Red Cell Aplasia Research Articles

A whistleblower direct antiglobulin test in chronic kidney disease: An interesting case of occult autoimmune hemolytic anemia in an undiagnosed lymphoma with pure red cell aplasia

Abstract A 67-year-old male, presented with urosepsis, severe anemia, advancing azotemia requiring blood transfusion. Patient grouped as O RhD positive. Antibody screening was pan-positive (4+). Similar strong pan-positivity seen on antibody identification with extended cell panel. DAT was 4+ positive for IgG and negative for complement C3. Repeated identification with eluate also showed pan-positive (4+) reaction. Serum haptoglobin markedly reduced. Bone marrow aspirate suggested pure red cell aplasia with suspicion of parvovirus-related changes. Bone marrow biopsy suggested T-cell lymphoproliferative disorder. Immunophenotyping elucidated a suspicious clone of CD7-negative T-cells with CD4 restriction. Histopathological examination revealed angioimmunoblastic T-cell lymphoma (AITL) with bystander Epstein–Barr virus-driven large B-cells. Owing to rarity and nonspecific symptoms, diagnosis of AITL is often challenging. Antibody screen acted as a whistleblower for an undiagnosed aggressive lymphoma. Thus, it will be prudent to look beyond the obvious in complex cases, and a detailed workup will help put together all parts of the jigsaw puzzle.

Toxoplasmosis in a 9‐month‐old Persian cat treated with prednisolone and ciclosporin for an idiopathic pure red cell aplasia

AbstractA 9‐month‐old Persian cat was presented with an acute onset of lethargy and decreased appetite. Investigations identified presence of a severe non‐regenerative anaemia. Bone marrow cytology and histopathology were consistent with a pure red cell aplasia. Prednisolone and ciclosporin were initiated, but the cat presented with an acute onset of dyspnoea 2 months after diagnosis despite good control of the haematocrit. Respiratory work‐up including a bronchoalveolar lavage identified a pulmonary toxoplasmosis. The cat underwent a cardiopulmonary arrest shortly after diagnosis. We describe the good response of a cat diagnosed with pure red cell aplasia to prednisolone and ciclosporin. Unfortunately, the cat was diagnosed with toxoplasmosis 2 months after diagnosis despite being indoor and being fed a commercial diet. Toxoplasma gondii IgG serology test was negative, suggesting acute infection. This case emphasises the importance of close monitoring of cats undergoing ciclosporin therapy and risk of acquired infection in immunosuppressed feline patients.

Successful Management of Post-Thymectomy Pure Red Cell Aplasia with Rituximab: A Case Report

Background: Pure red cell aplasia (PRCA) is a rare cause of anemia characterized by decreased red blood cell production, often associated with thymomas. While thymectomy is commonly performed to treat thymoma-associated PRCA, the development of PRCA post-thymectomy is less understood. Case Presentation: We present a case of a 25-year-old woman who developed PRCA and autoimmune diabetes mellitus (DM) following radical thymectomy for malignant thymoma. Initial treatment with prednisolone showed minimal improvement, leading to the inclusion of rituximab. This combination resulted in a significant increase in reticulocyte counts and transfusion independence. Discussion: This case highlights the potential for PRCA to develop after thymectomy and the challenges of treating PRCA in the context of additional conditions like autoimmune DM. While immunosuppressive therapies such as cyclosporin A and corticosteroids are standard, their side effects necessitated exploring alternative treatments. Rituximab proved effective and was well-tolerated, suggesting its potential as a primary option in similar cases. Conclusion: This case illustrates the occurrence of PRCA after thymectomy and highlights rituximab’s effectiveness as a treatment option, offering a viable alternative to standard therapies in managing this complex condition.

Major ABO Incompatibility in Non-Myeloablative Hematopoietic Stem Cell Transplant for Sickle Cell Disease-Not an Insurmountable Obstacle.

With advances in conditioning strategies and graft-versus-host disease (GvHD) prevention, hematopoietic stem cell transplantation (HSCT) is a safe, curative treatment option for pediatric patients with sickle cell disease (SCD). However, donor options have been limited in non-myeloablative matched sibling donor (MSD) setting by excluding recipients with major ABO blood group incompatible donors due to concern of the risk of significant complications such as pure red cell aplasia (PRCA). We present three cases of successful HSCT with major ABO incompatibility with their donors, and discuss strategies to safely expand the donor pool to include these donors.

Corticosteroid and immunosuppressive treatment are effective for acquired pure red cell aplasia in chronic kidney disease: a case report and literature review

Corticosteroid and immunosuppressive treatment are effective for acquired pure red cell aplasia in chronic kidney disease: a case report and literature review

Diagnosis of Diamond-Blackfan anemia in adulthood: case series and review of the literature

Diamond–Blackfan anemia (DBA) is a rare constitutional inherited bone marrow failure syndrome (iBMF) characterized by progressive severe non-regenerative anemia and congenital abnormalities. Diagnosis is made by identification of a DBA-causing variant, typically in a ribosomal protein gene. More than 99% of patients are diagnosed in the pediatric age, but clinical manifestation may be mild and severe anemia can occur later in the patient’s life. Moreover, the expanding availability of molecular testing is increasing the ability to identify DBA variants also in adults with a non-canonical DBA phenotype. Therefore, adult hematologists must maintain a high clinical suspicion and awareness towards possible DBA diagnosis in adulthood. In this context, the most common differential diagnoses are acquired BMFs such as pure red cell aplasia (PRCA) or hypoplastic myelodysplastic syndrome (MDS). Here, we present three adult patients diagnosed with DBA, where the identification of the causative mutation occurred several years from PRCA misdiagnosis or was made after screening for an affected relative. We also provide a review of 16 cases available in the literature and give hints on possible treatment strategies.

Concurrent inhibited erythropoiesis in a case of VEXAS syndrome.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a rare disease described by Beck et al. in 2020. Here we report a case of VEXAS syndrome with progressive worsening of pancytopenia. This patient demonstrated inhibited erythropoiesis along with normal granulopoiesis and megakaryopoiesis in the bone marrow. A diagnosis of myelodysplastic syndrome (MDS) was ruled out, while the patient presented with pure red cell aplasia (PRCA), a manifestation not previously described in the context of VEXAS syndrome. Therefore, VEXAS syndrome may also present with PRCA-like erythroid hypoplasia, which may aid in the better recognition of this disease.

Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes

The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. A multiple myeloma patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses reveal lenalidomide as a pivotal disruptor of erythropoiesis. Single-cell transcriptome analysis unveils hyperactive CD8+ T cells and impaired erythropoiesis in the patient’s bone marrow. Unexpectedly, the patient’s erythroid cells display abnormally high expression of genes in the antigen presentation pathway, particularly those for major histocompatibility class I (MHC-I) molecules. Functional assays demonstrate that lenalidomide treatment further augmented MHC-I expression in the patient’s erythroid cells. Blocking MHC-I or depleting T cells alleviates the defective erythropoiesis of PRCA, suggesting that the interaction between erythroid cells with elevated MHC-I and T cells in the bone marrow might contribute to PRCA. Taken together, our study implicates a mechanism underlying lenalidomide-induced PRCA in treating cancer patients.

The role of daratumumab in complications post-allogeneic hematopoietic stem cell transplantation: a single-center prospective study on PRCA and AIHA.

Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) post-hematopoietic stem cell transplantation (HSCT) are an unmet medical need with no established standard of care, significantly affecting the patient quality of life and posing a challenge for clinicians. The anti-CD38 IgG-kappa Daratumumab appears to be a safe and efficace treatment compared to prior drugs. Our study is a prospective monocentric investigation assessing the use of daratumumab in these complications following allo-HSCT. Here we describe our experience on six patients with a median age of 65 years. All treated patients, except one, who died because of sepsis during GVHD exacerbation, reached transfusion independence with erythropoietin suspension. Poor graft function remains a management challenge for clinicians and has a significant impact on the patient's quality of life. Currently, therapeutic options for PRCA and for the least common AIHA, appear ineffective, making it difficult to address the diverse needs of post-transplant patients. Although our data and those previously reported in the literature are preliminary, daratumumab prompts further reflection on its use in this setting of patients.

Surgical treatment of thymic epithelial tumor and myasthenia gravis.

Thymic epithelial tumors originate from the epithelial cells of the thymus and are typically diagnosed during the 5th and 6th decades of life. The incidence is consistent between men and women, averaging 1.7 cases per year. Thymomas, neuroendocrine tumors, and thymic carcinomas are subtypes of thymic epithelial tumors, with thymomas being the most prevalent (75%-80%) and thymic carcinomas following at 15%-20%. Thymoma and thymic carcinoma exhibit distinct disease courses; thymomas grow slowly and are confined to the thymus, while thymic carcinomas demonstrate rapid growth and metastasis. Overall survival rates vary, with a 78% 5-year survival rate for thymoma and a 30% rate for thymic carcinoma. Thymic epithelial tumors may be linked to paraneoplastic autoimmune diseases, including myasthenia gravis, hypogammaglobulinemia, pure red cell aplasia, Cushing's syndrome, systemic lupus erythematosus, and polymyositis. Staging of thymic epithelial tumors can be done according to Masaoka-Koga and/or TNM 8th staging systems. The treatment algorithm is primarily determined by resectability, with surgery (Extended Thymectomy) serving as the foundational treatment for early-stage patients (TNM stage I-IIIA, Masaoka-Koga stage I-III). Adjuvant radiotherapy or chemotherapy may be considered following surgery. In advanced or metastatic cases, chemotherapy is the first-line treatment, followed by surgery and radiotherapy for local control. Myasthenia gravis, an autoimmune disease presents with progressive muscle fatigue and diplopia. Positive antibodies (Anti-AChR, Anti-MuSK, LRP4) and electromyography aid in diagnosis, and approximately 10% of myasthenia gravis patients can also have thymoma. Treatment includes cholinesterase inhibitors and immunotherapy agents, with extended thymectomy serving as an effective surgical option for drug-resistant cases. Minimally invasive approaches (video-assisted thoracoscopic surgery or robot-assisted thoracoscopic surgery) have demonstrated comparable oncological outcomes to sternotomy, highlighting their effectiveness and reliability.

Sirolimus Plus Roxadustat in Patients with Pure Red Cell Aplasia: Results from a Prospective Multi-Center Clinical Trial

Sirolimus Plus Roxadustat in Patients with Pure Red Cell Aplasia: Results from a Prospective Multi-Center Clinical Trial

Pure Red Cell Aplasia after ABO Incompatible Hematopoietic Stem Cell Transplantation Successfully Treated with Daratumumab: A Case Report

Pure Red Cell Aplasia after ABO Incompatible Hematopoietic Stem Cell Transplantation Successfully Treated with Daratumumab: A Case Report

Desidustat Is Effective in Treating Pure Red Cell Aplasia Due to Recombinant Human Erythropoietin in Patients with Chronic Kidney Disease

Desidustat Is Effective in Treating Pure Red Cell Aplasia Due to Recombinant Human Erythropoietin in Patients with Chronic Kidney Disease

Daratumumab in the Management of Red Cell Aplasia Following Allogeneic Hematopoietic Stem Cell Transplantation.

Pure red cell aplasia (PRCA) is a rare but significant complication following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (HSCT). The persistence of recipient B lymphocytes producing anti-donor isohemagglutinins leads to reticulocytopenia and anemia, often resulting in transfusion dependence. Current treatment options for post-HSCT PRCA are limited and frequently yield suboptimal responses, complicating patient management. Herein, we report three cases of post-HSCT PRCA successfully managed with daratumumab, a monoclonal antibody targeting CD38-expressing plasma cells. All patients demonstrated rapid reticulocyte recovery and transfusion independence after daratumumab treatment, despite prior treatment failures. These findings suggest that daratumumab may provide a more effective therapeutic approach, with a favorable safety profile compared to traditional therapies. Given its demonstrated efficacy and safety, daratumumab warrants consideration as a first-line treatment for post-HSCT PRCA, potentially improving patient quality of life and reducing transfusion-related complications. Further studies should explore optimal dosing and long-term outcomes.

Roxadustat combined with immunosuppressants for treatment of pure red cell aplasia with kidney injury.

Pure red cell aplasia is a rare condition that may be congenital or associated with an underlying disease.Immunosuppressants are a commonly employed therapeutic option for the treatment of pure red cell aplasia;however, they are associated with considerable adverse effects, including nephrotoxicity. This case report describesa 74-year-old patient with pure red cell aplasia who developed long-term kidney injury following cyclosporinetherapy. Renal anemia is a common complication after chronic kidney injury and contributes to the poor outcome ofanemia treatment. Following a series of medication adjustments, the final treatment with roxarestat combined withsirolimus proved effective in delaying the impairment of this patient's kidney function, with the hemoglobin levelremaining above 100 g/L throughout. This case report demonstrates the efficacy of roxarestat in conjunction with animmunosuppressive agent in the treatment of pure red cell aplasia combined with kidney injury, with a dual effect ofalleviating the anemia and reducing serum creatinine levels.

RPS19 and RPL5, the most commonly mutated genes in Diamond Blackfan anemia, impact DNA double-strand break repair.

Diamond Blackfan anemia (DBA) is caused by germline heterozygous loss-of-function pathogenic variants (PVs) in ribosomal protein (RP) genes, most commonly RPS19 and RPL5 . In addition to red cell aplasia, individuals with DBA are at increased risk of various cancers. Importantly, the mechanism(s) underlying cancer predisposition are poorly understood. We found that DBA patient-derived lymphoblastoid cells had persistent γ-H2AX foci following ionizing radiation (IR) treatment, suggesting DNA double-strand break (DSB) repair defects. RPS19- and RPL5-knocked down (KD) CD34+ cells had delayed repair of IR-induced DSBs, further implicating these RPs in DSB repair. Assessing the impact of RPS19- and RPL5-KD on specific DSB repair pathways, we found RPS19-KD decreased the efficiency of pathways requiring extensive end-resection, whereas RPL5-KD increased end-joining pathways. Additionally, RAD51 was reduced in RPS19- and RPL5-KD and RPS19- and RPL5-mutated DBA cells, whereas RPS19-deficient cells also had a reduction in PARP1 and BRCA2 proteins. RPS19-KD cells had an increase in nuclear RPA2 and a decrease in nuclear RAD51 foci post-IR, reflective of alterations in early, critical steps of homologous recombination. Notably, RPS19 and RPL5 interacted with poly(ADP)-ribose chains noncovalently, were recruited to DSBs in a poly(ADP)-ribose polymerase activity-dependent manner, and interacted with Ku70 and histone H2A. RPL5's recruitment, but not RPS19's, also required p53, suggesting that RPS19 and RPL5 directly participate in DSB repair via different pathways. We propose that defective DSB repair arising from haploinsufficiency of these RPs may underline the cancer predisposition in DBA.

Anti‐donor antibody neutralization by donor type red cell challenge: A novel therapeutic strategy in refractory post‐transplant pure red cell aplasia

Anti‐donor antibody neutralization by donor type red cell challenge: A novel therapeutic strategy in refractory post‐transplant pure red cell aplasia

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

The Role of Daratumumab in Treating Pure Red Cell Aplasia After Allogeneic Transplant in Patients With ABO Incompatibility: A Systematic Review

The Role of Daratumumab in Treating Pure Red Cell Aplasia After Allogeneic Transplant in Patients With ABO Incompatibility: A Systematic Review

AML-214 The Role of Daratumumab in Treating Pure Red Cell Aplasia After Allogeneic Transplant in Patients With ABO Incompatibility: A Systematic Review

AML-214 The Role of Daratumumab in Treating Pure Red Cell Aplasia After Allogeneic Transplant in Patients With ABO Incompatibility: A Systematic Review