Red Cell Aplasia Research Articles

Immuno-Hematologic Complexity of ABO-Incompatible Allogeneic HSC Transplantation

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO incompatible. Immuno-hematologic investigations allow to estimate donor/recipient ABO mismatch and anti-A/B isohemagglutinin (IHA) titration in the pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can occur post HSCT. Some preventive measures take into consideration either decision-making algorithms based on the recipient’s IHA titration or clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Product manipulation through red blood cell (RBC) and/or plasma depletion can also be taken into account. Currently, the best approach in the management of ABO-incompatible transplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHA titration are not standardized. A transfusion strategy must consider both the donor’s and recipient’s blood group systems until the RBC engraftment catches on and ABO conversion (forward and reverse typing) is confirmed on two consecutive and independent samples. Therefore, ABO incompatibility in HSCT represents a demanding immuno-hematologic challenge and requires all necessary preventive measures, including the appropriate selection of ABO blood components for transfusion.

Good’s Syndrome With Pure Red Cell Aplasia and Subclinical Myasthenia Gravis: A Case Report and Review of Literature

Good’s Syndrome With Pure Red Cell Aplasia and Subclinical Myasthenia Gravis: A Case Report and Review of Literature

Gilteritinib combined with venetoclax and azacitidine for relapsed acute myeloid leukemia cocurrent with pure red cell aplasia after allogeneic hematopoietic stem cell transplantation: a case report.

Pure red cell aplasia (PRCA) is a rare bone marrow (BM) disorder characterized by ineffective erythropoiesis, reduced reticulocyte count, normocytic anemia, and the absence of erythroid precursors. Here, we present a rare instance of PRCA occurring after ABO-matched allo-HSCT in a refractory/relapsed acute myeloid leukemia (R/R AML) patient. In this case, the patient received a combination treatment of Gilteritinib, Venetoclax, and Azacitidine. Remarkably, this treatment not only reduced myeloblasts but also facilitated the restoration of erythroid hematopoiesis.

Use of IV immunoglobulin to treat steroid resistant, immune checkpoint inhibitor induced pure red cell aplasia. A case report

Use of IV immunoglobulin to treat steroid resistant, immune checkpoint inhibitor induced pure red cell aplasia. A case report

Roxadustat and transfusional iron overload induced hypothyroidism in a hemodialysis patient: a case report with a literature review

BackgroundAlthough roxadustat has been reported to cause central hypothyroidism, the details of the mechanisms and clinical characteristics of patients who are prone to developing hypothyroidism with roxadustat are uncertain.Case presentationA 53-year-old man with a 3-year history of hemodialysis due to diabetic kidney disease who had been treated with roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, for 2 years was admitted to the hospital because of worsening gait disturbance and impaired consciousness. He had also acquired pure red cell aplasia associated with T-cell large granular lymphocytic leukemia and received multiple blood transfusions. Because his serum concentration of thyroid hormones was low, we diagnosed him with hypothyroidism, and his consciousness level recovered to normal with thyroid hormone replacement therapy. Computed tomography revealed a high-intensity atrophic thyroid gland, and magnetic resonance imaging showed diffusely reduced T2 and T1 signals of the pituitary anterior gland. These findings confirmed the accumulation of iron in the pituitary and thyroid glands. Combined pituitary stimulation tests with thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and corticotropin-releasing hormone revealed that the patient had pan-hypopituitarism. After discontinuation of roxadustat, the patient was treated with another hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat. One month after switching medication, a stimulation test with thyrotropin-releasing hormone showed normal responses to thyroid-stimulating hormone. The patient was treated with levothyroxine 50 μg daily without any significant symptoms and is currently under follow-up observation as an outpatient.ConclusionsWe encountered a dialysis patient with roxadustat-induced hypothyroidism associated with transfusion iron overload. To our knowledge, this is the first case to clearly show that roxadustat can impair thyroid-stimulating hormone secretion in repeated thyrotropin-releasing hormone stimulation tests. Because the present patient had received roxadustat for more than 2 years before hypothyroidism became apparent, regular monitoring of the thyroid function may be needed in patients with renal anemia who have been treated with roxadustat, especially those at high risk of thyroid dysfunction.

Positive response of a hemodialysis patient with pure red cell aplasia on recombinant human erythropoietin therapy to cyclosporine and Roxadustat.

Recombinant human erythropoietin (rHuEPO) is commonly used to treat anemia associated with chronic kidney disease (CKD). EPO-induced Pure Red Cell Aplasia (PRCA) is a rare condition of profound anemia with EPO treatment. Upon finding the development of EPO-induced PRCA, the treatment requires immediate withdrawal of EPO therapy and initiate new treatments with immunosuppression or renal transplantation. Anti-EPO antibody assay is not always positive in EPO-induced PRCA. Here, we report a case on the sudden development of PRCA in a hemodialysis patient receiving EPO and how we treated the condition successfully with cyclosporine and subsequently maintained the hemoglobin with Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). Even though the anti-EPO antibody was negative by Enzyme Linked Immunosorbent Assay (ELISA) in our case, the clinical course, the markedly reduced reticulocyte count < 10,000/μL, the bone marrow (BM) biopsy revealing reduced erythroblasts, and its subsequent response to cyclosporine, were similar to EPO-induced PRCA. The clinical picture of EPO-induced PRCA, the limitation of the EPO-neutralizing antibody (Ab) assay, and treatment strategies were discussed.

Successful Clozapine Rechallenge After Clozapine-Induced Severe Anemia: A Case Report.

Clozapine, a second-generation antipsychotic (SGA), is considered the gold standard medication to treat patients with treatment-resistant schizophrenia (TRS). Despite its efficacy, clozapine is associated with adverse effects, notably neutropenia and agranulocytosis. Other hematological adverse effects are less common. Severe anemia is a rare adverse effect seldom reported in the literature and is typically associated with pure red cell aplasia (PRCA). Nevertheless, the benefits of clozapine in managing TRS make rechallenge a reasonable option. We present the case of a 35-year-old man with TRS, resistant to previous antipsychotics, who experienced severe anemia during clozapine treatment. An investigation for clozapine-induced anemia revealed PRCA on myelogram. After discontinuing clozapine, the patient's hemoglobin levels recovered. Subsequent treatments with olanzapine, zuclopenthixol, and aripiprazole proved ineffective, leading us to consider a clozapine rechallenge. The rechallenge, monitored for 58 days, resulted in improved psychiatric symptoms and stable hemoglobin levels. The patient remained stable during 6 months of follow-up, with no hematological changes. PRCA is a very rare adverse effect of clozapine. The cause of drug-induced PRCA is still unknown; for clozapine, there are no studies. Rechallenge after a severe and rare adverse effect is a complex decision. This case is the first to report a successful clozapine rechallenge following severe anemia without other blood dyscrasias, emphasizing the imperative need for close monitoring during the rechallenge process. Further study is warranted to understand the predictive factors for a successful outcome in clozapine rechallenges.

Bidirectional ABO Mismatch Is Associated With Elevated Mortality in Hematopoietic Stem Cell Transplantation: Insights From a Single-Center Experience.

Background Hematopoietic stem cell transplantation (HSCT) is a promising therapy for various disorders and provides new opportunities for patients. ABO incompatibility in allogeneic HSCT (allo-HSCT) remains a topic of debate because of its potential impact on clinical outcomes. This study aimed to analyze the survival outcomes of patients who underwent ABO-incompatible HSCT and evaluate the occurrence of pure red cell aplasia. Methods This retrospective study included 20 patients who underwent ABO-incompatible HSCT. Data on patient characteristics, transplant details, and follow-ups were collected. Conditioning regimens and graft-versus-host disease (GVHD) prophylaxis strategies were employed. Results Neutrophil and platelet engraftment durations did not differ significantly between major and bidirectional mismatches. Pure red cell aplasia occurred in 4 patients (20%) with major mismatches, all of whom responded well to bortezomib treatment. Patients with a bidirectional mismatch exhibited a 3.57-fold increase (hazard ratio [HR]: 0.28; p<0.05) in the risk of mortality compared to those in the major mismatch group. Conclusion The results indicate that ABO mismatch, whether bidirectional or major, does not significantly affect neutrophil and platelet engraftment duration, suggesting that ABO incompatibility may not be a major factor influencing hematological recovery in allo-HSCT. Interestingly, patients with bidirectional mismatch exhibited a significantly higher mortality rate than those with major mismatch. This finding suggests that a bidirectional ABO mismatch may have an unfavorable prognosis in terms of overall survival in allo-HSCT patients.

Successful treatment pure red cell aplasia after ABO major mismatched allogeneic hematopoietic stem cell transplantation with avatrombopag and low dose rituximab.

Pure red cell aplasia (PRCA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with ABO major incompatibility is characterized by transfusion dependent anemia. No standard treatment existed for PRCA following allo-HSCT yet. We conducted a retrospective study, and reported our experience with the use of avatrombopag and lower dose rituximab to treat five patients with PRCA subsequent to major ABO-incompatible allo-HSCT. Five cases of PRCA were identified from 72 patients who underwent allo-HSCT with major or bidirectional ABO mismatch. Cumulative incidence at Day +60 was 6.9% (5/72) at our center. All donor and recipient blood groups were A+ and O+ , respectively. In the first three cases we reported, patients received erythropoietin, plasma exchange, and donor lymphocyte infusion, but none of them had any effect. After 4 weeks of treatment with low dose rituximab (100 mg/week) combined with avatrombopag (40 mg/day), favorable outcomes were obtained. According to the aforementioned experience, Cases 4 and 5 were administered low-dose rituximab and avatrombopag in 3 months after transplantation, and erythroid response was observed on 3 weeks after treatment. Our patients tolerated low-dose rituximab and avatrombopag well and experienced rapid efficacy, with a median duration of 3 weeks. Furthermore, no severe infection or thrombocytosis necessitated a dose adjustment. Low-dose rituximab and avatrombopag may be an effective treatment for patients with PRCA after major ABO-incompatible allo-HSCT. The patients should be treated at least 90 days post transplantation if conventional erythropoietin therapy fails.

Efficacy and safety of daratumumab in pure red cell aplasia after allogeneic transplantation: Dutch real-world data

Efficacy and safety of daratumumab in pure red cell aplasia after allogeneic transplantation: Dutch real-world data

A nomogram model for predicting the efficacy of cyclosporine in patients with pure red cell aplasia.

Pure red cell aplasia (PRCA) is a rare bone marrow disorder characterized by a severe reduction or absence of erythroid precursor cells, without affecting granulocytes and megakaryocytes. Immunosuppressive therapies, particularly cyclosporine, have demonstrated efficacy as a primary treatment. This study aims to develop a predictive model for assessing the efficacy of cyclosporine in acquired PRCA (aPRCA). This retrospective study encompasses newly treated aPRCA patients at the General Hospital of Tianjin Medical University. Diagnosis criteria include severe anemia, and absolute reticulocyte count below 10 × 109/L, with normal white blood cell and platelet counts, and a severe reduction in bone marrow erythroblasts. Cyclosporine therapy was administered, with dose adjustments based on blood concentration. Response to cyclosporine was evaluated according to established criteria. Statistical analysis involved logistic multi-factor regression, generating a predictive model. The study included 112 aPRCA patients with a median age of 63.5years. Patients presented with severe anemia (median Hb, 56g/L) and reduced reticulocyte levels. Eighty-six patients had no bone marrow nucleated erythroblasts. Primary PRCA accounted for 62 cases (55.4%), and secondary PRCA accounted for 50 cases (44.6%). Univariate analysis revealed that ferritin, platelet to lymphocyte ratio (PLR), and CD4/CD8 ratio influenced treatment response. Multivariate analysis further supported the predictive value of these factors. A prediction model was constructed using ferritin, PLR, and CD4/CD8 ratio, demonstrating high sensitivity and specificity. The ferritin, PLR, and CD4/CD8-based nomogram showed good predictive ability for aPRCA response to cyclosporine. This model has potential clinical value for individualized diagnosis and treatment of aPRCA patients.

Monoclonal Gammopathy of Anemic Significance? Resolution of Pure Red Cell Aplasia With Daratumumab-Based Therapy

Monoclonal Gammopathy of Anemic Significance? Resolution of Pure Red Cell Aplasia With Daratumumab-Based Therapy

Trends in Thymic Epithelial Tumor Patients with Comorbid Autoimmune Disease

Thymic epithelial tumors (TETs) are rare malignancies originating from the thymus in the anterior mediastinum. TETs include thymic carcinoma and thymoma. Approximately 30-40% of thymomas have associated autoimmune paraneoplastic disorders, the most common being myasthenia gravis. A broad range of other paraneoplastic syndromes have also been reported. Currently, little is known about demographic or histological trends in thymoma patients with comorbid autoimmune disease. In this single institution retrospective chart review, we assessed the distribution of thymoma-associated paraneoplastic syndromes at the IU Simon Cancer Center (IUSCC) to identify trends within demographic and histological features. We created a database of IUSCC patients seen from 2000-2023 and identified 170 subjects with biopsy-proven malignant TET and associated autoimmune disease. Data was exported to excel and R for analysis. Factors analyzed included: age at diagnosis, sex assigned at birth, BMI, WHO (World Health Organization) classification, and Masaoka staging. Overall survival was also compared to matched controls without paraneoplastic syndrome. A total of 37 different paraneoplastic syndromes were identified in association with thymoma in IUSCC patients. The most prevalent was Myasthenia Gravis (110 patients), followed by Hypothyroidism (21 patients, 5 confirmed as Hashimoto’s thyroiditis), Good Syndrome (19 patients), and Pure Red Cell Aplasia (15 patients). Significant findings included: 36.4% of patients with paraneoplastic comorbidity had &gt;1 paraneoplastic syndrome, 51.8% presented with Stage IV disease, and 40.4% had WHO Type B2 tumor pathology, with Type B3 being second most common (25%). No significant demographic associations were identified. 10-year survival of TET patients with paraneoplastic syndromes was not significantly different from those without (p= 0.721). These results indicate potential associations between thymoma staging and grading and development of paraneoplastic disease. Further analysis with a larger data set is warranted. Serum and blood test analysis may also elucidate reasons behind the development of paraneoplastic disease in thymoma patients. 

Thymic hyperplasia as a rare etiology of pure red cell aplasia: A case report

Introduction. Thymic hyperplasia is a rare condition caused by an increase in cellular thymic mass and, in some cases, is associated with autoimmune diseases, such as pure red cell aplasia (PRCA). Thymectomy is considered the most effective therapy for PRCA associated with thymoma, with a 31.5% complete remission rate. Other treatments may induce partial remissions, but complete remission re-mains elusive. A case of PRCA attributed to thymic hyperplasia is presented, highlighting the effectiveness of thymectomy. Case report. A previously healthy 18-year-old woman presented with severe anemia and after hematological evaluation, including bone marrow biopsy confirmation, a diagnosis of PRCA was made. Immunological and virological analyses were unremarkable. Given the history of thymoma in the family and the known association between thymoma and PRCA, a chest magnetic resonance imaging was performed, which proved the existence of thymic hyperplasia. The patient underwent the least invasive surgical procedure ? total thymectomy using video-assisted thoracic surgery approach. Pathohistological examination of the operative material confirmed the presence of thymic hyperplasia with a simple intrathymic cyst. Following thymectomy, the patient?s hematological values significantly improved. Conclusion. The course and outcome of the patient?s treatment support the role of thymectomy in PRCA associated with thymic hyperplasia. However, further re-search and follow-up are needed to optimize management strategies for this rare condition.

Pure Red Cell Aplasia Secondary to Parvovirus B19 Infection as a Rare Cause of Anemia in a Dialysis Patient: A Case Report.

Parvovirus B19 infection can cause chronic pure red cell aplasia in immunosuppressed hosts or acute and transient aplastic crises in immunocompetent hosts. In dialysis patients, only transient aplastic crisis induced by parvovirus B19 infection has been reported. We herein report the first case of an adult dialysis patient who developed chronic pure red cell aplasia associated with parvovirus B19 infection. Repeated pneumonia and heart failure may contribute to an immunocompromised status, making the patient more vulnerable to parvovirus B19 infection. This case expands on the differential diagnosis of chronic anemia in patients undergoing dialysis.

HLA-B*46:01:01:01 and HLA-DRB1*09:01:02:01 are associated with anti-rHuEPO-induced pure red cell aplasia

Treatment of anemia in patients with chronic kidney disease (CKD) with recombinant human erythropoietin (rHuEPO) can be disrupted by a severe complication, anti-rHuEPO-induced pure red cell aplasia (PRCA). Specific HLA genotypes may have played a role in the high incidence of PRCA in Thai patients (1.7/1,000 patient years vs. 0.03/10,000 patient years in Caucasians). We conducted a case–control study in 157 CKD patients with anti-rHuEPO-induced PRCA and 56 controls. The HLA typing was determined by sequencing using a highly accurate multiplex single-molecule, real-time, long-read sequencing platform. Four analytical models were deployed: Model 1 (additive: accounts for the number of alleles), Model 2 (dominant: accounts for only the presence or absence of alleles), Model 3 (adjusted additive with rHuEPO types) and Model 4 (adjusted dominant with rHuEPO types). HLA-B*46:01:01:01 and DRB1*09:01:02:01 were found to be independent risk markers for anti-rHuEPO-induced PRCA in all models [OR (95%CI), p-values for B*46:01:01:01: 4.58 (1.55–13.51), 0.006; 4.63 (1.56–13.75), 0.006; 5.72 (1.67–19.67), 0.006; and 5.81 (1.68–20.09), 0.005; for DRB1*09:01:02:01: 3.99 (1.28–12.49), 0.017, 4.50 (1.32–15.40), 0.016, 3.42 (1.09–10.74), 0.035, and 3.75 (1.08–13.07), 0.038, in Models 1–4, respectively. HLA-B*46:01:01:01 and DRB1*09:01:02:01 are susceptible alleles for anti-rHuEPO-induced PRCA. These findings support the role of HLA genotyping in helping to monitor patients receiving rHuEPO treatment.

[Clinical characteristics and prognosis of 21 patients with thymoma-associated pure red cell aplasia].

[Clinical characteristics and prognosis of 21 patients with thymoma-associated pure red cell aplasia].

AB007. A case of myasthenia gravis, pure red cell aplasia and thymoma, but not in the order you might expect

AB007. A case of myasthenia gravis, pure red cell aplasia and thymoma, but not in the order you might expect

Abstract B041: Understanding T-cell large granular lymphocytic leukemia: Diagnosis and treatment options

Abstract Introduction: T-cell large granular lymphocytic leukemia, or T-LGL leukemia, is rare cancer affecting T-cells and natural killer cells. It is characterized by the abnormal proliferation of mature T-cells expressing specific markers. Standard treatments involve immunosuppressive therapies. Understanding the diagnosis and treatment options is crucial for optimal care. Case Presentation: A 54-year-old male with chronic anemia and iron overload was initially diagnosed with myelodysplastic syndrome (MDS). Vidaza followed treatment with Danazol due to negative MDS and myeloproliferative neoplasm (MPN) results. Concerns of red cell aplasia led to corticosteroid and cyclosporin administration, discontinued during the COVID-19 outbreak. A subsequent biopsy revealed pure red cell aplasia, and the patient was prescribed Cyclosporin and later switched to Danazol. The patient underwent Anti-Thymocyte Globulin (ATG) treatment at a cancer center. A bone marrow biopsy confirmed T-LGL leukemia with abnormal CD8-positive T-cells. PCR analysis confirmed clonal T-cell proliferation. Cytogenetics and mutation analyses were negative. The patient is currently receiving Cyclosporin, prednisone, and Jadenu. Conclusion: This case highlights the challenges in diagnosing and managing T-LGL leukemia, a rare lymphoproliferative disorder. The patient's complex medical history and mimicking of other hematologic disorders underscore the need for a multidisciplinary approach. Individualized therapy based on clinical response is necessary due to limited treatment options. Further research and prospective trials are essential to establish a standard of care. Citation Format: Aliya M. Khan, Kierston R. Patterson, Raj Patel, Sophia Navajas Urisote. Understanding T-cell large granular lymphocytic leukemia: Diagnosis and treatment options [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B041.

Acquired pure red cell aplasia: unraveling the immune pathogenesis

Acquired pure red cell aplasia (aPRCA) is a rare hematological disorder characterized by normochromic, normocytic anemia, reticulocytopenia, and the absence of erythroblasts. The pathogenesis of aPRCA has remained elusive. This review delves into the intricate web of immune mechanisms underlying the development of this enigmatic condition. By exploring immune responses, cytotoxic effects, and antibody-mediated processes, we dissect the immune-driven assault on erythroid progenitors. The classification of aPRCA, including its primary and secondary forms, is elucidated, with a particular emphasis on etiological factors such as viruses, drugs, thymoma, and large granular lymphocytic leukemia. Furthermore, we discuss the implications of cytogenetic changes in erythroid progenitors and immune cells in the pathophysiology of aPRCA. This comprehensive overview aims to shed light on the complex interplay between immune dysregulation and erythroid failure in aPRCA, offering insights that will be crucial for better understanding and treating this disease.