mycophenolic-acid and Red-Cell-Aplasia--Pure

Severe anemia requiring multiple blood transfusions in the posttransplant period can trigger rejection. The evaluation of anemia among transplant recipients is a challenging task. Awareness should be continued for tacrolimus to manage pure red cell aplasia, but further evidence is needed to prove whether tacrolimus is a real cause of posttransplant anemia. Our case patient, a 66-year-old male patient with end-stage renal disease due to diabetic nephropathy, underwent a preemptive living donor renal transplant in September 2018. He had received a coronary artery bypass graft with transcatheter aortic valve implantation 3 years before renal transplant. Initially, he was maintained on prednisolone, mycophenolate mofetil, and tacrolimus after basiliximab induction. One month later, he presented with low cardiac output symptoms. His complete blood count showed normocytic normochromic anemia with reticulocytopenia (his hemoglobin level dropped from 112 to 69 g/L), which necessitated regular blood transfusions. His iron profile, serum folate, and vitamin B12 were within normal limits, and he had negative hemolytic and autoimmune screening tests. A bone marrow biopsy revealed acquired pure red cell aplasia, which was most likely drug induced as viral profiles were negative for parvovirus B19, cytomegalovirus, and Epstein-Barr virus. The patient was managed by discontinuing mycophenolate mofetil, and the steroid dose was increased up to 20 mg/day but without improvement. With tacrolimus then considered, 3 weeks after presentation, we replaced tacrolimus with cyclosporine. Complete blood count follow-up showed improvement without any need for further blood transfusions. After 1 month of cyclosporine maintenance, mycophenolate mofetil was resumed with a steady increase of hemoglobin up to 150 g/L and serum creatinine of 122 μmol/L. Pure red cell aplasia is a rare disorder among renal transplant recipients, which could be induced by maintenance tacrolimus therapy.

Topics: Aged; Anemia; Cyclosporine; Epstein-Barr Virus Infections; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Red-Cell Aplasia, Pure; Tacrolimus; Transplant Recipients; Treatment Outcome

Topics: Adult; AIRE Protein; Female; Gene Rearrangement, T-Lymphocyte; Humans; Immunosuppressive Agents; Mutation; Mycophenolic Acid; Polyendocrinopathies, Autoimmune; Polymerase Chain Reaction; Red-Cell Aplasia, Pure; Transcription Factors

Human parvovirus B19 disease is an infrequent but recognized rare cause of anemia in immunocompromised patients. A few cases of parvovirus B19 infections have been reported in transplant recipients, of those only four patients underwent renal transplantation. The primary immunosuppressive therapy in these patients included prednisone with either cyclosporine or tacrolimus. In one patient the disease was self-limiting, while in three others the hematocrit improved following 10-15 d of treatment with commercial intravenous immunoglobulin (IVIG). Herein, we report the fifth case of pure red cell aplasia due to parvovirus B19 infection in a renal transplant recipient who responded to a 5-d course of IVIG. To our knowledge, this is the first case of parvovirus B19 infection in a patient with solid-organ transplantation whose immunosuppressive regimen included both mycophenolate mofetil and tacrolimus and in whom an excellent clinical response was achieved with a short course of IVIG infusion.

Topics: Adult; Anti-Inflammatory Agents; Cadaver; Cyclosporine; DNA, Viral; Hematocrit; Humans; Immunoblotting; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infusions, Intravenous; Kidney Transplantation; Male; Mycophenolic Acid; Parvoviridae Infections; Parvovirus B19, Human; Polymerase Chain Reaction; Prednisone; Red-Cell Aplasia, Pure; Remission Induction; Tacrolimus

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.. Lay abstract We report a case of 28-year-old women with relapsing remitting multiple sclerosis who was treated with alemtuzumab and subsequently developed a series of autoimmune complications. Several months after completing her second course of alemtuzumab the patient became breathless and noticed bruising on her legs. On investigation she was found to be anemic and had a low platelet level (which predisposed her to bruising). In addition, her immune system was also impaired meaning she was more prone to developing opportunistic infections. The patient was treated with a variety of different medications and required blood transfusions for several months before she recovered. Despite the multiple complications the patient developed from alemtuzumab her multiple sclerosis remains stable with no new relapses 3 years following treatment.

Topics: Adrenal Cortex Hormones; Adult; Alemtuzumab; Antineoplastic Agents, Immunological; Cyclosporine; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Multiple Sclerosis, Relapsing-Remitting; Mycophenolic Acid; Neutropenia; Purpura, Thrombocytopenic, Idiopathic; Red-Cell Aplasia, Pure; Rituximab; Treatment Outcome; Vincristine

BACKGROUND Pure red cell aplasia (PRCA) is an uncommon cause of anemia in end-stage kidney disease (ESKD). It is attributed to recombinant human erythropoietin (rHuEPO) administration. Although immunosuppression is the mainstay therapy, its effectiveness varies from 30% to 70%. PRCA in ESKD has been reported to improve following kidney transplantation. CASE REPORT A 46-year-old woman with ESKD secondary to lupus nephritis was treated for uremia at our center. She developed severe anemia. Bone marrow aspiration and biopsy revealed a reduction of erythroid precursors, consistent with PRCA. Because she had no sibling's blood group matched with her, ABO-incompatible kidney transplantation was an option for treatment. She underwent a desensitization protocol consisting of rituximab 375 mg/m2, tacrolimus, mycophenolate mofetil, and prednisolone 4 weeks before surgery, in addition to 3 sessions of double-filtration plasmapheresis (DFPP) every other day followed by intravenous immunoglobulin (IVIG) and 1 session of specific immunoadsorption (Glycosorb® B column) at pre-transplant day -1. She also received low-dose rabbit anti-thymocyte globulin (rATG) (Thymoglobulin®) (total 2.0 mg/kg). Maintenance therapy included tacrolimus, mycophenolate mofetil, and prednisolone. Allograft function normalized a few days after transplantation and her Hb gradually increased. CONCLUSIONS We report a rare case of PRCA in a patient with ESKD undergoing ABO-incompatible kidney transplantation. The outcome was satisfactory, with complete correction of anemia and kidney function.

Topics: ABO Blood-Group System; Blood Group Incompatibility; Erythropoietin; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Prednisolone; Red-Cell Aplasia, Pure; Renal Dialysis; Tacrolimus; Thailand

To retrospectively study the impacts of ABO incompatibility on early outcome after single unit unrelated cord blood transplantation（UCBT）, such as cumulative incidence of engraftment, incidence of acute graft- versus- host disease （aGVHD） and 180- day transplant- related mortality（TRM）.. 208 patients underwent single unit UCBT from April 2008 to October 2014 were analyzed, included 99 ABO- identical, 60 minor, 38 major and 11 bidirectional ABO- incompatible recipients. All the patients received intensified myeloablative conditioning, and a combination of cyclosporine A and mycophenolate mofetil was given for GVHD prophylaxis.. Cumulative incidences of neutrophil engraftment, platelet recovery, erythroid lineage reconstitution, Ⅱ-Ⅳ aGVHD, Ⅲ-Ⅳ aGVHD and 180- day TRM showed no significant difference among the patients receiving ABOidentical, minor, major, and bidirectional UCBT（all P>0.05, respectively）. What's more, none of the patients developed pure red- cell aplasia（PRCA）after UCBT. Group A donor and a group O recipient patients didn't appeared to influence the clinical results when compared with others（all P>0.05, respectively）.. Patients receive ABO- incompatible UCBT may not develop PRCA. The presence of ABO- incompatibility did not influence the hematopoietic reconstitution, the incidence of aGVHD and 180-day TRM in this cohort. There is not support for the need to regard ABO-compatibility as an UCB-graft selection criterion.

Topics: ABO Blood-Group System; Blood Group Incompatibility; Cord Blood Stem Cell Transplantation; Cyclosporine; Graft vs Host Disease; Humans; Mycophenolic Acid; Red-Cell Aplasia, Pure; Retrospective Studies; Tissue Donors; Transplantation, Homologous

Acquired pure red-cell aplasia is a rare disorder that can be either idiopathic or associated with certain autoimmune diseases, pregnancy, lymphoproliferative disorders, nutritional deficiencies, or medicines. We present a deceased-donor renal transplant patient who developed pure red-cell aplasia associated with mycophenolate mofetil or tacrolimus and was treated with cyclosporine. A 20-year-old woman was transplanted from a deceased donor 1 month earlier and presented to us with symptoms of fatigue, prostration, and palpitation. The results of a laboratory examination revealed anemia. A diagnostic work-up resulted in a diagnosis of pure red-cell aplasia. Mycophenolate mofetil was discontinued. Tacrolimus also was replaced with cyclosporine 2 months after mycophenolate mofetil was halted because of a lack of improvement in anemia. Three months later, her anemia improved with cyclosporine. Starting cyclosporine instead of tacrolimus or mycophenolate mofetil showed good improvement in our patient within 6 months of therapy.

Topics: Cyclosporine; Female; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Transplantation; Mycophenolic Acid; Red-Cell Aplasia, Pure; Tacrolimus; Treatment Outcome; Withholding Treatment; Young Adult

Anaemia is prevalent in patients with systemic lupus erythematosus (SLE). The anaemia is often a consequence of the disease itself but may also be secondary to drug treatments. Mycophenolate mofetil (MMF) is increasingly used in the management of patients with SLE and its associated anaemia. We describe the case of a 19-year-old girl, who presented acutely with SLE and renal involvement. Her disease was controlled with immunosuppression but she later developed severe transfusion-dependent anaemia. Several causes were considered before a bone marrow biopsy led to the diagnosis of erythroid hypoplasia. In the absence of clinical or laboratory markers of active lupus, MMF was implicated as the cause. Its discontinuation led to a rapid and sustained correction of the anaemia. Red cell aplasia linked to the use of MMF is uncommon and the manufacturers are aware of fewer than 50 cases. This is the first case report of evolving red cell aplasia induced by MMF in SLE.

Topics: Anemia; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Red-Cell Aplasia, Pure; Young Adult

Antibody (Ab)-mediated pure red cell aplasia (PRCA) is a rare hematologic disorder. For the first time here, the authors report the use of combination therapy which consists of mycophenolate mofetil 500-1000 mg/day, intravenous cyclophosphamide 600 mg monthly and monthly intravenous methylprednisolone 1 gm/day for 2 days followed by oral prednisolone 10 mg/day. A 62-year-old woman developed Ab-mediated PRCA after using subcutaneous erythropoietin-beta 3000 U weekly for 14 months at the predialysis stage. Ab-mediated PRCA was diagnosed based on (1) the transfusion need of more than 1 unit/wk to keep hemoglobin level stable, (2) corrected reticulocyte count 0.36% and (3) < 5% erythroblasts with normal myeloid cells and megakaryocytes in bone marrow biopsy. Serum assay confirmed the anti-erythropoietin antibody of 230 ng/mL. The patient recovered from PRCA after the triple immunosuppressive therapy for 3 months. The rapid recovery occurred despite the fact that the patient was receiving intravenous erythropoietin-alpha while having the antibody in the serum. The present case describes the acceleration of the recovery and successful resumption of erythropoietin concurrently despite the positive serum anti-erythropoietin antibody.

Topics: Cyclophosphamide; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Erythrocyte Transfusion; Erythropoietin; Female; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Middle Aged; Mycophenolic Acid; Prednisolone; Red-Cell Aplasia, Pure

Topics: BK Virus; Drug Labeling; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Mycophenolic Acid; Opportunistic Infections; Red-Cell Aplasia, Pure; United States; Virus Activation

The objective of this paper was to study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April 1997 to December 2005. Eleven out of the 42 patients developed PRCA (26.1%). All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n = 9) or blood group B donor (n = 2). The following factors were associated with an increased risk of PRCA: (1) blood group O recipient; (2) blood group A donor; and (3) blood group O/A in recipient/donor pair. Only blood group O/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Six patients who received donor-type plasma exchange did not develop PRCA and among them 5 cases were the blood group O recipients. Eight patients obtained spontaneous remission and in the remaining 3 patients 2 with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA. We conclude that blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange and anti-CD20 monoclonal antibody is an effective approach for the treatment of PRCA. PRCA could be prevented by plasma exchange prior to transplantation.

Topics: ABO Blood-Group System; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; beta-Thalassemia; Blood Group Incompatibility; Busulfan; Child, Preschool; Cyclosporine; Epstein-Barr Virus Infections; Female; Graft Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia; Lymphoproliferative Disorders; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Plasma Exchange; Red-Cell Aplasia, Pure; Remission, Spontaneous; Retrospective Studies; Risk Factors; Rituximab; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation

Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy.. Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005.. Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made.. We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.

Topics: Adult; Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Autoimmune Diseases; Bone Marrow; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphocyte Activation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pancreas Transplantation; Pilot Projects; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Red-Cell Aplasia, Pure; Retrospective Studies; T-Lymphocytes

After liver transplantation, reinfection of the newly engrafted liver with hepatitis C virus is essentially universal in patients who are viremic at the time of transplantation. Treatment with interferon preparations with or without ribavirin is recommended in patients with marked histologic injury; however, hematologic toxicity associated with therapy has been reported, which is usually treated with growth factor support, including erythropoietin analogues. We present the first reported case of anti-erythropoietin antibody-mediated pure red cell aplasia arising in the setting of hepatitis C virus therapy in a patient who underwent living donor liver transplantation.

Topics: Anemia; Antibodies; Antiviral Agents; Epoetin Alfa; Erythropoietin; Graft Rejection; Hematinics; Hepatitis C; Humans; Immunocompromised Host; Immunosuppressive Agents; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Polyethylene Glycols; Prednisone; Recombinant Proteins; Red-Cell Aplasia, Pure; Ribavirin; Secondary Prevention; Tacrolimus

Topics: Antiviral Agents; Hepatitis C; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Recurrence; Red-Cell Aplasia, Pure; Ribavirin

Topics: Adult; Cyclosporine; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Red-Cell Aplasia, Pure; Tacrolimus

Topics: Adult; Autoimmunity; Cyclosporine; Female; Humans; Lupus Erythematosus, Systemic; Mycophenolic Acid; Red-Cell Aplasia, Pure; T-Lymphocytes

Mycophenolate mofetil (MMF) is one of the new immunosuppressive drugs used in renal transplantation. MMF inhibits the de novo purine synthesis. Since this purine synthesis in lymphocytes entirely depends on the de novo pathway, MMF is considered to cause a selective inhibition of T- and B lymphocytes. Recently, 4 transplant patients out of 30 developed a severe anemia in the early post-transplantation period. Their immediate post-transplantation immunosuppression consisted of corticosteroids, cyclosporine and MMF. They all received anti-T-lymphocyte globulin (ATG) as induction treatment or because of rejection. In all 4 patients, iron supplementation and a treatment with erythropoietin were started. Blood loss, deficiencies, hemolysis, drug interactions or viral infections were excluded as causes of the anemia. Bone marrow biopsies were carried out, showing pure red cell aplasia that was ascribed to the use of MMF. Cessation or reduction of MMF was followed by a hematological improvement after 5-9 days. We hypothesized that MMF has a broader antiproliferative effect than its proposed lymphocyte-specific effect.

Topics: Adult; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Red-Cell Aplasia, Pure

Anemia secondary to mycophenolate mofetil (MMF) was recently described in experimental animals. A clinical association between MMF and anemia has been observed, but there are no proven reports. We describe a girl with chronic graft failure who developed erythroid aplasia under immunosuppression with MMF. She showed prompt resolution when MMF was discontinued and a recurrence of this clinical course when MMF was restarted. As re-challenge with a medication is the most definitive approach for showing a direct relationship between the drug and the side effect, this case clearly demonstrates that MMF can cause erythroid aplasia.

Topics: Adolescent; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Mycophenolic Acid; Postoperative Complications; Red-Cell Aplasia, Pure