Successful management of sirolimus toxicity in a hematopoietic stem cell transplant patient using automated red blood cell exchange.

BACKGROUND: Sirolimus is an immunosuppressive agent used in organ rejection prophylaxis in solid-organ transplantation, graft-vs-host disease prophylaxis in hematopoietic stem cell transplantation, and as an immune modulator for patients with lymphangioleiomyomatosis and vascular malformations. Sirolimus has a narrow therapeutic index with potential severe side effects, including hypertension, hepatotoxicity, nephrotoxicity, and neurotoxicity. CASE REPORT: We report a case of a 19-year-old woman with severe sickle cell disease who underwent a matched unrelated hematopoietic stem cell transplantation, whose course was complicated by sirolimus toxicity. This case was challenging because sirolimus has no specific antidote, is largely bound to red blood cells (RBCs), has a high distribution volume, and cannot be removed by dialysis or plasmapheresis. RESULT: Due to the concern for toxicity, we looked into possibilities for rapid sirolimus clearance using automated RBC exchange. The treatment was effective in decreasing blood sirolimus levels within the therapeutic ranges. CONCLUSION: The use of RBC exchange is potentially safe and effective in the management of a case of sirolimus toxicity.

Use of dual lumen ports for red blood cell exchange: A comparison of adults and children with sickle cell disease.

PURPOSE: Sickle cell patients receiving chronic RBC exchange require a form of long-term central venous access if peripheral access is inadequate. In adults, dual lumen (DL) ports have been utilized but associated with greater procedure complications and duration when compared to other forms of access. In the pediatric sickle cell population, the use of DL ports for RBC exchange has not been well described. In this retrospective cohort study, RBC exchange procedures utilizing DL ports in the pediatric vs adult sickle cell population were compared. METHODS: Medical records were reviewed for 685 RBC exchange procedures performed on 25 patients (11 pediatric and 14 adult) between November 2014 to November 2018. Patient-level characteristics and outcomes were compared between pediatric and adult patients using the Fisher-exact and Wilcoxon-rank sum test. Linear/logistic regression models examined procedure-level parameters and port characteristics with adjustment for clustering. RESULTS: Compared to adults, pediatric patients had slower average maximum inlet speed (42 vs 53 mL/min, P < .01), but shorter procedure time (60 vs 75 minutes, P < .01) and lower rate of access alarms (1% vs 11%, P < .01). Overall, 0.29 thrombotic events per 1000 port days and 0.04 infections per 1000 port days were observed. CONCLUSION: For adult and pediatric sickle cell patients, a DL port provides a viable option for RBC exchange. In comparison to adults, pediatric procedures with a DL port will typically be shorter and with less procedural complications due to smaller blood volumes and lower flow requirements.

Successful treatment of severe refractory autoimmune hemolytic anemia after hematopoietic stem cell transplant with abatacept.

BACKGROUND: After hematopoietic stem cell transplantation (HSCT) autoimmune hemolytic anemia (AIHA) is a known and fairly common complication. It is often refractory to conventional therapies including corticosteroids, intravenous immunoglobulin, splenectomy, and the more recently described use of monoclonal antibodies. The high morbidity associated with these severe persistent cases elucidates the gaps in alternative therapies available for treatment. STUDY DESIGN AND METHODS: We described the successful use of abatacept for severe refractory AIHA after HSCT in three patients. RESULTS: Three pediatric patients with refractory AIHA after allogeneic stem cell transplantation were observed to be unresponsive to multitude immunosuppressive therapies, resulting in persistent transfusion dependency. Treatment with abatacept, a fusion protein that inhibits T-cell activation by binding to CD80/CD86 on antigen-presenting cells (APCs), thus blocking the required CD28 interaction between APCs and T cells, resulted in the resolution of hemolysis. CONCLUSION: Abatacept may provide significant clinical benefit in the management of AIHA after HSCT.

Fresh whole blood versus reconstituted blood for pump priming in heart surgery in infants.

BACKGROUND: In an attempt to reduce the coagulopathic and inflammatory responses seen after cardiopulmonary bypass, the use of fresh whole blood during heart operations has become the standard of care for neonates and infants at many institutions. We compared the use of fresh whole blood with the use of a combination of packed red cells and fresh-frozen plasma (reconstituted blood) for priming of the cardiopulmonary bypass circuit. METHODS: We conducted a single-center, randomized, double-blind, controlled trial involving children less than one year of age who underwent open-heart surgery. Patients were assigned to receive either fresh whole blood that had been collected not more than 48 hours previously (96 patients) or reconstituted blood (104 patients) for bypass-circuit priming. Clinical outcomes and serologic measures of systemic inflammation and myocardial injury were compared between the groups. RESULTS: The group that received reconstituted blood had a shorter stay in the intensive care unit than the group that received fresh whole blood (70.5 hours vs. 97.0 hours, P=0.04). The group that received reconstituted blood also had a smaller cumulative fluid balance at 48 hours (-6.9 ml per kilogram of body weight vs. 28.8 ml per kilogram, P=0.003). Early postoperative chest-tube output, blood-product transfusion requirements, and levels of serum mediators of inflammation and cardiac troponin I were similar in the two groups. CONCLUSIONS: The use of fresh whole blood for cardiopulmonary bypass priming has no advantage over the use of a combination of packed red cells and fresh-frozen plasma during surgery for congenital heart disease. Moreover, circuit priming with fresh whole blood is associated with an increased length of stay in the intensive care unit and increased perioperative fluid overload.

Transfusion-related acute lung injury (TRALI) following allogeneic stem cell transplant for acute myeloid leukemia.

Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion characterized by dyspnea, hypoxemia, hypotension, fever, and bilateral pulmonary infiltrates. Although the frequency is estimated at 1/1,120 to 1/5,000 transfusions, few cases have been reported after hematopoietic stem cell transplant. We report a case occurring in an allogeneic transplant recipient who developed acute respiratory distress and bilateral pulmonary infiltrates 2 hr after a platelet transfusion due to the presence of anti granulocyte antibody HNA-3a in the product. As there is a wide differential diagnosis for pulmonary infiltrates developing post transplant, TRALI may be under-recognized and should be considered in this setting.