True thymic hyperplasia causing pure red cell aplasia: a case report

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved. Patients diagnosed with pure red cell aplasia should be investigated with a computerized tomographic scan to assess for thymic pathology and if present, this should be resected. Follow-up is essential to monitor for recurrence.     

肾移植术后人类微小病毒B19感染致纯红细胞再生障碍性贫血2例并文献复习

目的探讨肾移植术后人类微小病毒(HPV)B19感染致纯红细胞再生障碍性贫血(纯红再障)的诊断和治疗特点。方法总结南方医科大学南方医院器官移植科收治的2例肾移植术后HPV B19感染致纯红再障的病例,结合文献复习讨论该病的临床特点、诊断方法、治疗过程及预后。结果两例肾移植受者术后早发严重贫血且进行性加重,输血治疗无效。排除导致贫血的其他原因,综合骨髓穿刺活检、荧光聚合酶链反应(PCR)检测HPV DNA等方法诊断为HPV B19感染致纯红再障。经调整免疫抑制方案、静脉注射用免疫球蛋白(IVIG)等治疗后2例患者贫血症状明显改善。结论对于肾移植术后早期不明原因、进行性加重的贫血患者,特别是伴随网织红细胞缺乏者,应考虑HPV B19感染致纯红再障的可能性。骨髓穿刺及荧光PCR检测结果是诊断纯红再障的主要依据,免疫抑制剂减量和应用IVIG治疗是主要治疗措施。经治疗后,患者预后较好,但易复发。     

Major ABO-incompatible hematopoietic stem cell transplantation: study of post-transplant pure red cell aplasia and endothelial cell chimerism

BACKGROUND: In contrast to human leukocyte antigen (HLA) matching, ABO-blood group incompatibility plays a minor role in the success of allogeneic hematopoietic stem cell transplantation (HSCT). Incompatible ABH histo-blood group antigens, expressed on recipient endothelial cells (EC) and donor erythroid progenitor cells, may represent targets for graft-versus-host disease (GVHD) and host-versus-graft reactions, respectively. The aims of the current study were to investigate: (1) red blood cell (RBC) engraftment and (2) EC chimerism as a potential result of replacement of recipient EC by donor bone marrow (BM)-derived EC in a patient following major ABO-incompatible (A to O) and gender-mismatched HSCT, who died at day 350 of severe acute GVHD. METHODS: Blood counts and anti-A/B isoagglutinin titers were analyzed repeatedly. Heart and BM specimens were obtained at autopsy. The expression of ABH histo-blood group antigens was examined by immunhistochemistry, X/Y chromosomes were detected by chromogen in situ hybridization (CISH). RESULTS: RBC engraftment defined as appearance of 1% reticulocytes in the peripheral blood was delayed and correlated with anti-donor isoagglutinin titers. Circulating hematopoietic cells were exclusively of donor origin demonstrating full donor hematopoietic chimerism, whereas EC in heart and BM blood vessels were exclusively of the recipient type. CONCLUSIONS: Pure red cell aplasia (PRCA) after major ABO-incompatible HSCT was caused by anti-A/B isoagglutinins produced by recipient-type plasma cells. Using ABO and gender mismatch for discrimination, heart and BM blood vessels demonstrated no evidence for EC chimerism 11 months after ABO-incompatible HSCT. These findings suggest that EC replacement and chimerism do not represent major mechanisms responsible for tolerance induction after HSCT.     

Cyclosporine in the treatment of azathioprine-induced red cell aplasia following renal transplantation

Azathioprine, a well-known immunosuppressive agent, is used extensively in renal transplantation. There have been several case reports of pure red cell aplasia induced by this drug following a successful kidney transplant. Previous management of azathioprine-induced red cell aplasia included reduction of azathioprine dose, or treatment with cyclophosphamide. We propose the substitution of cyclosporine for azathioprine, in this clinical setting. Not only does cyclosporine allow recovery of bone marrow function, but it maintains a level of immunosuppression which stabilizes renal function in the post-transplant patient.     

ABO血型主要不合异基因造血干细胞移植后纯红细胞再生障碍的临床分析

目的探讨ABO血型主要不合者异基因造血干细胞移植（allo-HSCT）后并发纯红细胞再生障碍（PRCA）的危险因素、临床转归以及PRCA的治疗和预防。方法42例行allo-HSCT，其中供、受者AN）血型主要不合者33例，主次双向不合者9例，27例受者血型为O型。预处理后，13例行骨髓移植，25例行外周血干细胞移植，4例行脐血移植。6例移植前行供者型血浆置换。移植后采用环孢素A（CsA）及短程甲氨蝶呤（MTX）联用预防移植物抗宿主病（GVHD）。结果42例均获得供者细胞植入，11例移植后并发PRCA（26．2％），11例的血型均为O型，其供者9例为A型，2例为B型；移植前行供者型血浆置换的O型受者，移植后均未发生PRCA。并发PRCA的11例中，8例经红细胞输注后自然缓解，2例行供者型血浆置换，其凝集素滴度下降后缓解，1例予利妥昔单抗治疗后缓解。单因素分析表明，O型受者、A型供者以及A型供给O型者与PRCA的发生相关，多因素分析表明，A型供给0型者是发生PRCA的独立危险因素（RR为10．999，95％可信区间为1．975-61．258，P〈0．05）。结论A型供给O型者与PRCA的发生密切相关；移植前行供者型血浆置换可预防PRCA的发生；供者型血浆置换和利妥昔单抗可有效治疗PRCA。     

Pathogenesis and management of hyperparathyroidism in end-stage renal disease and after renal transplantation

SUMMARY: Secondary hyperparathyroidism is an adaptive response to progressive loss of renal function so as to maintain calcium and phosphate homeostasis, 1,25-dihydroxyvitamin D₃ levels and normal bone turnover, despite skeletal resistance to parathyroid hormone. As feedback regulation fails, complications of parathyroid overactivity develop, and by the commencement of dialysis abnormal bone histology is present in almost all patients, with hyperparathyroid changes most commonly found. Post transplantation, persisting hyperparathyroidism predisposes to osteoporosis. The risk of bone disease is reduced by early, carefully targeted dietary measures and suppressive therapy with calcitriol and calcium-based phosphate binders, while newer therapies include bisphosphonates and calcimimetics. Timely surgical intervention is necessary in some patients.     

Pure red cell aplasia following irradiation of an asymptomatic thymoma

An unusual case of pure red-cell aplasia (PRCA) developed sixteen days after irradiation of an asymptomatic thymoma. After removal of the encapsulated thymoma there was no improvement in the anemia, and no response to adrenocortical and anabolic steroid hormones or immunosuppressive agents. Presented at the 34th annual meeting of the Japanese Association for Thoracic Surgery on September 24–26, 1981, Tokyo.     

Pure red cell aplasia after major ABO-incompatible bone marrow transplantation: two case reports of treatment with recombinant human erythropoietin

A 34-year-old man with acute myelocytic leukemia (AML: MO) and a 32-year-old woman with AML: M2 developed pure red cell aplasia (PRCA) after receiving a major ABO-incompatible bone marrow transplant (BMT). The first patient responded to recombinant human erythropoietin (rhEPO) therapy, while the second did not. The second patient also received methylprednisolone (m-PSL) but developed reticulocytosis and hemolysis after the administration of m-PSL. Plasmapheresis was then performed and the patient promptly recovered from hemolysis and PRCA. We conclude that close attention must be paid when treating PRCA following major ABO-in-compatible BMT with rhEPO and m-PSL, as there is always the potential for massive hemolysis.     

Recovery from Pure Red Cell Aplasia Caused by Anti-Erythropoietin Antibodies After Kidney Transplantation

The use of recombinant human erythropoietin (rHuEPO) is a major advance in the treatment of patients with anemia caused by chronic renal failure (CRF). The development of antierythropoietin (anti-EPO) antibodies following treatment with rHuEPO has been observed in an increasing number of patients. This causes pure red cell aplasia (PRCA) and requires the definitive withdrawal of rHuEPO. Many patients require immunosuppressive therapy before anti-EPO antibodies disappear completely. We report a case of PRCA owing to anti-EPO in a 20-year-old hemodialyzed man who was receiving immunosuppressive therapy for a liver transplantation carried out in childhood. He required repeated red cell transfusions until a kidney transplantation was performed. He received an induction therapy with antithymocyte globulins and a maintenance regimen consisting of steroids, tacrolimus and mycophenolate mofetil. This new immunosuppressive treatment led to the complete disappearance of anti-EPO antibodies within a few weeks after the kidney transplantation. Erythropoiesis and endogenous erythropoietin synthesis were restored following transplantation, without leading to an increase in the titer of anti-EPO antibodies.     

胸腺瘤合并单纯红细胞再生障碍性贫血临床特点(附3例报告)

目的探讨胸腺瘤合并纯红再障的诊断和治疗。方法3例胸腺瘤合并纯红再障患者,均手术切除胸腺瘤,并于术后常规胸腺区放疗,观察术后纯红再障的缓解情况。对不能缓解者,给予皮质激素及免疫抑制剂治疗。结果2例术后达临床治愈,1例术后给予激素及免疫抑制剂治疗取得缓解或明显进步。结论胸腺瘤切除-术后胸腺区放疗-皮质激素及免疫抑制剂的运用是胸腺瘤合并纯红再障患者较理想的治疗模式。     

Acquired pure red cell aplasia in a hemodialyzed patient

A 68-year-old male had end-stage renal disease secondary to hypertension. He was placed on chronic dialytic therapy and was given recombinant human erythropoietin (epoetin) for renal anemia. One month later, rapidly progressing anemia was noted. The anemia was unresponsive to maximal doses of epoetin and the patient soon became transfusion-dependent. Erythroid hypoplasia was demonstrated by bone marrow biopsy. A detailed search for the cause of the erythroblastopenia revealed nothing. A diagnosis of acquired pure red cell aplasia was made. The use of immunosuppressive agents improved the patient's symptoms and laboratory data. Antibodies for erythropoietin (EPO) were negative after the treatment. It is suggested that patients with EPO-resistant anemia with no obvious etiology should be examined for underlying hematologic disorders.     

Antierythropoietin antibody-induced pure red cell aplasia: posttransplant evolution

Pure red cell aplasia is a rare complication of recombinant human erythropoietin (rHuEPO) treatment, which physicians should consider once the more frequent causes of hyporegenerative anemia have been excluded. To our knowledge, no pediatric cases have been described. In our patient, cyclosporin A treatment enabled a reduction in the number of transfusions and the risk of hyperimmunization. After transplantation, our patients hemoglobin level has remained normal and stable.     

Successful reintroduction of a different erythropoiesis-stimulating agent after pure red cell aplasia: relapse after successful therapy with prednisone.

We report a 3-year case history that describes a 78-year-old woman with recurrent transfusion-dependent pure red cell aplasia (PRCA) secondary to recombinant epoetin use that was responsive to immunosuppressant therapy. The patient had kidney disease of unknown aetiology (estimated glomerular filtration rate of 13 ml/min/1.73 m2) and was not on dialysis. After 16 months of therapy with subcutaneous Eprex, she developed anti-erythropoietin antibody-confirmed PRCA and was started on high dose prednisone (50 mg per day). Within 5 months, the patient's serum was clear of antibodies and, under the cover of low dose prednisone (5-7.5 mg per day), therapy with a different erythropoiesis-stimulating compound (Aranesp) was initiated due to persistent fatigue and anaemia. At 3 months of therapy, the serum anti-erythropoietin antibodies remained negative and, due to the patient's requests, and after discussion, prednisone therapy was discontinued. Unfortunately, 3 months after cessation of prednisone, a recurrence of PRCA was confirmed by the development of profound anaemia and reappearance of anti-erythropoietin antibodies in the patient's serum. High dose prednisone (50 mg per day) was reinstituted, whereupon, 2 months later, antibodies were again confirmed to be negative. This case report demonstrates the responsiveness of PRCA to simple immunosuppressive therapy, and the ability to introduce different erythropoiesis-stimulating agents in the presence of such therapy. It appears that there may be problems associated with discontinuation of immunosuppressive therapy in the presence of sustained erythropoiesis-stimulating agent therapy in those in whom the condition has occurred previously.     

外科治疗胸腺瘤合并单纯红细胞再生障碍性贫血(附5例报告及国内文献复习)

目的：探讨国人胸腺瘤合并单纯红细胞再生障碍性贫血（PRCA）的临床特征及其外科治疗效果。方法：总结1980年至1997年间5例胸腺瘤合并PRCA病人接受胸腺瘤手术治疗的资料，并通过中国生物医学文献数据库光盘进行文献检索，对中国大陆已报道的这类病例进行文献复习和讨论。结果：本组胸腺瘤合并PRCA者占同期胸腺瘤病人的8．3％（5／60例）。全部均经胸骨正中切口切除胸腺瘤及胸腺组织和前纵隔脂肪，术后45d死亡1例，PRCA复发2例，长期生存2例，迄今为止，国内共检索出此类病人21例，术后早期PRCA情况明显改善，按术后随访满2年，且无PRCA复发征象作为手术有效标准，有效率为38．5％，结论：胸腺瘤合并PRCA是一种少见疾病，其预后取决于PRCA的缓解程度，胸腺瘤切除术对治疗PRCA是有效的，外科治疗是本病的首选治疗手段，也是其他综合性治疗方法的前提和基础。