Remission of pure red cell aplasia associated with nonthymic malignancy.

Two patients with acquired pure red cell aplasia associated with malignancy are presented. One patient has breast cancer and the other had poorly differentiated nodular lymphoma; neither patient had evidence of a serum inhibitor of hemoglobin synthesis and both achieved complete hematologic remission following prolonged immunosuppressive therapy. The literature describing the association of pure red cell aplasia and nonthymic malignancy is reviewed and potential for responsiveness discussed.     

Metastatic thymoma with myasthenia gravis and pure red cell aplasia.

Metastatic malignant thymoma developed in a 64-year-old man after a 9-year history of myasthenia gravis. Following good response to irradiation of the mediastinal mass and osseous metastasis, pure red cell aplasia developed.     

Lymphocytotoxic T lymphocytes in a patient with B-chronic lymphocytic leukemia and pure red cell aplasia

The peripheral blood T cells of a hypertransfused patient with B-chronic lymphocytic leukemia and pure red cell aplasic were found to exhibit unusual spontaneous cytotoxic activity in vitro. The patient's E-rosette positive cells were cytotoxic for K562 (cultured human crythroleukemia cells) and allogeneic B and T lymphocytes freshly isolated from the peripheral blood of normal and CLL donors. They failed to kill autologous B cells, erythroid progenitors present in allogeneic bone marrow, and a number of cultured human tumor cells (Malme, CAKI) even after prolonged (36 h) co-culture. Peripheral blood T cells isolated from normal controls, other CLL patients, and hypertransfused individuals (n=13) (lid not exhibit spontaneous lymphocytotoxic activity. Circulating cytotoxic T cells having the ability to kill freshly isolated allogeneic lymphocytes have, heretofore, not been reported in humans. Our findings suggest that among this patient's peripheral blood T cells, there exists a subpopulation of lymphocytotoxic cells that closely resemble cytotoxic T cells generated in vitro after priming with allogeneic target cells. Although the lymphocytotoxic cells could have been induced in this patient by previous HLA-mismatched transfusions, it is possible they may have arisen spontaneously and underly the patient's erythroblastopenic state.     

Thymomas associated with pure red cell aplasia. Histologic and follow-up studies

Seventeen cases of pure red cell aplasia (PRCA) with thymoma were studied clinically, histologically, and immunologically. Two cases were associated with myasthenia gravis (MG), and three with hypogammaglobulinemia. Coombs test and antinucleus antibody test were positive in five cases. All thymomas were spindle cell types, and the adjacent thymuses had no germinal center, but showed epithelial clusters frequently. All patients, except one whose tumor was unresectable, had thymo-thymomectomy. The operation was effective in six cases (37.5%), and the effects were not different between two operative procedures (simple and extended thymectomy). Myasthenic symptoms in two patients remitted after the operation, but effects on hypogammaglobulinemia were conincident with those on PRCA.     

Angioimmunoblastic T-cell lymphoma-associated pure red cell aplasia with abdominal pain

Angioimmunoblastic T-cell lymphoma (AITL) is a unique type of peripheral T-cell lymphoma with a constellation of clinical symptoms and signs, including weight loss, fever, chills, anemia, skin rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and polyclonal hypergammaglobulinemia. The histological features of AITL are also distinctive. Pure red cell aplasia is a bone marrow failure characterized by progressive normocytic anemia and reticulocytopenia without leucopenia or thrombocytopenia. However, AITL with abdominal pain and pure red cell aplasia has rarely been reported. Here, we report a rare case of AITL-associated pure red cell aplasia with abdominal pain. The diagnosis was verified by a biopsy of the enlarged abdominal lymph nodes with immunohistochemical staining.     

Lymphocytes and antibody in retrovirus-induced feline pure red cell aplasia

The possible role of antibody and T-lymphocytes was investigated in the pure red cell aplasia (PRCA) associated with feline leukemia virus, subgroup C (FeLV-C), infection. In previous studies, erythroid colony-forming cells were undetectable in marrow culture of cats with PRCA. Yet erythroid burst-forming cells (BFU-E) remained, suggesting that BFU-E were able to differentiate in vitro but not in vivo. It was inferred that immunologic suppression may contribute to the pathogenesis of feline PRCA, and the interactions of antibody and T-lymphocytes with erythroid and granulocyte-macrophage progenitors were studied. Incubation of normal or PRCA marrow cells with PRCA serum or IgG concentrated from this serum and then complement (C') failed to decrease hematopoietic colony growth when compared to the results obtained with cultures of marrow cells incubated with C' alone. In crossover coculture studies, T-cells from Safari cats with PRCA had no inhibitory effect on colony growth from normal or autologous PRCA marrow cells. For the determination of whether feline PRCAs were associated with a clonal T-cell process, lymphocytes were obtained periodically from glucose-6-phosphate dehydrogenase (Glc-6-PD) heterozygous cats following FeLV-C infection and were expanded with a crude preparation of interleukin-2. The ratios of Glc-6-PD enzyme types in these samples did not change as cats developed anemia, suggesting that the inhibition of erythropoiesis was not associated with the clonal expansion of T-cells. These studies, therefore, do not support the premise that feline PRCA results from the interaction of antibody or T-cells with erythroid progenitors.     

Bile duct adenocarcinoma with Leser-Trelat sign and pure red blood cell aplasia

A case of adenocarcinoma of the bile duct complicating longstanding ulcerative colitis and associated with the rapid onset and growth of multiple seborrheic keratosis (Leser-Trelat sign) and pure red blood cell aplasia is described. This is the first report of a case of the coexistence of the Leser-Trelat sign and pure red blood cell aplasia in a patient with a malignancy. Both manifestations have been doubted as truly paraneoplastic manifestations because of their rarity in clinical medicine. Their co-existence in the present case would support their associaton with malignancy.     

Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia

Two patients with pure red cell aplasia (PRCA) refractory to anti-thymocyte globulin, prednisolone, cyclophosphamide, fludarabine, mitoxantrone, dexamethasone and cyclosporine, were treated with alemtuzumab (anti-CD52 antibody). Case 1, a 35-year-old man with idiopathic PRCA, remitted completely with 130 mg of alemtuzumab. Case 2, a 42-year-old man with PRCA due to T-cell large granular lymphocyte (T-LGL) leukaemia, achieved complete remission of the PRCA with 490 mg of alemtuzumab, although the T-LGL leukaemia responded only transiently. There were no significant side effects, and normalization of erythropoiesis was durable. Alemtuzumab is active in PRCA that is idiopathic or secondary to T-cell lymphoproliferative diseases.     

Cyclosporin A for the treatment of pure red cell aplasia associated with myelodysplasia

Recent reports have highlighted an associated of pure red cell aplasia (PRCA) with myelodysplasia (MDS). There are minimal data on the response of PRCA in this context to immunosuppression; in particular the role of cyclosporin A (CSA) has not been evaluated. We describe a patient with PRCA/MDS in whom CSA and low dose prednisolone led to restoration of marrow erythropoietic activity. Tests indicated the PRCA was likely to be mediated by cytotoxic lymphocytes rather than an inhibitory effect of cytokines. These observations suggest that CSA, due to its suppressive effect on cytotoxic T cell activity, is a rational therapy in this context.     

Philadelphia negative,Bcr-Abl positive chronic myeloid leukemia associated with pure red cell aplasia

Pure red cell aplasia (PRCA) is a rare disorder which is associated with thymoma, viral infections and autoimmune diseases. A few cases of PRCA during the clinical course of CML have been reported and these usually terminate in blastic crisis and death, suggesting a poor prognosis. However, only one case of Philedelphia chromosome negative, Bcr-Abl positive CML associated with PRCA has been reported. Here, we present a second case report of a Philedelphia negative, Bcr-Abl positive CML associated with PRCA who was unresponsive to all the chemotherapeutic regimens. We conclude that the present case supports the idea that the development of PRCA in the course of CML may be a bad prognostic sign.     

Primary amyloidosis, pure red cell aplasia, and Kaposi's sarcoma in a single patient.

A patient who developed primary amyloidosis, pure red cell aplasia, and Kaposi's sarcoma is described. This is the second reported coincidence of Kaposi's sarcoma and pure red cell aplasia and the first coincidence of Kaposi's sarcoma and primary amyloid, thus enlarging the spectrum of plasma cell and immunoglobulin abnormalities seen in Kaposi's sarcoma. Because immunologic abnormalities have been described in all these diseases, it is felt that some primary immune dysfunction is the underlying cause of the three diseases in this patient.     

Clonality of acquired primary pure red cell aplasia: effectiveness of antithymocyte globulin

Primary pure red cell aplasia (PRCA) was diagnosed in two male patients, 65 and 69 years old respectively. In both, surface markers of peripheral blood nuclear cells revealed the presence of TCR alphabeta+ phenotype. Clonality of T cells was confirmed by the polymerase chain reaction in both patients, in whom, prednisone at a dose of 1 mg/kg/day improved the anemia and lower doses caused its renewal, resulting in the reappearance of the patient's transfusion requirement. On the other hand, the anemia seems to have been treated permanently (second case) with horse antithymocyte globulin (ATG) (20 mg/kg/day 1 to 8 +) since his hemoglobin was about 15 g/dl at the time of writing. In the first patient, the hemoglobin level was 10.5 g/dl one month after the administration of ATG (15 mg/kg/d 1 to 5 +), but unfortunately, the patient died because of a massive gastrointestinal bleeding on the fortieth day following this treatment. We, therefore, suggest that, patients with acquired primary PRCA should be screened to detect the presence of a T-cell clone and recommend that, treatment should start earlier with ATG, if the PRCA is due to a T-cell clonal disorder.     

Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia

Basal cell carcinoma (BCC) is usually a benign and indolent cancer cured in greater than 95 percent of cases. Nevertheless, it can be locally destructive or occasionally metastasize to distant organs. We report a case of BCC metastatic to the lungs, occurring 17 years after the primary BCC was noticed, that responded to carboplatin and paclitaxel on 3 occasions. The patient also developed pure red cell aplasia (PRCA). Work-up did not reveal underlying thymoma or infectious, rheumatologic, or lymphoproliferative disorders. Parvovirus serologies were negative, and antibodies against erythropoetin were not detected. There was no history of exposure to drugs associated with PRCA. Bone marrow biopsy on 2 different occasions did not show evidence of myelodysplasia. PRCA may represent an unusual paraneoplastic syndrome associated with BCC as reported with other carcinomas. This is the first report of PRCA associated with metastatic BCC or the drugs carboplatin and paclitaxel, which were used to treat it. The literature on chemotherapy for metastatic BCC is reviewed.