1.
More precisely defining risk peri-HCT in pediatric ALL: pre- vs post-MRD measures, serial positivity, and risk modeling
Bader, P., Salzmann-Manrique, E., Balduzzi, A., Dalle, J. H., Woolfrey, A. E., Bar, M., Verneris, M. R., Borowitz, M. J., Shah, N. N., Gossai, N., et al
Blood advances. 2019;3(21):3393-3405
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Editor's Choice
Abstract
Detection of minimal residual disease (MRD) pre- and post-hematopoietic cell transplantation (HCT) for pediatric acute lymphoblastic leukemia (ALL) has been associated with relapse and poor survival. Published studies have had insufficient numbers to: (1) compare the prognostic value of pre-HCT and post-HCT MRD; (2) determine clinical factors post-HCT associated with better outcomes in MRD+ patients; and (3) use MRD and other clinical factors to develop and validate a prognostic model for relapse in pediatric patients with ALL who undergo allogeneic HCT. To address these issues, we assembled an international database including sibling (n = 191), unrelated (n = 259), mismatched (n = 56), and cord blood (n = 110) grafts given after myeloablative conditioning. Although high and very high MRD pre-HCT were significant predictors in univariate analysis, with bivariate analysis using MRD pre-HCT and post-HCT, MRD pre-HCT at any level was less predictive than even low-level MRD post-HCT. Patients with MRD pre-HCT must become MRD low/negative at 1 to 2 months and negative within 3 to 6 months after HCT for successful therapy. Factors associated with improved outcome of patients with detectable MRD post-HCT included acute graft-versus-host disease. We derived a risk score with an MRD cohort from Europe, North America, and Australia using negative predictive characteristics (late disease status, non-total body irradiation regimen, and MRD [high, very high]) defining good, intermediate, and poor risk groups with 2-year cumulative incidences of relapse of 21%, 38%, and 47%, respectively. We validated the score in a second, more contemporaneous cohort and noted 2-year cumulative incidences of relapse of 13%, 26%, and 47% (P < .001) for the defined risk groups.
PICO Summary
Population
Paediatric patients (age 1-21 years) with acute lymphoblastic leukaemia (n=616)
Intervention
An international database of patients in complete remission following myeloablative allogeneic transplant, with at least one minimal residual disease (MRD) measurement prior to transplant
Comparison
None
Outcome
Although high and very high MRD pre-HCT were significant predictors in univariate analysis, with bivariate analysis using MRD pre-HCT and post-HCT, MRD pre-HCT at any level was less predictive than even low-level MRD post-HCT. Patients with MRD pre-HCT must become MRD low/negative at 1 to 2 months and negative within 3 to 6 months after HCT for successful therapy. Factors associated with improved outcome of patients with detectable MRD post-HCT included acute graft-versus-host disease.
2.
Allogeneic hematopoietic stem cell transplantation from unrelated donors is associated with higher infection rates in children with acute lymphoblastic leukemia - A prospective international multicenter trial on behalf of the BFM-SG and the EBMT-PDWP
Pichler, H., Lawitschka, A., Glogova, E., Willasch, A. M., von Luettichau, I., Lehrnbecher, T., Matthes-Martin, S., Lang, P., Bader, P., Sykora, K. W., et al
American journal of hematology. 2019
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Editor's Choice
Abstract
Severe infections (SI) significantly impact on non-relapse mortality after hematopoietic stem cell transplantation (HSCT). We assessed 432 children and adolescents with acute lymphoblastic leukemia (ALL) after total body irradiation based myeloablative HSCT within the multicenter ALL-BFM-SCT 2003 trial for SI grade 3 or higher according to common terminology criteria for adverse events. A total 172 patients experienced at least one SI. Transplantation from matched unrelated donors (MUD) was associated with any type of SI in the pre-engraftment period (hazard ratio [HR]: 2.57; P < 0.001) and with any SI between day +30 and + 100 (HR: 2.91; P = 0.011). Bacterial (HR: 2.24; P = 0.041) and fungal infections (HR: 4.06; P = 0.057) occurred more often in the pre-engraftment phase and viral infections more often before day +30 (HR: 2.66; P = 0.007) or between day +30 and + 100 (HR: 3.89; P = 0.002) after HSCT from MUD as compared to matched sibling donors. Chronic GvHD was an independent risk factor for any type of SI after day +100 (HR: 2.57; P < 0.002). We conclude that allogeneic HSCT from MUD in children and adolescents with pediatric ALL is associated with higher infection rates, which seems attributable to an intensified GvHD prophylaxis including serotherapy and methotrexate.
PICO Summary
Population
Children and adolescents with acute lymphoblastic leukemia (n=432)
Intervention
Total body irradiation based myeloablative HSCT
Comparison
None
Outcome
A total 172 patients experienced at least one severe infection (SI). Transplantation from matched unrelated donors (MUD) was associated with any type of SI in the pre-engraftment period and with any SI between day +30 and + 100. Bacterial and fungal infections occurred more often in the pre-engraftment phase and viral infections more often before day +30 or between day +30 and + 100 after HSCT from MUD as compared to matched sibling donors. Chronic GvHD was an independent risk factor for any type of SI after day +100.