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.

Adverse effects of therapeutic phlebotomies: Prospective study of 587 procedures.

BACKGROUND: Therapeutic phlebotomy (TP), a widely used medical procedure, can be performed on diverse patients with iron overload or polyglobulia. However, its adverse events are not well known as most of the information on phlebotomy is derived from healthy blood donors (0.1%-5.3%). In contrast, TP is applicable to a broader, more complex population with comorbidities and old age. To ascertain the incidence of adverse events in phlebotomies, we conducted a prospective study on patients who attended our Unit. STUDY DESIGN AND METHODS: We prospectively gathered data from patients referred to our Unit for TP. Data regarding demographics, health status, and adverse events within at least 24 h of phlebotomy were gathered via a structured questionnaire during each visit. RESULTS: Between August 2021 and September 2022, 189 patients underwent 587 procedures. Most patients were men, over 60 (57.3%) had comorbidities, and 93% underwent at least two procedures during the study period. Twenty patients (10.8%) presented 25 adverse events (4.3% of phlebotomies), usually vasovagal reactions, none of which were clinically relevant, and all were managed by nursing staff on site, with full patient recovery. DISCUSSION: The rate of adverse events (<5%) in patients undergoing TP was low and comparable to that seen in healthy blood donors. Consequently, even old patients and those with some comorbidities can safely undergo TP when the process is carefully managed.

Early and out-of-hospital use of COVID-19 convalescent plasma: An international assessment of utilization and feasibility.

BACKGROUND AND OBJECTIVES: The use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) in the treatment of patients with severe acute respiratory syndrome-2 infection has been controversial. Early administration of CCP before hospital admission offers a potential advantage. This manuscript summarizes current trials of early use of CCP and explores the feasibility of this approach in different countries. MATERIALS AND METHODS: A questionnaire was distributed to the International Society of Blood Transfusion (ISBT) CCP working group. We recorded respondents' input on existing trials on early/outpatient CCP and out-of-hospital (OOH)/home transfusion (HT) practices in their countries and feedback on challenges in initiating home CCP infusion programmes. In addition, details of existing trials registered on clinicaltrials.gov were summarized. RESULTS: A total of 31 country representatives participated. Early/OOH CCP transfusion studies were reported in the United States, the Netherlands, Spain and Brazil. There were a total of six published and five ongoing trials on the prophylactic and therapeutic early use of CCP. HT was practised in Australia, the UK, Belgium, France, Japan, Nigeria, the Netherlands, Spain, Italy, Norway, the United States and some provinces in Canada. Thirty-four representatives indicated a lack of OOH CCP or HT in their institutions and countries. Barriers to implementation of OOH/HT included existing legislation, lack of policies pertaining to outpatient transfusion, and associated logistical challenges, including lack of staffing and resources. CONCLUSION: Early administration of CCP remains a potential option in COVID-19 management in countries with existing OOH/HT programmes. Legislation and regulatory bodies should consider OOH/HT practice for transfusion in future pandemics.

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.

Mortality in acquired thrombotic thrombocytopenic purpura in the pre-caplacizumab era.

Despite the effectiveness of plasma exchange (PEX) and immunosuppressants in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), a number of patients still die as a result of the disease. Whether caplacizumab could rescue these patients remains still unsettled. The objective of this study was to characterise mortality patterns and prognostic factors in the first episode of aTTP.We queried the Spanish TTP Registry for patients with a diagnosis of aTTP in their presenting episode who fulfilled complete clinical and follow-up data (n = 102). The patients were diagnosed between 2004 and 2018, and all were treated with daily PEX and corticosteroids. Clinical and laboratory data were analysed at diagnosis and during the treatment course.Eight patients (7.7%) died between 12 h and 36 days after presentation, and could be classified into three patterns: death before treatment, early death driven by acute cardiac or neurologic events, and late death due to unremitted aTTP. Stupor or coma at diagnosis and platelet count < 20 × 109 /L by the 6th treatment day were independently associated with increased risk of death.Stupor or coma at diagnosis and lack of response to PEX by the 6th day in patients experiencing the first episode of aTTP are strong predictors of mortality. These patients could be rescued by novel agents aimed at halting the microvascular thrombosis until adequate immunosuppression is achieved.

Convalescent plasma treatment for patients of 80 years and older with COVID-19 pneumonia.

BACKGROUND: Older patients, frequently with multiple comorbidities, have a high mortality from COVID-19 infection. Convalescent plasma (CP) is a therapeutic option for these patients. Our objective is to retrospectively evaluate the efficacy and adverse events of CP treatment in this population group. METHODS: Forty one patients over 80 years old with COVID-19 pneumonia received CP added to standard treatment, 51.2% with high anti-SARS-CoV-2 IgG titers and 48.8% with low titers. Median time between the onset of symptoms and the infusion of plasma was 7 days (IQR 4-10). A similar group of 82 patients who received only standard treatment, during a period in which CP was not available, were selected as a control group. RESULTS: In-hospital mortality was 26.8% for controls and 14.6% for CP patients (P = 0.131) and ICU admission was 8.5% for controls and 4.9% for CP patients (P = 0.467). Mortality tended to be lower in the high-titer group (9.5%) than in the low-titer group (20%), and in patients transfused within the first 7 days of symptom onset (10%) than in patients transfused later (19.1%), although the differences were not statistically significant (P = 0.307 and P = 0.355 respectively). There was no difference in the length of hospitalization. No significant adverse events were associated with CP treatment. CONCLUSIONS: Convalescent plasma treatment in patients over 80 years old with COVID-19 pneumonia was well tolerated but did not present a statistically significant difference in hospital mortality, ICU admission, or length of hospitalization. The results should be interpreted with caution as only half the patients received high-titer CP and the small number of patients included in the study limits the statistical power to detect significant differences. TRIAL REGISTRATION: CEIm Cantabria # 2020.127.

Compliance with temperature and time requirements during in-hospital distribution of blood components: A national survey among transfusion services.

INTRODUCTION: Temperature and time conditions during storage and distribution of blood components (BC) and their permissible deviations are strictly regulated. The degree of compliance with these requirements in daily practice of transfusion services (TS) is not well known. MATERIALS AND METHODS: We conducted a survey among Spanish hospital TS covering different aspects of BC management in their daily activity. RESULTS: Eighty-three TS managing 56 % of total transfusions answered the survey. Monitoring of red blood concentrates (RBC) temperature during in-hospital distribution was routinely performed by only 12 % of the TS. The main criterion for BC re-entry into the stock was the total time spent outside controlled temperature. Up to 41 % of the TS apply the "30-minute rule" to distributed RBC, while most services use a 60-minute rule for PC. No adverse events were detected when RBC that had remained longer than 30 or 60 min outside the TS were transfused. Fresh frozen plasma is usually thawed 2 h preissue and stored at 4 °C up to 24 h. DISCUSSION AND CONCLUSIONS: In the Spanish context, the 30- and 60-minute rules for re-entry of RBC and PC into the TS stock are loosely followed. Feedback for a large number of TS suggests that the extension of the 30-minute RBC rule to at least 60 min is feasible, if other safety requirements are met. Flexibility with some requirements could help reduce product loss without deleterious effect on BC safety.

Methylene blue-treated plasma, versus quarantine fresh frozen plasma, for acute thrombotic thrombocytopenic purpura treatment: Comparison between centres and critical review on longitudinal data.

INTRODUCTION: Therapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial. PATIENTS AND METHODS: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. RESULTS: During the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). CONCLUSION: MBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.

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.