sirolimus and Red-Cell-Aplasia--Pure

Some patients with acquired pure red cell aplasia (aPRCA) have no response or are intolerant to cyclosporine A. From April 2017 to August 2020, patients diagnosed with aPRCA at Peking Union Medical College Hospital who were refractory/recurrent/intolerant to at least 6 months of full-dose cyclosporin A (CsA) with/without steroids were recruited and treated with sirolimus for at least 6 months. Finally, a total of 64 patients were enrolled. The overall response rate and complete response rate after 3, 6 and 12 months of sirolimus were 60.9%, 84.4%, and 73.5% and 50.0%, 65.6%, and 66.0%, respectively. At a median of 14.5 (6-47) months of follow-up, 14.8% (8/54) of the patients relapsed. Apart from haemoglobin improvement, patients had decreased creatine levels and serum ferritin levels at the end of the follow-up compared with the baseline (169.3 μmol/L vs. 146.4 μmol/L, p = 0.041; 2121.5 ng/mL vs. 1018.3 ng/mL, p = 0.013). Adverse events were recorded in 19 patients, including infections and increase of creatine. Secondary aPRCA with stable underlying diseases had similar results as those with primary aPRCA. In summary, sirolimus is effective for patients with refractory/recurrent/intolerant aRPCA with a low recurrence rate and toxicities.

Topics: Creatine; Cyclosporine; Humans; Immunosuppressive Agents; Prospective Studies; Red-Cell Aplasia, Pure; Sirolimus; Treatment Outcome

Anti-erythropoietin (anti-EPO) antibody-mediated pure red cell aplasia (PRCA) is a rarely seen disease. Anti-EPO antibodies were mostly found in patients with chronic kidney disease who received recombinant human erythropoietin (rHuEPO) injections subcutaneously. The treatment against anti-EPO antibody-mediated PRCA included discontinuation of rHuEPO, immunosuppressive agents, intravenous immunoglobulin, plasmapheresis, or kidney transplantation. We reported a case of kidney transplant recipient with anti-EPO antibody-mediated PRCA, who had no trend of recovery after stopping rHuEPO, receiving regular induction and maintenance immunosuppressive regimens. He was further given 6 consecutive plasmapheresis sessions, cyclophosphamide, and adjusted maintenance immunosuppressive regimen into cyclosporine, sirolimus and prednisone. We monitored his anti-EPO antibody levels with a self-created simple mixing test. At 10 months post kidney transplant, his anti-EPO antibody finally turned negative, and his reticulocyte count dramatically increased. Cyclosporine, sirolimus and prednisone combined with roxadustat eventually alleviated the patient's anti-EPO antibody-mediated PRCA. Our self-created simple mixing test for anti-EPO antibody titer was very helpful in disease monitoring and therapeutic guidance.

Topics: Antibodies; Cyclosporine; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Prednisone; Recombinant Proteins; Red-Cell Aplasia, Pure; Sirolimus

Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic clonal plasma cell or lymphoplasmacytic proliferative disorder. Recently, some case reports have described the association of pure red cell aplasia (PRCA) with MGUS, even with a relatively low monoclonal immunoglobulin burden. T large granular lymphocyte leukemia (T-LGLL) is a chronic lymphoproliferative disorder characterized by clonal expansion of T large granular lymphocytes, which is rare in China. There are some reports about T-LGL leukemia in patients with B-cell lymphoma; however, it is very rare that T-LGLL coexists with MGUS and clonal B-cell lymphoproliferative disorders (CB-LPD).. A 77-year-old man was hospitalized because of anemia. He was diagnosed with MGUS, CB-LPD, and PRCA. During the development of the disease, a group of abnormal T lymphocytes was detected by flow cytometry of peripheral blood.. Combining clinical manifestations with the result of T cell receptor gene rearrangement and immunophenotype, it was consistent with the diagnosis of T large granular lymphocyte leukemia.. The patient was treat with bortezomib and dexamethasone regimen, Rituximab and sirolimus.. The patient was transfusion independent after therapies.. We report a patient with 4 concomitant hematological disorders: T-LGLL, MGUS, CB-LPD, and PRCA, aiming to represent the clinical and flow cytometry characteristics of these concomitant diseases, analyze the mechanism between diseases, and provide a clinical reference.

Topics: Aged; Anemia; Antineoplastic Agents; Bendamustine Hydrochloride; Bortezomib; Dexamethasone; Humans; Leukemia, Large Granular Lymphocytic; Lymphoproliferative Disorders; Male; Monoclonal Gammopathy of Undetermined Significance; Red-Cell Aplasia, Pure; Rituximab; Sirolimus

Our aim is to investigate the clinical characteristics of low- and intermediate-risk myelodysplastic syndrome (MDS) with pure red cell aplasia (PRCA).. We retrospectively reviewed the patients of low- and intermediate-risk MDS patients who had been diagnosed with PRCA in our hospital between January 2010 and December 2019.. There were 6 low- and intermediate-risk MDS patients with PRCA in our study, 1 male and 5 females, with a median age of 63.5 (50-75) years. It accounted for 7.7% (6/78) of all diagnosed PRCA cases and 1.67% (6/359) of diagnosed MDS cases during the same period. All patients were treated with multiple drugs, including recombinant human erythropoietin, cyclosporine, glucocorticoids, androgen, sirolimus, intravenous immunoglobulin and decitabine. Two patients achieved complete remission, two patients achieved partial remission and became blood transfusion independent. Two patients had no response and one patient died.. Low- and intermediate-risk MDS with PRCA was difficult to treat, but the prognosis was good.

Topics: Aged; Androgens; Cyclosporine; Erythropoietin; Female; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Red-Cell Aplasia, Pure; Retrospective Studies; Sirolimus

For patients with pure red cell aplasia (PRCA), cyclosporine (CsA) is the first line therapy. Occasionally, some patients who suffer from renal insufficiency cannot tolerate CsA. To explore the efficacy and tolerance of sirolimus treatment for those patients, twelve PRCA patients with renal insufficiency from May 2014 to May 2018 in Peking Union Medical College Hospital were enrolled, treated with sirolimus, and followed up at the median time of 16 (10-50) months. Eleven patients (91.7%) responded to sirolimus, with 58.3% complete response (CR) and 41.7% partial response (PR). The median time to achieve the optimum effect was 4 (1-7) months. The serum creatinine level remained stable or even reduced during the treatment period for eleven patients. Seven patients (58.3%) reported adverse events during sirolimus therapy, including increased blood glucose, infection, skin rash, elevated triglyceride or total cholesterol, and elevated serum creatinine compared with baseline. No treatment-related death was noticed during the follow-up time. Three patients relapsed with an overall response rate of 75.0% at 1 year. These results suggested that sirolimus was effective and tolerable for patients with PRCA complicated with renal insufficiency.

Topics: Adult; Aged; Aged, 80 and over; Creatinine; Cyclosporine; Drug Eruptions; Drug Evaluation; Drug Substitution; Female; Humans; Hyperglycemia; Hypertriglyceridemia; Immunosuppressive Agents; Male; Middle Aged; Recurrence; Red-Cell Aplasia, Pure; Remission Induction; Renal Insufficiency; Retrospective Studies; Sirolimus; Treatment Outcome

Topics: Aged; Antibiotics, Antineoplastic; Female; Humans; Male; Middle Aged; Red-Cell Aplasia, Pure; Sirolimus

A 9-month-old boy with life-threatening multiresistant pure red cell anemia/autoimmune hemolytic anemia within the frame of a possible, undiagnosed immune-mediated disease was initially treated with prednisone. Further-line therapies of the following 7 relapses included immunoglobulins, rituximab, cyclophosphamide, and alentuzumab followed by other maintenance treatments as cyclosporine, methotrexate, and mycophenolate. After all the administered therapies failed, the patient was successfully treated by splenectomy followed by fludarabine and then sirolimus as maintenance treatment. Relapses might have been caused by the lack of a complete debulking of triggering cells and/or ineffective maintenance therapy. Splenectomy and sirolimus may have played a complementary role in the management of both situations.

Topics: Anemia, Hemolytic, Autoimmune; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Resistance; Humans; Infant; Male; Red-Cell Aplasia, Pure; Sirolimus; Splenectomy; Treatment Outcome; Vidarabine