1.
Cytogenetic abnormalities predict survival after allogeneic hematopoietic stem cell transplantation for pediatric acute myeloid leukemia: a PDWP/EBMT study
Sharma, A., Galimard, J. E., Pryce, A., Bhoopalan, S. V., Dalissier, A., Dalle, J. H., Locatelli, F., Jubert, C., Mirci-Danicar, O., Kitra-Roussou, V., et al
Bone marrow transplantation. 2024
Abstract
Poor-risk (PR) cytogenetic/molecular abnormalities generally direct pediatric patients with acute myeloid leukemia (AML) to allogeneic hematopoietic stem cell transplant (HSCT). We assessed the predictive value of cytogenetic risk classification at diagnosis with respect to post-HSCT outcomes in pediatric patients. Patients younger than 18 years at the time of their first allogeneic HSCT for AML in CR1 between 2005 and 2022 who were reported to the European Society for Blood and Marrow Transplantation registry were subgrouped into four categories. Of the 845 pediatric patients included in this study, 36% had an 11q23 abnormality, 24% had monosomy 7/del7q or monosomy 5/del5q, 24% had a complex or monosomal karyotype, and 16% had other PR cytogenetic abnormalities. In a multivariable model, 11q23 (hazard ratio [HR] = 0.66, P = 0.03) and other PR cytogenetic abnormalities (HR = 0.55, P = 0.02) were associated with significantly better overall survival when compared with monosomy 7/del7q or monosomy 5/del5q. Patients with other PR cytogenetic abnormalities had a lower risk of disease relapse after HSCT (HR = 0.49, P = 0.01) and, hence, better leukemia-free survival (HR = 0.55, P = 0.01). Therefore, we conclude that PR cytogenetic abnormalities at diagnosis predict overall survival after HSCT for AML in pediatric patients.
2.
Clofarabine and Treosulfan as conditioning for matched related and unrelated HSCT: results from the phase II trial "Clo3o"
Peccatori, J., Mastaglio, S., Giglio, F., Greco, R., Crocchiolo, R., Patriarca, F., Forno, B., Deola, S., Assanelli, A., Stanghellini, M. T. L., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for patients with hematological malignancies. The ideal conditioning regimen before allogeneic HSCT has not been established. We conducted a phase II study to evaluate tolerability and efficacy of Clofarabine and Treosulfan as conditioning regimen before allo-HSCT. Primary objective was evaluation of the cumulative incidence of non-relapse mortality (NRM) on day +100. Forty-four patients (36 acute myeloid leukemias, 5 acute lymphoblastic leukemias, 3 myelodysplastic syndromes) were enrolled. Median age was 47 years. Median follow-up was 27 months. Conditioning regimen was based on Clofarabine 40 mg/m(2) (day -6 to -2) and Treosulfan 14 g/m(2) (day -6 to -4). Allogeneic haematopoietic stem cells were derived from a sibling (n=22) or a well-matched unrelated donor (n=22). Graft versus host disease (GvHD) prophylaxis consisted of Thymoglobuline, Rituximab, Cyclosporine and short course Methotrexate. The regimen allowed rapid engraftment and 100 days NRM of 18%, mainly because of bacterial infections. Grade 2-4 acute and chronic GvHD were 16% and 19% respectively. Overall survival (OS), progression free survival and relapse incidence at 2-year were 51%, 31% and 50%. A significantly different outcome was observed between patients with "low/intermediate" vs "high/very high" disease risk index (DRI; 1-year OS 78% and 24%). Treosulfan and Clofarabine as conditioning regimen for allo-HSCT is feasible, with 78% 1-year OS in low/intermediate DRI. However 1-year NRM was 18% and, despite the intensification of the conditioning regimen, relapse incidence is still a major issue in patients with poor prognostic risk factors.