0
selected
-
1.
Longitudinal Clinical Data Improves Survival Prediction after Hematopoietic Cell Transplantation Using Machine Learning
Zhou, Y., Smith, J., Keerthi, D., Li, C., Sun, Y., Mothi, S. S., Shyr, D., Spitzer, B., Harris, A. C., Chatterjee, A., et al
Blood advances. 2023
Abstract
Serial prognostic evaluation of patients after allogeneic hematopoietic cell transplantation (alloHCT) might help identify patients at high risk of developing potentially lethal organ dysfunction. Current prediction algorithms are based on models that do not incorporate changes to the patients' clinical condition that occur after alloHCT in the model development, which limits their predictive ability. We developed and validated a robust risk-prediction algorithm to predict short-term and long-term survival after alloHCT in pediatric patients that includes baseline biological variables, as well as changes in the patients' clinical status after alloHCT. The model was developed using clinical data from children and young adults treated at a single academic quaternary-care referral center. The model was created using a randomly split training dataset (70% of the cohort), internally validated (remaining 30% of the cohort from the same center), and then externally validated on patient data from another tertiary-care referral center. Repeated clinical measurements performed from 30 days before alloHCT to 30 days afterwards were extracted from the electronic medical record and incorporated into the model to predict survival at 100 days, 1-year, and 2-years after alloHCT. Of the 738 patients who underwent their first alloHCT at our institution between 2000 and 2020, 517 (70%) were randomly included in the training dataset and 221 (30%) constituted the validation dataset. When compared with models constructed from baseline variables alone, the naïve-Bayes machine learning models incorporating longitudinal data were significantly better at predicting whether patients would be alive or deceased at the given timepoints. This proof-of-concept study demonstrates that unlike traditional prognostic tools that use fixed variables for risk assessment, incorporating dynamic variability using clinical and laboratory data improves the prediction of mortality in patients undergoing alloHCT.
-
2.
An ISCT Stem Cell Engineering Committee Position Statement on Immune Reconstitution: the importance of predictable and modifiable milestones of immune reconstitution to transplant outcomes
Bertaina, A., Abraham, A., Bonfim, C., Cohen, S., Purtill, D., Ruggeri, A., Weiss, D., Wynn, R., Boelens, J. J., Prockop, S.
Cytotherapy. 2022;24(4):385-392
Abstract
Allogeneic stem cell transplantation is a potentially curative therapy for some malignant and non-malignant disease. There have been substantial advances since the approaches first introduced in the 1970s, and the development of approaches to transplant with HLA incompatible or alternative donors has improved access to transplant for those without a fully matched donor. However, success is still limited by morbidity and mortality from toxicity and imperfect disease control. Here we review our emerging understanding of how reconstitution of effective immunity after allogeneic transplant can protect from these events and improve outcomes. We provide perspective on milestones of immune reconstitution that are easily measured and modifiable.
-
3.
Outcomes of pediatric patients with therapy-related myeloid neoplasms
Sharma, A., Huang, S., Li, Y., Brooke, R. J., Ahmed, I., Allewelt, H. B., Amrolia, P., Bertaina, A., Bhatt, N. S., Bierings, M. B., et al
Bone marrow transplantation. 2021
Abstract
Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.
-
4.
Phenotypic and Functional Characterization of NK Cells in aßT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia
Meazza, R., Falco, M., Loiacono, F., Canevali, P., Della Chiesa, M., Bertaina, A., Pagliara, D., Merli, P., Indio, V., Galaverna, F., et al
Cancers. 2020;12(8)
Abstract
NK cells can exert remarkable graft-versus-leukemia (GvL) effect in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Here, we dissected the NK-cell repertoire of 80 pediatric acute leukemia patients previously reported to have an excellent clinical outcome after aßT/B-depleted haplo-HSCT. This graft manipulation strategy allows the co-infusion of mature immune cells, mainly NK and ?dT cells, and hematopoietic stem cells (HSCs). To promote NK-cell based antileukemia activity, 36/80 patients were transplanted with an NK alloreactive donor, defined according to the KIR/KIR-Ligand mismatch in the graft-versus-host direction. The analysis of the reconstituted NK-cell repertoire in these patients showed relatively high proportions of mature and functional KIR(+)NKG2A(-)CD57(+) NK cells, including the alloreactive NK cell subset, one month after HSCT. Thus, the NK cells adoptively transfused with the graft persist as a mature source of effector cells while new NK cells differentiate from the donor HSCs. Notably, the alloreactive NK cell subset was endowed with the highest anti-leukemia activity and its size in the reconstituted repertoire could be influenced by human cytomegalovirus (HCMV) reactivation. While the phenotypic pattern of donor NK cells did not impact on post-transplant HCMV reactivation, in the recipients, HCMV infection/reactivation fostered a more differentiated NK-cell phenotype. In this cohort, no significant correlation between differentiated NK cells and relapse-free survival was observed.
-
5.
Hematopoietic stem cell transplantation for isolated extramedullary relapse of acute lymphoblastic leukemia in children
Gabelli, M., Zecca, M., Messina, C., Carraro, E., Buldini, B., Rovelli, A. M., Fagioli, F., Bertaina, A., Lanino, E., Favre, C., et al
Bone marrow transplantation. 2018
Abstract
Relapse of acute lymphoblastic leukemia (ALL) may occur in extramedullary sites, mainly central nervous system (CNS) and testis. Optimal post-remissional treatment for isolated extramedullary relapse (IEMR) is still controversial. We collected data of children treated with hematopoietic stem cell transplantation (HSCT) for ALL IEMR from 1990 to 2015 in Italy. Among 281 patients, 167 had a relapse confined to CNS, 73 to testis, 14 to mediastinum, and 27 to other organs. Ninety-seven patients underwent autologous HSCT, 79 received allogeneic HSCT from a matched family donor, 75 from a matched unrelated donor, and 30 from an HLA-haploidentical donor. The 10-year overall survival was 56% and was not influenced by gender, ALL blast immune-phenotype, age, site of relapse, duration of first remission, and type of HSCT. In multivariable analysis, the only prognostic factors were disease status at HSCT and year of transplantation. Patients transplanted in third or subsequent complete remission (CR) had a risk of death 2.3 times greater than those in CR2. Children treated after 2000 had half the risk of death than those treated before that year. Our results suggest that both autologous and allogeneic HSCT may be considered for the treatment of pediatric ALL IEMR after the achievement of CR2.