1.
Impact of early candidemia on the long-term outcome of allogeneic hematopoietic stem cell transplant in non-leukemic patients: an outcome analysis on behalf of IDWP-EBMT
Cesaro, S., Tridello, G., Knelange, N. S., Blijlevens, N., Martin, M., Snowden, J. A., Malladi, R., Ljungman, P., Deconinck, E., Gedde-Dahl, T., et al
Bone marrow transplantation. 2021
Abstract
We assessed the incidence and outcome of early candidemia after hematopoietic stem cell transplant (HSCT). The analysis included all first HSCTs performed from 2000 to 2015 in adult and pediatric patients with a non-leukemic disease and recorded in the EBMT registry. Overall survival (OS), non-relapse mortality (NRM), and relapse mortality (RM) were evaluated. Candidemia was diagnosed in 420 of 49,852 patients at a median time of 17 days post HSCT (range 0-100), the cumulative incidence being 0.85%. In 65.5% of episodes, candidemia occurred by day 30 after HSCT. The mortality rate by day 7 was 6.2%, whereas 100-day NRM was higher (HR 3.47, p?0.0001), and 100-day OS was lower (HR 3.22, p?0.0001) than that of patients without candidemia. After a median follow-up of 4.3 years, 5-year OS, NRM, and RM for patients with and without candidemia were 50.5% vs. 60.8%, p?0.0001, 28.2% vs.18.8%, p?0.0001, and 25.3% vs. 27.2%, p?=?0.4, respectively. In conclusion, in non-leukemic transplant patients, the occurrence of an early episode of candidemia is rare but it is still associated with a negative effect on the outcome.
2.
Single vs double-unit cord-blood transplantation in children and young adults with residual leukemic disease
Balligand, L., Galambrun, C., Sirvent, A., Roux, C., Pochon, C., Bruno, B., Jubert, C., Loundou, A., Esmiol, S., Yakoub-Agha, I., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 does not decrease the risk of transplantation failure but may enhance alloreactivity. We present here the influence of pre-transplant minimal residual disease (MRD) on leukemia relapse and survival after single versus double-UCB transplantation. Among 137 children and young adults who were transplanted in the randomized study, 115 had available MRD assessment immediately before their conditioning regimen. MRD was considered positive when ≥ 10(-4), which was the case of 43 out of 115 patients. Overall, the 3-year survival probability was 69.1+/-4.4% and it was not significantly influenced by the MRD level: 70.7+/-5.4% in MRD- (<10(-4)) patients (n=72), 71.1+/-9.4% in MRD+ with 10(-4)≤MRD<10(-3) (n=26), and 58.8+/-11.9% in MRD+ ≥ 10(-3) patients (n=17). In the MRD+ group, we found a significantly lower risk of relapse in the double- versus single-unit arm (10.5+/-7.2% vs 41.7+/-10.4%; p=0.025) leading to a higher 3-year survival rate (82.6+/-9.3% vs 53.6+/-10.3%, p=0.031). This difference was only observed in patients who had not received anti-thymocyte globulin (ATG) during their conditioning regimen. In the MRD- group, no difference was found between the single- and the double-unit arms. We conclude that, even in case of positive pre-transplant MRD, UCB transplantation in children and young adults with acute leukemia results in a high cure rate and that a double-unit strategy may enhance graft-vs-leukemia effect and survival in these patients.
3.
Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome
Michel, G., Galambrun, C., Sirvent, A., Pochon, C., Bruno, B., Jubert, C., Loundou, A., Yakoub-Agha, I., Milpied, N., Lutz, P., et al
Blood. 2016;127(26):3450-7
Abstract
Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 x 10(7) nucleated cells/kg for the first and >1.5 x 10(7) for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% +/- 4.9% vs 14.9% +/- 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% +/- 6.0%, 67.6% +/- 6.0%, and 5.9% +/- 2.9% after single-unit transplantation compared with 74.8% +/- 5.5%, 68.1% +/- 6.0%, and 11.6% +/- 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% +/- 5.7% vs 14.7% +/- 4.3%, P = .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300.