Photo by Chad McNeeley
A retrospective study suggests that, for patients with hematologic disorders, a haploidentical hematopoietic stem cell transplant (HSCT)
can be roughly as safe and effective as a fully matched HSCT.
The study showed that, when patients received an identical conditioning regimen, graft T-cell dose, and graft-vs-host disease (GVHD) prophylaxis, haploidentical and fully matched HSCTs produced comparable results.
Patients had similar rates of overall and progression-free survival, relapse, non-relapse mortality, and chronic GVHD.
However, patients who received haploidentical transplants had higher rates of grade 2-4 acute GVHD and cytomegalovirus reactivation.
Researchers reported these results in Biology of Blood and Marrow Transplantation.
“This is the first study to compare the gold standard to a half-match using an identical protocol,” said Neal Flomenberg, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
“The field has debated whether the differences in outcomes between full and partial matches were caused by the quality of the match or by all the procedures the patient goes through before and after the donor cells are administered. We haven’t had a clear answer.”
With that in mind, Dr Flomenberg and his colleagues compared 3-year outcome data from patients who received haploidentical HSCTs (n=50) or fully matched HSCTs (n=27), when both groups of patients were treated with a 2-step protocol.
The patients had acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=20), myelodysplastic syndromes/myeloproliferative neoplasms (n=7), non-Hodgkin lymphoma (n=11), and aplastic anemia (n=1).
The 2-step protocol
All patients received a myeloablative conditioning regimen consisting of 12 Gy of total body irradiation administered in 8 fractions over 4 days. After the last fraction, they received a fixed T-cell dose (2 x 108 cells/kg), which was followed, 2 days later, by cyclophosphamide at 60 mg/kg/day for 2 days.
Twenty-four hours after they completed cyclophosphamide, patients received CD34-selected peripheral blood stem cells from a half-matched or fully matched donor.
On day -1, patients began taking tacrolimus and mycophenolate mofetil as GVHD prophylaxis. They also received growth factor support (granulocyte-macrophage colony-stimulating factor at 250 μg/m2) starting on day +1.
In the absence of GVHD, mycophenolate mofetil was discontinued on day 28 and tacrolimus was tapered, starting on day +60 after HSCT.
Results
The researchers said that early immune recovery was comparable between the patient groups in nearly all assessed T-cell subsets. The exception was the median CD3/CD8 cell count, which was significantly higher at day 28 in the fully matched group than the haploidentical group (P=0.029).
Survival rates were comparable between the groups. The estimated 3-year overall survival was 70% in the haploidentical group and 71% in the fully matched group (P=0.81). The 3-year progression-free survival was 68% and 70%, respectively (P=0.97).
The 3-year cumulative incidence of non-relapse mortality was 10% in the haploidentical group and 4% in the fully matched group (P=0.34). The 3-year cumulative incidence of relapse was 21% and 27%, respectively (P=0.93).
The 100-day cumulative incidence of grade 2-4 acute GVHD was significantly higher in the haploidentical group than the fully matched group—40% and 8%, respectively (P<0.001). But there was no significant difference in the incidence of grade 3-4 acute GVHD—6% and 4%, respectively (P=0.49).
The cumulative incidence of chronic GVHD at 2 years was not significantly different between the haploidentical and fully matched groups—19% and 12%, respectively (P=0.47). The same was true for severe chronic GVHD—4% and 8%, respectively (P=0.49).
The cumulative incidence of cytomegalovirus reactivation was significantly higher in the haploidentical group than the fully matched group—68% and 19%, respectively (P<0.001).
There were no deaths from infections or GVHD in either group.
“The results of the current study are certainly encouraging and suggest that outcomes from a half-matched, related donor are similar to fully matched donors,” said study author Sameh Gaballa, MD, also of Thomas Jefferson University.
“It might be time to reassess whether half-matched, related transplants can be considered the best alternative donor source for patients lacking a fully matched family member donor. For that, we’ll need more evidence from a randomly controlled, prospective trial, rather than studies that look at patient data retrospectively, to help solidify our findings here.”
