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Cord-blood transplantation may be preferable for patients with minimal residual disease
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Patients with pretransplantation minimal residual disease achieved comparable outcomes after receipt of a hematopoietic cell transplantation from an umbilical cord blood source or HLA–matched unrelated donor, according to retrospective study results.
Further, transplantation with umbilical cord blood demonstrated superior outcomes compared with transplantation with a mismatched unrelated donor in these patients. Cord-blood transplant recipients also had a lower relapse risk.
Approximately 70% of patients in need of an allogeneic hematopoietic stem cell transplantation do not have an HLA–matched sibling donor. Alternative transplantation strategies are needed, especially for high-risk patients with minimal residual disease.
“Patients going into transplant with minimal residual disease have very dismal outcomes,” Filippo Milano, MD, PhD, assistant professor of medicine at University of Washington School of Medicine and associate director of cord blood transplantation at Fred Hutchinson Cancer Research Center, said in a press release.
Milano and colleagues sought to determine whether transplants from cord-blood donors had comparable outcomes to transplants from HLA–matched or –mismatched unrelated donors in patients with acute leukemia or myelodysplastic syndrome.
The researchers identified 582 patients who underwent a first myeloablative HSCT at Fred Hutchinson Cancer Research Center between 2006 and 2014.
The majority of patients received a transplant from a matched unrelated donor (n = 344; bone marrow transplant, n = 107; peripheral blood transplant, n = 237); 98 patients received a transplant from a mismatched unrelated donor (bone marrow, n = 28; peripheral blood, n = 70), and 140 patients received a cord-blood transplant.
Patients who received a cord-blood transplantation tended to be younger (median age, 29 years), of nonwhite race or ethnicity (54%), and seropositive for cytomegalovirus (61%).
Minimal residual disease was detected in 33% (n = 45) of patients in the cord-blood group, 31% (n = 104) of the HLA–matched group and 39% (n = 35) of the HLA–mismatched group.
The researchers noted 44 deaths in the cord-blood group, 116 deaths in the HLA–matched group and 52 deaths in the HLA–mismatched group. These corresponded with unadjusted 4-year survival rates of 71% (95% CI, 62-77) for cord blood, 63% (95% CI, 57-68) for HLA–matched transplant and 49% (95% CI, 38-58) for HLA–mismatched transplant.
Patients who underwent HLA–mismatched transplantation had a higher risk for death than those who underwent cord-blood transplantation (HR = 1.91; 95% CI, 1.23-2.98). The risk for death was similar among cord-blood and HLA–matched transplant recipients (HR = 1.12; 95% CI, 0.77-1.63).
The adjusted risk for relapse was significantly higher among HLA–matched (HR = 1.95; 95% CI, 1.16-3.27) and HLA–mismatched (HR = 1.97; 95% CI, 1.04-3.73) transplant recipients than cord-blood recipients.
However, risk for death and relapse between the group varied according to the presence of minimal residual disease prior to transplantation.
Among patients with minimal residual disease, those who underwent HLA–mismatched transplantation had a greater risk for death than cord-blood recipients (HR = 2.92; 95% CI, 1.52-5.63). HLA–matched transplantation recipients also had a higher risk for death than cord-blood recipients; however, the difference failed to reach statistical significance (HR = 1.69; 95% CI, 0.94-3.02).
Among patients without minimal residual disease, the association with worse outcomes persisted in the HLA–mismatched transplantation group compared with cord-blood recipients, although to a lesser degree that did not reach statistical significance (HR = 1.36; 95% CI, 0.76-2.46). Outcomes appeared comparable between patients who received cord blood or HLA–matched transplantation (HR = 0.78; 95% CI, 0.48-1.28).
Compared with patients who underwent cord-blood transplantation, the risk for relapse associated with HLA–matched and –mismatched transplantation was greater in patients with minimal residual disease (HLA–matched, HR = 2.92; HLA–mismatched, HR = 3.01) than without minimal residual disease (HLA–matched, HR = 1.3; HLA–mismatched, HR = 1.28).
The researchers did not observe any significant differences in the rates of mortality without relapse or chronic graft-versus-host disease.
“[These findings] bring home the point that cord blood should not be called an alternative donor,” Colleen Delaney, MD, MSc, associate professor of pediatrics at University of Washington School of Medicine and director of cord blood transplantation at Fred Hutchinson Cancer Research Center, said in a press release. “The outcomes are the same as a conventional donor. This paper shows that if you have high-risk disease and are at high risk for relapse post-transplant, transplant with a cord blood donor may be the best option.” – by Cameron Kelsall
Disclosures: Milano and Delaney report nonfinancial support and other support from medac GmbH outside the submitted work. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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