Brave new world: expanding home care in stem cell transplantation and advanced therapies with new technologies.

Hematopoietic stem cell transplantation and cell therapies like CAR-T are costly, complex therapeutic procedures. Outpatient models, including at-home transplantation, have been developed, resulting in similar survival results, reduced costs, and increased patient satisfaction. The complexity and safety of the process can be addressed with various emerging technologies (artificial intelligence, wearable sensors, point-of-care analytical devices, drones, virtual assistants) that allow continuous patient monitoring and improved decision-making processes. Patients, caregivers, and staff can also benefit from improved training with simulation or virtual reality. However, many technical, operational, and above all, ethical concerns need to be addressed. Finally, outpatient or at-home hematopoietic transplantation or CAR-T therapy creates a different, integrated operative system that must be planned, designed, and carefully adapted to the patient's characteristics and distance from the hospital. Patients, clinicians, and their clinical environments can benefit from technically improved at-home transplantation.

Use of plerixafor to mobilize haematopoietic progenitor cells in healthy donors.

Increased transplant activity calls for improved stem cell collection, especially when peripheral blood is the preferred source of haematopoietic progenitor cells (HPCs). Plerixafor is a bicyclam molecule that mobilizes CD34+ cells by reversibly disrupting CXCR4-CXCL12-supported HPC retention. Plerixafor is given with granulocyte colony-stimulating factor (G-CSF) to help harvest autologous CD34+ cells for transplantation when mobilization with G-CSF fails. Mobilization protocols with the same doses of plerixafor and G-CSF have been used off-label in healthy allogeneic donors, with equal success and scarce side effects, both in adult and paediatric patients. Plerixafor has also been used as a sole mobilization agent. Plerixafor alone or coupled with G-CSF might lead to harvesting distinct cellular populations conferring improved engraftment properties and increased survival. Those characteristics might make plerixafor an especially attractive mobilization agent, particularly for non-related donations. However, available data are limited, and long-term follow-up is needed to clarify the best scenario for using plerixafor with or without G-CSF in healthy donors. In this review, we will summarize the evidence supporting this practice, highlighting the practical aspects and providing clues for an expanded use of plerixafor.

Elevated FANCA expression determines a worse prognosis in chronic lymphocytic leukemia and interferes with p53 function.

Chronic lymphocytic leukemia (CLL) is characterized by a failure in the mechanisms of apoptosis that leads to an accumulation of mature B cells in peripheral blood, bone marrow, and lymphoid organs. The molecular basis of CLL remains unknown. Certain cytogenetic and molecular markers determine a bad prognosis in CLL. Fanconi anemia complementation (FANC) proteins have been related to chromosomal instability and alterations in the mechanisms of p53 activation, control of cell cycle, and apoptosis. We investigated the role of certain FANC proteins in CLL. Our data identified a group of patients with CLL with high expression of FANCA in peripheral B-CLL cells and we established its relationship with the deletion of 11q23 and a worse prognosis. When we investigated the molecular mechanisms of this bad prognosis, we observed a reduction in the expression of 2 p53 target genes, p21 and ∆Np73, in CLL primary cells transfected with FANCA. Functional studies demonstrated an impairment of p53 by FANCA. Moreover, we obtained evidence of a cooperation between FANCA and the NEDD8-interacting protein NUB1L in the destabilization of p53. For the first time, FANCA is reported as a bad prognosis marker by a mechanism other than its role in the Fanconi anemia-breast cancer DNA repair pathway.-Bravo-Navas, S., Yáñez, L., Romón, Í., Pipaón, C. Elevated FANCA expression determines a worse prognosis in chronic lymphocytic leukemia and interferes with p53 function.

ABO-mismatched marrow processing for transplantation: Comparative results of 80 procedures performed with Cobe Spectra and Spectra Optia.

BACKGROUND: removal of incompatible red blood cells (RBCs) or plasma is usually required to avoid hemolysis during infusion of ABO incompatible bone marrow (BM) allogeneic transplants. This process often involves separation of buffy coat (BC) by centrifugation in automated devices. We have evaluated the Spectra Optia™ (Optia) apheresis system to determine its effectiveness in BC concentration, volume reduction and RBCs depletion of ABO-incompatible BM compared with our previous method using Cobe Spectra™ (Cobe). MATERIALS AND METHODS: 28 processes were performed with Optia and 52 with Cobe. We compared volume reduction, RBCs depletion, and recovery of total nucleated cells (TNCs), mononuclear cells (MNCs), CD34+ and CD3+ cells in the final product. Hematopoietic engraftment was ascertained. We used Saphiro-Wilks and Kolmorgorov- Smirnov tests to test normality and Mann-Whitney's U test to compare means between both groups. RESULTS: We found statistically significant differences favoring Optia versus Cobe in TNCs recovery (62% vs. 37%), CD34+ cell recovery (98 vs 84%), volume reduction (91 vs 84%), and RBCs depletion (99 vs. 97%), but not in processing time or time to engraftment. CONCLUSION: Optia achieves high RBCs and volume depletion of BM, while providing excellent CD34+ recovery in clinical routine. Some parameters compare favorably with Cobe Spectra.

Home transfusion: three decades of practice at a tertiary care hospital.

BACKGROUND: Hospital at Home (HH) provides specialized care at the patients' homes. Keeping patients in familial surroundings can result in better outcomes reducing readmission to hospital, mortality, and costs of care. Home transfusion (HT) can be a key element in HH management but is scarcely deployed due to concerns about safety and cost. We have reviewed our HT practice to assess its feasibility and safety. STUDY DESIGN AND METHODS: We prospectively reviewed data collected from 1985 to 2015, focusing specially on feasibility and procedural safety, looking for adverse events of transfusion. We also assessed the situation in similar hospitals in Spain with a survey about their practice. RESULTS: A total of 613 patients received 2260 blood components in 2126 transfusion episodes. A total of 93% patients received fewer than 10 transfusions. Most patients were treated for blood diseases (32%) or cancers (20%). The rate of adverse effects was 2.68% and decreased significantly with time. Fever was the most common adverse reaction. Patients who received transfusion of more than one blood product in a day were at higher risk of adverse events. No errors or near-miss events were detected, and no patient had to be readmitted to hospital for this cause. The survey on HT practices in similar hospitals showed great variation in practice. CONCLUSION: HT is feasible, sustainable, and safe, when performed on selected patients by dedicated HH units with well-trained staff, under specific protocols.

Quality indicators for Transfusion Medicine in Spain: a survey among hospital transfusion services.

BACKGROUND: Transfusion services in the European Union must implement quality management systems to improve quality. Quality indicators (QI) play a key role in quality management because they can supply important information about the performance of the transfusion service, which can then be used for benchmarking. However, little is known about the actual use of QI in hospitals. We tried to ascertain the use and characteristics of QI in Spanish hospital transfusion services. MATERIALS AND METHODS: We performed a survey among transfusion services in order to learn which QI they use. We classified indicators into categories and concepts, according to the steps of the transfusion process or the activities the indicators referred to. RESULTS: Seventy-six hospitals (17.9% of the hospitals actively transfusing in the country) reported 731 QI. Twenty-two of them (29%) were tertiary level hospitals. The number of indicators per hospital and by activity varied greatly. QI were assigned to some basic categories: transfusion process (23% of indicators), transfusion activity and stock management (22%), haemovigilance (20%), stem cell transplantation (9%), transfusion laboratory (9%), quality management system (8%), blood donation (3.4%), apheresis and therapeutic activities (2.5%) and immunohaematology of pregnancy (2%). DISCUSSION: Although most hospitals use QI in their quality management system and share a core group of indicators, we found a great dispersion in the number and characteristics of the indicators used. The use of a commonly agreed set of QI could be an aid to benchmarking among hospitals and to improving the transfusion process.

Mapping the HLA diversity of the Iberian Peninsula.

The polymorphism of HLA genes can be used to reconstruct human peopling history. However, this huge diversity impairs successful matching in stem cell transplantation, a situation which has led to the recruitment of millions of donors worldwide. In parallel to the increase of recruitment, registries are progressively relying on information from population genetics to optimize their donor pools in terms of HLA variability. In this study, the HLA data of 65,000 Spanish bone marrow donors were analyzed together with 60,000 Portuguese individuals to provide a comprehensive HLA genetic map of the Iberian Peninsula. The frequencies of many alleles were shown to vary continuously across the Peninsula, either increasing or decreasing from the Mediterranean coast to the Atlantic domain or from the Strait of Gibraltar to the Pyrenees and Bay of Biscay. Similar patterns were observed for several haplotypes. In addition, within some regions neighboring provinces share a close genetic similarity. These results outline the genetic landscape of the Iberian Peninsula, and confirm that the analysis of the HLA polymorphism may reveal relevant signatures of past demographic events even when data from donor registries are used. This conclusion stimulates future developments of the Spanish registry, presented here for the first time.

∆Np73 is capable of inducing apoptosis by co-ordinately activating several BH3-only proteins.

Inactivation of p53 is one of the most relevant events in human cancer, since it allows transformed cells to escape their own proliferation control and leave them irresponsive to drugs that aim to damage their DNA. When p53 falls, other members of its family may become targets to attack tumoural cells. p73 has shown capacity to mediate these attacks. However, its N-terminal truncated isoforms have been associated with oncogenesis due to their capacity to act as dominant negatives of p53 and the transactivation (TA) isoforms of p73. We previously found a relationship between the overexpression of N-terminus-truncated p73 isoform (∆Np73) and that of the proapoptotic gene Bcl-2-interacting killer (BIK). In the present report we demonstrate that ∆Np73-α has the capacity to induce apoptosis through the co-ordinated activation of a group of genes harbouring GC-rich elements in their regulatory regions. ∆Np73-α synergizes with specificity protein (Sp1) on these elements but the overall response of these genes probably depends on the additional presence of consensus p53 elements. We explore the domains of ∆Np73-α involved in this transactivation capacity and found divergences with the previously described functions for them. Moreover, we found that the transforming mutation V12 of HRas impairs this transactivation capacity of ∆Np73-α, further supporting the anti-tumoural function of this later. Our data add complexity to the action of p73 on the induction of apoptosis and tumourogenesis, opening new interpretations to the expression profile of p73 isoforms in different human neoplasias.