Intravenous chelation therapy during transplantation for thalassemia

Thalassemia patients with heavy iron overload risk further increase of body iron stores after bone marrow transplantation (BMT) due to intensive red-cell transfusions in the post BMT course and to massive mobilization of iron deposits from marrow cells following the conditioning regimen. Nevertheless, iron chelation has not yet been used during the transplant period, mainly for concerns related to the toxicity and antiproliferative properties of the drug.

Fifteen thalassemic patients received desferrioxamine (DFO) before and during BMT according to two different schedules (first: from day -9 to day +60, and second: from day -9 to day -2, then from day +28 to day +60) at a dose of 40 mg/kg/day as a 24-hour intravenous infusion.

The median time to neutrophil, platelet and erythrocyte recovery showed no difference between DFO-treated patients and the control group (18 days vs. 15, 16 vs. 18 and 22 vs. 23, respectively; p: N.S.). The incidence of acute GVHD was 23% in the DFO group and 13% in controls (p: N.S.). The median serum ferritin (SF) at 6 months after BMT was significantly lower in the DFO-treated patients (2081 versus 4187; p: 0.007) than in the control group. This difference continued to be evident, though not statistically significant, during longer follow-up.

Intravenous DFO therapy during BMT does not seem to have affected the engraftment parameters or the incidence of infections or GVHD. No adverse effects were observed during the therapy. Therefore thalassemic patients with heavy iron overload can be candidates for a course of i.v. chelation during the transplant period. This therapy could also be followed by post-BMT iron removal (i.e. phlebotomies or desferrioxamine) to accelerate the clearance of body iron deposits.