Cord-Blood Transplantation in Patients with Minimal Residual Disease

Abstract

BACKGROUND The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donor-cell sources. METHODS In this retrospective analysis, we compared outcomes in 582 consecutive patients with acute leukemia or the myelodysplastic syndrome who received a first myeloablative hematopoietic-cell transplant from an unrelated cord-blood donor (140 patients), an HLA-matched unrelated donor (344), or an HLA-mismatched unrelated donor (98). RESULTS The relative risks of death and relapse between the cord-blood group and the two other unrelated-donor groups appeared to vary according to the presence of minimal residual disease status before transplantation. Among patients with minimal residual disease, the risk of death was higher in the HLA-mismatched group than in the cord-blood group (hazard ratio, 2.92; 95% confidence interval [CI], 1.52 to 5.63; P = 0.001); the risk was also higher in the HLA-matched group than in the cord-blood group but not significantly so (hazard ratio, 1.69; 95% CI, 0.94 to 3.02; P = 0.08). Among patients without minimal residual disease, the hazard ratios were lower (hazard ratio in the HLA-mismatched group, 1.36; 95% CI, 0.76 to 2.46; P = 0.30; hazard ratio in the HLA-matched group, 0.78; 95% CI, 0.48 to 1.28; P = 0.33). The risk of relapse among patients with minimal residual disease was significantly higher in the two unrelated-donor groups than in the cord-blood group (hazard ratio in the HLA-mismatched group, 3.01; 95% CI, 1.22 to 7.38; P = 0.02; hazard ratio in the HLA-matched group, 2.92; 95% CI, 1.34 to 6.35; P = 0.007). Among patients without minimal residual disease, the magnitude of these associations was lower (hazard ratio in the HLA-mismatched group, 1.28; 95% CI, 0.51 to 3.25; P = 0.60; hazard ratio in the HLA-matched group, 1.30; 95% CI, 0.65 to 2.58; P = 0.46). CONCLUSIONS Our data suggest that among patients with pretransplantation minimal residual disease, the probability of overall survival after receipt of a transplant from a cord-blood donor was at least as favorable as that after receipt of a transplant from an HLA-matched unrelated donor and was significantly higher than the probability after receipt of a transplant from an HLA-mismatched unrelated donor. Furthermore, the probability of relapse was lower in the cord-blood group than in either of the other groups.

Alloreactivity: the Janus-face of hematopoietic stem cell transplantation

“…They clarify the role of matching in times when HSCT should provide for each patient a better outcome regarding overall survival, quality of life and costs; 19 they add caution to current concepts to 'find a donor option for every patient. [12][13][14][15][16][17] They fit with recent studies that well-matched unrelated donor HSCT showed results similar to those with matched sibling donors. They suggest complete HLA-typing (12 out of 12 antigens) of unrelated donors 26,27 before decision-making.…”

“…Some early promising results have triggered a rapid expansion in the use of haploidentical donors; still, they await confirmation. [12][13][14][15][16] Recent results from a large EBMT study with high-risk AML patients indicate a similar outcome at 2 years after haploidentical as compared to 10/10 antigen matched unrelated donor transplants. Non-relapse mortality was reported to be higher, relapse incidence to be lower after haploidentical HSCT, 28 follow-up was short and risk profiles of the patients different.…”

“…Some approaches postulate' a donor option' for every patient. 16 Indeed, the ready availability and the promising early results have led to a substantial increase in the use of haploidentical mismatched family-donor transplants. 12,17 Results from large series and with a long follow-up, however, are lacking.…”

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

“…On the other hand, CB has a powerful GVL effect which is crucial in eliminating the drug‐resistant malignant cells. Milano et al 37. reported that among patients with pretransplantation minimal residual disease, OS after CBT was as favorable as HCT with HLA‐matched unrelated donor and much higher than HCT with HLA‐mismatched unrelated donor, and the probability of relapse was lower in the cord‐blood group than in either of the other groups, which indicated that cord blood may have a stronger GVL effect than other graft sources.…”

Allogeneic transplantation of hematopoietic stem cells: Perspectives and alternatives, own experience

“…Соглас-но, преимущественно ретроспективным данным, показатели выживаемости (без лейкоза и ОВ) при использовании различных альтернативных доноров сходные, однако они более низкие после использова-ния пуповинной крови, чем после ТГСК от совмести-мых доноров (родственных и неродственных) [100]. Среди пациентов с острыми лейкозами и МДС (Fred Hutchinson Cancer Research Center), имевших мини-мальную остаточную болезнь перед трансплантацией, вероятность ОВ после трансплантации неродствен-ной пуповинной крови (4-6/6, n = 140) была, как минимум, так же благоприятна, как после трансплан-тации от HLA-идентичного неродственного донора (10/10, n = 344) и значительно выше, чем вероятность после трансплантации HLA-частично совместимого неродственного донора (9/10, n = 98), а вероятность рецидива была ниже в группе трансплантированных с использованием пуповинной крови, чем в любой из двух других групп [101].…”