HSCT approach provides ‘excellent’ survival in FA
SALT LAKE CITY—A “risk-adjusted” approach leads to “excellent” survival in patients with Fanconi anemia (FA) undergoing alternative donor hematopoietic stem cell transplant (HSCT), according to a speaker at the 2018 BMT Tandem Meetings.
All FA patients who received personalized doses of busulfan in place of total body irradiation (TBI) were alive and disease-free after undergoing HSCT for bone marrow failure or myelodysplastic syndrome (MDS).
None of the patients developed graft-vs-host disease (GVHD), and the most common toxicity was viral infection.
Parinda A. Mehta, MD, of Cincinnati Children’s Hospital Medical Center in Ohio, presented these results at this year’s BMT Tandem Meetings as abstract 109.*
“We all know that inherent chemotherapy and radiation sensitivity makes transplant for patients with Fanconi anemia quite challenging,” Dr Mehta began. “In our recently published, prospective, multi-institutional study, we showed excellent outcomes of alternative donor transplant in patients with Fanconi anemia without using radiation.”
“In that study,** TBI was replaced by pharmacokinetically adjusted busulfan. It proved that, yes, we can do alternative donor transplant successfully without radiation by showing an overall survival of 80% for a total of 45 patients. We were quite ecstatic to see these numbers.”
The study also showed that younger patients fared better with this regimen, and younger patients did best with the lowest dose of busulfan tested (0.6 mg/kg vs 0.8 to 1.0 mg/kg). In addition, patients who underwent HSCT for bone marrow failure had better outcomes than patients who had MDS.
This led Dr Mehta and her colleagues to hypothesize that adjusting busulfan dosing based on a patient’s age and disease status at HSCT could minimize toxicity and improve outcomes.
Patients
The researchers tested their theory in 22 FA patients. They had a median age of 7 (range, 4-27), and most (n=13) were female.
Twelve patients had pancytopenia, 6 had severe single-lineage cytopenia, 3 had low-grade MDS, and 1 patient had acute myeloid leukemia (AML).
Eighteen patients had a history of transfusions, and 3 had a history of androgen use.
Treatment
The preparative regimen consisted of 4 doses of busulfan (every 12 hours on day -7 to -6), followed by cyclophosphamide at 10 mg/kg/day (on day -5 to -2), fludarabine at 35 mg/m2/day (on day -5 to -2), and rabbit antithymocyte globulin at 2.5 mg/kg/day (on day -5 to -2).
Busulfan doses were adjusted according to age and disease status.
Children (age 18 and younger) with bone marrow failure received busulfan at 0.6 to 0.8 mg/kg. Children with MDS/AML received busulfan at 0.8 to 1.0 mg/kg. Adults (19 and older) received the lowest dose of busulfan—0.4 mg/kg—regardless of disease status.
“At the first sight, this will look counterintuitive . . . ,” Dr Mehta said. “However, based on our previous experience, in general and also from results of our previous study, this was specifically designed to avoid upfront TRM [transplant-related mortality] for these adult patients.”
All 22 patients received CD34-selected, T-cell-depleted peripheral blood stem cells from unrelated donors. Eleven patients received a fully matched graft (10/10), 8 patients had a 9/10 match, and 3 had an 8/10 match.
The median number of CD34+ cells/kg was 23.9 x 106 (range, 4.9-76.6), and the median number of CD3 cells/kg was 1 x 104 (range, 0.003-3.1).
T-cell depletion was the only GVHD prophylaxis used.
Patients with MDS/AML could receive azacitidine at day 42 after HSCT, an option intended to prevent relapse in these patients.
Toxicity
There were no cases of acute or chronic GVHD.
