tacrolimus and Anemia--Hemolytic--Autoimmune

Autoimmune hemolytic anemia (AIHA) occurring after solid organ transplantation is an infrequently reported entity. We describe in this report six cases of AIHA in pediatric liver or combined liver and small bowel transplant patients.. We retrospectively identified and reviewed the records of pediatric liver or combined liver and small bowel transplant patients with both serologic and clinical evidence of AIHA. We also performed an English language literature review for prior publications of AIHA occurring after solid organ transplantation.. We identified six patients presenting with severe hemolysis 9 months to 14 years after transplantation. All six developed warm AIHA, and two had concomitant cold agglutinins. All except one patient received various therapeutic combinations including steroids, intravenous immune globulin, rituximab, plasmapheresis, splenectomy, and vincristine. Five patients achieved remission 2 weeks to 3 months after presentation. Although tacrolimus has been speculated to play a causative role in the development of AIHA after organ transplantation, our case series demonstrated slightly better outcomes despite continuing tacrolimus compared to published cases where most patients either received significantly reduced doses of tacrolimus or were switched to a different immunosuppressant (83% vs. 76% cumulative literature remission rate).. AIHA may occur in solid organ transplant patients at a much higher frequency than previously believed. Hemolysis is often severe and resistant to steroid treatment alone. Thus early diagnosis and institution of aggressive multimodality treatment, including the use of rituximab, may be needed to achieve remission.

Topics: Adolescent; Anemia, Hemolytic, Autoimmune; Female; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Male; Organ Transplantation; Steroids; Tacrolimus

Cytopenias are common among pediatric SOT; however, autoimmune cytopenias are infrequently reported. We report five cases of autoimmune cytopenias in pediatric LT patients: two with isolated IgG-mediated AIHA, two with ITP, and one with Evans syndrome (ITP and AIHA). All patients were maintained on tacrolimus as immunosuppression. Viral illness commonly preceded the autoimmune cytopenias. All patients responded well to medical therapy (steroids, intravenous immunoglobulin, and rituximab) and lowering tacrolimus serum level. Prognosis appears to be worse when more than one cell line (e.g., Evans syndrome) is affected, and/or there is no preceding viral illness. A critical literature review of autoimmune cytopenias in children following SOT is conducted. Autoimmune cytopenias are a rarely reported complication of pediatric SOT, but clinicians taking care of pediatric transplant recipients need to be aware of this complication.

Topics: Anemia, Hemolytic, Autoimmune; Child; Female; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Male; Organ Transplantation; Purpura, Thrombocytopenic, Idiopathic; Tacrolimus

The aim of this study was to evaluate the efficacy, safety, and steroid-sparing effect of tacrolimus in patients with autoimmune cytopenia, including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and Evans syndrome (ES). Patients in the tacrolimus group were treated with tacrolimus in combination with steroids, and the control group received only steroids. Of the 318 patients finally enrolled, 87 (27.4%) were males, with a median age of 45 (14-90) years. The tacrolimus group comprised 144 patients, including 120 ITP, 19 AIHA, and 5 ES patients, and the control group comprised 174 patients, including 141 ITP, 25 AIHA, and 8 ES patients. The optimal ORR of the tacrolimus group was comparable to that of the control group, and the optimal CRR was higher (p < 0.05). Patients receiving tacrolimus had a decreased relapse rate and prolonged relapse-free survival (p < 0.05) compared with the controls for both the whole cohort and the ITP and AIHA subgroups. Compared with the control group, the tacrolimus group had a lower cumulative steroid dosage and earlier discontinuation of steroids (p < 0.05), which resulted in a decreased incidence of steroid-related adverse events (p < 0.05) although the total side effects were similar between the two groups. Similar drug expenses were observed between the tacrolimus and control groups at the 18-month follow-up. In conclusion, the early addition of tacrolimus had a similar ORR, better CRR, lower relapse rate, and prolonged relapse-free survival compared to steroids alone, with reduced steroid-related adverse events.

Topics: Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Steroids; Tacrolimus; Thrombocytopenia

Topics: Anemia, Hemolytic, Autoimmune; Biomarkers; Calcineurin Inhibitors; Child, Preschool; Glucocorticoids; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Prednisone; Tacrolimus; Thrombocytopenia; Treatment Outcome

Acquired pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) are rare complications of immunosuppression in pediatric solid organ transplant patients. We report a 14-month-old female child who developed Coombs positive hemolytic anemia and reticulocytopenia while on tacrolimus after cardiac transplantation. She was successfully treated with rituximab after failing treatment with corticosteroids and intravenous immunoglobulins. Clinicians should consider PRCA differential diagnosis in a patient presenting with reticulocytopenia and hemolysis. In addition, the coexistence of PRCA with AIHA, and the response to therapy with rituximab, supports a common immune-mediated pathogenesis for both disorders.

Topics: Anemia, Hemolytic, Autoimmune; Female; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Red-Cell Aplasia, Pure; Rituximab; Tacrolimus

Topics: Anemia, Hemolytic, Autoimmune; Disease Management; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Lymphoproliferative Disorders; Middle Aged; Salvage Therapy; Sirolimus; Tacrolimus; Transplantation, Homologous; Waldenstrom Macroglobulinemia

Topics: Adult; Anemia, Hemolytic, Autoimmune; Female; Humans; Immunosuppressive Agents; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Tacrolimus; Thrombocytopenia

Immune cytopenias are a recognized life-threatening complication following pediatric solid organ transplants (SOT), but treatment responses and overall outcome are not well described. The aim of this study was to evaluate the demographic characteristics, response to treatments, and outcomes of a cohort of patients who developed immune cytopenias following SOT.. In this single center retrospective review, patients with immune cytopenias after SOT were identified by electronic medical record (EMR) search and transplant databases from 1995-2012.. Of 764 SOT patients, 19 (2.4%) developed immune cytopenias. Incidence varied widely by transplant type from 1.2% (renal) to 23.5% (multivisceral). Autoimmune hemolytic anemia (AIHA) was the most common immune cytopenia. Overall median time from transplant to immune cytopenia was 8 m and varied by transplant type from 3 m (liver) to 74 m (heart). Standard therapies for immune cytopenias were often used and ineffective. The most effective therapy for the immune cytopenia was changing immunosuppression from tacrolimus to another agent. Three of 19 patients died; none directly attributed to the immune cytopenia.. Immune cytopenias are not rare after SOT, and patients usually do not respond well to traditional first line therapies. Provided that the risk of organ rejection is otherwise manageable, temporary cessation of tacrolimus could be more widely explored in this challenging clinical context. Pediatr Blood Cancer 2015;62:214-218. © 2014 Wiley Periodicals, Inc.

Topics: Anemia, Hemolytic, Autoimmune; Child; Child, Preschool; Female; Humans; Immunologic Factors; Immunosuppressive Agents; Infant; Male; Neutropenia; Organ Transplantation; Retrospective Studies; Rituximab; Tacrolimus; Thrombocytopenia; Treatment Outcome

AIHA is a rare and serious complication of solid organ transplantation. Herein, we report four cases of warm or mixed AIHA in pediatric patients following combined liver, small bowel and pancreas transplant. The hemolysis was refractory to multiple treatment modalities including steroids, rituximab, IVIG, plasmapheresis, cytoxan, discontinuation of prophylactic penicillin, and a change in immunosuppression from tacrolimus to cyclosporine. All patients had resolution or marked improvement of hemolysis after discontinuation of maintenance of CNI and initiation of sirolimus immunosuppression. One patient developed nephrotic syndrome but responded to a change in immunosuppression to everolimus. Three of the four patients continue on immunosuppression with sirolimus or everolimus without further hemolysis, evidence of rejection or medication side effects. Based on our experience and review of similar cases in the literature, we have proposed a treatment algorithm for AIHA in the pediatric intestinal transplant patient population that recommends an early change in immunosuppressive regimen from CNIs to sirolimus therapy.

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Murine-Derived; Calcineurin; Cyclophosphamide; Cyclosporine; Everolimus; Female; Hemolysis; Humans; Immunoglobulins, Intravenous; Immunosuppression Therapy; Immunosuppressive Agents; Infant; Intestines; Liver Transplantation; Male; Medical Records; Nephrotic Syndrome; Pancreas Transplantation; Penicillins; Plasmapheresis; Retrospective Studies; Rituximab; Sirolimus; Steroids; Tacrolimus; TOR Serine-Threonine Kinases; Transplantation; Treatment Outcome

Topics: Anemia, Hemolytic, Autoimmune; Child; Cholangitis, Sclerosing; Cyclosporine; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Syndrome; Tacrolimus; Treatment Outcome

Autoimmune hemolytic anemia (AIHA) has been reported to occur after renal transplantation, and typically does so in the first few weeks post-transplant. We report on a 3-yr-old child who developed cold AIHA nearly 1 yr after an ABO identical, living donor renal transplant from his mother. Numerous transfusions, pulse steroids, repeat plasma exchange treatments, and IVIG were unsuccessful. Nearly 3 wk into his illness, tacrolimus was changed to cyclosporine, and then to sirolimus, and resulted in a prompt response. He currently has a normal renal function and a normal hemoglobin level on sirolimus monotherapy.

Topics: Anemia, Hemolytic, Autoimmune; Child, Preschool; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Nephrotic Syndrome; Sirolimus; Tacrolimus; Time Factors; Treatment Outcome

Topics: Adenoviridae Infections; Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Bone Marrow Transplantation; Cyclophosphamide; Female; Graft vs Host Disease; Humans; Methotrexate; Myelodysplastic Syndromes; Tacrolimus; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome

Standard treatment for autoimmune hemolytic anemia (AIHA) due to warm antibodies includes combinations of glucocorticoids, immunosuppressive drugs (mainly azathioprine) and splenectomy. Patients who are refractory or intolerant to these therapies constitute an important therapeutic challenge. Rituximab, an anti-CD20 chimeric monoclonal antibody, can effectively deplete B-cells and is commonly used in B-cell non-Hodgkin lymphoma. In addition, it is being increasingly used in autoimmune disorders, such as idiopathic thrombocytopenic purpura, AIHA, systemic lupus erythematosus or vasculitis. We report a case of warm AIHA associated to primary antiphospholipid syndrome (APS). The patient was refractory to high-dose corticosteroids. Splenectomy was discarded in view of the high risk of thrombotic and/or hemorrhagic perioperative complications, due to the presence of APS. After treatment with four weekly doses of rituximab the patients had a rapid and sustained response which allowed progressive tapering of prednisone dose to 5 mg/d. In addition, IgM anticardiolipin titres decreased from > 600 MPL to < 100 MPL. Thirteen further cases of warm AIHA in adults treated with rituximab have been reviewed, showing excellent tolerance and high response rates. Rituximab may be considered prior to splenectomy in patients with refractory AIHA and high risk of complications following splenectomy.

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antiphospholipid Syndrome; Contraindications; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Methylprednisolone; Middle Aged; Postoperative Complications; Prednisone; Remission Induction; Rituximab; Splenectomy; Stroke; Tacrolimus; Vasculitis

Topics: ABO Blood-Group System; Anemia, Hemolytic, Autoimmune; Cyclosporine; Humans; Immunosuppressive Agents; Isoantibodies; Kidney Transplantation; Male; Middle Aged; Tacrolimus

Tacrolimus (formerly known as FK506) is a macrolide immunosuppressant that has been used to prevent rejection of solid organ allografts. Acute hemolytic anemia is one of the side effects associated with tacrolimus therapy, and two mechanisms have been described to account for acute hemolytic anemia in patients receiving tacrolimus: drug-induced hemolysis and alloimmune hemolysis resulting from donor lymphocytes derived from the allograft (passenger lymphocyte syndrome). We report a case of a liver transplant recipient who developed fatal autoimmune hemolytic anemia while under treatment with tacrolimus for allograft rejection, and in whom postmortem examination revealed a clinically unsuspected posttransplant lymphoproliferative disorder. This case implicates autoimmune hemolytic anemia as a novel mechanism of acute hemolysis in patients treated with tacrolimus and further suggests that acute hemolytic anemia in this group of patients may herald an occult lymphoproliferative disorder.

Topics: Anemia, Hemolytic, Autoimmune; Child; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Lymphoproliferative Disorders; Male; Postoperative Complications; Tacrolimus