Primary Pure Red Cell Aplasia Research Articles

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.

Exploration of B and T Cell Receptor Repertoires Reveals Distinct Mechanisms in Pure Red Cell Aplasia, Autoimmune Hemolytic Anemia, and Aplastic Anemia

Background: Pure red cell aplasia (PRCA), autoimmune hemolytic anemia (AIHA) and aplastic anemia (AA) are immune-mediated diseases that mainly attack erythrocyte or erythroid progenitor cells. This study aimed to investigate changes related to autoimmunity in the B cell receptor (BCR) and T cell receptor (TCR) repertoires in these diseases. Methods: Patients with newly diagnosed primary PRCA, AIHA, and AA and healthy individuals with matched age and sex (normal controls, NC) were recruited. Peripheral blood was collected, and BCR and TCR repertoires were sequenced by next-generation immunosequencing. The diversity and clonal expansion of the repertoires, gene and gene combination usage, somatic hypermutation (SHM) of BCR, and the sequence length, hydrophobicity, motifs of the most diverse epitope encoded (complementary-determining region 3, CDR3), T cell clustering, and BCR light chain and TCRα chain were analyzed. Results: 10 PRCA, 10 AIHA, 10 AA, and 7 NC were finally enrolled. For the broad repertoire metrics analysis, only the TCR repertoire of the AA group was more diverse compared with NC (p＜0.05). For BCR and TCR repertoires, PRCA, AIHA, and AA showed uniform characteristics in gene usage. The preferential gene usage of PRCA immunoglobulin heavy (IGH) chains such as IGHV3-23, IGHV3-74 were correlated with memory cells and red blood cell antigen recognition; the higher usage of IGHV4-31 in the AIHA group was associated with secretion of auto-antibodies; whereas AA patients had more gene usage of neutralizing antibodies (p＜0.05). In the gene usage in T cell receptor β (TRB) chains, PRCA patients had skewed usage of genes associated with T cell dysregulation and hyperinflammation such as TRBV1 and TRBV11-2; the increased gene usage in AIHA and AA were also found in other autoimmune diseases, which correlated with abnormal antigen recognition. PRCA and AA also had specific TRBV-J gene combination usage. Only PRCA had higher BCR SHM compared with NC (p＜0.05). The length of CDR3 was similar but the hydrophobicity was different among different disease groups. 12, 28, and 22 motifs were found respectively in BCR of PRCA, AIHA, and AA; and 13, 6, and 6 motifs were found in TCR. Compared with NC, PRCA, AIHA, and AA showed a considerable lack of physiology T cell clusters, and 147, 98, and 141 disease-specific T cell clusters in each disease was found, respectively. For light chain of BCR, PRCA and AIHA had the tendency of more usage of κ chains, whereas AA had more usage of λ chains. For TCRα chains, the three diseases used more genes related to hypersensitivity reactions (p＜0.05). Conclusion: PRCA, AIHA, and AA had different BCR and TCR repertoire characteristics in gene and gene combination usage, hydrophobicity and motifs of CDR3, and T cell clustering, which might contribute to autoimmune antigen recognition. The abnormalities were mainly T cell-related for PRCA, B cell-related for AIHA and both for AA. Keywords: pure red cell aplasia; autoimmune hemolytic anemia; aplastic anemia; BCR; TCR

Clinical characteristics and outcomes of 100 adult patients with pure red cell aplasia

Adult pure red cell aplasia (PRCA) is a rare syndrome characterized by a severe normocytic anemia, reticulocytopenia, and absence of erythroblasts from bone marrow. The standard treatment has not yet been established for PRCA, although cyclosporine (CsA), corticosteroids (CS) showed a response in PRCA. We retrospectively analyzed the clinical data of 60 primary and 40 secondary adult patients with acquired PRCA. The proportion of secondary PRCA is relatively high and commonly associated with large granular lymphocyte leukemia (LGLL) (28 cases, 70.0%). The remission-induced regimens included CS, CsA, or other agents, and the response rate was 66.7%, 71.4%, and 50%, respectively (P = 0.336). When treating with CsA, the response rate of LGLL-associated PRCA was lower than primary PRCA (42.1% vs 85.7%, P = 0.001). Logistic regression analysis showed that ORR was inversely related to LGLL-associated PRCA. LGLL-associated PRCA had poor therapeutic efficacy to CsA.

Recurrent STAT3 Mutations in the Lymphocytes of Pure Red Cell Aplasia without T-Cell Large Granular Lymphocytic Leukemia

▪Background: Activating somatic mutations of STAT3 are one of the most frequently recognized genetic alterations in T-cell lymphoma including T-cell large granular lymphocytic leukemia (T-LGLL). T-LGLL is associated with certain proportions of patients (pts) with acquired aplastic anemia (AA) and/or myelodysplastic syndromes (MDS). Pure red cell aplasia (PRCA), especially acquired PRCA, is a syndrome defined by an anemia with marked reduction or absence of erythroid production associated with immunological mechanisms. PRCA is classified into primary and secondary types including T-LGLL. Previous reports have described that T-LGLL with STAT3 mutations was closely associated with PRCA. However, it is yet to be clear whether STAT3-mutated T cells would be involved in the pathogenesis of other cytopenias, such as AA, MDS, primary PRCA or secondary PRCA without (w/o) T-LGLL. In this study, we analyzed the profiles of STAT3 gene mutations in bone marrow failure syndrome (BMFS)s including AA/MDS and PRCA.Methods: Peripheral blood samples were collected from 94 patients with BMFSs, including AA, MDS, AA/PNH, and PRCA with or w/o T-LGLL. When possible, T-cell receptor (TCR) Vβ repertoire of the patients was determined by flow cytometry. DNA was extracted from mononuclear cells (MNC), and STAT3 Y640F and D661Y, two hot spot mutations, were detected with sensitive allele specific-PCR (AsPCR) methods. Then we performed deep amplicon sequencing analysis of STAT3 in PRCA pts. CD8+ T cells were sorted if possible, and also subjected to the analyses.Results: The recruited pts included 38 AA, 20 MDS, 7 AA/PNH, 11 PRCA with T-LGLL, and 18 PRCA w/o T-LGLL. Among PRCA pts w/o apparent T-LGLL, 10 had primary PRCA and 8 had secondary PRCA including 2 with thymoma. The clinical characteristics of PRCA are shown in Table 1. TCR Vβ repertoire analysis were performed in 8 PRCA w/o T-LGLL and 5 PRCA with T-LGLL. All pts with PRCA associated with T-LGLL showed restricted Vβ repertoire. On the other hand, only 1pt showed monoclonal Vβ pattern in PRCA w/o TLGLL. AsPCR did not detect Y604F or D661Y mutations in any of 65 pts with AA, MDS, or AA/PNH. In contrast, 2 pts with PRCA and 4 pts with PRCA-T-LGLL were positive for either of the mutations, suggesting STAT3 mutations may be unique to PRCA pts. Further analysis with deep amplicon analysis in the 29 PRCA pts revealed STAT3 mutations in 11 pts (61%) of PRCA w/o T-LGLL, which included 6 pts with primary PRCA and 5 pts with secondary PRCA associated with autoimmune diseases (n=2), 2 thymoma (n=2) and thymic cancer (n=1). The median variant allele frequency of STAT3 mutations was 2.3% (0.2-48.9). N538Y and I653V were most frequent mutations in PRCA w/o T-LGLL. Eight pts (73%) with T-LGLL-associated PRCA were also positive for STAT3 mutation. Thirty-nine % and 70% of STAT3 mutation were found in SH2 domain in PRCA w/o T-LGLL and PRCA with T-LGL, respectively. There was no difference in clinical features between pts with and w/o STAT3 mutations.Discussion: The high frequency of STAT3 mutations in PRCA pts regardless of etiology and the absence of the mutation in pts with AA/MDS suggest that STAT3 mutations may serve as a molecular marker of PRCA. The discordant results with regard to AA/MDS pts from a previous report which detected STAT3 mutations in 4.9% of AA/MDS patients by AsPCR methods (Jerez et al. BLOOD 2013) may be due to the difference in ethnic backgrounds of the pts studied. Given very low frequencies of STAT3 mutations in AA and MDS that were revealed by several previous studies, JAK/STAT signaling systems in the axis of STAT3 mutations may have unique roles in the pathogenesis of PRCA.Conclusion: STAT3 mutations are frequently detected in pts with PRCA even in pts w/o T-LGLL and the JAK/STAT pathway may therefore be therapeutic targets of PRCA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Immunosuppression therapy is effective for both acquired tumor-associated and primary pure red cell aplasia: a match pair case-control study.

No agreement had been reached on the treatment of patients with pure red cell aplasia (PRCA) secondary to indolent malignancies. Data was collected from patients with acquired PRCA from May, 2014 to May, 2018 in Peking Union Medical College Hospital. Tumor-associated PRCA and primary PRCA patients were matched at a ratio of 1:2 with compatible baseline characteristics. All patients had been treated with CsA or sirolimus for at least 6 months with the efficacy and adverse events recorded. Twelve tumor-associated PRCA patients (3 thymoma, 8 lymphoproliferative disorders, and 1 smoldering multiple myeloma) with stable underling disease and 24 acquired primary PRCA patients were selected. 83.3% tumor-associated PRCA patients and 100% primary PRCA patients (P = 0.436) responded to immunosuppression therapy (IST) at a median of 2.5 and 3.5 months (P = 0.137), respectively. No different was found in side effects. The ORR at the end of a median of 21.5-month follow-up was 75% and 70.8% (P = 0.795), respectively. No tumor progression was reported except one secondary patient had lymphoma relapse after 2 years of IST and was given chemotherapy again. These results suggested IST had similar effect, safety on patients with tumor-associated, and primary PRCA patients when the tumors were stable.

Etiologies and Treatment Burden in Adult Patients with Pure Red Cell Aplasia: A Single-Center Experience and Review of Literature.

Background Pure red cell aplasia (PRCA) is less common blood disorder; the causes and the treatments of PRCA are varied. Methods We conducted a retrospective study during January 2010–December 2017, to explore the etiologies and to evaluate the response and treatment burden in adult patients with PRCA. Results Of 32 PRCA patients, median age was 57 years (18–90 years). Median hemoglobin level and reticulocyte count at the time of diagnosis were 5.6 g/dL (3.3–7.3 g/dL) and 0.3% (0.1–0.7%), respectively. Median time to hematologic recovery was 12 weeks (3–72 weeks), and median number of red blood cell transfusion (RBC) was 20 units (4–100 units). Causes of PRCA were erythropoiesis-stimulating agent (ESA) (47%), parvovirus B19 infection (19%), thymoma (13%), zidovudine (6%), primary autoimmune PRCA (6%), Kaposi's sarcoma (3%), systemic lupus erythematosus (3%), and ABO-mismatched stem cell transplantation (3%). Only 9 out of 24 treated patients achieved hematologic response within 8 weeks of treatment. Intravenous immunoglobulin therapy provided 100% response rate in patients with parvovirus B19-associated PRCA and primary autoimmune PRCA. Low response rate was found in patients receiving immunosuppressants and chemotherapy for the treatment of ESA and thymoma-associated PRCA, respectively. Conclusions Treatment outcome of PRCA depended upon the causes and the types of treatment, and the burden of RBC transfusion was very high in patients with ESA and thymoma-associated PRCA.

Pure red cell aplasia, a disease of a great diversity

Pure red cell aplasia (PRCA) is a type of normocytic or sometimes macrocytic anemia characterized by reticulocytopenia. The cause of hypo erythropoiesis is varied. It could be of a congenital or an acquired type. A congenital PRCA is different than anemia caused by congenital dyserythropoiesis. The classification of acquired PRCA can be primary when no cause is identified or secondary due to underling or associated pathology. The primary PRCA is a disease of exclusion. There are many disorders such as autoimmune disorders, hematological and nonhematological malignancies, some infections, and medications that cause secondary PRCA. Immune-mediated mechanism plays an important role in both primary and secondary types. Therefore, immunomodulating agents are important in the treatment of primary type and many secondary types. Other therapy modalities include surgery, plasmapheresis, and hemopoietic stem cell transplantation. The assessment of hemoglobin level and absolute reticulocyte count with the frequency of blood transfusion are important to monitor therapy response achievement. Achievement of complete response is important to eliminate demands for blood transfusion and to avoid blood-transfusion risks. Herein, we review this disorder which has broad diversity, its causes, approach to its cause, therapy modalities.

Primary pure red cell aplasia association with Johnson-blizzard syndrome cured by homeopathy

Primary pure red cell aplasia association with Johnson-blizzard syndrome cured by homeopathy

Analysis and observation of T lymphocyte subsets and curative effects in patients with acquired pure red cell aplasia

Objectives To investigate distribution of T lymphocyte subsets, absolute value and proportion of large granular lymphocyte(LGL) in peripheral blood and bone marrow of acquired pure red cell aplasia (PRCA) patients, and to evaluate patients′ immune function and efficacy of immunosuppressive agents. Methods From January 2002 to November 2015, a total of 25 patients with acquired PRCA who were treated at Department of Hematology, People′s Hospital of Xinjiang Uygur Autonomous Region at first-visit were enrolled into this study, as study group. Inclusion criteria of study group: patients′ diagnoses were conformed to the diagnostic criteria of PRCA in Diagnosis and Curative Effect of Hematology (3rd edition) and clinical data were complete. Exclusion criteria: other anemia disease and clinical data were not complete. In 25 cases of PRCA patients, 5 cases were secondary PRCA with T cell-large granular lymphocyte leukemia (T-LGLL), other 20 cases were primary PRCA. And 25 cases of health people who were receiving physical examination at the People′s Hospital of Xinjiang Uygur Autonomous Region during the same period were recruited into control group randomly, by simple random method. Inclusion criteria of control group: no abnormality in blood routine examination and biochemical test. Exclusion criteria: abnormality in blood routine examination, and suffering from immune disease, tumor. T lymphocyte subsets of subjects in study group and control group were detected by flow cytometry. Blood routine examination and bone marrow examination were carried out in study group before and after treatment. Then absolute value and proportion of LGL in bone marrow, peripheral blood and curative effect after drug treatment of cyclosporine A and so on of 25 acquired PRCA patients were analyzed retrospectively and compared statistically. The study protocol was approved by the Ethical Review Board of Investigation in Human at People′s Hospital of Xinjiang Uygur Autonomous Region. There were no statistically significant differences of subjects′ clinical data, such as age and gender ratio, between two groups (P>0.05). Results ①Compared with control group, helper T lymphocyte (Th) proportion and Th/suppressor T lymphocyte (Ts) ratio of acquired PRCA patients in study group were significantly lower, Th proportion: (36.6±3.8)% vs (45.1±2.1)%; Th/Ts ratio: 1.2±0.2 vs 2.2±0.4; there were significant differences (t=9.161, 12.174, P=0.032, 0.021), and Ts proportion of study group was significantly higher than that of control group, (30.5±2.8)% vs (20.2±1.9)%; there was significant difference (t=13.460, P=0.021). There was no statistically significant difference of natural killer (NK) cell proportion between two groups, (11.3±1.8)% vs (10.3±1.3)%; and t=1.572, P=0.344. In study group, Th proportion, Th/Ts ratio of secondary PRCA patients with T-LGLL were lower than those of primary PRCA patients, Th proportion: (36.1±3.7)% vs (39.1±6.1)%; Th/Ts ratio: 1.0±0.2 vs 1.2±0.1; but the differences were not significant (t=2.293, 2.513; P=0.301, 0.297), and Ts proportion of secondary PRCA patients with T-LGLL was higher than that of primary PRCA patients, (31.0±2.7)% vs (28.4±2.0)%; but the difference was not significant (t=1.472, P=0.384). There was no statistically significant difference of NK cells proportion between two groups, (11.3±1.8)% vs (11.1±2.7)%; and t=1.572, P=0.364. ② Among 25 acquired PRCA patients in study group, 16 cases had higher proportion of lymphocytes in peripheral blood (64%, 16/25), and 10 cases had 2~3 granules LGL (40%, 10/25); 8 cases had more than 20% LGL of total lymphocytes (32%, 8/25). Four cases had 2~3 granules LGL in bone marrow (16%, 4/25); 3 cases had more than 20% LGL of total lymphocytes (12%, 3/25). The ratio of patients with LGL in peripheral blood was significantly higher than that in the bone marrow (χ2=6.595, P=0.003). ③ After treatment, hemogram of 18 cases returned to normal, including four cases with normal myelogram, fourteen cases with decreased bone marrow erythroid cell hyperplasia, which was higher than that before treatment. Effectiveness evaluation of study group was as follows: four PRCA patients were cured basically; fourteen cases achieved remission; six cases achieved significant progress; one case was invalid. The total effective rate of treatment was 96% (24/25). Five secondary PRCA patients with T-LGLL didn′t need blood transfusion after treatment, but unlike primary PRCA patients, their hemoglobin levels didn′t recover to normal reference range. Conclusions The disorder of T lymphocyte subsets in patients with acquired PRCA caused the disorder of cellular immune function, and LGL detected in peripheral blood would help the diagnosis of acquired PRCA. Effect of cyclosporin A treatment on acquired PRCA was very significant, but curative effect of secondary PRCA patients with T-LGLL was poorer than that of primary PRCA. Key words: Red-cell aplasia, pure; Anemia, aplastic; T-lymphocyte subsets; Leukemia, large granular lymphocytic; Cyclosporine

Primary acquired chronic pure red cell aplasia refractory to standard treatments: remission with rituximab.

TO THE EDITOR: Pure red cell aplasia (PRCA) is a rare syndrome caused by erythropoietic hypoplasia in the absence of leukocytopenia and thrombocytopenia. It is characterized by severe normocytic and reticulocytopenic anemia, with a normally cellular bone marrow (BM) but devoid of erythroblasts [1]. The acquired form of PRCA is a chronic illness that is often diagnosed in conjunction with a variety of diseases [1], such as lymphoproliferative disorders [2], viral infections, autoimmune hemolytic anemia (AIHA) [3], rheumatologic disorders [4], and allogeneic stem cell transplantation [5]. However, this disorder is rarely diagnosed as an idiopathic condition. Acquired PRCA is managed as an immunologically mediated disease, using immunosuppressive therapy (IST) with corticosteroids and cyclosporine A (CSA) as the treatments of first choice [1]. As alternative and salvage treatment, rituximab has been reported to be highly effective [2,3,4,5]; however, to the best of our knowledge, no case of idiopathic PRCA managed with this agent has been reported. A 63-year-old woman was diagnosed in June 2003 as having PRCA after the discovery of isolated normocytic and reticulocytopenic anemia, the course of which had been insidious and progressive. All other possible underlying causes of erythroblastopenia were ruled out by appropriate investigations (Table 1); other laboratory and radiological evaluations revealed no abnormal findings. The patient had required transfusions of almost 2 units of packed red blood cells (RBC) every 2 to 3 weeks. Once the diagnosis was made, she was started on CSA plus corticosteroids, and soon achieved full recovery from BM erythropoiesis and attained normalization of peripheral blood counts. The patient no longer required transfusions. This was considered complete remission (CR) of PRCA. Therefore, the dosage of CSA was gradually reduced and discontinued. However, there was a progressive loss of response, and CSA was resumed in February 2007 due to a full relapse. The patient achieved a second CR, and the dosage of CSA was carefully tapered. However, the patient experienced progressive chronic renal failure (CRF) in January 2011, which fully resolved after discontinuation of CSA. PRCA recurred soon after, and the patient again required frequent RBC transfusions. When she required approximately 4 RBC units per month, steroids were retried, but without any benefit. Azathioprine was tried without any response. By May 2013, the need for transfusions had reached about 6 RBC units/month, and direct and indirect Coombs blood compatibility tests became positive with the appearance of anti-IgG autoantibody; therefore, the availability of required transfusions became a concern due the difficulty of finding compatible RBC units. In view of this life-threatening complication and a severe hematological condition refractory to all standard treatments for PRCA [1], rituximab was started as a salvage measure at a dose of 375 mg/m2/week for a total of 4 cycles, after the patient gave properly informed consent. Given the lack of experience with rituximab in the setting of primary PRCA, this treatment schedule was derived from that reported as safe and effective in patients with PRCA secondary to lymphoproliferative disorders [2]. After the second dose of rituximab, she exhibited a striking rise in her reticulocyte count and an increase in hemoglobin level. Thus, a third CR was achieved and was maintained during the subsequent 24 months (Fig. 1). In conclusion, the present letter describes a case of acquired chronic primary PRCA of idiopathic origin, refractory to standard measures, with remission on rituximab salvage treatment. To the best of our knowledge, this is the first report of idiopathic PRCA managed with rituximab. In our experience, this agent provided important clinical benefits in an elderly patient with a 12-year PRCA history, during which she had become intolerant/unresponsive to the majority of immunosuppressive agents used in this difficult-to-treat disorder. The course of disease and repeated responses to IST pointed to a possible underlying autoimmune pathogenesis. Although this hypothesis has not been proven by extensive clinical and laboratory evaluations; for this case, rituximab was highly effective in inducing long-lasting remission without any adverse effects.

Acquired pure red cell aplasia: updated review of treatment

Pure red cell aplasia (PRCA) is a syndrome characterized by a severe normocytic anaemia, reticulocytopenia, and absence of erythroblasts from an otherwise normal bone marrow. Primary PRCA, or secondary PRCA which has not responded to treatment of the underlying disease, is treated as an immunologically-mediated disease. Although vigorous immunosuppressive treatments induce and maintain remissions in a majority of patients, they carry an increased risk of serious complications. Corticosteroids were used in the treatment of PRCA and this has been considered the treatment of first choice although relapse is not uncommon. Cyclosporine A (CsA) has become established as one of the leading drugs for treatment of PRCA. However, common concerns have been the number of patients treated with CsA who achieve sustained remissions and the number that relapse. This article reviews the current status of CsA therapy and compares it to other treatments for diverse PRCAs.

Spectrum of pure red cell aplasia in adult population of north-west India

Pure red cell aplasia (PRCA) is a rare haematological disorder characterised by selective inhibition of red cell precursors in the bone marrow. We conducted a retrospective analysis of nine cases of PRCA seen in our adult haematology clinic from January 2000 to December 2003. All patients had baseline hemogram, bone marrow examination, CT scan of chest, autoimmune and infectious disease markers. The diagnosis of PRCA was made on bone marrow examination showing normal granulocytic and megakaryocytic series with erythroblastopenia. The age range was 14–68 years (median: 40 years) and a male to female ratio of 3 : 1. In five patients, the aetiology of PRCA could not be identified with available investigations and were labelled as primary PRCA. The secondary causes of PRCA included three cases of thymoma and one case of non-Hodgkin lymphoma. Out of nine patients, three patients had died and two lost to follow-up. At the last available follow-up till December 2006, three patients (one secondary and two primary PRCA) are maintaining normal haemoglobin and one patient still has active disease. The retrospective review shows that causes and outcome of PRCA in the developing world are different to those seen in the West.

Long-term outcome of patients with acquired primary idiopathic pure red cell aplasia receiving cyclosporine A. A nationwide cohort study in Japan for the PRCA Collaborative Study Group

Cyclosporine A (CsA) has become one of the leading agents for the treatment of pure red cell aplasia (PRCA). However, further studies are necessary to determine the relapse-free survival (RFS) and overall survival (OS) of patients treated with this drug, the minimum duration of therapy for induction of remission, and whether or not there is need for maintenance treatment. We conducted a nationwide survey in Japan. From a total of 185 patients (with 73 primary idiopathic PRCA and 112 with secondary PRCA), we evaluated 62 patients with primary idiopathic PRCA for this report. The remission induction therapy for these patients included CsA (n=31), corticosteroids (CS) (n=20) or other drugs (n=11). CsA and CS produced remissions in 23 (74%) and 12 (60%) patients, respectively. The salvage treatment produced remissions in 58 patients (94%). Forty-one and 15 patients were maintained on CsA+/-CS (CsA-containing group) or CS alone (CS group), respectively. The median RFS in the CsA-containing group was 103 months, longer than that seen in the CS group (33 months) (p<0.01). Of 14 patients whose CsA was discontinued, 12 patients (86%) relapsed after a median of 3 months (range 1.5 to 40 months), while only 3 of 27 patients (11%) relapsed during CsA-containing maintenance therapy. Thus, the discontinuance of maintenance therapy was strongly correlated with relapse (p<0.001). Four patients in the CsA-containing group died; however, the OS of this group was not significantly different from that of the CS-groups (p=0.104). CsA-containing regimens sustain prolonged RFS more effectively than CS in primary idiopathic PRCA and seem to be important to prevent relapse.

Primary pure red cell aplasia in dogs: 13 cases (1996-2000).

To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA). Retrospective study. 13 dogs with severe nonregenerative anemia and bone marrow erythroid aplasia. Medical records of dogs determined to have PRCA on the basis of results of blood and bone marrow analysis between 1996 and 2000 were reviewed. Criteria for inclusion in the study were severe nonregenerative anemia (Hct < 20%; reticulocyte count < 1.0%), selective erythroid aplasia in bone marrow, and lack of underlying diseases that may have caused the anemia. Median age of dogs was 6.5 years. Females were significantly overrepresented. Median Hct was 10%, and median reticulocyte count was 0.1%. Direct Coombs' test results were negative for all dogs tested, and spherocytosis was evident in 2 dogs. All dogs were treated with prednisolone, and 2 dogs were treated with prednisolone and cyclophosphamide. Responses to treatment were complete, partial, and poor in 10, 1, and 2 dogs, respectively. Median time required to achieve an increase of 5% or more in Hct was 38 days, and median time to complete remission was 118 days. Of 10 dogs for which follow-up information was available, only 1 required long-term immunosuppressive treatment. Dogs with PRCA appear to respond readily to treatment with immunosuppressive drugs; however, hematologic responses may not be observed for weeks to months after initiation of treatment.

Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes

Acquired pure red cell aplasia (PRCA) can be associated with lymphoproliferative disease of granular T lymphocytes (T-LDGL), also known as T-cell large granular lymphocyte leukemia. Fifteen adult patients with PRCA associated with T-LDGL comprise this study. Neutropenia and rheumatoid arthritis were uncommon. All patients responded to immunosuppressive therapy. The 2 most commonly used treatments were prednisone and cyclophosphamide +/- corticosteroids, producing overall response rates of 50% and 60%, respectively. Treatment with cyclophosphamide was associated with a more durable remission (median, 60 versus 7.5 months). After a median follow-up of 67 months, 2 patients died of treatment-related complications, one from myelodysplasia and another from cyclosporine-induced renal failure. The clinical course and treatment responses of PRCA associated with T-LDGL in this series were similar to the general group of PRCA. Because T-LDGL is frequently underdiagnosed, it is likely that a significant proportion of idiopathic or primary PRCA is in fact secondary to T-LDGL.

Clonality of acquired primary pure red cell aplasia

Acquired primary pure red cell aplasia (PRCA) has frequently been shown to be associated with T cells that inhibit marrow erythropoiesis. A 41-year-old female presented with anemia in December 1985. Bone marrow examination revealed 1.8% erythroid cells. A diagnosis of PRCA was made. She received prednisolone, and her hemoglobin level recovered to 12 g/dl. In February 1995, her hemoglobin level decreased to 5.8 g/dl, and acquired primary PRCA recurred. Surface markers of peripheral blood mononuclear cells demonstrated CD4/8 ratio inversion. The T-cell receptor (TCR)-β chain gene showed germ line configuration by Southern blot analysis of the mononuclear cells in peripheral blood. However, stepdown polymerase chain reaction analysis revealed that the TCR-β gene of peripheral blood mononuclear cells was rearranged. With highly sensitive polymerase chain reaction analysis, clonality of T cells was confirmed. We propose that some acquired primary PRCA patients have a T-cell clonal disorder, similar to some PRCA patients with large granular lymphocytes leukemia or thymoma. Am. J. Hematol. 62:193–195, 1999. © 1999 Wiley-Liss, Inc.

Studies on Pure Red Cell Aplasia. XI. Results of Immunosuppressive Treatment of 37 Patients

Abstract Thirty-seven patients with pure red cell aplasia (PRCA) were seen between 1966 and 1982. Ten patients had accompanying diseases described in association with PRCA, while the remainder had primary PRCA. All but two patients were treated with some form of immune manipulation, including corticosteroids, cytotoxic drugs, antithymocyte globulin, splenectomy, thymectomy, and plasmapheresis. Twenty-three patients (66%) had a remission induced by immunosuppression. In addition, there were 5 spontaneous remissions (14%). Cytotoxic drugs administered in combination with corticosteroids were the most effective form of treatment, producing 18/32 remissions (56%). Twelve of these remissions were in patients resistant to corticosteroids or in patients who had relapsed while taking them. Thirteen of the 23 patients in whom remissions were induced and one-fifth of the patients with spontaneous remissions have relapsed to date. However, with additional treatment, a second remission was induced in 10/13. Fifty-four percent of the patients with induced remissions remained transfusion-free during most of the follow-up period. Median survival in patients with primary PRCA was greater than 10 yr, whereas in patients with secondary PRCA, it was 4 yr. Infection was a major cause of morbidity and mortality. This study demonstrates the value of a variety of immunosuppressive treatments of patients with PRCA.

Studies on pure red cell aplasia. XI. Results of immunosuppressive treatment of 37 patients

Thirty-seven patients with pure red cell aplasia (PRCA) were seen between 1966 and 1982. Ten patients had accompanying diseases described in association with PRCA, while the remainder had primary PRCA. All but two patients were treated with some form of immune manipulation, including corticosteroids, cytotoxic drugs, antithymocyte globulin, splenectomy, thymectomy, and plasmapheresis. Twenty-three patients (66%) had a remission induced by immunosuppression. In addition, there were 5 spontaneous remissions (14%). Cytotoxic drugs administered in combination with corticosteroids were the most effective form of treatment, producing 18/32 remissions (56%). Twelve of these remissions were in patients resistant to corticosteroids or in patients who had relapsed while taking them. Thirteen of the 23 patients in whom remissions were induced and one-fifth of the patients with spontaneous remissions have relapsed to date. However, with additional treatment, a second remission was induced in 10/13. Fifty-four percent of the patients with induced remissions remained transfusion-free during most of the follow-up period. Median survival in patients with primary PRCA was greater than 10 yr, whereas in patients with secondary PRCA, it was 4 yr. Infection was a major cause of morbidity and mortality. This study demonstrates the value of a variety of immunosuppressive treatments of patients with PRCA.

Studies on Pure Red Cell Aplasia. X. Association With Acute Leukemia and Significance of Bone Marrow Karyotype Abnormalities

Thirty-one patients with chronic primary pure red cell aplasia (PRCA) had blood and marrow cell karyotypes performed prior to immunosuppressive treatment. Only one patient had an abnormal marrow cell karyotype, which revealed a clone of hyperdiploid cells with 47 chromosomes (47, XY, + G). His blood cell karyotype was normal. This patient had no erythroid response to prednisone and cyclophosphamide, or splenectomy, and after 3 yr he developed acute myelomonocytic leukemia with the emergence of a new clone of hyperdiploid cells with multiple ring chromosomes (46,XY/47,XY, + G/49,XY,–G,+4r) in the blood and marrow. These studies indicate that chronic primary PRCA probably has a much lower incidence of abnormal karyotypes and acute leukemia than other refractory anemias (myelodysplastic syndromes), but that an abnormal marrow karyotype may portend a leukemia. The role of cytotoxic immunosuppressive drugs in the treatment of PRCA patients with an abnormal karyotype remains unknown.