Implementation of a vascular access team and an intravenous therapy programme: A first-year activity analysis.

BACKGROUND: Creating Vascular Access Teams (VAT) provides an expert nursing role that contributes to the training and continuous improvement of healthcare personnel. They can offer greater clinical safety, reducing complications and costs. Peripherally inserted central catheters (PICCs) and midline catheters (ML) can be safe and cost-effective alternatives to other types of venous access (VA). The aim of the study was to analyse our centre's VAT first 12 months of activity. The primary outcome was reported complications. Secondary outcomes were cause of catheter removal, consultancy activity and economic impact of VAT implantation. METHODOLOGY: A longitudinal, descriptive study was carried out from March 2019 to March 2020. Using consecutive sampling, all VA inserted, and all consults received were included. Patients under 18 years of age were excluded. RESULTS: The VAT inserted 1257 catheters into 1056 patients (291 MLs, 966 PICCs). The mean dwell time was 14.9 days for MLs and 59.07 days for PICCs. The main reason for removing VA was end of treatment (80.7%). During VA follow-up confirmed infection was detected in 1 ML (0.3%) and nine PICCs (0.9%). Symptomatic thrombosis was reported in 2 MLs (0.7%) and 16 PICCs (1.7%). The VAT received 367 consultations, and the main reason for consultation was to resolve doubts regarding the management of VA (80.9%). The insertion of ML and PICC catheters represented annual estimated economic savings of €867,688.44€. CONCLUSIONS: Our study provides a detailed analysis of VAT's activity, its relevance to clinical safety, and to efficient resource management within our hospital. It demonstrates how VAT establishment can be a safe and efficient intervention that enhances care quality.

Effect of CD34+ Cell Dose on the Outcomes of Allogeneic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide.

The impact of infused CD34+ cell dose on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) using standard graft-versus-host disease (GVHD) prophylaxis remains controversial. Information on this subject is scarce for alloHSCT using high-dose post-transplantation cyclophosphamide (PTCy). We aimed to assess the effect of CD34+ cell dose in peripheral blood stem cell (PBSC) grafts on the outcome of alloHSCT using PTCy-based GVHD prophylaxis. To do so, we conducted a single-center retrospective analysis of 221 consecutive adult patients who underwent PTCy alloHSCT from HLA-matched sibling donors (MSDs; n = 22), HLA-matched unrelated donors (MUDs; n = 83), mismatched unrelated donors (MMUDs; n = 73), and haploidentical donors (n = 43). Based on the binary partitioning method, 5 × 106/kg was used as the optimal cutoff for CD34+ cell dose. According to our institutional protocol, the maximum CD34+ cell dose was capped at 8 × 106/kg. The study cohort was divided into 2 groups based on CD34+ cell dose: high dose (>5 to 8 × 106/kg) and low dose (≤5 × 106/kg). Patients receiving high-dose CD34+-containing grafts had significantly shorter median times to neutrophil engraftment and platelet engraftment compared to those who received low-dose CD34+ (19 days versus 21 days [P = .002] and 16 days versus 22 days [P = .04], respectively). There were no differences between the high-dose and low-dose groups in the cumulative incidence of day +100 acute GVHD (grade II-IV: 25% versus 23% [P = .7]; grade III-IV: 5% versus 4% [P = .4], respectively) or 2-year chronic GVHD (moderate/severe GVHD: 9% versus 6%; P = .5). There was no impact of CD34+ cell dose on survival outcomes with the use of MSDs, MUDs, or MMUDs. Recipients of haploidentical alloHSCT using low-dose CD34+ cells had significantly worse overall survival (hazard ratio [HR], 6.01; P = .004) and relapse-free survival (HR, 4.57; P = .004). In recipients of PBSC PTCy alloHSCT, infused CD34+ cell doses >5 to 8 × 106/kg were associated with faster neutrophil and platelet engraftment, independent of donor type. Our study suggests an impact of CD34+ cell dose on survival outcomes only with haploidentical donors, for whom the administration of a CD34+ cell dose ≤5 × 106/kg significantly decreased survival outcomes.

Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide.

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ≤ 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ≤ 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD.

PTCY and Tacrolimus for GVHD Prevention for Older Adults Undergoing HLA-Matched Sibling and Unrelated Donor AlloHCT.

The use of post-transplantation cyclophosphamide (PTCY) for graft-versus-host disease (GHVD) prevention is becoming prevalent in the transplantation community when HLA-identical sibling and 10/10 HLA-matched (MUD) and 9/10 mismatched unrelated donors are selected for alloHSCT. However, reported evidence on outcomes from elderly patients receiving PTCY-containing GVHD prophylaxis remains limited. This study aims to compare the outcomes of PTCY- tacrolimus (TK) prophylaxis and conventional GVHD prophylaxis in patients aged >50 years undergoing peripheral blood alloHSCT from a single institution. A total of 161 consecutive patients aged >50 years undergoing alloHSCT between January 2014 and February 2021 were included. Data were collected retrospectively and updated in December 2021. Patients received grafts from HLA-identical sibling, and from 10/10 and 9/10 HLA matched and mismatched unrelated donors. Overall, median age was 60 years, and 91 (54.8%) received PTCY-TK for GVHD prevention. Time to neutrophil and platelet engraftment was longer in the PTCY-TK group (20 versus 16 days and 19 versus 11 days, P < .001). The cumulative incidences of grade II-IV and III-IV acute GVHD (aGVHD) at day 100 and moderate/severe chronic GVHD (cGVHD) at 2 years were 18.2%, 5.7%, and 9.5% for patients receiving PTCY-TK, and 26.0%, 9.6% and 39.5% for those who did not. The multivariate analysis showed that PTCY-TK reduced the probability of grade II-IV aGVHD (hazard ratio [HR] 0.41, P = .035), of cGVHD (any grade: HR 0.43 [P = .014], and of moderate/severe cGVHD [HR 0.15 {P < .001}]). At 2 years, the overall survival (65.4% versus 65.6%, P = .472), non-relapse mortality (17.4% versus 13.7%, P = .967), and cumulative incidence of relapse rates (24.2% versus 27.5%, P = .712) were comparable between both cohorts; GVHD-free/relapse-free survival (GRFS) was higher in the PTCY-TK group (2 years: 50.2% versus 21.8%; HR 0.42, P = .001). In patients aged ≥50 years. PTCY-TK was safe and a more effective drug combination than non-PTCY containing GVHD prophylaxis, even with the use of matched and mismatched unrelated donors, and resulted in comparable relapse rates and better GRFS.

A reproducible and safe at-home allogeneic haematopoietic cell transplant program: first experience in Central and Southern Europe.

In 2015, we implemented an at-home allogeneic haematopoietic cell transplant (allo-HCT) program. Between 2015 and 2018, 252 patients underwent allo-HCT; 41 patients underwent allo-HCT in the at-home program (46% myeloablative; 63% unrelated donor; 32% posttransplant cyclophosphamide), and these patients were compared with 39 in-patients; safety, capacity to release beds for other programs, and economic efficiency cost were evaluated. We observed a lower incidence of febrile neutropenia in the at-home group compared with that in the in-patient group (32% versus 90%; p < 0.0001), whereas the incidence of aspergillosis was similar among groups (at-home 1% versus in-patient 3%; p = 0.5). The at-home patients showed a lower incidence of 1-year severe graft-versus-host disease (GVHD; 10% versus 29%; p = 0.03). There were no differences in 1-year transplant-related mortality, relapse, or overall survival among groups. The re-admission rate in the at-home group was 7%. The at-home setting was less expensive (9087 €/transplant), and its implementation increased capacity by 10.5 allo-HCTs/year. Moreover, a chimeric antigen receptor T-cell program could be established without increasing beds. Thus, our at-home allo-HCT program may be a safe modality to reduce febrile neutropenia and acute GVHD, resulting in lower re-admission rates.

Improving security of autologous hematopoietic stem cell transplant in patients with light-chain amyloidosis.

Autologous stem cell transplant (ASCT) has demonstrated to be an effective treatment for patients with light-chain (AL) amyloidosis. However, a high transplant-related mortality (TRM) rate was reported in previous series of patients and questioned the role of transplant in this disease. Recently, experienced groups have shown a significant TRM decrease that has been attributed to an accurate selection of patients. Moreover, application of several supportive measures has decreased toxicity over amyloid-involved organs. We analyzed a series of 66 patients with AL amyloidosis, who underwent ASCT at a single institution and evaluated the impact of these measures beyond patient selection. Four temporary groups were established: group-A (non-selection plus post-transplant G-CSF use) with 29 patients, group-B (selection) with 13, group-C (selection and G-CSF avoidance) with 14, and group-D (selection, G-CSF avoidance and corticosteroid's prophylaxis) with 10. A decreasing TRM was observed over time from group-A (38%), to group-D (0%); p = 0.02. We also observed a progressive increase of three-year OS from 62% in group-A to 100% in group-D; p = 0.049. On the multivariate analysis, cardiac involvement was the only independent predictor of survival. Therefore, tailored selection policy together with transplant supportive measures have allowed ASCT to be a safe procedure in AL amyloidosis.

Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies).

OBJECTIVES: This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies. BACKGROUND: Current chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy. METHODS: In this randomized, controlled study, 90 patients with recently diagnosed acute leukemia (n = 36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT) (n = 54) and without LVSD were randomly assigned to a group receiving enalapril and carvedilol (n = 45) or to a control group (n = 45). Echocardiographic and cardiac magnetic resonance (CMR) imaging studies were performed before and at 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction (LVEF). RESULTS: The mean age of patients was 50 ± 13 years old, and 43% were women. At 6 months, LVEF did not change in the intervention group but significantly decreased in controls, resulting in a -3.1% absolute difference by echocardiography (p = 0.035) and -3.4% (p = 0.09) in the 59 patients who underwent CMR. The corresponding absolute difference (95% confidence interval [CI]) in LVEF was -6.38% (95% CI: -11.9 to -0.9) in patients with acute leukemia and -1.0% (95% CI: -4.5 to 2.5) in patients undergoing autologous HSCT (p = 0.08 for interaction between treatment effect and disease category). Compared to controls, patients in the intervention group had a lower incidence of the combined event of death or heart failure (6.7% vs. 22%, p = 0.036) and of death, heart failure, or a final LVEF <45% (6.7% vs. 24.4%, p = 0.02). CONCLUSIONS: Combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy. The clinical relevance of this strategy should be confirmed in larger studies. (Prevention of Left Ventricular Dysfunction During Chemotherapy [OVERCOME]; NCT01110824).

Prevention of chemotherapy-induced left ventricular dysfunction with enalapril and carvedilol: rationale and design of the OVERCOME trial.

BACKGROUND: The current treatment of hematologic malignancies includes diverse potentially cardiotoxic chemotherapy agents, including high-dose myeloablative regimens used in autologous hematopoietic stem cell transplantation (HSCT). Many of these treatments could induce left ventricular dysfunction (LVD), and limit their efficacy. Angiotensin-converting enzime inhibitors and beta-blockers prevent LVD and prolong survival after infarction, and recent animal and pilot clinical studies suggest that they can prevent the development of chemotherapy-induced cardiac toxicity. METHODS: This is a prevention, parallel-assignment, randomized, controlled, clinical efficacy study. Ninety patients recently diagnosed of acute leukemia or undergoing autologous HSCT and with normal LV ejection fraction will be randomized to enalapril and carvedilol or to the control group. Echocardiogram and a cardiac magnetic resonance imaging studies will be performed at baseline and 6-9 months after randomization. The primary efficacy endpoint is the change from baseline in LV ejection fraction. Secondary endpoints include the assessment of LV volumes and diastolic function, and the incidence of death, heart failure, or LVD. CONCLUSIONS: The OVERCOME study will be the first clinical trial to test the preventive efficacy on LVD of combined treatment with enalapril and carvedilol administered to patients with hematologic malignancies submitted to current treatment with intensive chemotherapy.