Complications of red cell exchange for anemia management in patients with transfusion-dependent thalassemia.

BACKGROUND: In the Rare Blood Disorders clinic at the University of Alberta in Edmonton, red cell exchange (RCE) was utilized in transfusion-dependent thalassemia (TDT) patients with severe iron overload despite oral chelation and no access to iron infusion pumps for parenteral chelation. It was hypothesized that RCE would be less iron loading compared to simple transfusion. The purpose of this study is to document observations of the potential risks and benefits of RCE in TDT patients. STUDY DESIGN AND METHODS: TDT patients treated with RCE were identified and consented for enrolment according to local research ethics standards. Seven patients were enrolled in the study. Charts were retrospectively reviewed from the time of initiation of RCE to the time of the most recent RCE or clinic follow-up. Outcomes were documented and analyzed by descriptive analysis. RESULTS: The average age was 30 years. 85.7% were male. 100% were on oral chelation therapy and had hyperferritinemia at baseline. Outcomes included hepatic iron overload (5 of 7), cardiac dysfunction (3 of 7), worsening splenomegaly or extramedullary hematopoiesis (5 of 7), syncopal events during RCE (2 of 7), and new antibodies (1 of 7). Iron overload improved after escalated oral chelation, not in relation to RCE initiation. DISCUSSION: We hypothesize complications were higher than expected due to inadequate hematocrit increment and lack of suppression of ineffective erythropoiesis. With no observed benefit in iron status, and high complication rates, we did not find evidence to recommend RCE in patients with TDT. This case series is a hypothesis-generating study on transfusion techniques in TDT.

The fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline-based therapy for the treatment of acute myeloid leukemia for patients with pre-existing cardiac disease.

We conducted a retrospective study assessing FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor) as first-line treatment in 56 newly diagnosed acute myeloid leukemia patients considered ineligible for anthracycline-based treatment due to advanced age, significant comorbidities, or pre-existing cardiac disease. The median age was 69 (21-80); 46% received FLAG for pre-existing cardiac disease and others due to age (32%), non-cardiac comorbidities (20%), or previous anthracycline exposure (2%). The induction mortality was 16% and, among evaluable patients, 48% achieved a complete remission after the first induction course with an additional patient achieving a remission after a second course for a total complete remission rate of 50%. Four patients proceeded to an allogeneic stem cell transplant including two with pre-existing cardiac disease. Among non-transplanted patients, the relapse rate (RR) was 47%. When censored at time of stem cell transplant, the median relapse-free survival was 14.7 months. The median overall survival was 9.3 months with 1- and 2-yr survivals of 44% and 22%, respectively. There was no difference in clinical outcomes between patients treated with FLAG for cardiac reasons vs. other reasons. In conclusion, FLAG is a useful alternative to anthracycline-based induction for Acute myeloid leukemia in those with significant comorbidities including pre-existing cardiac disease.