Hematologic abnormalities in children and young adults receiving tacrolimus-based immunosuppression following cardiothoracic transplantation

To define the incidence, course, and etiology of hematologic abnormalities in children on tacrolimus-based immunosuppression, we reviewed records of 106 transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to 1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous anemia and neutropenia with or without thrombocytopenia). Common etiologies included: infections, post-transplant lymphoproliferative disease, and medications. Eleven episodes (seven anemia, one neutropenia, and three simultaneous anemia and neutropenia) had unclear etiologies and process of elimination suggested an association with tacrolimus. Interventions included filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a median of 5 days) and epoetin alfa (effective in five of 16 patients, including four of four patients with anemia possibly related to tacrolimus). Five patients (two with neutropenia and three with simultaneous neutropenia and anemia) were switched to cyclosporin A (CsA); rapid resolution occurred in four of the five patients, suggesting a possible association of the hematologic abnormalities with tacrolimus. In summary, hematologic abnormalities are common in children on tacrolimus-based immunosuppression. Most of these hematologic abnormalities are caused by common etiologies; however, a sub-population exists where tacrolimus may be the etiologic agent. Anemia and neutropenia respond to treatment with epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA may be warranted.