Outcomes after reduced-intensity conditioning allogeneic HSCT vary by graft type
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Use of cryopreserved grafts following reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation appeared associated with poorer outcomes, according to results presented at TCT Meetings Digital Experience.
Patients treated with this approach achieved shorter OS and experienced a higher rate of graft failure than those who received fresh allografts.
“Our study represents only a small population of patients undergoing allogeneic hematopoietic cell transplantation,” Andriyana Bankova, MD, postdoctoral research fellow in the division of blood and marrow transplantation at Stanford University, told Healio. “However, our data demonstrate that patients receiving reduced-intensity conditioning and allogeneic unrelated cryopreserved grafts were more prone to develop primary graft failure compared with those receiving fresh grafts.”
Challenges related to donor availability and product transport that emerged due to the COVID-19 pandemic prompted many centers to implement cryopreservation of allogeneic donor apheresis products.
Multiple studies that reported outcomes after allogeneic HSCT with cryopreserved grafts yielded conflicting results with regard to OS, engraftment and hematopoietic recovery, according to study background.
“Graft failure is a rare occurrence,” Bankova said. “We observed a cluster of graft failures beginning in spring 2020 that were highly unusual. Before the COVID-19 pandemic, cryopreservation was not a standard approach for our center. Therefore, we decided to assess systematically if there might be an association with the cryopreserved grafts and clinical outcomes.”
Bankova and colleagues assessed posttransplantation outcomes of 29 patients (median age, 57 years; range, 26-74) who underwent allogeneic HSCT with cryopreserved peripheral blood stem cells from March 2020 to August 2020.
Researchers compared outcomes of this group with those of a control cohort of 60 patients (median age, 61 years; range, 21-71) who received fresh peripheral blood stem cell allogeneic HSCT between March 2019 and August 2020.
OS and graft failure served as primary endpoints. Secondary endpoints included hematopoietic recovery and graft-versus-host disease.
The cryopreserved group included a higher percentage of HLA-matched unrelated donors (72.4% vs. 41.7%), whereas the fresh group included higher percentages of HLA-matched related donors (33.3% vs. 6.9%) and haploidentical/HLA-mismatched donors (25% vs. 20.6%).
A comparable percentage of patients in the cryopreserved and fresh groups underwent reduced-intensity conditioning (69% vs. 65%).
Researchers reported a higher median post-collection dose of CD34+ cells in the fresh group (9.3 x 106/kg vs. 7 x 106/kg) but no difference between groups in the dose of CD3+ cells (2.4 x 106/kg vs. 2.7 x 106/kg).
Four patients (13.8%) in the cryopreserved group and one patient (1.7%) in the fresh group developed primary graft failure (P = .03). All four patients in the cryopreserved group who developed primary graft failure received HLA-matched unrelated grafts after reduced-intensity conditioning. The patient in the fresh cohort received a haploidentical graft after myeloablative conditioning.
Patients who received cryopreserved grafts after reduced-intensity conditioning allogeneic HSCT achieved shorter OS (HR = 4.2; 95% CI, 1.22-14.4). Results also showed delayed recovery of platelets (P = .006) and absolute neutrophil count in this group, although the latter did not reach statistical significance. Researchers reported no difference in acute GVHD between groups.
“We were surprised to observe the higher incidence of graft failure over this limited period of time in 2020 compared with our historical experience,” Bankova said. “It was also unexpected that graft failures occurred primarily in patients who received reduced-intensity conditioning.”
Multivariate analysis performed for OS and graft failure — adjusted for patient age, sex, donor type, CD34 cell dose and conditioning intensity — supported the inferiority of cryopreserved grafts, Bankova and colleagues wrote.
Investigators performed flow cytometry on five available samples in the cryopreserved group and compared them with four prospectively collected fresh apheresis samples from allogeneic donors. Results showed significantly lower absolute counts of natural killer cells in cryopreserved samples (P = .0159), but they observed no differences in content of T, B or CD34+ cells or hematopoietic stem cell compartments between graft types.
“It will be important that future studies with more patients examine the role of fresh vs. cryopreserved products on the clinical outcomes of allogeneic stem cell transplantation,” Bankova told Healio. “To determine if there is a biologic basis for the differences in clinical outcomes that we observed, we are performing extended cell phenotype analyses of the cryopreserved vs. fresh apheresis products. Such analyses may allow us to determine if differences in cell composition exist because of the cryopreservation.”
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Bankova AK, et al. Abstract LBA6. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); Feb. 8-12, 2021.
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