ORLANDO—Low doses of alemtuzumab were effective in preventing graft-versus-host disease (GVHD) in leukemia patients receiving sibling and matched unrelated hematopoietic cell transplants.
A small, prospective study from Greece found alemtuzumab 10 mg effective in reducing GVHD among patients receiving stem cell transplants to treat acute leukemias. Alexandros Spyridonidis, MD, PhD, presented the results at the 52nd American Society of Hematology annual meeting and exposition.
Spyridonidis and colleagues from the hematology/bone marrow transplantation unit at the University of Patras enrolled 18 consecutive patients. Thirty-nine percent underwent sibling and 61% unrelated allogeneic transplantation to treat acute myeloid leukemia or acute lymphoblastic leukemia. Thirty-nine percent of the patients had advanced disease at transplant.
The participants received a total dose of 10 mg of alemtuzumab, 5 mg/day for the 2 days before transplant as part of the conditioning regimen. Typical doses are as high as 100 mg and are often associated with infections. The patients also received cyclosporine posttransplant but no methotrexate.
“What we’ve done is reduce the dose to very low,” Spyridonidis said. “We got serum [alemtuzumab] levels of about 200 ng/mL with good results. We got to prevent graft-versus-host disease, and we didn’t have problems with infection. We still have serum levels that are lymphotoxic.”
Two patients developed severe opportunistic infections. Seven patients experienced acute GVHD: three grade 1, two grade 2, and one each of grade 3 and 4 (both of which occurred after stopping cyclosporine early). In addition, two patients developed chronic GVHD, including a fulminant and fatal liver GVHD at day 143.
Another patient died at day 201 of H1N1 pneumonia while under immunosuppression for acute gut GVHD. Another patient died on day 486 of bronchiolisis obliterans, after donor leukocyte infusions.
“Seventy-seven percent of patients survived 1 year,” Spyridonidis said.
The median alemtuzumab serum peak level was 176 ng/mL on the day of transplantation, with levels declining slowly until reaching a median serum level on day 7 of 78 ng/mL. At day 20, the serum levels were just above the detection limit, with a median of 42 ng/mL.
Spyridonidis suspects that with sibling donors, the dose could be lower, but research would need to determine that. He also suggests that a large, prospective randomized trial will be required to confirm his group’s results.
“We are now giving the lower dose in clinical practice,” said Spyridonidis, adding that some other transplant centers have begun using the lower dose of alemtuzumab as well. He said, “The benefits we saw were fast engraftment, especially for platelets; a low infection rate; and a low relapse rate. And we can control graft-versus-host disease.”