Acute graft-versus-host disease of the heart.

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality after bone marrow transplantation. Acute GVHD most commonly involves the skin, gastrointestinal tract, and liver. Involvement of other organ systems is rare and remains controversial. We report a patient with GVHD who suffered a fatal ventricular arrhythmia shortly after bone marrow transplantation. Autopsy of the heart showed lymphocyte infiltration. Investigations for cardiotrophic viruses were negative, and chimerism analysis of the heart showed both donor and recipient DNA. We conclude that the cause of death was possibly graft-versus-host disease of the heart. A review of the literature revealed a total of 14 cases of possible cardiac GVHD. All but one of the reported cases have occurred in pediatric patients and six of those patients died, suggesting that this may be a rare but frequently fatal complication of pediatric allogeneic stem cell transplant.

Sustained engraftment post bone marrow transplant despite anti-platelet antibodies in Glanzmann thrombasthenia.

BACKGROUND: Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life-threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type I GT and discuss the risk and management of anti-platelet antibodies. PATIENTS AND RESULTS: Diagnosis of GT was made through abnormal platelet aggregation studies or the absence of GPIIb/IIIa by flow cytometry. All patients had severe bleeding requiring multiple red blood cell transfusions. One patient received an unrelated donor transplant and two received matched sibling donor transplants following conditioning therapy with busulfan, cyclophosphamide, and fludarabine. Two patients developed an anti-platelet antibody, treated in one with intravenous immune globulin (IVIG). Engraftment of white blood cells and platelets was achieved on day +13 to +14 and +17 to +25, respectively. Complete donor chimerism and GPIIb/IIIa+ platelets are sustained at +22 to +30 months post transplant. CONCLUSIONS: In summary, patients with GT and history of severe hemorrhage can be cured with BMT, but the presence of anti-platelet antibodies should be sought and platelet transfusions minimized prior to transplant. IVIG may be helpful in cases of refractory immune thrombocytopenia related to anti-platelet antibodies. Improvement in transplant-related complications with current transplant regimens allows consideration of BMT for life-threatening non-malignant disorders such as GT.

Diagnosis and treatment of children with aplastic anemia.

BACKGROUND: Long-term survival rates among children diagnosed with severe aplastic anemia (SAA) are excellent due to the success of human leukocyte antigen (HLA)-identical related hematopoietic stem cell transplantation (HSCT), concurrent advances in immunosuppressive treatment (IST), and improved supportive care. The challenge in making treatment recommendations for children with SAA, therefore, is to balance the apparent chronicity and morbidity following IST, with the potential up-front toxicity and complications of HSCT. METHODS: This review provides an update on the diagnosis and a risk-based treatment algorithm for children with acquired SAA. Recent experience using alternative donor HSCT and efforts to extend HSCT eligibility through advances in donor matching, de-escalation of conditioning regimens, and potential marrow graft engineering are highlighted. We discuss IST response rates, risks of relapse, and complications including clonal evolution. CONCLUSIONS: While good treatment options exist for a majority of children diagnosed with SAA, novel non-transplantation treatments for unresponsive and relapsed patients without suitable transplant donors are needed. Further improvements in outcome will ultimately require a more complete understanding of the pathophysiology of aplastic anemia (AA).