Autologous Patients Research Articles

Factors Associated with Catheter-Related Thrombosis in Autologous Stem Cell Transplant Patients: Can We Predict Risk?

Central venous catheters (CVCs) are central to the process of autologous hematopoietic stem cell transplantation (AHCT) for hematologic malignancies. Large bore (14F to 15F) CVCs are routinely used for stem cell collection, administration of medications and blood products, and total parental nutrition. Up to 20% of patients experience catheter-related thrombosis (CRT), a major complication typically requiring at least 3 months of anticoagulation. This can lead to bleeding, further complicating the post-transplant course. Factors associated with CRT include endothelial damage due to conditioning regimens, bacteremia, and immobilizations. Furthermore, in ambulatory patients with cancer, increased risk of venous thromboembolism has been seen in patients with low hemoglobin (<10 g/dL), elevated pre-chemotherapy leukocyte count (>11 x 109/L), elevated pre-chemotherapy platelet count (>350 x 109/L), those receiving erythropoiesis-stimulating agents, and obesity (body mass index > 35 kg/m2). We hypothesized that these factors may also confer CRT risk in those undergoing AHCT. To test this hypothesis and to further refine our understanding of the risks of CRT in this population, we compare characteristics of patients with CRT to those without in this retrospective, case-control study. Using prospectively collected data from the University of Minnesota Blood and Marrow Transplantation Database, we studied 1049 consecutive adults (age > 18 years) with lymphoma or multiple myeloma who underwent AHCT between 2006 and 2019. Available medical records were manually curated for the occurrence of CRT. We identified 92 subjects with CRT events, which were defined as mural thrombus with partial or total occlusion of a vessel, pulmonary embolism, or right atrial thrombus in which a catheter was present or had been present within the prior 30 days. CRT diagnosis was made by imaging, which was performed for either symptoms or signs of venous thrombosis, or for routine disease surveillance. We then identified 184 controls who were matched for age, sex, disease, and transplant date. We excluded from our control group those who received prophylactic anticoagulation in the peri-transplant period. In a univariate analysis, we observed an increased risk in CRT in those patients with history of VTE (OR 32.00, 95% CI: 4.24-241.30), mucositis in the peri-transplant period (OR 1.65, 95% CI: 1.00-2.73), hemoglobin increased above the median of 10.3 g/dL (OR 1.48, 95% CI: 1.26-1.73), those with indwelling port in addition to CVC (OR 1.76, 95% CI: 1.02-3.05), and those with body mass index (BMI) > 35 kg/m2 (OR 2.44, 95% CI: 1.12-5.34). Multivariate conditional logistic regression analysis upheld the impact of BMI > 35 kg/m2 (OR 2.53, 95% CI: 1.05-6.13). CRT is a major contributor to morbidity in the AHCT setting. Mucositis, presence of a port, and history of VTE have previously been associated with CRT events. Our study elucidates additional risk factors that may contribute to CRT risk, including obesity and higher than average hemoglobin concentration in comparison to the controls. Further study in larger cohorts is warranted to clarify the magnitude of risk of these factors in the adult AHCT population. Figure Disclosures Bachanova: BMS: Research Funding; Incyte: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; FATE: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees. Shah:Aspen Pharma: Research Funding.

Peripheral Blood Progenitor Cell Mobilization of CD34+ Cells with Combine G-CSF and GM-CSF in Pediatric Patient Outcome and Economic Advantage

Background: Clinical trials to mobilize PBPC for autologous and allogeneic harvesting prior to high dose chemotherapy/radiotherapy include chemotherapy, cytokines, or chemotherapy combine with cytokines. PBPC mobilized by G-CSF or GM-CSF reduces the hematological toxicity and supportive care requirements in recipients of autologous and allogeneic transplants, in our study we combined G-CSF and GM-CSF to mobilize PBPC for transplantation. Methods: We selected 63 patients with different cancers to participate in the study and 7 healthy donors. We utilize to mobilize in all the patient the combination of G-CSF and GM-CSF (10μg/Kg/day each) administered for 5 consecutive days. Then we proceed it to harvest the PBPC until we obtain a threshold of 2.0 x 10^6/Kg CD34+ cells. A total of 31 PBPC transplants were performed (27 autologous and 8 allogeneic). Neutrophil engraftment was defined as ANC> 500/mm³ and, platelet engraftment was defined as a platelet count > 30,000/mm³ (transfusion independent) for more than 48 hours. Results: Data on PBC 24, 48, 72, and 96hrs. For the 31 PBPC autologous transplant patients, the median days to ANC>500 was 10.6 days; 11 days for the allogeneic. None of the subject's experience bone pain, headache, flu like side effects or a documented or proven infection. Median days to platelet engraftment following infusion CD34+ cells, was 13.2 for the autologous PBPC; 13 days for the allogeneic. Conclusions: The combination the G-CSF and GM-CSF (10μg/kg/day x 5 days) was well tolerated. We can appreciate that there is a reduction in the duration and severity of neutropenia as well of thrombocytopenia in both types of transplant (autologous/allogeneic). The GVHD incidence were not increase by the use of G-CSF and GM-CSF. We conclude that this procedure is cost effective and a suitable way to mobilize an average number of PBPC (from 1-3 apheresis) in a shorter amount of time indicating an economic advantage. It is proven to be less expensive than other agent used to mobilize stems cells for transplant. Disclosures No relevant conflicts of interest to declare.

Efficacy of Oral Ribavirin in Respiratory Syncytial Virus Infection in Hematopoietic Stem Cell Transplant Patients: A Single-Centre Experience

Background: Respiratory syncytial virus (RSV) is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematological malignancy or a hematopoietic stem cell transplantation (HSCT). In immunocompromised patients including HSCT recipients, RSV can progress to a more severe lower respiratory infection (LRI), often complicated by respiratory failure leading to increased morbidity and mortality. Little is known about the best management strategy in this immunocompromised group and strategies to manage RSV is challenging. Data on aerosolized ribavirin to treat RSV infections in HSCT recipients come from small, retrospective studies with heterogeneous treatment combinations but nevertheless, have shown to prevent poor outcomes. There is very little data on oral ribavirin treatment but the retrospective data so far has been promising. Aim: To evaluate the effectiveness of oral ribavirin in HSCT patients with RSV infection at our centre in London, Ontario. Methods: Eighteen HSCT patients with RSV were analyzed retrospectively. In 2012, there were 5 patients treated with supportive care alone. After 2012, there were 13 patients treated with oral ribavirin. RSV diagnosis was established by polymerase chain reaction assay via nasopharyngeal swabs. Oral ribavirin was initiated at 15 mg/kg/day in three divided doses for 7-10 days with possibility of extension in persistently symptomatic patients. An immunodeficiency scoring index (ISI) was used to classify patients as low, moderate, or high risk for progression to lower respiratory infection (LRI) or death. Findings: An outbreak of RSV occurred in our oncology unit in early 2012 where 5 HSCT patients ((3 autologous HSCT and 2 allogeneic HSCT patients) contracted RSV infection as well. No definitive treatment options were available during this period and patients were managed with supportive care alone. 4/5 HSCT patients died of RSV infection leading into an 80% mortality rate. This experience led to the development of a protocol for the HSCT patients focusing on prevention of nosocomial transmission, early PCR testing and treatment with oral ribavirin for those confirmed with RSV infection and signs of pneumonia or LRI. Since 2012, 13 HSCT patients (4 autologous HSCT patients and 9 allogeneic HSCT patients) were diagnosed with RSV infection and promptly treated with oral ribavirin. The median treatment duration was 10 days (range: 7-12). All patients treated with oral ribavirin survived the infection. Oral ribavirin was well tolerated with minor adverse effects. Conclusion: We found that HSCT patients with lower respiratory RSV infections can be successfully managed by use of prevention strategies and oral ribavirin. Although, our experience reflects a small sample size, the protocol was associated with decreased mortality compared to patients who received supportive care alone. Our experience supports the use of oral ribavirin for the early treatment of HSCT patients with RSV associated LRI and may be an alternative to aerosolized RBV. But ongoing review of our experience with this protocol is necessary and large prospective studies are needed to determine the optimal therapy in this patient group. Disclosures No relevant conflicts of interest to declare.

Incidence of acute kidney injury in bone marrow transplant patients; investigation of consequences within one to three years

Introduction: Previous studies have demonstrated that acute kidney injury (AKI) is a serious complication following hematopoietic stem cell transplantation (HSCT). The incidence of AKI in association with HSCT varies considerably because of several definitions for AKI. Objectives: In this study, we determined the rate of AKI after bone marrow transplantation (BMT) and its effects on patients’ outcomes according to modern definitions of AKI to conclude whether all these criteria can be useful for predicting AKI occurrence after BMT or not. Patients and Methods: We conducted a retrospective study of 271 patients undergoing HSCT, and after obtaining written informed consent from all patients, the required information was reviewed. AKI was defined according to RIFLE, KDIGO, and AKIN criteria. Renal function was assessed by calculating creatinine clearance, urine output, and estimated glomerular filtration rate (eGFR), determined through the MDRD equation. Results: Allogeneic and autologous transplantations were performed on 38 (14.02%) and 233 (85.97%) patients, respectively. According to the RIFLE criteria, 96 patients (35.42%) suffered from AKI, and based on AKIN, and KDIGO criteria, 101 patients (37.26%) were afflicted with it after BMT. The one-year mortality rate in allogeneic transplant patients with a history of AKI was 30.43% and 53.33% in patients without a history of AKI. The three-year mortality rate in allogeneic transplant patients with and without a history of AKI was 52.17% and 73.33% respectively, which showed no statistically significant difference. The three-year mortality rate in autologous transplant patients with and without a history of AKI was 60.27% and 22.5%, respectively. Conclusion: The one-year and three-year mortality rates, survival of patients, and AKI’s diagnosis were similar in all three criteria. Therefore, all these criteria can be useful for the prediction of AKI occurrence after BMT.

Prevalence and Utilization of Obturator Artery Anatomic Variant in Autologous Breast Reconstruction.

The objective of this study is to quantify the prevalence and describe the utilization of an anatomic vascular variant in which the obturator artery (OA) arises from the trunk of the deep inferior epigastric artery (DIEA) in stacked/dual-pedicled autologous breast reconstruction. When this variant is identified preoperatively on computed tomography angiography (CTA), it may be utilized in a "flow-through" fashion to direct antegrade internal mammary artery (IMA) flow into a second free flap to facilitate anastomotic arrangement and optimize perfusion. Preoperatively obtained abdomen/pelvis CTA imaging of 121 autologous breast reconstruction patients were retrospectively reviewed for the unilateral or bilateral presence of the OA branch arising from the DIEA (OA variant). The results were analyzed using descriptive statistics. Our analysis revealed the presence of the OA variant in 60 of the 121 (49.6%) breast reconstruction candidates, either unilaterally or bilaterally. Out of these patients, the variant was present unilaterally in 33 (55%) and bilaterally in 27 (45%) patients. Of the unilateral variants, 12 (36.4%) patients demonstrated right-sided laterality, while 21 (63.6%) patients demonstrated left-sided laterality. Clinically, this anatomic variant has been utilized in several cases of autologous breast reconstruction with flap survival in all cases. Utilization of this anatomic variant in stacked or dual-pedicled autologous breast reconstruction results in antegrade IMA perfusion of both primary and secondary flaps, as well as improved size match compared with other anastomotic options. Knowledge of the vascular anatomy and variations in the inferior epigastric system is crucial to both preventing complications and optimizing flap planning and outcome.

Does shipping vitrified embryos to a long-term storage bank affect outcomes?

Objective To assess the pregnancy rate associated with an aggressive policy of moving vitrified embryos to off-site storage. Design Retrospective comparative study Materials and methods Frozen embryo transfers (FETs) in 2019 were reviewed. Only embryos vitrified from autologous patients at the blastocyst stage were included in this evaluation. FETs were grouped into No Shipping (Group A) and Shipping (Group B) categories. The Group A embryos always remained on site, while Group B embryos were shipped to one of two off-site storage facilities and then returned to us when the patient was ready to undergo FET. Shipping included both courier transport and UPS transport. Shipping tanks were unloaded following a procedure developed and validated in our laboratory. Only patients with ongoing pregnancies are included. Results The shipping of vitrified embryos to a long-term storage bank did not decrease pregnancy rates when compared to embryos which remain on site. The increase in pregnancy rate in the shipping group is logical. The patients with embryos shipped off-site were clinically pregnant and not planning on using them soon, while the embryos that were never shipped off-site were patients that were utilizing their frozen embryos. Nearly 80% of patients that had embryos shipped off-site for storage achieved a pregnancy when the embryos were returned to the clinic. Conclusions Shipping vitrified embryos to off-site storage is not detrimental to outcome with subsequent FET. This is a successful strategy for IVF biolaboratories to pursue. Outsourcing storage can ultimately decrease clinic liability and the conundrum of what to do with abandoned embryos. The physical space needed for storage can be greatly reduced. Disclosures Nothing to disclose Funding None

Female sex as an independent prognostic factor in the development of oral mucositis during autologous peripheral stem cell transplantation

Oral mucositis (OM) is a frequent complication of stem cell transplantation-associated toxicity in haematological malignancies, contributing to mortality. Therapy still remains mainly supportive. We assessed risk factors in retrospective analysis of 192 autologous peripheral stem cell transplantation patients with lymphoma and multiple myeloma (MM), respectively. Futhermore, we examined the hormone levels both in serum and saliva during transplantation in 7 postmenopausal female patients with lymphoma compared to healthy controls using electrochemiluminescence immunoassay (ECLIA). Multivariable analysis revealed neutrophil engraftment (p < 0.001; p = 0.021) and female sex (p = 0.023; p = 0.038) as independent predictive factors in the combined patient group and in the lymphoma group, and neutrophil engraftment (p = 0.008) in the MM group. Of the 85 female participants 19 were pre- and 66 postmenopausal. Fifteen of the pre-, and 49 of the postmenopausal women developed ulcerative mucositis (p = 0.769), more often with lymphoma than MM (p = 0.009). Serum estrogen decreased significantly both in postmenopausal controls and transplantated patients compared to premenopausals, with no difference in saliva. Serum progesterone level was significantly (p = 0.026) elevated at day + 7 of transplantation, while salivary progesterone increased at day + 7 and + 14. Our results indicate a predominantly negative effect of female sex hormones on oral immunity with role in the aetiopathogenesis of OM.

Salivary antioxidant enzymes associated with oral toxicity in haematopoietic cell transplantation: An observational study.

In haematopoietic cell transplantation (HCT), oral mucositis and xerostomia are related to conditioning-related oxidative stress. The role of salivary antioxidant enzymes in oral toxicity is poorly described. The aim of this study was to verify the association between salivary antioxidant enzymes and oral mucositis and xerostomia in HCT. Saliva from autologous and allogeneic HCT patients (n = 77) was selected before conditioning (T0), during the neutropenia period (T1) and after marrow engraftment (T2). Salivary flow, total salivary proteins, and superoxide dismutase, catalase and glutathione reductase activities were measured. There were no significant differences in salivary flow, total salivary proteins and catalase at the three HCT time points. Glutathione reductase levels were reduced at T1 compared to T0 (P=.013) and T2 (P=.001). Superoxide dismutase levels were increased from T0 to T2 (P=.013). Neither of these enzymes was associated with oral mucositis. Increased superoxide dismutase levels were associated with xerostomia frequency. Levels of this enzyme also showed significant correlation with days of xerostomia in T2 (ρ=.40, P=.002). Salivary antioxidant enzymes changed before and during early periods after HCT. The increase in salivary superoxide dismutase suggested partial activation of the salivary antioxidant system and was associated with xerostomia.

Chirurgie secondaire des reconstructions mammaires par prothèses. Évaluation de la satisfaction des patientes selon la technique chirurgicale : conservation d’implant vs conversion autologue

Breast reconstruction with implants has long-term disadvantages and is leading an increasing number of patients to request secondary corrective surgery. Two surgical strategies are possible: implant replacement (associated with capsulectomy/capsulotomy and/or lipofilling procedures) and implant removal associated with the provision of autologous tissue (flap and/or lipofilling). Between 2010 and 2018, 54 patients underwent secondary surgery for correction of a first implant breast reconstruction. The reasons for dissatisfaction with the initial reconstruction, the procedures performed, and postoperative complications were analysed. Patient well-being and satisfaction were evaluated using the BREAST-Q questionnaire. Thirty-four patients benefited from a prosthesis change and 20patients benefited from a permanent removal of their prosthesis combined with the addition of autologous tissue. The presence of a periprosthetic shell, pain, fixed appearance of the breast and breast asymmetry were the most frequent reasons for dissatisfaction. With a mean follow-up of 2.6years, autologous conversion patients were generally more satisfied with the appearance of their breasts than patients who retained a breast implant (P<0.0001). In cases of poor esthetic or functional outcomes of implant-based breast reconstruction, removal of the prosthesis in combination with autologous reconstruction provides better results in terms of well-being and satisfaction than implant replacement.

Patient-Reported Outcomes of Three Different Types of Breast Reconstruction with Correlation to the Clinical Data 5 Years Postoperatively.

The aim of this study was to compare long-term clinical and patient-reported outcomes in terms of satisfaction and health-related quality of life (HRQoL) following postmastectomy breast reconstruction using BREAST-Q in patients undergoing implant-based reconstruction, abdominal-based autologous reconstruction, and combined reconstruction (with implant and LD flap or implant and TDAP flap). A cross-sectional study was conducted. Patients had undergone delayed postmastectomy breast reconstruction and completed the BREAST-Q reconstruction module. The results were related to the clinical data obtained from the clinic's patient record system. A 5-year examination was included. Mean scores and standard deviations were calculated. Kruskal-Wallis test, Chi-square goodness of fit test and Chi-square test were used for the statistical analysis. Overall, 110 patients (n = 24 implant, n = 38 autologous, n = 48 combination) were included. Patients with autologous reconstruction reported greater postoperative satisfaction with breasts (p < 0.001), satisfaction with outcome (p < 0.001), psychosocial well-being (p = 0.001), and sexual well-being (p = 0.051). This study represents a comprehensive long-term examination of postmastectomy breast reconstruction. Autologous reconstruction patients had higher postoperative satisfaction and HRQoL than patients receiving other types of reconstruction despite having more intense oncological therapy and the highest mean number of follow-up surgical procedures. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cellular therapy options for genetic skin disorders with a focus on recessive dystrophic epidermolysis bullosa.

Combinatorial cell and gene therapies for life-threatening inherited skin disorders have shown tremendous potential for preclinical and clinical implementation with significant progress made for recessive dystrophic epidermolysis bullosa (RDEB). To date, various cell lineages including resident skin cells and adult stem cells have been investigated for gene and cell therapy for RDEB reaching the clinical trial stage. Sources of data are key recent literature, ClinicalTrials.gov, Clinicaltrialsregister.eu and pharma press releases. Cell-based gene transfer using autologous patients' cells has demonstrated positive outcomes in preclinical and clinical trials and highlighted the importance of targeting resident skin stem cells to achieve a meaningful long-term effect. Additionally, adult stem cells, such as mesenchymal stromal cells, have the potential to ameliorate systemic manifestations of the disease. While proven safe, the clinical trials of localized treatment have reported only modest and transient improvements. On the other hand, the risks associated with systemic therapies remain high and should be carefully weighed against the potential benefits. It is unclear to what extent adult stem cells can contribute to skin regeneration/wound healing. Further research is warranted in order to fulfil the potential of cellular therapies for RDEB. The development of combinatorial gene and cell-based approaches is required to achieve long-term clinical benefits. Induced pluripotent stem cells can potentially provide a valuable source of autologous patient material for cellular therapies. In addition, recent advances in the field of gene editing can overcome hurdles associated with conventional gene addition approaches. No new data were generated or analysed in support of this review.

Central Line Associated Blood Stream Infection Incidence and Outcomes in a Large Autologous and Allogeneic Bone Marrow Transplant Cohort

<h3>Background</h3> Patients undergoing bone marrow transplant (BMT) requiring central venous access are at high risk of central line associated blood stream infections (CLABSI) due to prolonged immunosuppression. Currently, there is limited literature directly comparing outcomes and incidences of CLABSIs in the autologous and allogeneic BMT populations. Here, we describe the incidence and outcome of CLABSIs in a large prospective cohort of allogeneic and autologous BMT patients at a quaternary adult oncology center. <h3>Methods</h3> A descriptive analysis was performed on a prospectively assembled cohort of BMT patients collected over a 30-month period between 2017 and 2019. CLABSI determination was made by infection control practitioners and physicians using standardized definitions. Outcomes, including 30-day hospitalization, ICU admission, and all-cause mortality were determined through chart reviews. Chi-square tests were used to assess statistical significance to compare simple proportions. <h3>Results</h3> Of 1278 patients in the cohort, 136 (11%) developed CLABSIs. A significantly higher proportion of allogeneic BMT patients developed CLABSI compared to the autologous BMT patients (21% and 5% of their respective populations, p<0.001). Of 136 patients, 43.4% required admission, 7.4% required ICU admission and 7.7% died within 30-days of the CLABSI onset. Although there were no significant differences between allogeneic and autologous cases in these outcomes, allogeneic cases had a significantly longer time to developing a CLABSI from transplant than autologous cases (median 53 days vs 10 days). <h3>Conclusions</h3> In this large prospective study of patients receiving bone marrow transplants, we found that allogeneic BMT patients are at higher risk for developing a CLABSI compared with autologous BMT patients. Furthermore, these infections are associated with a high degree of morbidity and mortality in both populations. Review of clinical and infection control protocols regarding central line access and maintenance are needed in order to reduce the incidence of this highly morbid complication.

Impact of the CD4:CD8 ratio in bone marrow on stem cell mobilization and engraftment in autologous stem cell transplant patients.

Bone marrow (BM) damage after previous chemotherapy, such as that involving alkylating agents, and radiation therapy alone cannot explain poor hematopoietic progenitor cell mobilization. We examined the T lymphocytes of BM in 67 autologous peripheral blood stem cell transplant (auto-PBSCT) patients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) to establish whether the cellular phenotype predicts mobilization and engraftment between January 2000 and January 2020 at the Japanese Red Cross Society Wakayama Medical Center. The total number of mobilized CD34+ cells was <2 × 106 /kg in 30 patients (group A) and ≥2 × 106 /kg in 37 (group B). The median absolute number of CD3+CD4+ cells was lower in group A than in group B (P = .013), and the median absolute number of CD3+CD8+ cells was higher in group A than in group B (P = .016). A low CD4:CD8 ratio was observed in all patients in group A, whereas all patients in group B showed a normal CD4:CD8 ratio (P < .001). A strong correlation was found between the CD4:CD8 ratio and median total CD34+ cells yield (r = .723, P < .001). The present results showed that a lower CD4:CD8 ratio correlated with later neutrophil and platelet engraftment (r = .662, P = .007 and r = .571, P = .008, respectively). The present results indicate that the CD4:CD8 ratio in BM contributes to the prediction of mobilization and engraftment in auto-PBSCT patients.

Effect of a Nurse-Led Protocol on Time to Treatment of Partial Occlusions in Central Venous Access Devices in Pediatric Oncology.

Central venous access devices (CVADs) are the standard of care in pediatric oncology. Occlusion is a common complication that can lead to delays in therapy, readmission, and CVAD removal and reinsertion. Early treatment of partial occlusions using a standardized protocol may restore patency and increase life span of CVADs. The objective of this study was to develop and evaluate a nurse-led protocol to manage partial CVAD occlusions in pediatric oncology and autologous bone marrow transplant patients. The protocol enabled nurses to manage partially occluded CVADs by administering thrombolytic therapy following an algorithm and patient-specific standing order. The primary outcome was time from recognition of the partial occlusion to instillation of a thrombolytic. Secondary outcomes were thrombolytic dwell time, number of complete occlusions, and CVAD life span. We used a quasi-experimental, after-only, nonequivalent control group design to compare patients not exposed (retrospective cohort, n = 137) and patients exposed (prospective cohort, n = 101) to the nurse-led protocol. Mann-Whitney U tests were used to compare time to treatment, dwell time, and CVAD life span between cohorts, and χ2 was used to compare the proportion of occlusions classified as complete. Time to treatment was significantly lower in the prospective cohort (M = 99.9 minutes) versus the retrospective cohort (M = 483.7 minutes), U = 1366.50, p < .01, as was thrombolytic dwell time, U = 282.50, p < .01. Proportion of complete occlusions and CVAD life span did not differ between cohorts. The nurse-led protocol was effective to manage partial CVAD occlusions in pediatric oncology patients.

Effect of malnutrition-driven nutritional support protocol on clinical outcomes in autologous stem cell transplantation patients.

Poor nutrition status in patients receiving high-dose chemotherapy and autologous stem cell transplant (ASCT) has been associated with inferior clinical outcomes. We aim to determine whether a malnutrition-driven nutritional support protocol can improve these outcomes. In this prospective cohort study, we assessed adults for malnutrition who were consecutively admitted for ASCT between October 2017 and March 2019 (n = 251), and provided enteral or parenteral nutrition (EN/PN) to patients who were malnourished early in the transplantation admission. We compared their clinical outcomes with those of a historical cohort admitted between May 2016 and October 2017 (n = 257) for whom nutrition assessment and initiation of EN/PN were not protocol-driven. Patients receiving ASCT during the intervention period experienced decreased odds of prolonged hospital stay (p = 0.023), central line-associated bloodstream infection (p = 0.015), mucosal barrier injury (p = 0.037), and high weight loss (p = 0.002), in a multivariate analysis as compared with those receiving ASCT during the control period. Outcomes for ICU transfer, deconditioning on discharge, time to platelet engraftment, and unplanned 30-day hospital readmission did not differ significantly between groups. A malnutrition-driven nutritional support protocol may improve outcomes for ASCT patients.

De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia

Febrile neutropenia (FN) is a common serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT) requiring urgent evaluation and initiation of empiric broad spectrum antibiotics (BSA). The appropriate duration of BSA for FN in patients with negative cultures and no identifiable infection remains undefined. We retrospectively analyzed allogenic and autologous HSCT patients with FN and negative infectious work-up at our facility from 2012 to 2018. The early de-escalation group (EDG) included those who had BSA de-escalation to fluoroquinolone prophylaxis at least 24 h prior to absolute neutrophil count (ANC) recovery after the patient was fever-free for at least 48 h. Among 297 patients undergoing their first HSCT who experienced FN with negative infectious work-up, 83 patients were de-escalated early with the remaining 214 in the standard of care group (SCG) whose BSA were continued until ANC was > 500. Duration of broad-spectrum antibiotics was shorter in EDG compared to SCG (3.86 days vs. 4.62 days, p = 0.03). Rates of mortality, new infections, and clinical decompensation requiring intensive care unit transfer and/or pressor use within 30 days were all similar between the two groups (0% vs. 0.4% p = 1.00, 0% vs. 1.4% p = 0.56, 13.2% vs. 8.4% p = 0.27). This indicates that it is safe to de-escalate antibiotics prior to ANC recovery, leading to less BSA exposure.

Immunogenicity of Inactivated Varicella Zoster Vaccine in Autologous Hematopoietic Stem Cell Transplant Recipients and Patients With Solid or Hematologic Cancer.

BackgroundIn phase 3 trials, inactivated varicella zoster virus (VZV) vaccine (ZVIN) was well tolerated and efficacious against herpes zoster (HZ) in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and patients with solid tumor malignancies receiving chemotherapy (STMc) but did not reduce HZ incidence in patients with hematologic malignancies (HMs). Here, we describe ZVIN immunogenicity from these studies.MethodsPatients were randomized to ZVIN or placebo (4 doses). Immunogenicity was assessed by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and VZV interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in patients receiving all 4 doses without developing HZ at the time of blood sampling.ResultsEstimated geometric mean fold rise ratios (ZVIN/placebo) by gpELISA and IFN-y ELISPOT ~28 days post–dose 4 were 2.02 (95% confidence interval [CI], 1.53–2.67) and 5.41 (95% CI, 3.60–8.12) in auto-HSCT recipients; 1.88 (95% CI, 1.79–1.98) and 2.10 (95% CI, 1.69–2.62) in patients with STMc; and not assessed and 2.35 (95% CI, 1.81–3.05) in patients with HM.ConclusionsZVIN immunogenicity was directionally consistent with clinical efficacy in auto-HSCT recipients and patients with STMc even though HZ protection and VZV immunity were not statistically correlated. Despite a lack of clinical efficacy in patients with HM, ZVIN immunogenicity was observed in this population. Immunological results did not predict vaccine efficacy in these 3 populations.Clinical trial registrationNCT01229267, NCT01254630.

Editorial introductions

Editorial introductions

At three years, patients with acute lymphoblastic leukaemia are still at risk for relapse. Results of the international MRC UKALLXII/ECOG E2993 trial.

SummaryLate relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37–144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. Out of the 1 752 patients who achieved CR, 11·7% underwent autologous and 40·6% allogeneic transplant, while in CR1. Of the autologous patients, 43·2% relapsed early and 3·4% relapsed late. However, among the allogeneic patients, 13·2% relapsed early and only 1·3% late. The five‐year overall survival from relapse was 5·8% and 20% in the early and late relapse patients respectively. In conclusion, late relapse in adults with ALL is not uncommon, and is associated with better outcome after relapse compared to early relapse.

Hematopoietic Stem Cell Transplant Recipients Surviving at Least 2 Years from Transplant Have Survival Rates Approaching Population Levels in the Modern Era of Transplantation.

The health and outcomes of long-term survivors after hematopoietic cell transplant (HCT) are areas of evolving interest as short-term transplant outcomes improve. Because recent changes in transplant practice have likely changed the survivor population, we sought to assess the survival of a contemporary cohort of patients who were alive and free of disease 2 years after HCT. Data were extracted from first transplants documented between 2002 and 2011 in the Australasian Bone Marrow Transplant Recipient Registry on patients who received an allogeneic HCT for acute myeloid leukemia (AML), acute lymphoblastic leukemia, chronic myeloid leukemia (CML), non-Hodgkin lymphoma, and myelodysplastic syndromes or an autologous HCT for myeloma or lymphoma. Patients were included if they had survived at least 2 years without disease relapse or progression. Mortality rates were compared with standard Australian and New Zealand populations using relative-survival analysis. A total of 1562 allogeneic and 3822 autologous HCT patients were included, with a median follow-up of 5.6 years. Compared with a matched group of patients from our previous study from 1992 to 2001, the contemporary cohort of allogeneic HCT recipients was older and more likely to receive peripheral blood stem cells and from unrelated donors. Allogeneic HCT for AML increased, wheresa transplants for CML fell from 32% to 8%. Increasing use of reduced-intensity conditioning and unrelated donors was also seen. Long-term survival after allogeneic and autologous HCT were very similar to the previous 1992 to 2001 cohort despite changes in practice over time. Recipients of autologous HCT for myeloma demonstrated substantially lower overall survival than HCT for other indications with no clear plateau. Annual relative survival for survivors of allogeneic HCT was 96% to 99% of the general population but only 89% to 96% of the general population for recipients of autologous HCT. Late deaths were primarily due to nonrelapse causes after allogeneic HCT, but relapse or disease progression remained prominent for recipients of autologous HCT, particularly for myeloma. The management of late HCT effects is important to improve long-term survival of transplant recipients but should be tailored to the risks specific to the primary disease and transplant type. Future planning should account for the impact of the expected increase in transplant activity and number of survivors on resource utilization.