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ABSTRACT 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. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO) is a pivotal hormone that regulates red blood cell production, predominantly synthesized by the kidneys and also produced by the liver. Since the introduction of recombinant human EPO (rh-EPO) in 1989 through recombinant DNA technology, the therapeutic landscape for anemia has been improved. rh-EPO's market expansion has been substantial, with its application extending across various conditions such as chronic kidney disease, cancer-related anemia, and other disorders. Despite its success, significant concerns remain regarding the stability of EPO, which is critical for preserving its biological activity and ensuring therapeutic efficacy under diverse environmental conditions. Instability issues, including degradation and loss of biological activity, challenge both drug development and treatment outcomes. Factors contributing to EPO instability include temperature fluctuations, light exposure, and interactions with other substances. To overcome these challenges, pharmaceutical research has focused on developing innovative strategies such as stabilizing agents, advanced formulation techniques, and optimized storage conditions. This review article explores the multifaceted aspects of EPO stability, examining the impact of instability on clinical efficacy and drug development. It also provides a comprehensive review of current stabilization strategies, including the use of excipients, lyophilization, and novel delivery systems. [ABSTRACT FROM AUTHOR]

The tumor suppressor p53 has well known roles in cancer development and germline cancer predisposition disorders, but increasing evidence supports the role of activation of this transcription factor in the pathogenesis of inherited bone marrow failure and chromosomal instability disorders. Here we report a patient with red cell aplasia, which was steroid responsive, as well as intellectual disability, seizures, microcephaly, short stature, cellular radiosensitivity, and normal telomere lengths, who had a germline heterozygous C‐terminal frameshift variant in TP53 similar to others that activate the transcription factor. This is the third reported individual with a germline p53 activation syndrome, with several unique features that refine the clinical disease associated with these variants. [ABSTRACT FROM AUTHOR]

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., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Anemia after solid organ transplantation is common and can be infectious or noninfectious. We present a case of recurrent PV infection in a patient of renal transplant. Early diagnosis and management of such infection is very important.

Background: Human parvovirus B19 (HPV-B19) is the etiologic agent of erythema infectiosum, of transient aplastic crises in individuals with underlying chronic hemolytic disorders, and of chronic pure red cell aplasia in immunocompromised individuals. Case report: We describe a 14-year-old girl with long-standing Evans syndrome, who presented with severe anemia, reticulocytopenia and thrombocytopenia. A bone marrow aspirate revealed severe erythroid hypoplasia along with the presence of giant pronormoblasts, while serological studies and real-time PCR of whole blood were positive for acute parvovirus B19 infection. The patient was initially managed with corticosteroids, but both cytopenias resolved only after administration of intravenous gamma globulin 0.8g/kg. Conclusion: Acute parvovirus B19 infection should be suspected in patients with immunologic diseases, who present reticulocytopenic hemolytic anemia and thrombocytopenia. In this setting, intravenous gamma globulin is effective for both cytopenias. [ABSTRACT FROM AUTHOR]

Although the symptoms of systemic lupus erythematosus (SLE) worsen during pregnancy, few previous studies have reported lupus enteritis in pregnant women with SLE. A 29-year-old pregnant Japanese woman presented with acute abdomen. Six years before pain onset, she developed pure red cell aplasia and tested positive for anti-Ro (SS-A) and anti-La (SS-B) antibodies. Anti-DNA antibodies were detected two and a half years later. The patient remained asymptomatic until she developed acute abdomen. A mild increase in anti-DNA antibody levels and a mild decrease in complement levels were observed, and abdominal ultrasound and magnetic resonance imaging revealed the presence of large-volume ascites and edematous thickening of the small intestinal wall. These findings established the diagnosis of lupus enteritis. Her condition improved after treatment with prednisolone 50 mg/day, and she delivered a female infant weighing approximately 1810 g at 37 weeks of gestation. Our study suggests that lupus enteritis should be suspected in female patients with autoimmune disease who develop acute abdomen during pregnancy, and that magnetic resonance imaging is useful in its diagnosis. [ABSTRACT FROM AUTHOR]

Anemia after solid organ transplantation is common and can be infectious or noninfectious. We present a case of recurrent PV infection in a patient of renal transplant. Early diagnosis and management of such infection is very important. [ABSTRACT FROM AUTHOR]

Persistent parvovirus B19 ( PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation ( HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patient's family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic. [ABSTRACT FROM AUTHOR]

Abstract: Myelodysplastic syndrome with erythroid hypoplasia or erythroblastopenia has not yet been clearly defined, and in most patients it is mistaken for acquired pure red cell aplasia. Including one additional patient reported in this article, a literature review revealed only 50 cases over the last 20 years. These patients were predominantly elderly males, all required regular packed red cell transfusions, and they had a poor prognosis, mainly because of acute transformation. The mechanisms of erythroid aplasia remain unclear. However, recent data suggest the association of an intrinsic stem cell defect with immunological implication. [ABSTRACT FROM AUTHOR]

The acquired form of pure red cell aplasia (PRCA) presents either as an acute self-limited disease, predominantly seen in children, or as a chronic illness more frequently seen in adults with rare spontaneous remissions. A 14-year-old boy presented with pallor, without hepatosplenomegaly, jaundice, lymphadenopathy, petechiae, or any other apparent abnormalities. Isolated anemia in the presence of normal white cell and platelet counts with a marrow of normal cellularity and absence of erythroblasts but normal myeloid cells and megakaryocytes revealed the diagnosis of PRCA. All possible investigations excluded secondary causes of PRCA. The patient required packed red cell transfusions every 2 to 3 weeks. He failed therapy with intravenous immunoglobulin, corticosteroids, cyclosporine A plus corticosteroids, antithymocyte globulin, anti-CD 20 (rituximab), and erythropoietin (EPO). He showed a severe, resistant, and transfusion-dependent PRCA. Spontaneous remission with normal hemoglobin and reticulocyte levels was dramatic 6.5 years after the diagnosis of PRCA and 3.6 years after his last treatment. [ABSTRACT FROM AUTHOR]

Diamond Blackfan anaemia (DBA) is a severe congenital failure of erythropoiesis. Despite mutations in one of several ribosome protein genes, including RPS19, the cause of the erythroid specificity is still a mystery. We hypothesized that, because the chromatin of late erythroid cells becomes condensed and transcriptionally inactive prior to enucleation, the rapidly proliferating immature cells require very high ribosome synthetic rates. RNA biogenesis was measured in primary mouse fetal liver erythroid progenitor cells; during the first 24 h, cell number increased three to fourfold while, remarkably, RNA content increased sixfold, suggesting an accumulation of an excess of ribosomes during early erythropoiesis. Retrovirus infected siRNA RPS19 knockdown cells showed reduced proliferation but normal differentiation, and cell cycle analysis showed a G1/S phase delay. p53 protein was increased in the knockdown cells, and the mRNA level for p21, a transcriptional target of p53, was increased. Furthermore, we show that RPS19 knockdown decreased MYB protein, and Kit mRNA was reduced, as was the amount of cell surface KIT protein. Thus, in this small hairpin RNA murine model of DBA, RPS19 insufficient erythroid cells may proliferate poorly because of p53-mediated cell cycle arrest, and also because of decreased expression of the key erythroid signalling protein KIT. [ABSTRACT FROM AUTHOR]

Diamond-Blackfan anaemia: understanding an old disease Keywords: Diamond-Blackfan anaemia; bone marrow failure syndrome; red cell aplasia EN Diamond-Blackfan anaemia bone marrow failure syndrome red cell aplasia 14 15 2 07/01/20 20200701 NES 200701 Diamond-Blackfan anaemia (DBA [MIM: 105650]), is an inherited bone marrow failure syndrome, originally referred as red cell aplasia by Josephs in 1936 and as congenital hypoplastic anaemia by Diamond and Blackfan in 1938. Diamond-Blackfan anaemia, bone marrow failure syndrome, red cell aplasia. [Extracted from the article]

Cites the publication by the Japanese Society for Dialysis Therapy guideline committee of the "Guidelines for Renal Anemia in Chronic Hemodialysis Patients" manual. Offer of the definition and diagnosis of anemia; Evaluation of the usage of recombinant human erythropoietin; Argument on the prognosis and quality of life of Japanese hemodialysis patients; Description of the target hemoglobin level in hemodialysis patients; Discussion of the markers of iron deficiency.

We describe 21 patients with severe and life-threatening autoimmune cytopenias resistant to standard immunosuppression who were treated with the monoclonal antibody Campath-1H. Four patients had autoimmune neutropenia, four had autoimmune haemolytic anaemia, four had pure red cell aplasia, one had immune thrombocytopenia purpura (ITP), three had autoimmune haemolytic anaemia and ITP (Evan's syndrome), three had autoimmune pancytopenia (ITP, autoimmune neutropenia and autoimmune haemolytic anaemia), one had ITP (associated with acquired Glanzmann's disease) and autoimmune neutropenia, and one had ITP and red cell aplasia. Campath-1H was administered at a dose of 10 mg/d as an intravenous infusion for 10 d. Responses were seen in 15 patients, which were sustained in six. Relapse occurred in eight patients after Campath-1H treatment. Patients entering the study later, received cyclosporine after Campath-1H in an attempt to reduce the incidence of relapse. Three patients received a second course of Campath-1H; all responded but later relapsed. Fourteen patients are alive at a median of 12 months (range 4–61) after Campath-1H. Campath-1H represents an alternative therapeutic option for severe, refractory autoimmune cytopenias. [ABSTRACT FROM AUTHOR]

Background: The autoimmune cytopenias encompass the disorders of immune thrombocytopenia purpura (ITP), pure red-cell aplasia (PRCA), autoimmune hemolytic anemia (AIHA), autoimmune neutropenia and various combinations of these conditions. T lymphocytes are thought to play an important role in the pathogenesis of autoimmune cytopenias, and the presence of autoantibody may represent an epiphenomenon, rather than the primary pathogenetic mechanism. The majority of patients usually respond to standard immunosuppressive therapy and can mostly be treated as out-patients. A small proportion, however, have severe, resistant and life-threatening disease, or may experience major morbidity from side effects of drugs given to treat their disease. Methods: We have treated 21 patients with autoimmune cytopenias with the MAb Campath-1H, and for later patients in this series, in combination with low dose CYA. Results: Responses were seen in 14 of 20 evaluable patients, although relapse occurred in seven patients. In many patients corticosteroid therapy could be discontinued or greatly reduced. Discussion: We conclude that Campath-1H can induce remissions in autoimmune cytopenias and we critically review its role in the treatment of these disorders. [ABSTRACT FROM AUTHOR]

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of abnormal lymphocyte apoptosis, leading to chronic lymphoproliferation. It presents as lymphadenopathy, hepatosplenomegaly and autoimmune phenomena. Pure red cell aplasia is characterized by normochromic normocytic anemia, reticulocytopenia, and absence of erythroblasts from a normal bone marrow. Only few lymphoproliferative disorders have been associated with erythroid aplasia. The authors are reporting a case of ALPS associated with red cell aplasia in a 7-y-old girl. [ABSTRACT FROM AUTHOR]

We report on the presentation and outcome of a 28-year-old female who developed red cell aplasia following alemtuzumab therapy for relapsing remitting multiple sclerosis. The patient also developed synchronous immune thrombocytopenia and immune neutropenia, but not aplastic anemia. This patient received high dose steroids, intravenous immunoglobulin (iv.Ig), rituximab, red cell transfusions, vincristine, G-CSF, cyclosporin and mycophenolate to treat the combination of cytopenias over a period of 6 months with subsequent improvement in bone marrow function. While alemtuzumab has several recognized autoimmune complications, little is known about the potential hematological side effects. The combination of red cell aplasia, immune thrombocytic purpura and autoimmune neutropenia has not previously been described in the literature following alemtuzumab immunotherapy and highlights the importance of monthly blood monitoring post alemtuzumab administration.

B19 parvovirus is an important pathogen in man. Acute infection produces fifth disease (erythema infectiosum) in normal individuals, transient aplastic crisis in the patient with haemolysis, and pure red cell aplasia in the immunologically incompetent host. Fetal infection can lead to hydrops fetalis. The target cell of the virus is the marrow erythroid progenitor. The immune response to the virus is largely humoral and directed against limited numbers of epitopes. Persistent infection is due to failure to produce neutralizing antibodies. Because viral infection is prevalent in the population, therapeutic immune globulin preparations are a good source of anti-B 19 antibodies. IgG administration can lead to cure of anaemia in the congenitally immunodeficient patient and to its amelioration in AIDS patients with persistent parvovirus infection. [ABSTRACT FROM AUTHOR]