| The following article features coverage from the Tandem Meetings 2022. Click here to read more of Cancer Therapy Advisor’s conference coverage. |
A haploidentical transplant approach appears effective for pediatric patients with high-risk hematologic malignancies, according to research presented at the Tandem Meetings 2022.
Grafts depleted of CD45RA-positive T cells, with natural killer (NK) cells added back, produced low rates of graft failure, viral infections, and relapse. The approach did result in a relatively higher rate of graft-vs-host disease (GVHD), however.
“Despite a higher incidence of GVHD compared to other T-cell-depleted transplants, our approach translated into promising long-term outcomes in this high-risk patient population,” said Swati Naik, MBBS, of St. Jude Children’s Research Hospital in Memphis, when presenting this research at the meeting.
Continue Reading
Dr Naik and colleagues conducted this prospective trial (ClinicalTrials.gov Identifier: NCT01807611) in pediatric patients with high-risk hematologic malignancies.
The study included 72 patients — 29 with acute lymphoblastic leukemia (ALL), 40 with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), and 5 with other hematologic cancers. The median age of the patients was 8.1 years (range, 0.6-20.8 years).
Before transplant, 25 patients were in first complete remission (CR1), 24 were in CR2, 4 were in CR3 or greater, and 19 had refractory disease. Among the 53 patients in CR, 22 had minimal residual disease (MRD) at the time of transplant.
Most donors were the patient’s parent (n=65), though 6 patients received grafts from a sibling or other donor. In most cases, 4 of 8 loci were mismatched (n=54). There were 17 cases with 3 mismatched loci and 1 case with 2 mismatched loci.
For conditioning, patients received fludarabine, thiotepa, melphalan, cyclophosphamide, and total lymphoid irradiation. Patients received a CD34-positive selected graft on day 0, a CD45RA T-cell-depleted graft on day 1, and NK cells on day 6. For GVHD prophylaxis, patients received mycophenolate mofetil (n=61) and/or sirolimus (n=8) until day 42.
Results
The median time to neutrophil engraftment was 11 days (range, 9-13 days), and the median time to platelet recovery was 17 days (range, 10-85 days). One patient had primary graft failure but was successfully re-transplanted.
At 180 days, the cumulative incidence of cytomegalovirus and adenovirus viremia was 32% and 7%, respectively. The cumulative incidence of GVHD at 180 days was 36% for acute GVHD of any grade, 29% for grade 3-4 acute GVHD, and 24% for chronic GVHD.
The median follow-up was 3.1 years. At 3 years, the event-free survival (EFS) rate was 62%, and the overall survival rate was 69%. The 3-year EFS rate was similar between patients with ALL and those with AML/MDS — 62% and 59%, respectively.
Dr Naik noted that disease status at transplant played a role in EFS. The 3-year EFS rate was 88% for patients in CR1, 71% for patients in CR2, and 21% for patients with refractory disease (P <.0001). There was no significant difference in EFS according to MRD status (P =.87).
For the entire cohort, at 3 years, the cumulative incidence of relapse was 26.4%, and the non-relapse mortality rate was 11.5%.
Read more of Cancer Therapy Advisor’s coverage of Tandem Meetings 2022 by visiting the conference page.
Reference
Naik S, Talleur A, Li Y, et al. CD45RA-depleted haploidentical transplantation combined with NK cell addback results in promising long-term outcomes in pediatric patients with high-risk hematologic malignancies. Tandem Meetings 2022; April 23-26, 2022. Abstract 128.
