HOUSTON – Use of an alemtuzumab/fludarabine conditioning regimen – without any radiation or alkylating agents – was effective in patients with a systemic regenerative disease who experienced myeloid failure after allogeneic transplantation, according to an investigator.
Of the 20 patients with dyskeratosis congenita who received the regimen, 19 achieved primary engraftment within 42 days of transplant, according to Suneet Agarwal, MD, PhD, of Dana-Farber/Boston Children’s Cancer & Blood Disorders Center and Harvard Medical School, Boston.
However, these findings may have broader implications beyond this rare disease, as this is the first reported series of patients undergoing allogeneic bone marrow transplant to achieve durable myeloid engraftment without receiving alkylating agents or radiation, Dr. Agarwal said at the Transplantation & Cellular Therapy Meetings.
In a late-breaking clinical trial presentation of the results, Dr. Agarwal noted that patients in this study all had telomere disease, defined by clinical syndrome, gene mutation, or short lymphocyte telomere length. That’s because the investigators hypothesized that telomere defects would result in a “replicative disadvantage” in hematopoietic and immune cells, which would favor engraftment.
Dyskeratosis congenita is a prototypic telomere biology disorder caused by mutations that impair telomere maintenance, he said, adding that the disease has high rates of cancer, pulmonary disease, and hepatic disease.
While allogeneic transplants are curative in the disorder, outcomes after transplantation are typically poor, with high rates of bone marrow failure, he added. By eliminating radiation and alkylator exposure, the investigators hoped salvage bone marrow transplant would be more feasible, with lower risks of organ failure and secondary malignancy.
The 20 patients Dr. Agarwal reported on were aged from 30 months to 65 years. They all received alemtuzumab/fludarabine conditioning starting at day 9 before bone marrow graft, along with graft-versus-host disease (GVHD) prophylaxis through the pre- to posttransplant period. Two had matched siblings, while 18 had unrelated donors.
Of those 20 patients, 19 achieved primary engraftment at a median of 22 days after transplant, Dr. Agarwal reported. There was no acute GVHD and four cases of chronic GVHD that resolved with oral or topical steroids.
Of the 20 patients, 18 were alive at a median follow-up of 24 months, which compares favorably with historically reported cases, according to the investigator. There was one disease-related death and one treatment-related death caused by fungal infection at 3 months post transplant, he said.
These results suggest the radiation- and alkylator-free conditioning regimen is “effective,” Dr. Agarwal said, adding that exposure to those modalities is not required for myeloid engraftment in certain clinical settings.
The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Agarwal reported having no conflicts of interest.
SOURCE: Agarwal S et al. TCT 2019, Abstract LBA2.