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Graft failure remains concern following umbilical cord blood transplantation for leukemia
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ATLANTA —Twelve percent of adults with acute myeloid or acute lymphoblastic leukemia who received umbilical cord blood transplantation experienced graft failure, according to a large European retrospective study presented at the ASH Annual Meeting and Exposition.
“Our aim was to assess the outcomes of patients with acute leukemia who experience graft failure after umbilical cord blood transplantation,” Frederic Baron, MD, PhD, principal investigator at University of Liege in Belgium, said during his presentation. “We defined graft failure as no neutrophil recovery 60 days after transplant.”
Baron and colleagues reported similar findings in a previous study published in Journal of Hematology & Oncology. To support their data, the European Society for Blood and Marrow Transplantation and EUROCORD sponsored a multicenter retrospective registry study on 1,836 adults with AML or ALL receiving an initial single or double umbilical cord blood transplantation (UCBT) between 2005 and 2016.
Overall, 215 patients (11.7%; median age, 43 years; range, 18-68; 53% men) experienced graft failure. Of them, 160 had AML and 55 had ALL, and their median year of transplantation was 2010. At the time of transplantation, 67% of the patients were in complete remission and 33% had advanced disease.
Most patients (n = 128; 60%) underwent myeloablative conditioning, and the other 87 patients (40%) received reduced-intensity conditioning. One hundred one patients received anti T-cell globulin.
One hundred twenty-six patients received a single UCBT and 49 patients received a double UCBT.
Among the 215 patients with graft failure, 54 underwent a second allogeneic (n = 53) or autologous (n = 1) transplantation after a median of 62 days (range, 16-700) following the first UCBT. Researchers reported a 1-year cumulative incidence of second transplantation of 24%.
OS among patients not undergoing a second transplantation was 21.9 % (95% CI, 16.3-29.3) at 100 days and 10.6 % (95% CI, 6.7-16.8) at 1 year.
Among the 53 patients who underwent a second allogeneic transplantation, the second donor was unrelated (n = 34), HLA haploidentical (n = 17) or an HLA-identical sibling (n = 2).
Stem cell source consisted of single (n = 13) or double (n = 13) umbilical cord blood, peripheral blood stem cells (n = 17), bone marrow (n = 7), or a combination of peripheral blood stem cells plus umbilical cord blood (n = 3) or peripheral blood stem cells plus bone marrow (n = 1).
Eight-seven percent of patients underwent reduced-intensity conditioning for the second transplantation.
Thirty-three patients (61%) achieved sustained engraftment after the second transplantation.
After second transplantation, incidence of relapse was 21% at 1 year and 28% at 3 years, nonrelpase mortality was 47% at 1 year and 52% at 3 years, OS was 40% at 1 year and 23% at 2 years, and leukemia-free survival was 33% at 1 year and 21% at 2 years.
Main causes of 39 deaths following second transplantation included infection (n = 14) and leukemia relapse/progression (n = 12).
Among the 17 patients receiving a haploidentical transplantation as second graft, 51.8 % (95% CI, 32.4-82.7) achieved 1-year OS and 41.4 % (95% CI, 21.8-78.6) achieved 3-year OS.
In a multivariate Cox model assessing factors predicting OS among UCBT patients with graft failure, transplantation for advanced disease (HR = 2.3; 95% CI, 1.6-3.3) as well as graft failure after the salvage transplantation (HR = 2.8; 95% CI, 1.6-5) predicted poor OS. Use of reduced-intensity conditioning for the first transplantation improved OS.
“We saw that in the 12% who had incidence of graft failure, advanced disease predicted that failure,” said Baron, who recommended patient screening for donor-specific anti-HLA antibodies. “A second transplantation could be performed among only 24% of patients with high transplant-related mortality, but led to an OS of 23%. Results were more encouraging in the 17 patients who received a salvage HLA-haploidentical transplantation because they had a 1-year OS of 52%.” – by Chuck Gormley
Reference:
Baron F, et al. Abstract 661. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Baron reports no relevant financial disclosures. Other researchers report honoraria and research funding from, consultant and speakers bureau roles with Amgen, Bristol-Myers Squibb, Celgene, Jazz Pharmaceuticals, Janssen, Novartis, Sanofi and Takeda,
Perspective
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Filippo Milano, MD, PhD
Like many registry studies, this one is biased because it puts together results from different centers with different expertise; that’s one big limitation of the study. I was really surprised by the graft failure rate of 12% after both single and double umbilical cord transplants, which is much higher than what we usually see in our single-center experience. For instance, at our center in Seattle, umbilical cord rejection is less than 5%. It’s possible Baron and colleagues’ data are high because that center in Liege, Belgium might not be doing a high amount of second transplants, which may result in a failure of the transplant itself.
Overall, this is a good study and shows that you can rescue at least a quarter of patients with the second transplant with a decent OS after 1 year (40%) and 3 years (23%). At 3 years, at least one out of four patients can survive, and these are patients without any other possibility of surviving without the transplant.
It is worth noting that this study has a big time range (2006-2015) and I am willing to bet that from 2006 to 2010, there was a graft failure rate of 15% to 20%. If you look at more recent data, it is probably much better. Failure is happening less often, and I would assume that at least in the United States graft failure is actually between 5% and 10%.
What concerns me is that in this type of field, people may avoid transplantation because they fear graft failure. By using the expansion of stem cell technology, we are avoiding graft failure and these events are becoming very rare.
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