T-cell replete cord transplants give superior outcomes in high-risk and relapsed/refractory pediatric myeloid malignancy

Abstract

Stem cell transplant (SCT) outcomes in high-risk (HR) and relapsed/refractory (R/R) paediatric acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) have been poor historically. Cord blood allows T-cell replete transplant (TRCB), enabling enhanced graft-versus-leukaemia. We collected data from 367 consecutive patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for paediatric AML/MDS in the UK and Ireland between January 2014 and December 2021. Data was collected about patient's demographics, disease and its treatment including previous transplant, measurable residual disease (MRD) status at transplant, HLA-match, relapse, death, graft versus host disease (GvHD) and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6% and 5.1% respectively in the comparator group (all p <0.001). Within the TRCB cohort, Event Free Survival (EFS) was 64.1%, 50% in MRD positive patients and 79% in MRD negative (p= 0.009). To allow for the imbalance in baseline characteristics, a multivariable analysis was performed: the TRCB cohort had significantly improved EFS (0.57[0.35-0.91], p=0.019), time to relapse (0.46[0.26-0.81), p=0.008), and reduced chronic GVHD (HR 0.28 [95% CI 0.11-0.70]; p=0.007), with some evidence of improved Overall Survival (OS) (0.65[0.39-1.07], p = 0.088). The effect appeared similar regardless of MRD status, (interaction p-value= 0.29). CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy.

Small but mighty: T-replete cords for myeloid disease

“…In this issue of Blood Advances , through a multicenter analysis of 367 pediatric patients, Horgan et al have reported that T-replete umbilical cord stem cell (TRCB) transplants against myeloid disease provide superior disease-free survival and event-free survival (EFS) compared with that provided by all other donor sources, including matched unrelated donor, matched sibling donor, mismatched unrelated donor, haploidentical, and T-depleted cord. 1 Similar to other reports, in young and adult patients from single institutions, the power of cord-derived T cells during transplantation appeared greatest in those children with measurable residual disease (MRD) before transplant. 2 Horgan et al found similar EFS and overall survival in patients from all groups who had no MRD before transplant, including those who received transplants using other alternative donor sources, including haploidentical grafts.…”

Granulocyte transfusion during cord blood transplant for relapsed, refractory AML is associated with massive CD8+ T‐cell expansion, significant cytokine release syndrome and induction of disease remission

“…We have previously reported that relapse risk is reduced following CBT for myeloid malignancy 4 . It remains, however, the commonest cause of treatment failure.…”

“…We have previously reported that relapse risk is reduced following CBT for myeloid malignancy. 4 It remains, however, the commonest cause of treatment failure. We have previously serendipitously noted and reported T-cell expansion in patients receiving granulocytes during CBT.…”

“…2,3 We have previously reported a large, retrospective, national experience of HSCT in AML describing that cord blood transplant (CBT) reduces the risk of disease relapse in children, compared with other stem cell sources. 4 Similar analysis of adults with acute leukaemia has demonstrated reduced relapse rate with CBT for those with residual disease. 5 This is likely because CBT can be performed without T-cell-depleting serotherapy allowing more rapid T-cell reconstitution, and there is greater tolerance and use of human leukocyte antigen (HLA) mismatch.…”

“…We have previously reported a large, retrospective, national experience of HSCT in AML describing that cord blood transplant (CBT) reduces the risk of disease relapse in children, compared with other stem cell sources 4 . Similar analysis of adults with acute leukaemia has demonstrated reduced relapse rate with CBT for those with residual disease 5 .…”