Outcomes of unrelated cord blood transplantation in pediatric recipients

Abstract

Summary:We report results of unrelated cord blood transplants (UCBT) in 29 pediatric recipients in one center and the risk factors associated with survival. Median age: 9 years (0.5-20); diagnosis: ALL (9), AML (4), CML (1), HD (3), HLH (1), NHL (3), NBL (2); B-thal (1), FA (1), FEL (1), Krabbe (1), WAS (1), SAA (1); median follow-up: 11 months; conditioning: total body irradiation (TBI)-ablative (14), chemotherapy-ablative (6) and reduced intensity chemotherapy (9); GVHD prophylaxis: MMF/FK506 (18), cyclosporin A (CsA) þ steroids7MMF (7) or CsA þ methotrexate (MTX) (4); median total nucleated cells (TNC): 3.8 Â 10 7 /kg (1.1-11); median CD34 þ : 2.3 Â 10 5 /kg (0.2-9.9); and HLA match: 2 (6/6), 5 (5/ 6), 22 (4/6). Neutrophil engraftment by cumulative incidence curves 63% (median 28 (95% confidence interval (CI) 18-32)). Probability of Xgrade II acute graft-versus-host disease (aGVHD) by day þ 60 27%, Xgrade III aGVHD 20% and chronic graft-versus-host disease 3%. Estimated 1-year overall survival (OS) 46% (95% CI 30-71) and standard risk 60% (95% CI 29-100%). Variables associated with improved survival by multivariate analysis include non-TBI-ablative conditioning (P ¼ 0.024), CD34 þ /kg (P ¼ 0.038) and gender (P ¼ 0.048). These results suggest that CD34/kg cell dose and non-TBI-ablative conditioning may be important variables influencing OS following UCBT in pediatric recipients. Given the small number of patients, these results should be viewed cautiously.

Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group

“…Survival after unrelated UCBT has been found to be influenced by age, HLA match, higher cell doses, disease status at the time of transplant and treatment indication (malignant or non-malignant disease). 6,10,11,21,23 Additionally, when comparing UCB recipients with BM recipients, studies indicate that survival after 1-2 HLAmismatched unrelated UCBT are comparable with those observed after HLA-matched BMT. [20][21][22] In our study, HLA-matching and nucleated cell dose together appeared to influence survival.…”

“…TRM for our entire study cohort was 25% at day 100 and 32% at 2 years, which is comparable to other studies. 2,10,11,21,23,34,36 TRM in adult recipients of UCB after a myeloablative regimen has been reported to be as high as 60%. 7,10,14,17,19,[30][31][32][33] Comparing UCBT to BMT, Rocha et al 22 compared the outcomes of 541 children transplanted for the treatment of acute leukaemia receiving a UCBT (n ¼ 99), unmanipulated BMT (n ¼ 262), or T-cell-depleted BMT (n ¼ 180).…”

“…The importance of CD34 cell dose has been replicated in other studies. 11,34 Interestingly, unlike unrelated BM or peripheral blood stem cells, the effect of HLA disparity appears to have a less convincing impact on neutrophil engraftment in unrelated UCB transplantation. 10 In our study cohort, the Kaplan-Meier estimate of neutrophil engraftment was 89% overall, which is similar to that reported in other studies.…”

“…2,10,11,21,23,36 However, data comparisons between studies are difficult as there is heterogeneity in eligibility criteria, underlying diagnosis, treatment, supportive care plans and definitions of end points. OS in our study was 61% at 1-year post transplant and 45% at 5-years post transplant, which is comparable to earlier reports.…”

“…[1][2][3][4][5][6][7] Unrelated UCB has been used successfully for patients with a range of malignant and non-malignant diseases including leukaemia and lymphoma, constitutional and acquired BM failure syndromes, severe congenital immunodeficiency syndromes, haemoglobinopathies and selected metabolic disorders. [1][2][3][4]6,[8][9][10][11] It has been estimated that more than 95% of patients are able to find at least one potential 4 of 6 HLA matched cord blood unit on the National Marrow Donor Registry, with the majority finding a potential five of six match. 12 The known advantages of unrelated UCB over unrelated BM are well documented and include increased speed of availability, 13 absence of risk to the donor, reduced transmission of viral illnesses such as CMV, tolerance of HLA disparity between the donor and recipient, 9,14,15 better minority representation in UCB banks and reduced risk and severity of acute GVHD when compared to BM grafts.…”