Feasibility of allogeneic hematopoietic stem cell transplantation in advanced age.

Although it is known that increasing age is associated with increased morbidity and mortality in allogeneic transplantation (allo-HSCT), individualization of the process may allow to perform it in progressively older patients.This study analyzed the outcome of 97 patients older than 60 years with a first allo-HSCT performed at our institution between 2011 and 2019.Median age was 66 years (range 60-79) and 15.4% were older than 70 years. The most frequent diagnosis was acute leukemia (50.5%), and 58.8% received a myeloablative conditioning. With a median follow-up of 33.9 months (range 7.9-111.5), at 3-years overall survival (OS) was 50%; progression-free survival (PFS), 46%; cumulative incidence of relapse, 22%; and non-relapse mortality (NRM), 32%. There were no significant differences in OS (p = 0.415), PFS (p = 0.691), cumulative incidence of relapse (p = 0.357) or NRM (p = 0.658) between patients of 60-64 years (n = 37), 65-69 (n = 45) and ≥ 70 years (n = 15). No differences were observed either depending on the intensity of the conditioning regimen in terms of OS (p = 0.858), PFS (p = 0.729), cumulative incidence of relapse (p = 0.416) or NRM (p = 0.270).In conclusion, older adults can safely and effectively undergo allo-HSCT with proper patient selection and individualized transplantation procedures.

Feasibility of a Hospital-at-Home Program for Autologous Hematopoietic Stem Cell Transplantation.

The Hospital at Home (HaH) model has been positioned as an appropriate therapeutic strategy for selected patients undergoing autologous hematopoietic stem cell transplantation (ASCT). This care model provides hospital-equivalent care, in terms of both quality and quantity, with medical and nursing staff that go to the patient's home. Here we describe our experience with a full HaH model for patients undergoing ASCT during the phase of aplasia. The patients met the eligibility criteria between January 1997 and December 2019 and were discharged from the hospital and admitted into the HaH-ASCT program on the same day they in which hematopoietic stem cells were infused. A total of 84 patients were included. The median patient age was 54 years (range, 16 to 74 years), and the median duration of participation in the HaH program was 17 days (range, 3 to 86 days). Only 10 of these patients (12%) required hospital readmission to the hematology department, 9 of them due to sepsis and 1 because of family care support claudication. Seventy-two patients (86%) experienced an episode of neutropenic fever during the HAH admission, with a median duration of 2 days (interquartile range [IQR], 1 to 11 days); all were treated with empiric i.v. antimicrobial therapy. Most patients (88%) presented with mucositis (44% with grade 3-4). Parenteral nutrition was administered in 26% of patients for a median of 6 days (IQR, 1 to 12 days). Most patients (94%) required at least 1 blood product transfusion at home. There was no transplantation-related mortality during the HaH-ASCT program or in the patients who were readmitted. With careful selection of patients and a comprehensive and well- experienced multidisciplinary team (doctors, nurses, and auxiliary nurses) in the HaH department and in close collaboration with the hematology department, complete at-home management of ASCT recipients immediately after transplantation is possible. This allows patients undergoing an aggressive procedure such as ASCT to remain in their own familiar environment, providing a better quality of life with a program that has demonstrated to be effective and safe, with a low incidence of complications and no associated mortality.

Cyclin C stimulates ß-cell proliferation in rat and human pancreatic ß-cells.

Activation of pancreatic ß-cell proliferation has been proposed as an approach to replace reduced functional ß-cell mass in diabetes. Quiescent fibroblasts exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces pancreatic ß-cell proliferation. We hypothesized that cyclin C overexpression would induce ß-cell proliferation through G0 exit, thus being a potential therapeutic target to recover functional ß-cell mass. We used isolated rat and human islets transduced with adenovirus expressing cyclin C. We measured multiple markers of proliferation: [(3)H]thymidine incorporation, BrdU incorporation and staining, and Ki67 staining. Furthermore, we detected ß-cell death by TUNEL, ß-cell differentiation by RT-PCR, and ß-cell function by glucose-stimulated insulin secretion. Interestingly, we have found that cyclin C increases rat and human ß-cell proliferation. This augmented proliferation did not induce ß-cell death, dedifferentiation, or dysfunction in rat or human islets. Our results indicate that cyclin C is a potential target for inducing ß-cell regeneration.