A retrospective comparison of IgE-mediated cow's milk protein allergy management strategies in pediatric cohorts.

BACKGROUND: Complete avoidance of milk is the usual management for IgE-mediated cow's milk protein allergy (CMPA). A baked milk ladder is a method of dietary advancement therapy in IgE-mediated CMPA in Ireland, while in Spain, avoidance of milk awaiting natural tolerance acquisition through an oral food challenge (OFC) is employed. The aim of this study was to evaluate the use of dietary advancement therapy using a milk ladder compared with complete avoidance of milk for managing IgE-mediated CMPA. METHODS: This is a retrospective chart review of 371 pediatric patients from the population who have been treated for IgE-mediated CMPA between 2011 and 2020, with the milk ladder (Ireland) or complete avoidance followed by an OFC (Spain). The main outcome was the introduction of cow's milk. RESULTS: Milk ladder patients were 3.67 times more likely to succeed in comparison with milk avoidance (p < .001). Anaphylaxis during the treatment period occurred in 34 patients in the milk avoidance groups, while three patients in the milk ladder group experienced anaphylaxis due to accidental exposure to milk (p < .001). Failure to complete treatment was associated with a higher skin prick test in the milk avoidance group and a raised specific IgE in the milk ladder group. CONCLUSION: This is the first study that compares outcomes of dietary advancement therapy to complete avoidance for CMPA management, demonstrating that cow's milk can be successfully and safely reintroduced using dietary advancement therapy using a milk ladder.

The prevalence of burnout in oncology professionals: an overview of systematic reviews with meta-analyses including more than 90 distinct studies.

PURPOSE: This overview of reviews aimed to summarize the prevalence of burnout and the dimensions of burnout (emotional exhaustion, depersonalization, and personal accomplishment) in oncology professionals around the world. METHODS: The CINAHL, Embase, PsycINFO, and PubMed databases were searched from inception to September 13, 2023. AMSTAR 2 was used to assess the quality of reviews. The overlap between reviews was calculated. RESULTS: Twelve reviews were included. Overall, reviews showed that burnout was prevalent in oncologists and oncology nurses. On the other hand, no reviews meta-analyzed the prevalence of burnout in oncology radiation therapists. In addition, the dimensions of burnout, high emotional exhaustion, high depersonalization, and low personal accomplishment were highly prevalent across reviews in oncologists, oncology nurses, and oncology radiation therapists. In oncologists, the Americas (specifically Canada) showed the highest prevalence rates for high emotional exhaustion, whereas high depersonalization and low personal accomplishment were mainly prevalent in Europe and Asia, respectively. In oncology nurses, high emotional exhaustion and high depersonalization were mainly prevalent in Asia, whereas low personal accomplishment was more prevalent in the Americas (specifically Canada). The prevalence of overall levels of burnout was not meta-analyzed by continents. CONCLUSION: Some methodological improvements may help to make more robust the findings of this overview (e.g., specific subgroup meta-analyses by oncology specialties), which may help readers reach more precise, direct, and consistent findings. PROTOCOL REGISTRATION: https://doi.org/10.17605/OSF.IO/QPWG5 .

Psoriatic arthritis with psychological comorbidities: an overview of systematic reviews on incidence, prevalence, and geographic disparities.

Systematic reviews and meta-analysis evaluating the prevalence, incidence, and psychological comorbidities of psoriatic arthritis (PsA) are increasing, so it's time to perform an overview of systematic reviews. To summarize the pooled prevalence, incidence, and psychological comorbidities rates of PsA, and to explore possible continent disparities. In this overview of systematic reviews the CINAHL, EMBASE, PsycINFO, and PubMed were searched to October 25, 2023. This overview included systematic reviews with meta-analysis of people with PsA, providing the pooled prevalence or incidence rates of PsA in general, or clinical populations and/or psychological comorbidities. The Preferred Reporting Items for Overviews of Reviews (PRIOR) statement was followed. AMSTAR-2 assessed the quality of reviews. The degree of overlap was calculated using the corrected covered area (CCA). Maps were developed using the location of where primary studies were conducted using DataWrapper App. The protocol was prospectively registered with Open Science Framework registry. Pooled prevalence and incidence rates of PsA or its associated psychological comorbidities in general or specific populations. We also collected locations from the primary studies of the included meta-analyses. Only the assessment of prevalence rates of PsA in people with psoriasis showed slight overlap (CCA = 3.3%). Items 2, 3, 4, 7, 8, 10, 12, and 13 were poorly reported in AMSTAR-2. The pooled prevalence of PsA ranged from 0.13 to 0.15% in the general population, and 15.5% to 19.7% in people with psoriasis. The pooled incidence of PsA ranged from 8.26 to 9.27 cases per 100,000 inhabitants to 0.87 cases in individuals with hidradenitis suppurativa. The pooled prevalence of psychological comorbidities was 11.9-20% for depression, 19-33% anxiety, 38% alexithymia, and 72.9% in poor sleep quality. Only the pooled incidence of depression was assessed with 21.3 per 1000-person year. PsA seems to be prevalent and incident not only in people with psoriasis, but also in general population. Depression and anxiety symptoms may be present in some patients with PsA. Finally, continent disparities exist, and methodological and clinical issues were found, which could be helpful in the future agenda of the epidemiology of PsA.

Multimodal exercise programs may improve posttraumatic stress disorders symptoms and quality of life in adults with PTSD: An overview of systematic reviews with meta-analysis.

OBJECTIVE: This overview of reviews aimed to summarize the effectiveness of exercise, regular physical activity or mind-body exercises on posttraumatic stress disorder (PTSD) symptoms and comorbidities associated with PTSD (e.g. depression symptoms) among individuals without age, gender, race, ethnicity or setting restrictions. DATA SOURCES: The CINAHL, Embase, PubMed and SPORTDiscus databases were searched from inception to November 16, 2023. REVIEW METHODS: Systematic reviews with meta-analysis of randomized clinical trials evaluating exercise, regular physical activity or mind-body exercises were considered. Control groups and outcome measures were not restricted. AMSTAR 2 assessed the methodological quality of reviews. The overlap between reviews was calculated. RESULTS: A total of 14 systematic reviews were included meta-analyzing 23 distinct randomized clinical trials. There was a very high overlap between reviews (corrected covered area = 16%). PTSD symptoms, depression symptoms, anxiety symptoms, sleep quality, substance abuse and quality of life were meta-analyzed. No reviews meta-analyzed the effects of regular physical activity. Overall, the meta-analyses found multicomponent exercise programs may have positive results in reducing PTSD symptoms and improving quality of life. In addition, the results of yoga were inconsistent across the meta-analyses for PTSD symptoms, and no differences between groups were found in favor of yoga for depression symptoms. Finally, no specific conclusions could be made about anxiety symptoms, sleep quality and substance abuse. CONCLUSION: A multicomponent exercise program may be effective in improving PTSD symptoms and quality of life, whereas yoga may be ineffective for depression symptoms in adults with PTSD.

Poor graft function after haploidentical stem cell transplantation with post-transplant cyclophosphamide.

This is a retrospective cohort study of consecutive adult patients who received a haploidentical-SCT (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a single centre. Poor graft function (PGF) was defined as the occurrence of either persistent neutropenia (ANC < 0.5 × 109/µL) with poor response to granulocyte colony-stimulating factors (G-CSF) and/or thrombocytopenia (platelets < 20 × 109/L) with transfusion dependence, with complete donor chimerism and without concurrent severe GVHD or underlying disease relapse, during the first 12 months after transplantation. Forty-four (27.5%) out of 161 patients were diagnosed with PGF. Previous CMV reactivation was significantly more frequent in patients with PGF (88.6% versus 73.5%, p = 0.04) and the number of reactivations was also higher in these patients. Besides, early CMV reactivations in the first 6 months post-SCT were also significantly more frequent among patients with PGF (88.6% versus 71.8% p = 0.025). Thirty-two percent of patients with PGF were treated with increasing doses of thrombopoietin-receptor agonists (TRA) and 7 patients were treated with a donor CD34 + selected boost. In total, 93.2% of patients reached adequate peripheral blood counts in a median time of 101 days (range 11-475) after diagnosis. PGF is a frequent complication after haplo-SCT with PT-Cy. CMV reactivation might be the most relevant factor associated to its development. Even when most patients recover peripheral counts with support therapy, there is a group of patients with persistent cytopenias who can effectively be treated with TRA and/or a boost of CD34 + selective cells.

Meaning and purpose in life, happiness, and life satisfaction in cancer: Systematic review with meta-analysis.

OBJECTIVE: To summarize current evidence on the potential cross-sectional and longitudinal association between meaning or purpose in life and subjective happiness or life satisfaction among cancer patients. METHODS: A systematic review with meta-analysis and meta-regression was conducted. CINAHL (via EBSCOhost), Embase, PubMed, and PsycINFO (via ProQuest) were searched from inception to 31 December 2022. In addition, manual searches were performed. The risk of bias in cross-sectional and longitudinal studies was assessed using the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies and the Quality in Prognosis Studies tool, respectively. Certainty in the evidence was judged using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Meta-regressions and sensitivity analyses were performed to explore potential sources of heterogeneity. RESULTS: We included 13 cross-sectional studies, comprising 12 different samples, and a longitudinal study. A total of 4968 individuals with cancer were interviewed across included studies. Certainty in the evidence was judged as very low for all outcomes, which was associated to serious concerns on risk of bias and imprecision of the results, and very serious concerns on indirectness of evidence. The assessed studies showed a marked heterogeneity in terms of participants' clinical (i.e., disease stage) and sociodemographic factors. A lack of reporting of these clinical and sociodemographic aspects were also evident among included studies. CONCLUSIONS: The wide number of methodological flaws detected in this systematic review preclude to make any clinical recommendation. More rigorous high-quality observational studies should guide future research on this topic.

Psychological and spiritual interventions to enhance meaning in adults diagnosed with cancer: a systematic review with meta-analysis and meta-regression.

OBJECTIVE: To summarize the evidence on the effectiveness that psychological and/or spiritual interventions may have to change the levels of meaning, measured with the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), in adults diagnosed with cancer. METHODS: Systematic review with meta-analysis and meta-regression. CINAHL (via EBSCOhost), Embase, PubMed, PsycINFO (via ProQuest), and the Cochrane Library were searched from inception to 21st October 2022. Manual searches were conducted. Only randomized clinical trials (RCTs) were included. The risk of bias was assessed with the Cochrane Risk of Bias tool 2. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to judge the certainty of the evidence. RESULTS: Eight RCTs were included (N = 1682). Although some individual studies showed positive effects to enhance meaning using mindfulness or dignity therapy, the overall and individual meta-analyses showed a lack of effect of psychological and spiritual interventions in comparison to comparator interventions (MD (95%CI) = -0.19 (-0.45 to 0.06), p = 0.11, Tau2 = 0.0015, I2 = 2%). Publication bias was undetected (Egger's test = 0.35). Furthermore, no RCTs were judged to have a low risk of bias and the overall certainty of the evidence was judged as low. Meta-regression and subgroups meta-analyses also found possible sources of heterogeneity such as some cancer characteristics, the educational stage, or the religious affiliation. CONCLUSIONS: Despite some RCTs may show promising results following mindfulness or dignity therapy, no effects were observed in the meta-analysis. Moreover, important methodological and clinical concerns precluded us to make sound clinical recommendations with the available evidence. OPEN SCIENCE FRAMEWORK DOI REGISTRATION: https://doi.org/10.17605/OSF.IO/4YMTK .

No effects were found in favor of Hatha or Iyengar yoga exercises for improving cancer-related fatigue, depression symptoms, or quality of life: a systematic review with meta-analysis and metaregression.

OBJECTIVE: To summarize the evidence on the effectiveness of Hatha or Iyengar yoga exercises on cancer-related fatigue, depression symptoms, and the overall quality of life in adults with cancer. METHODS: A systematic review with meta-analysis was conducted. The CINAHL (via EBSCOhost), Embase, PubMed, and SPORTDiscus (via EBSCOhost) databases were searched from inception to 7th November 2022. Clinical trials evaluating cancer-related fatigue, depression symptoms, and the overall quality of life were included. The risk of bias was assessed using the Cochrane Risk of Bias tool 2. The Template for Intervention Description and Replication (TIDieR) checklist was used to check if the interventions reviewed were described in detail to be implemented in the clinical setting. The Grading of Recommendations, Assessment, Development, and Evaluations approach was used to rate the certainty of evidence. Meta-regressions, sensitivity analyses, and subgroup meta-analyses were conducted to explore sources of heterogeneity. RESULTS: Eleven studies were included (N = 777 participants). Overall, Hatha, Iyengar, and the combination of both yoga styles did not improve any of the outcomes of interest. In addition, five studies had a high risk of bias, and six studies had some concerns about biases. Weaknesses in reporting modifications during the development of the study were observed (TIDieR item 10). The certainty of evidence ranged from low to very low across the outcomes. CONCLUSIONS: We could not make sound clinical recommendations with the current quality of the findings.

Yoga-based interventions may reduce anxiety symptoms in anxiety disorders and depression symptoms in depressive disorders: a systematic review with meta-analysis and meta-regression.

OBJECTIVE: To summarise the effect of mind-body exercises on anxiety and depression symptoms in adults with anxiety or depressive disorders. DESIGN: Systematic review with meta-analysis and meta-regression. DATA SOURCES: Five electronic databases were searched from inception to July 2022. Manual searches were conducted to explore clinical trial protocols, secondary analyses of clinical trials and related systematic reviews. ELIGIBILITY CRITERIA: Randomised clinical trials evaluating qigong, tai chi or yoga styles with anxiety or depression symptoms as the outcomes were included. No intervention, waitlist or active controls were considered as control groups. The risk of bias and the certainty of the evidence were assessed. Meta-analyses, meta-regressions and sensitivity analyses were performed. RESULTS: 23 studies, comprising 22 different samples (n=1420), were included. Overall, meta-analyses showed yoga interventions were superior to controls in reducing anxiety symptoms in anxiety disorders. Furthermore, yoga-based interventions decreased depression symptoms in depressive disorders after conducting sensitivity analyses. No differences between groups were found in the rest of the comparisons. However, the certainty of the evidence was judged as very low for all outcomes due to concerns of high risk of bias, indirectness of the evidence, inconsistency and imprecision of the results. In addition, there was marked heterogeneity among yoga-based interventions and self-reported tools used to evaluate the outcomes of interest. CONCLUSION: Although yoga-based interventions may help to improve mental health in adults diagnosed with anxiety or depressive disorders, methodological improvements are needed to advance the quality of clinical trials in this field. PROSPERO REGISTRATION NUMBER: CRD42022347673.

Dropout Rate of Participants in Randomized Clinical Trials That Use Virtual Reality to Train Balance and Gait in Parkinson's Disease. A Systematic Review With Meta-analysis and Meta-regression.

Virtual reality is an effective system to train balance and gait in Parkinson's disease, but attrition of this intervention needs to be further examined. This study aims to review and meta-analyze the dropouts of participants in randomized clinical trials that used virtual reality for balance and gait training in people with Parkinson's disease. An electronic search was conducted in PubMed, Web of Science, Scopus and CINAHL. The PEDro scale and Revised Cochrane risk-of-bias tool for randomized trials 2.0 were employed to assess methodological quality. Proportions meta-analysis calculated dropout rate. Odds ratio meta-analysis under 1 indicated lower attrition in experimental participants. Meta-regression identified possible dropouts' moderators. A total of 18 studies were included. The pooled dropout rates were 5.6% (95% CI, 3.3%-9.3%) for all groups, 5.33% (95% CI, 3.03%-9.21%) in virtual reality, and 6.60% (95% CI, 3.84%-26.31%) in comparators. No statistical differences were found in the dropout occurred between the groups (OR 0.83; 95% CI, 0.62-1.12). Number of weeks was the unique moderator (coefficient 0.129, 95% CI 0.018- 0.239; p=0.02). Our overall pooled dropout should be considered in the sample size calculation of future studies. Adequate follow-up of the CONSORT guidelines in the loss report and their reasons could help design suitable retention strategies.

Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy.

BACKGROUND: A variable incidence of profound cytopenia has been described in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). This complication leads to severe infection in some cases, especially those who present additional risk factors including prior hematopoietic stem cell transplantation (HSCT). STUDY DESIGN AND METHODS: We report a case of breakthrough invasive fungal infection in a patient with prolonged neutropenia after CAR-T cell therapy administered for relapsed B-cell ALL after allogeneic haploidentical HSCT. RESULTS: After disease progression was discarded, therapy with antifungal agents, G-CSF and thrombopoietin analogue was started. However, no sign of haematological recovery or infection improvement was observed. A fresh mobilized selected CD34-stem cell boost from her haploidentical transplant donor was infused without further conditioning. Within 15 days of mobilized CD34-boost administration the patient showed complete resolution of both the aplasia and fungal infection. DISCUSSION: This case illustrates as proof-of-concept the efficacy and safety of selected CD34-stem cell boost from prior donor as salvage treatment of prolonged cytopenias after CAR-T cell therapy.

Dropout Rate in Digital Health Interventions for the Prevention of Skin Cancer: Systematic Review, Meta-analysis, and Metaregression.

BACKGROUND: Digital strategies are innovative approaches to the prevention of skin cancer, but the attrition following this kind of intervention needs to be analyzed. OBJECTIVE: The aim of this paper is to assess the dropouts from studies focused on digital strategies for the prevention of skin cancer. METHODS: We conducted this systematic review with meta-analyses and metaregression according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statements. Search terms for skin cancer, digital strategies, and prevention were combined to search PubMed, Scopus, Web of Science, CINAHL, and Cochrane Library from inception until July 2022. Randomized clinical trials that reported dropouts of participants and compared digital strategies with other interventions to prevent skin cancer in healthy or disease-free participants were included. Two independent reviewers extracted data for analysis. The Revised Cochrane Collaboration Bias tool was employed. We calculated the pooled dropout rate of participants through a meta-analysis of proportions and examined whether dropout was more or less frequent in digital interventions against comparators via an odds ratio (OR) meta-analysis. Data were pooled using a random-effects model. Subgroup meta-analyses were conducted in a meta-analysis of proportions and OR meta-analysis to assess the dropout events when data were sorted by digital interventions or control comparator. A univariate metaregression based on a random-effects model assessed possible moderators of dropout. Participants' dropout rates as pooled proportions were calculated for all groups combined, and the digital and comparator groups separately. OR>1 indicated higher dropouts for digital-based interventions. Metaregressions were performed for age, sex, length of intervention, and sample size. RESULTS: A total of 17 studies were included. The overall pooled dropout rate was 9.5% (95% CI 5.0-17.5). The subgroup meta-analysis of proportions revealed a dropout rate of 11.6% for digital strategies (95% CI 6.8-19.0) and 10.0% for comparators (95% CI 5.5-17.7). A trend of higher dropout rates for digital strategies was observed in the overall (OR 1.16, 95% CI 0.98-1.36) and subgroup OR meta-analysis, but no significant differences were found between the groups. None of the covariates moderated the effect size in the univariate metaregression. CONCLUSIONS: Digital strategies had a higher dropout rate compared to other prevention interventions, but the difference was not significant. Standardization is needed regarding reporting the number of and reasons for dropouts. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42022329669; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329669.

Dropout rate in randomised controlled trials of balance and gait rehabilitation in multiple sclerosis: is it expected to be different for virtual reality-based interventions? A systematic review with meta-analysis and meta-regression.

To assess and meta-analyse the pooled dropout rate from the randomised control trilas that use virtual reality for balance or gait rehabilitation in people with multiple sclerosis. A systematic review of randomised control trials with meta-analysis and meta-regressions was performed. A search was conducted in PubMed, Scopus, Web of Science, the Physiotherapy Evidence Database, the Cochrane Database, CINHAL, LILACS, ScienceDirect, and ProQuest. It was last updated in July 2022. After the selection of studies, a quality appraisal was carried out using the PEDro Scale and the Revised Cochrane risk-of-bias tool for randomised trials. A descriptive analysis of main characteristics and dropout information was performed. An overall proportion meta-analysis calculated the pooled dropout rate. Odds ratio meta-analysis compared the dropout likelihood between interventions. The meta-regression evaluated the influence of moderators related to dropout. Sixteen studies with 656 participants were included. The overall pooled dropout rate was 6.6% and 5.7% for virtual reality and 9.7% in control groups. The odds ratio (0.89, p = 0.46) indicated no differences in the probability of dropouts between the interventions. The number, duration, frequency, and weeks of sessions, intervention, sex, multiple sclerosis phenotype, Expanded Disability Status Scale score, and PEDro score were not moderators (p > 0.05). Adverse events were not reported and could not be analysed as moderators. Dropouts across the virtual reality and control comparators were similar without significant differences. Nonetheless, there is a slight trend that could favour virtual reality. Standardisation in reporting dropouts and adverse events is recommended for future trials. PROSPERO database, registration number ID CRD42021284989. Supplementary Information: The online version contains supplementary material available at 10.1007/s10055-022-00733-4.

Post-transplant cyclophosphamide for GVHD prophylaxis compared to ATG-based prophylaxis in unrelated donor transplantation.

Post-transplant cyclophosphamide (PTCY) effectively prevents graft-versus-host disease after unmanipulated HLA-haploidentical HSCT. The use of PTCY in the unrelated donor HSCT setting is less explored. We conducted a retrospective study of 132 consecutive patients undergoing a matched or 9/10 mismatched unrelated donor HSCT in 4 centers in Spain, 60 with anti-thymocyte globulin (ATG)-based prophylaxis combined with MTX-CsA, and 72 using a PTCY-based regimen. Peripheral blood stem cells were used as graft in most patients (111 patients, 84%); mMUD donors were balanced between groups. Cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days were lower in the PTCy group (46% vs. 67%, p = 0.008; 3% vs. 34%, p = 0.003), without statistically significant differences in the 2-year cumulative incidence of chronic moderate-severe GVHD. At 2 years, no significant differences were observed in overall survival, event-free survival, cumulative incidence of relapse, and non-relapse mortality. GVHD was the most frequent cause of NRM in the ATG group. No differences were observed between groups in the composite endpoint of GVHD-free and relapse-free survival. In this study, PTCy combined with additional immunosuppression after MUD/mMUD HSCT showed a reduction of aGVHD rate with safety results comparable to those obtained with the ATG-based prophylaxis.

Obstetric and Perinatal Outcomes after Very Early Preterm Premature Rupture of Membranes (PPROM)-A Retrospective Analysis over the Period 2000-2020.

Background and Objectives: Pre-term premature rupture of membranes (PPROM) responds for one third of preterm births, and it is associated with other complications that increase the risk of maternal or fetal poor outcome. To reduce uncertainty and provide accurate information to patients, the analysis of the large series is of great importance. In order to learn about the evolution over the time of the obstetric and perinatal outcomes in cases of PPROM at, or before, 28 weeks (very early PPROM) managed with an expectant/conservative protocol, we have designed the present study. Materials and Methods: We retrospectively studied all cases of very early PPROM attended in Malaga University Regional Hospital from 2000 to 2020. Results: Among 119,888 deliveries assisted, 592 cases of PPROM occurred in pregnancies at or before 28 weeks (0.49% of all deliveries, 3.9% of all preterm births and 12.9% of all cases of PPROM). The mean duration of the latency period between PPROM and delivery was 13.5 days (range 0 to 88 days), enlarging over the years. The mean gestational age at delivery was 27 weeks (SD 2.9; range 17-34). The proportion of cesarean deliveries was 52.5%. The overall perinatal mortality rate was 26.5%, decreasing over the period with a significant correlation Pearson's coefficient -0.128 (p < 0.05). Conclusions: In the period 2000-2020, there was an improvement in the outcomes of very early PPROM cases and perinatal mortality showed a clear trend to decrease.

Transjugular Intrahepatic Portosystemic Shunt for Very Severe Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) after Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation with Post-transplantation Cyclophosphamide.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT), with high mortality rates despite early medical treatment, including the use of defibrotide (DF). We retrospectively analyzed 185 unmanipulated haploidentical (haplo-) HSCT with post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis performed consecutively between 2011 and June 2019 in a single center. Seventeen patients (9.2%) were diagnosed with VOD/SOS. Based on revised European Society for Blood and Marrow Transplantation severity criteria, the VOD/SOS cases were classified as mild in 2 patients (11.7%), moderate in 2 (11.7%), severe in 2 (11.7%), and very severe in 11 (64.9%). Thirteen patients (76%) were treated with DF, including all patients with severe or very severe VOD/SOS, except 1 patient with CNS hemorrhage. Sixteen patients (94%) were alive at day +100 after HSCT. Seven patients (41%) with very severe VOD/SOS were treated with transjugular intrahepatic portosystemic shunt (TIPS) owing to rapid clinical or analytical deterioration or refractory hepatorenal syndrome despite medical treatment, including DF. TIPS insertion was performed at a median time since VOD/SOS diagnosis of 4 days (range, 1 to 28 days) without technical complications in any case. The median hepatic venous pressure gradient before and after TIPS treatment was 24 mmHg (range, 14 to 29 mmHg) and 7 mmHg (range, 2 to 11 mmHg), respectively, with a median drop of 16 mmHg (range, 9 to 19 mmHg). Following TIPS insertion, all patients showed clinical improvement with hepatomegaly, ascites, and renal failure resolution, and all showed analytical improvement with reduced alanine aminotransferase (ALT), creatinine, and international normalized ratio values, except for patient 2, whose indication for TIPS was refractory hepatorenal syndrome with a normal ALT level. The 6 patients who had initiated DF before TIPS insertion completed 21 days of treatment. All patients met the criteria for complete remission (CR) at a median of 8 days after TIPS insertion (range, 2 to 82 days). The 100-day overall survival was 100%. For patients with rapid progressive VOD/SOS, early TIPS insertion allowed completion of DF therapy. The use of TIPS together with DF resulted in CR and no associated complications with no VOD/SOS-associated mortality despite high severity. In our experience, timely and individualized use of TIPS significantly improves outcomes of very severe VOD/SOS after haplo-HSCT. Therefore, TIPS should be promptly considered in rapidly progressive cases.

Frequency, characteristics, and outcome of PTLD after allo-SCT: A multicenter study from the Spanish group of blood and marrow transplantation (GETH).

Post-transplant lymphoproliferative disorder (PTLD) is an infrequent complication of allogeneic stem cell transplant (allo-SCT). AIMS: To estimate the frequency and management of PTLD in Spain and to identify prognostic factors influencing outcomes. METHODS: Multicenter, retrospective analysis of allo-SCT performed in 14 transplant units over a 15-year period. RESULTS: 102 PTLD were diagnosed among 12 641 allo-SCT, leading to an estimated frequency of 0.8%. PTLD was diagnosed at a median of 106 days after SCT. Eighty-seven cases (85%) were diagnosed between 2007 and 2013. At diagnosis, 22% and 17% of the patients had gastrointestinal tract and CNS involvement. Eighty-seven (85%) received rituximab treatment, alone or in combination with immunosuppression reduction, with an ORR of 50.6%. With a median follow-up for survivors of 58 months, the 2-year overall survival (OS) was 33% and the PTLD-related mortality 45%. Age ≥ 40 years, malignant underlying disease, non-response to rituximab, and severe thrombocytopenia or lymphocytopenia at PTLD diagnosis were associated with worse overall survival. CONCLUSIONS: Only a small proportion of allografted patients were diagnosed a PTLD. Its clinical course was highly aggressive, and prognosis poor, especially in those failing rituximab. The prognostic impact found of the platelet, and lymphocyte count at diagnosis requires further confirmation.

Factors predicting peripheral blood progenitor cell mobilization in healthy donors in the era of related alternative donors: Experience from a single center.

BACKGROUND: Poor mobilization results are unexpected after G-CSF-induced peripheral blood stem cell collection in healthy donors. However, 2%-5% of the donors are poor mobilizers. Factors predicting CD34+-cell yield after mobilization in related alternative donors are still poorly known. PATIENTS AND METHODS: Baseline characteristics and efficacy results of G-CSF induced mobilization of 159 adult healthy donors in our institution from 2008 to 2016 were retrospectively analyzed. All donors received 10 µg/kg of G-CSF once a day subcutaneously for 4 days. Leukapheresis started on the 5th day of G-CSF treatment. Donors were classified as poor mobilizers if they had less than 20 000 CD34 + cell/mL peripheral blood count in the 5th day of G-CSF treatment or if they needed three or more leukapheresis for graft collection. RESULTS: Age, weight, and platelet count before and after mobilization were significantly different between poor and good mobilizers. Poor mobilizers (n = 16) were older (50.6 vs 41.7 years, P = 0.002), weight lower (64 vs 75 kg, P = 0.00) and showed a lower platelet count before (199.5 vs 219.0 × 109 /L, P = 0.03) and after (192.5 vs 206 × 109 /L, P = 0.019) mobilization. In the multivariate analysis only the 30% of the variability of mobilization was explained by the model (sensitivity 80%, specificity 70%). CONCLUSION: In this cohort of healthy donors in a single institution, older age, less weight, and lower platelet count was associated with poorer mobilization. With clinical and analytic factors it is not possible to predict more than 30% of the variability. Further studies are needed to investigate new variables.