Patients with relapsed or refractory acute myeloid leukemia (AML) have a poor prognosis and treatment remains challenging. For the majority of relapsed or refractory acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment approach. Stem cell transplant (SCT) outcomes in high-risk and relapsed/refractory pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have also been historically poor. Median overall survival was 5.5 months, and for patients achieving composite complete remission, this was 21.6 months. One-year estimated overall survival was 38%.

In 2016 the Fred Hutchinson Cancer Research Centre, in the United States, reported from a review done in patients they compared outcomes after receipt of a transplant from a cord-blood donor with outcomes, after receipt of a transplant from an HLA-matched or HLA-mismatched unrelated donor in patients with acute leukemia or the myelodysplastic syndrome who underwent a first myeloablative allogeneic transplantation. All patients with acute myeloid or lymphoid leukemia or myelodysplastic syndrome who received a first allogeneic hematopoietic-cell transplant from an unrelated donor between January 2006 and December 2014 (582 patients), with the source of stem cells being cord blood, bone marrow, or peripheral blood. All cord-blood grafts were matched for four, five, or six loci at HLA-A and HLA-B (at the antigen level) and at the allele level for HLA-DRB1. In the unrelated-donor groups, which included bone marrow and peripheral-blood stem-cell sources from adult volunteer donors, patients were matched with the donor at the allele level for HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 (HLA-matched group) or were mismatched for a single allele (HLA-mismatched group). In the HLA-matched and HLA-mismatched groups, the stem-cell source was determined largely according to treatment protocol and in some cases according to donor or patient preference. HLA-matched unrelated donors were generally selected as the primary source if patients did not have an HLA-matched related donor.

These results showed that in patients with minimal residual disease, the use of cord blood as the donor source for hematopoietic-cell transplantation led to a higher rate of survival and a lower rate of relapse than the use of a transplant from an HLA-mismatched unrelated donor.

Another similar review of the literature was done by another major cancer centre in the United Kingdom comparing transplants from various children’s cancer hospitals in England in 2023. This review, similar to the United States study, found that in patients at high risk of relapse after transplant, cord blood transplant recipients have better survival outcomes when they have high-risk and relapsed/refractory paediatric myeloid malignancy (1-3).

The United States study reviewed outcomes for 582 patients who received stem cell transplants from 2006, until 2014. Of those, 140 patients received cord blood transplants. In the United Kingdom study, a review of 367 patients received transplants; of these 112 patients received cord blood transplants, whilst 255 received transplants from other sources, between January 2014 and December 2021. Both these studies concluded that patients that received a cord blood transplant had better survival and less relapse than patients that received stem cells from adult, unrelated donors.

Cord blood transplantation has been associated with less chronic graft-versus-host disease (GVHD) and “could enable nearly all patients to have an available donor”. On the other hand, haploidentical cord transplants are being used increasingly, even in older patients, and maybe another alternative for better outcomes. In addition, the expansion of cord blood provides another level of availability for paediatric and adult patients that require an urgent transplant.

In a large, retrospective registry study of Japanese adult patients with non-remission AML, the relapse rate was reduced in cord blood stem cell transplant recipients compared with matched family donors, and their disease-free survival was better. The low incidence of chronic GvHD combined with the Graft-versus-leukemia effect that cord blood affords has also resulted in superior chronic GvHD-free relapse-free survival (GFRFS) for cord blood compared with other donor sources in further studies (4).

All three of these studies, therefore, highlight and show that currently, if patients have high-risk disease and are at high risk for relapse post-transplant, a transplant with a cord blood donor may be the best option.

References

1. Milano F, et al. Cord-Blood Transplantation in Patients with Minimal Residual Disease. N Engl J Med. 2016 Sep 8;375(10):944-53. doi: 10.1056/NEJMoa1602074. PMID: 27602666; PMCID: PMC5513721.
2. Saultz JN. Cord Blood Transplants in Patients With MRD: The New Preferred Alternative Donor Source? The Hematologist (2017) 14 (1)
3. Horgan C, et al. T-cell replete cord transplants give superior outcomes in high-risk and relapsed/refractory pediatric myeloid malignancy. Blood Adv. 2023 May 23;7(10):2155-2165. doi: 10.1182/bloodadvances.2022009253. PMID: 36649566; PMCID: PMC10206437.
4. Shimomura Y, Sobue T, Hirabayashi S, et al. Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia. Leukemia. 2022;36(4):1132-1138.