink the thymoma. Cyclosporin may be an effective drug for the reduction of thymoma as well as for pure red cell aplasia.     

Thymoma Associated with Pure Red Cell Aplasia, Immunoglobulin Deficiency and an Inhibitor of Antigen-induced Lymphocyte Transformation

A case of thymoma associated with pure red cell aplasia and hypogammaglobulinaemia is described in which the anaemia was of abrupt onset, following removal of the tumour. Tests of immunological function showed abnormalities of both humoral and cellular immunity. The patient was found to have a serum inhibitor of antigen-induced lymphocyte transformation which disappeared after immunosuppressive therapy at the same time that erythroblasts reappeared in the marrow. It is suggested that the triad of thymoma, pure red cell aplasia and immunoglobulin deficiency are manifestations of 'pluripotent' stem cell failure; in this case the inhibitor of lymphocyte transformation may have been related to the factor which also inhibited red cell maturation.     

Rheumatoid arthritis and pure red cell aplasia

Three patients with severe, deforming, and long-standing rheumatoid arthritis developed pure red cell aplasia that did not remit after withdrawal of medications, ran a chronic course, and in two patients remitted only after cytotoxic immunosuppressive treatment. An IgG inhibitor of autologous erythroid colony-forming and burst-forming unit growth in vitro was found in the serum of one patient. This specific erythropoietic inhibitor persisted in lower titer in the patient's serum even after an azathioprine-induced remission of pure red cell aplasia, indicating the possible need for maintenance immunosuppressive therapy. Chronic pure red cell aplasia may be another extra-articular manifestation of rheumatoid arthritis and should be considered when severe anemia develops in the absence of blood loss or hemolysis.