tacrolimus and Anemia--Hemolytic

A calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens.

Topics: Adult; Aged; Anemia, Hemolytic; Everolimus; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Sirolimus; Survival Rate; Tacrolimus; Transplantation, Homologous

Initial reports indicated the possibility of severe anemia associated with tacrolimus (TC) therapy. We investigated the degree of anemia under TC treatment in comparison to cyclosporine A (CsA) treatment in children after renal transplantation. A cross-sectional analysis of 95 children successfully transplanted for at least 3 months was performed. Eighty-five children received CsA and 10 TC. TC-treated patients were compared with CsA-treated patients who were matched according to age, gender, creatinine clearance, and time after transplantation. No patient received additional therapy with mycophenolate mofetil or azathioprine. The creatinine clearance of the whole group of transplanted children was 58 ml/min per 1.73 m2. The patients within the matched-pair analysis had a lower creatinine clearance (TC 46 and CsA 48 ml/min per 1.73 m2). The hemoglobin was 10.3 g/dl for the TC-treated children and 10.4 g/dl among the CsA-treated patients. Numerically, EPO was higher and iron lower in the TC group than in the CsA group. Among children with functioning renal grafts, a correlation exists between Hb and creatinine clearance. A significant difference in the degree of anemia between TC- and CsA-treated children could not be found.

Topics: Adolescent; Anemia, Hemolytic; Child; Cross-Sectional Studies; Cyclosporine; Humans; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Severity of Illness Index; Tacrolimus

We report a 17-yr-old boy who developed a microangiopathic hemolytic anemia presumed secondary to tacrolimus shortly following a living-related donor renal transplant. This was initially managed by plasmapheresis. Reinstitution of calcineurin inhibition using cyclosporine led to recurrence of hemolysis, so an alternative agent was needed. He was commenced on monthly intravenous belatacept, with no further recurrence of the hemolysis, and subsequent stable graft function. Modulation via CTLA-4 offers an alternative immunosuppressive tactic if current regimens produce graft threatening adverse effects. The method of administration and frequency of dosage of belatacept also lends itself well to the high-risk period of adolescence and transition. We propose that belatacept may therefore also have utility in difficult cases complicated by poor concordance, common in the adolescent age group.

Topics: Abatacept; Adolescent; Anemia, Hemolytic; B7-1 Antigen; B7-2 Antigen; Calcineurin; CTLA-4 Antigen; Graft Rejection; Hemolysis; Humans; Immunoconjugates; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Plasmapheresis; Postoperative Complications; Recurrence; Tacrolimus; Treatment Outcome

TMA is a rare complication of tacrolimus. Disruption of endothelial cells, platelet aggregation, and intravascular mechanical fragmentation of red cells are core mechanisms of injury; however, exact pathways of toxicity are not clear. The clinical presentation may vary but TMA is a potentially life-threatening condition usually demanding aggressive treatment. We present the case of TMA in a child after living-related liver transplantation (LRLTx) on tacrolimus-based immunosuppressive regiment successfully converted to sirolimus.

Topics: Anemia, Hemolytic; Biopsy; Erythrocytes; Female; Graft Survival; Humans; Immunosuppressive Agents; Infant; Liver Failure; Liver Transplantation; Living Donors; Platelet Aggregation; Sirolimus; Tacrolimus; Thrombotic Microangiopathies; Treatment Outcome

Immunosuppressive drugs used post-transplantation are among the most common causes of thrombotic thrombocytopenic purpura (TTP). Diagnosis is often confounded not only by its myriad presentations, but also because these manifestations may be explained by the comorbidities or complications of transplantation. A 61-year-old female who had a single lung transplant for severe chronic obstructive pulmonary disease maintained on corticosteroids, tacrolimus and mycophenolate mofetil, was admitted for fever, headache with confusion and lethargy. She was mildly anemic and thrombocytopenic. Peripheral smear showed rare fragmented red cells. Muddy brown casts were present on urinalysis. She was diagnosed with TTP. Tacrolimus was discontinued and the mental status of the patient, anemia and thrombocytopenia improved significantly.

Topics: Anemia, Hemolytic; Female; Humans; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Purpura, Thrombotic Thrombocytopenic; Tacrolimus; Urinalysis

Transplant-associated microangiopathy (TAM) is a life-threatening complication after allogeneic HSCT, particularly with the use of calcineurin inhibitors as post-transplantation immunosuppressive therapy. We report our experience with TAM after HSCT with tacrolimus-based GVHD prophylaxis in a single-center study. Sixty-six of 1219 transplant recipients developed TAM with a cumulative incidence of 5.9%. Risk factors for TAM were female gender, lymphoid malignancy, receipt of a matched unrelated donor, and grade II-IV aGVHD. Most patients had infection and/or active GVHD at the diagnosis of TAM (82%). In the absence of renal dysfunction or encephalopathy, tacrolimus was generally continued, maintaining blood levels within the lower therapeutic range. Sixty-three patients were treated with plasma exchange. The cumulative incidence of response of TAM was 60%. Only 1 patient had a response of TAM without resolution of concomitant infections or GVHD. Six-month survivals were 0% and 50% for TAM nonresponders and responders, respectively. In conclusion, TAM is a common, life-threatening complication of allogeneic hematopoietic transplantation using tacrolimus prophylaxis. Control of TAM generally requires response of associated infections and GVHD. TMA response may occur despite continuation of tacrolimus treatment.

Topics: Adult; Anemia, Hemolytic; Cohort Studies; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Plasma Exchange; Proportional Hazards Models; Retrospective Studies; Risk Factors; Tacrolimus; Thrombocytopenia; Transplantation, Homologous

The aim of the study was to demonstrate clinical course of the first reported cases of PLS in pediatric kidney transplantation and therapeutic outcome for such condition using a combination of high-dose corticosteroid and tacrolimus. We report a single case (a nine-year-old Thai boy) with end-stage kidney disease secondary to obstructive uropathy developed immune-mediated hemolytic anemia from the PLS at second week after a pre-emptive living-related kidney transplantation. The alloimmune hemolysis was a result of anti-B antibodies, derived from blood group O-donor lymphocytes. Using a combination of high-dose corticosteroid and a substitution of cyclosporin with tacrolimus, there was no further hemolysis although the anti-B antibodies remained detectable until the eighth week post-transplantation. An impairment of the graft function because of hemoglobinuria was resolved after the hemolysis was stopped. The alloimmune hemolysis caused by PLS in pediatric kidney transplantation could be controlled with a combination of high-dose corticosteroid and tacrolimus.

Topics: Anemia, Hemolytic; Child; Cyclosporine; Glucocorticoids; Humans; Kidney Transplantation; Living Donors; Male; Methylprednisolone; Mycophenolic Acid; Prednisolone; Tacrolimus

Topics: Agglutinins; Anemia, Hemolytic; Autoantibodies; Biliary Atresia; Child; Cryoglobulins; Cyclosporine; Drug Therapy, Combination; Family; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Methylprednisolone; Postoperative Complications; Tacrolimus; Treatment Outcome

Microangiopathic haemolytic anaemia (MAHA) describes intravascular haemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels. It is well recognized as a complication of cyclosporin A therapy in solid organ transplantation but has been uncommonly reported in association with tacrolimus therapy and never before in the setting of lung transplantation. Discussed is a 54-year-old female recipient of a left single lung transplant who developed anaemia, thrombocytopenia and red blood cell fragmentation consistent with MAHA following lung volume reduction surgery (VRS) of the native right lung in the setting of high serum tacrolimus levels. Treatment with fresh frozen plasma and plasmapharesis plus supportive therapy with blood and platelet transfusions resulted in successful resolution of the haemolytic process. Cyclosporin A was substituted for tacrolimus and 18 months later there has been no evidence of recurrence. Tacrolimus therapy is a rare cause of MAHA in solid organ transplants but the diagnosis should be considered if there is an unexplained fall in haemoglobin and/or platelet count in the context of high serum tacrolimus levels.

Topics: Anemia, Hemolytic; Diagnosis, Differential; Emphysema; Female; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Plasmapheresis; Tacrolimus; Thrombocytopenia

Alloimmune hemolytic anemia is a rare complication following allogeneic organ transplantation. Despite that some other drugs have also been reported, in the majority of cases this complication has been associated with cyclosporine therapy. We here present a case of severe alloimmune hemolytic anemia due to ABO minor incompatibility after renal transplantation in a patient treated with tacrolimus.

Topics: ABO Blood-Group System; Adult; Anemia, Hemolytic; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Postoperative Complications; Tacrolimus

Microangiopathic hemolytic anemia (MAHA) is a well-described complication of stem cell transplantation. Plasmapheresis is one modality utilized as therapy for patients who develop this complication. However, plasmapheresis may alter whole blood levels of certain medications and its effect on tacrolimus in bone marrow transplant patients is unknown. Because tacrolimus has a narrow therapeutic range, the effect of plasmapheresis on whole blood concentrations would be important to know. We report three allogeneic BMT patients who were receiving tacrolimus as acute GVHD therapy while undergoing plasmapheresis for MAHA. Tacrolimus levels seemed unaffected by plasmapheresis in these patients.

Topics: Adult; Anemia, Hemolytic; Bone Marrow Transplantation; Female; Humans; Immunosuppressive Agents; Infant; Plasmapheresis; Tacrolimus; Transplantation, Homologous

A case of X-linked autoimmune enteropathy was successfully treated with cyclosporine A (CsA) or tacrolimus (FK506) and developed extremely high serum levels of IgE during the immunosuppressive therapy. Serum IgE levels increased from 190 to 1,000-2,500 IU/ml with CsA therapy and as high as 80,000 IU/ml with subsequent FK506 therapy. Serum IgG2 and IgG4 levels were slightly elevated compared to serum IgE levels. Thereafter, serum IgE levels progressively decreased in parallel with a reduced dosage of FK506. Total serum IgG levels and peripheral eosinophil counts, however, showed no significant changes during the course. These observations suggest that both CsA and FK506, potent immunosuppressants, could paradoxically enhance some immune responses, possibly through the action of CsA-/FK506-resistant immune systems.

Topics: Anemia, Hemolytic; Child; Cyclosporine; Humans; Immunoglobulin E; Intestinal Diseases; Male; Polyendocrinopathies, Autoimmune; Tacrolimus

We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.

Topics: Adrenal Cortex Hormones; Anemia, Hemolytic; Aspirin; Dipyridamole; Heart Transplantation; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Plasma; Plasma Exchange; Tacrolimus

Topics: Adult; Anemia, Hemolytic; Bone Marrow Transplantation; Complement System Proteins; Erythrocytes; Female; Hemolysis; Humans; Liver Transplantation; Male; Tacrolimus