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Background: We report our updated experience of allogeneic transplantation in lympho-proliferative disorders using a reduced-intensity conditioning regimen combining BEAM (plus fludarabine in three cases) with pre-transplant CAMPATH. Post-transplant donor lymphocytes have been infused for persisting disease or relapse, and both chimerism and minimal residual disease have been monitored utilizing molecular techniques. Methods: Thirty patients with median age 47.6 years underwent allogeneic transplantation for relapsed or high-risk lymphoproliferative disease using HLA-identical (sibling n = 25, unrelated n = 2) or one antigen mismatched sibling donors (n = 3). Twenty-one had NHL, three had HD and six had CLL/PLL. Stem-cell source was PBSC (n = 24), BM (n = 5) or both (n = 1) with a median CD34 dose of 4.5 × 10[sup 6]/kg. GvHD prophylaxis was with CYA and MTX. Results: Engraftment was prompt in the majority of patients, with a median of 15 days to both ANC > 0.5 and platelets > 20. There have been three transplant-related deaths secondary to viral pneumonitis or bacterial pneumonia. Seven patients developed Grade I–II acute GvHD post-transplant. Of 28 evaluable patients, 18 achieved a CR at assessment 2–3 months post-transplant and a further patient converted from PR to CR following DLI, to give an overall CR rate of 68%. Three patients had early progressive disease and six have relapsed from CR or progressed from PR (two of whom have achieved CR following DLI therapy). Overall survival is 67% and event-free survival 48% at 3 years. With a median follow-up of 1.3 years 57% of patients are currently alive and lymphoma-free. A molecular remission has been achieved in nine of 12 informative patients. Discussion: These encouraging results show that this reduced-intensity conditioning regimen is effective, with a low-toxicity profile compared with conventional TBI-based conditioning, and certainly merits further evaluation in this setting. [ABSTRACT FROM AUTHOR]

Achilles tendon injuries occur throughout the lifespan and can negatively affect quality of life and overall health. Achilles tendinopathy is generally classified as an overuse injury associated with fusiform tendon thickening, neovascularization, and interstitial tendon degeneration. Current literature suggests these structural changes are associated with symptoms and lower physical activity levels, as well as symptoms and lower extremity function in the long term. Surgically and non-surgically managed Achilles tendon ruptures result in increased tendon cross-sectional area (CSA) and a lengthened Achilles tendon. Both structural outcomes have clinical implications, as larger CSA positively predicts function, whereas increased tendon lengthening predicts reduced function after Achilles tendon rupture. Given the relationship between structural changes associated with Achilles tendon injuries for both injury severity and injury recovery, it is critical to be able to quantify Achilles tendon structure reliably and accurately. Silbernagel's group has established a valid and reliable method for efficiently evaluating triceps surae muscle and tendon structure. In this protocol, B-mode musculoskeletal ultrasound imaging is used to measure triceps surae structure, including Achilles tendon thickness and CSA, soleus thickness, and the presence of additional findings (calcifications and bursitis). B-mode extended field-of-view is used to measure Achilles tendon length and gastrocnemius anatomical CSA. Finally, power Doppler is used to identify intratendinous neovascularization. Quantification of triceps surae structure allows for comparison between limbs as well as longitudinal changes in response to exercise and treatment for healthy individuals and those with Achilles tendon injuries. This protocol has been used in many research studies to date and proves valuable in understanding the relationship between tendon structure and injury development, severity, and recovery. As ultrasound devices are becoming more affordable and portable, this protocol proves promising as a clinical tool, given its quick and efficient methods.

We examined perceived risk of future sports injury and athlete burnout among uninjured adolescent athletes. Uninjured high school athlete participants completed the Athlete Burnout Questionnaire (ABQ) and a questionnaire assessing attitudes toward likelihood of sustaining a future sport-related injury. We compared ABQ responses between injury risk perception groups: those who expected injury versus those who did not. Half of the participants reported a somewhat/very high likelihood of future sport-related injury ( n = 98; 52% female; age = 15.3 ± 1.9 years), while the other half reported it was unlikely/not possible ( n = 98; 45% female; age = 15.3 ± 1.3 years). A significantly greater proportion of those in the expected injury group reported a history of bone/muscle/ligament/tendon injury (56% vs 24%; P < .001). Those in the expected injury group reported higher athlete burnout scores (median = 28 [interquartile range = 25-34] vs 25 [23-30]; P = .002). Adolescent athletes who reported they were likely to experience a future injury in their sport also reported greater levels of burnout.

Context: Sever's disease (calcaneal apophysitis) is a common condition in youth athletes, including those who participate in barefoot sports. Health care professionals often recommend that young athletes with Sever's disease wear heel cups in their shoes while active, but barefoot athletes are unable to use heel cups., Objective: To compare the efficacy of 2 braces used by barefoot athletes with Sever's disease., Design: Randomized controlled clinical trial., Setting: Pediatric sports medicine clinic., Patients or Other Participants: A total of 43 barefoot athletes aged 7 to 14 years were enrolled, and 32 completed the study (age = 10.3 ± 1.6 years; 29 girls, 3 boys)., Intervention(s): Participants were randomized to the Tuli's Cheetah heel cup (n = 16) or Tuli's The X Brace (n = 16) group for use during barefoot sports over the 3-month study period., Main Outcome Measure(s): Participants completed self-reported assessments after diagnosis (baseline) and 1, 2, and 3 months later. The primary outcome was the Oxford Ankle Foot Questionnaire for Children (OxAFQ-C) physical score (3 months postenrollment). The secondary outcomes were OxAFQ-C school or play and emotional scores and the visual analog scale pain score., Results: The percentage of time wearing the brace during barefoot sports was not different between the Cheetah heel cup and The X Brace groups (82% versus 64% of the time in sports; P = .08). At 3 months, we observed no differences for the OxAFQ-C physical (0.79 versus 0.71; P = .80; Hedges g = 0.06), school or play (0.94 versus 1.00; P = .58; Hedges g = 0.26), or emotional (1.00 versus 1.00; P = .85; Hedges g = 0.21) score. Visual analog scale pain scores during activities of daily living and sports were lower (better) at the 2- and 3-month time points than at baseline (P < .001)., Conclusions: Both groups demonstrated improvements in ankle and foot function across time, but no between-groups differences were seen at 3 months. Given these results, barefoot athletes with Sever's disease may consider using either brace with barefoot activity to help improve pain and functional status., (© by the National Athletic Trainers' Association, Inc.)

Background: The outcome of chemotherapy in patients older than 40 years with acute lymphoblastic leukaemia is poor and myeloablative allogeneic haematopoietic stem-cell transplantation (HSCT) has a high transplant-related mortality (TRM) in this age cohort. The aim of this study was to assess the activity and safety of reduced-intensity conditioned allogeneic HSCT in this patient population., Methods: This was a single-arm, prospective study within the UKALL14 trial done in 46 centres in the UK, which recruited patients to the transplantation substudy. Participants in UKALL14 had B-cell or T-cell acute lymphoblastic leukaemia, were aged 25-65 years (BCR-ABL1-negative) or 18-65 years (BCR-ABL1-positive), and for this subcohort had a fit, matched sibling donor or an 8 out of 8 allelic matched unrelated donor (HLA-A, HLA-B, HLA-C, and HLA-DR). On June 20, 2014, the protocol was amended to allow 7 out of 8 matched unrelated donors if the patient had high risk cytogenetics or was minimal residual disease (MRD)-positive after the second induction course. Patients were given fludarabine, melphalan, and alemtuzumab (FMA; intravenous fludarabine 30 mg/m 2 on days -6 to -2, melphalan 140 mg/m 2 on day -2, and alemtuzumab 30 mg on day -1 [sibling donor] and days -2 and -1 [unrelated donor]) before allogeneic HSCT (aged ≥41 years patient pathway). Donor lymphocyte infusions were given from 6 months for mixed chimerism or MRD. The primary endpoint was event-free survival and secondary and transplantation-specific endpoints included overall survival, relapse incidence, TRM, and acute and chronic graft-versus-host disease (GVHD). This study is registered with ClinicalTrials.gov, NCT01085617., Findings: From Feb 22, 2011, to July 26, 2018, 249 patients (236 aged ≥41 years and 13 younger than 41 years) considered unfit for a myeloablative allograft received an FMA reduced-intensity conditioned HSCT. 138 (55%) patients were male and 111 (45%) were female. 88 (35%) participants received transplantations from a sibling donor and 160 (64%) received transplantations from unrelated donors. 211 (85%) participants had B-precursor acute lymphoblastic leukaemia. High-risk cytogenetics were present in 43 (22%) and another 63 (25%) participants were BCR-ABL1-positive. At median follow-up of 49 months (IQR 36-70), 4-year event-free survival was 46·8% (95% CI 40·1-53·2) and 4-year overall survival was 54·8% (48·0-61·2). 4-year cumulative incidence of relapse was 33·6% (27·9-40·2) and 4-year TRM was 19·6% (15·1-25·3). 27 (56%) of 48 patients with TRM had infection as the named cause of death. Seven (15%) of 48 patients had fungal infections, 13 (27%) patients had bacterial infections (six gram-negative), and 11 (23%) had viral infections (three cytomegalovirus and two Epstein-Barr virus). Acute GVHD grade 2-4 occurred in 29 (12%) of 247 patients and grade 3-4 occurred in 12 (5%) patients. Chronic GVHD incidence was 84 (37%) of 228 patients (50 [22%] had extensive chronic GVHD). 49 (30%) of 162 patients had detectable end-of-induction MRD, which portended worse outcomes with event-free survival (HR 2·40 [95% CI 1·46-3·93]) and time-to-relapse (HR 2·41 [1·29-4·48])., Interpretation: FMA reduced-intensity conditioned allogeneic HSCT in older patients with acute lymphoblastic leukaemia in first complete remission provided good disease control with moderate GVHD, resulting in better-than-expected event-free survival and overall survival in this high-risk population. Strategies to reduce infection-related TRM will further improve outcomes., Funding: Cancer Research UK., Competing Interests: Declaration of interests DIM reports educational events, consulting, and advisory boards for Pfizer, Amgen, Kite, and Novartis. MC declares grants or contracts with Incyte and Cyclacel; speakers bureau or honoraria for Incyte, Novartis, Pfizer, Astellas, Jazz, and Gilead; and advisory boards for Novartis, Pfizer, Jazz, and Daiichi-Sankyo. AM received educational honoraria and payments for advisory boards and travel sponsorship from Roche; advisory board honoraria from Amgen; educational and travel payments from BMS and Celgene; and advisory board honoraria from AbbVie. TFM declares travel grants from Amgen, Jazz, Pfizer, Bayer, Kyowa Kirin, Celgene, Kite/Gilead, Janssen, and Takeda; advisory board honoraria from Kite/Gilead, Amgen, Novartis, Pfizer, Celgene, Daiichi Sankyo, Atara, and Roche; lecture honoraria from Kite/Gilead, Takeda, Janssen, Roche, Servier, Novartis, and Celgene; and research funding from Janssen, AstraZeneca, and Novartis. AVM received honoraria for an educational event for Amgen. MNP received honoraria and meeting support from Kite. NM received speaker fees from Amgen, Janssen, and AbbVie; attended advisory boards of AbbVie and Kite; and had conference support from AbbVie and Takeda. CJR reports paid educational events for Kite and Incyte; and advisory boards for Kite, Novartis, Amgen, and Pfizer. AKF reports consulting for Amgen. BP received honoraria from Pfizer and Amgen. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Here we show that the fluorescence of fluorescein isothiocyanate (FITC) is not altered by its reaction with primary amines. However, the fluorescence is rapidly quenched upon reaction with small molecular weight thiols including cysteine, glutathione, homocysteine, dithiothreitol, and sulfide. We have taken advantage of the thiol-dependent quenching of FITC to devise a sulfide specific assay by utilizing polydimethylsiloxane (PDMS) membranes that are permeable to hydrogen sulfide but not to larger charged thiols. In addition, we have discovered that the fluorescein dithiocarbamate (FDTC) formed by the reaction with sulfide can specifically react with S-nitrosothiols (RSNO) to regenerate FITC, thus serving as a specific, fluorogenic reagent to detect picomol levels of RSNO. FDTC was tested as an intracellular RSNO-sensor in germinating tomato seedlings (Solanum lycopersicum) via epifluorescence microscopy. Control plant roots exposed to FDTC showed low intracellular fluorescence which increased ∼3-fold upon exposure to extracellular S-nitrosoglutathione and ∼4-fold in the presence of N6022, a S-nitrosoglutathione reductase (GSNOR) inhibitor, demonstrating that FDTC can be used to visualize intracellular RSNO levels., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To examine the effect of sleep disturbances on concussion symptom recovery and to examine the effect of melatonin prescription on symptom improvement among concussed adolescents with sleep problems., Design: Longitudinal test-retest., Setting: Sports medicine clinic., Participants: Patients aged 8 to 18 years, diagnosed with a concussion, evaluated within 14 days after injury, and evaluated again 15 to 35 days after injury., Independent Variables: We grouped patients based on whether they reported sleep disturbances within 14 days of injury., Main Outcome Measures: Outcome measures included symptom severity, headache severity, melatonin prescription, and the change in symptom severity between visits., Results: Two hundred twenty-five patients were included: 36% who reported sleep problems (44% female; age = 14.4 ± 2.0 years; evaluated 7.3 ± 3.8 and 23.2 ± 5.4 days after injury) and 64% who did not (32% female; age = 14.6 ± 2.3 years; evaluated 7.2 ± 3.4 and 23.0 ± 5.3 days after injury). Those with sleep problems reported higher symptom severity than those without across the 2 visits (22.1 ± 14.3 vs 14.6 ± 12.5; P < 0.001). There was no significant difference in the change in symptom severity between visits among those who received [median = 9-point improvement; interquartile range (IQR) = 1-14] and did not (median = 9, IQR = 2-18) receive a melatonin prescription (P = 0.80)., Conclusions: Sleep problems among pediatric patients within 2 weeks of concussion are associated with more severe symptoms. Melatonin prescription was not associated with faster symptom recovery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective : Pediatric primary care sports medicine physicians and pediatric sports medicine orthopedic surgeons, in conjunction with physician assistants (PAs), often manage patients with fractures. We sought to determine if pediatric patients with fractures seen by primary care sports medicine physicians had similar outcomes and satisfaction as those seen by orthopedic surgeons. Methods : We performed a retrospective chart review of four to 18-year-old patients who were treated by a sports medicine provider (primary care or orthopedic surgeon/PA) for a fracture of the radius, ulna, tibia, or fibula. Patients or their parents completed a patient satisfaction survey (Short Assessment of Patient Satisfaction [SAPS]) and an injury location-specific patient-reported functional outcome tool: the Foot and Ankle Ability Measure (FAAM) or the Disabilities of the Arm, Shoulder, and Hand (DASH) Scale. Results : Fifty-seven (70%) of the 82 patients were treated by pediatric primary care sports medicine physicians and 25 (30%) were treated by a pediatric sports medicine orthopedic surgeon or surgical PA. The median time from injury to clinically confirmed healing was similar between the two groups (47 vs 60.5 days; p = 0.54), as was the patient satisfaction (SAPS median score = 26 [range = 19-28] vs 24 [range = 9-28]; p = 0.12). Patient-reported outcomes did not differ significantly between groups for the functional outcome tools. Conclusions : Patients seen by pediatric primary care sports medicine physicians and sports medicine orthopedic surgeons have similar patient-reported fracture outcomes and similar satisfaction with care. Pediatric patients with fractures will likely have favorable outcomes when cared for by either of these subspecialty providers.

Purpose: To examine the effect of age on postural control outcomes among patients being seen during their initial post-concussion clinical visit., Methods: Youth patients were seen≤14 days post-concussion, and completed a series of postural control evaluations: tandem gait, Romberg, and Balance Error Scoring System (BESS) tests., Results: We included 109 children 8-12 years of age (24% female, evaluated median = 7 [interquartile range = 4-10] days post-injury) and 353 adolescents aged 13-18 years (36% female, evaluated median = 7 [4-10] days post-injury). There was a higher proportion of children who demonstrated abnormal tandem gait relative to adolescents (26% vs. 11%; p < 0.001). They also made more BESS errors in single (median = 5 [2-10] vs. 4 [2-6] errors) and tandem (median = 3 [1-6] vs. 2 [0-4]) firm stances. After covariate adjustment, children demonstrated worse tandem gait (adjusted odds ratio = 3.05, 95% CI = 1.68-5.53) and more firm surface BESS errors (double stance β=0.51, 95% CI = 0.22-0.80; single stance β= 1.18, 95% CI = 0.42-1.95; tandem stance β= 0.98, 95% CI = 0.28-1.68) than adolescents., Conclusions: Tandem gait and BESS performance following concussion differ in children compared to adolescents who present within 2 weeks of injury. Clinicians assessing and managing concussion should recognize age differences in postural control performance when assessing those with concussion.

Context: Understanding how parents and their children perceive concussion symptoms may provide insights into optimal concussion-management strategies., Objective: To examine patient-parent correlations and agreement on concussion-symptom ratings, to identify differences in patient-parent symptom reporting between children (8-12 years of age) and adolescents (13-18 years of age), and to evaluate the correlation between patient and parent initial symptom-severity ratings with symptom duration and return-to-play time., Design: Cross-sectional study., Setting: Primary care sports medicine clinic., Patients or Other Participants: A total of 267 patients aged 8 to 18 years seen for care within 21 days of sustaining a concussion. Patients were classified as children (n = 65; age = 11.3 ± 1.4 years; age range, 8-12 years) or adolescents (n = 202; age = 15.5 ± 1.4 years; age range, 13-18 years)., Main Outcome Measure(s): Each patient and his or her parent (or legal guardian) completed a concussion-symptom-frequency inventory, the Health and Behavior Inventory (HBI), at the initial postinjury examination. Patients were followed until they no longer reported concussion symptoms (symptom-resolution time) and were allowed to return to unrestricted sport participation (return-to-play time)., Results: At the initial examination (8.9 ± 5.2 days postinjury), the symptom-frequency correlation between children and their parents was high (rs = 0.88; 95% confidence interval [CI] = 0.80, 0.95). Adolescents' symptom-frequency reports were also highly correlated with those of their parents (rs = 0.78; 95% CI = 0.71, 0.85). However, the child-parent correlation was higher than the adolescent-parent agreement (z = 2.21, P = .03). Greater patient (consolidated child and adolescent) HBI ratings were associated with longer symptom-resolution times (coefficient = 0.019; 95% CI = 0.007, 0.031; P = .002) and longer return-to-play times (coefficient = 0.012; 95% CI = 0.002, 0.022; P = .02), whereas parent HBI ratings were not., Conclusions: Our findings may help to set expectations regarding concussion-symptom durations and return-to-play timing for pediatric patients and their families. Given the patient-parent correlations in our sample, substantial reporting discrepancies between patients and their parents may be a relevant factor for clinicians to investigate further during concussion evaluations., (© by the National Athletic Trainers' Association, Inc.)

The reported influence of donor Killer-cell Immunoglobulin-like Receptor (KIR) genes on the outcomes of haematopoietic cell transplantation (HCT) are contradictory, in part due to diversity of disease, donor sources, era and conditioning regimens within and between different studies. Here, we describe the results of a retrospective clinical analysis establishing the effect of donor KIR motifs on the outcomes of 119 HLA-matched, unrelated donor HCT for adult acute myeloid leukaemia (AML) using myeloablative conditioning (MAC) in a predominantly T-cell deplete (TCD) cohort. We observed that HCT involving donors with at least one KIR B haplotype were more likely to result in non-relapse mortality (NRM) than HCT involving donors with two KIR A haplotypes (p = 0.019). Upon separation of KIR haplotypes into their centromeric (Cen) and telomeric (Tel) motif structures, we demonstrated that the Cen-B motif was largely responsible for this effect (p = 0.001). When the cause of NRM was investigated further, infection was the dominant cause of death (p = 0.006). No evidence correlating donor KIR B haplotype with relapse risk was observed. The results from this analysis confirm previous findings in the unrelated, TCD, MAC transplant setting and imply a protective role for donor-encoded Cen-A motifs against infection in allogeneic HCT recipients.

Objectives: The purpose of our investigation was to compare post-concussion symptom profiles and postural control measures among female youth artistic athletes (gymnasts and cheerleaders) relative to female ball sport athletes (volleyball or basketball)., Methods/findings: We compared 27 artistic athletes (median age = 15.0 years; evaluated median = 13 days post-injury) and 49 ball sport athletes (median age = 15.3 years; evaluated median = 10 days post-injury) within 21 days of sustaining a concussion on measures of symptom profiles and postural control (Balance Error Scoring System [BESS]), tandem gait, and Romberg tests. After adjusting for the independent effect of time from injury-evaluation, concussion history, and pre-morbid migraine history, we observed that artistic athletes performed the BESS tandem stance foam condition with fewer errors than ball sport athletes (β = -2.4; 95% CI = -4.7, -0.2; p = .03). Artistic athletes demonstrated a higher, yet not statistically significant, headache severity than ball sport athletes (median = 4.5 vs 4.0, p = .07)., Conclusions: Overall, artistic athletes had similar symptom profiles to ball sport athletes. Postural control measures, other than the BESS tandem stance foam condition, were not significantly different from ball sport athletes. This suggests that although their sports may require higher levels of balance, artistic athletes' performance on post-concussion balance tests may be similar to athletes of other disciplines.

Background: Female gymnasts have a greater prevalence of back pain compared to other female athletes. There is little evidence that female artistic gymnasts with and without back pain demonstrate different movement patterns during gymnastics skills. The purpose of this study was to determine if there were differences in back movements during back walkovers and back handsprings among female artistic gymnasts., Methods: Female artistic gymnasts (8-18 years old) with and without back pain wore inertial sensors on their torso, arms, and legs while performing back walkovers (N = 14) and back handsprings (N = 15) on the floor and balance beam at their training gymnastics facilities., Findings: Gymnasts with back pain had similar spine peak extension, peak flexion, and range of motion during back walkovers and back handsprings compared to gymnasts without back pain. Additionally, no differences in sagittal plane spine kinematics were found between the groups at any specific time point during either the back walkover or back handspring skills. However, a large portion of the data collected was excluded during quality assurance, thus our final sample sizes are small., Interpretation: These findings suggest that gymnasts with back pain have similar sagittal plane movements to those without back pain. The relationship between back pain and gymnastics training load/intensity is currently unclear. We suggest future studies to investigate common artistic gymnastics skills and back pain prevalence with more participants, full-body motion analysis with kinetic measurement capabilities, and longitudinally for those demonstrating back pain., (Copyright © 2020. Published by Elsevier Ltd.)

Our objective was to examine the effect of current neck or shoulder pain on concussion outcomes. Variables included symptom resolution and return-to-sport time, symptom severity, amount of school missed, and sleep disturbances. Three hundred twelve patients (37% female; median age = 15.0 years; evaluated median = 9 days postinjury) reported experiencing current neck or shoulder pain at initial evaluation, and 268 did not (31% female; median age = 14.7 years; evaluated median = 8 days postinjury). Neck or shoulder pain was associated with longer symptom resolution time (β = 6.38, 95% confidence interval [CI] = 2.44, 10.31; P = .002), more severe symptoms (β = 7.06, 95% CI = 4.91, 9.21; P < .001), and greater odds of missing >5 days of school (adjusted odds ratio [aOR] = 1.89, 95% CI = 1.23, 2.93; P = .004), and postinjury sleep problems (aOR = 2.20, 95% CI = 1.51, 3.21; P < .001). Experiencing neck or shoulder pain during the initial postinjury clinical evaluation was associated with worsened clinical outcomes. Clinicians may consider referral to early rehabilitation following concussion among those who report neck or shoulder pain.

Objective: The objective of the study was to evaluate the clinical outcomes among patients who did and did not report engaging in early physical activity (PA) following sport-related concussion., Methods: We evaluated pediatric patients seen within 21 days of concussion. The independent variable was early PA engagement (since the injury and before initial clinical evaluation). Dependent variables included demographics, injury details, medical history, Health and Behavior Inventory (HBI) score, and balance, vestibular, and oculomotor function tests., Results: We examined data from 575 pediatric patients: Sixty-nine (12%) reported engaging in early PA (mean age=14.3±2.4 years; 30% female). The no PA group (mean age=14.5±2.4 years; 35% female) had significantly longer symptom resolution times than the early PA group (median= 16 [interquartile range (IQR)=8-24] vs. 10.5 [IQR=4-17] days; p=0.02). When controlling for pre-existing headache history and time from injury-evaluation time, the early PA group demonstrated lower odds of reporting current headache (adjusted odds ratio=0.14; 95% CI=0.07, 0.26), and reported lower symptom frequency ratings than the no PA group (b=-5.58, 95% CI=-8.94, -2.22)., Conclusions: Patients who did not engage in early PA had longer symptom duration, greater odds of post-injury headache, and greater symptoms at initial clinical evaluation. We cannot determine if patients engaged in early PA due to the lower symptom burden and higher functioning at the time of assessment, or if early PA positively affected outcomes. However, as early PA was associated with better post-injury outcomes, clinicians may consider supervised and structured early PA programs as a method to improve clinical outcomes following concussion., Relevance for Patients: Children and adolescents who were engaged in PA after concussion presented to a clinic with less severe symptoms and had symptoms that resolved sooner compared to those who did not engage in early PA after concussion., Competing Interests: The authors declare that they have no conflicts of interest related to the study., (Copyright: © Whioce Publishing Pte. Ltd.)

We examined the association between sleep quality and quality of life (QOL) among uninjured high school athletes. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile 25 questionnaire. One hundred ten athletes reported poor sleep quality (mean PSQI: 6.6 ± 2.0; mean age: 15.3 ± 1.1; 62% female); 162 athletes reported good sleep quality (mean PSQI: 2.3 ± 1.3; mean age: 15.1 ± 1.7; 33% female). After adjusting for sex and age, worse sleep quality was associated with higher physical function/mobility (β = 0.034; 95% confidence interval [CI] = 0.007-0.060; P = .01), anxiety (β= 0.391; 95% CI = 0.263-0.520; P < .001), depressive symptom (β = 0.456; 95% CI = 0.346-0.565; P < .001), fatigue (β = 0.537; 95% CI = 0.438-0.636; P < .001), pain interference (β = 0.247; 95% CI = 0.119-0.375; P < .001), and pain intensity (β = 0.103; 95% CI = 0.029-0.177; P = .006) ratings. Poor self-reported sleep quality among adolescent athletes was associated with worse QOL ratings. Clinicians should consider assessing sleep hygiene to provide guidance on issues pertaining to reduced QOL.

Context: Many factors can affect the injury risk and quality of life among high school athletes. Early sport specialization and club sport participation may be components to consider when assessing the injury risk and quality of life., Objective: To investigate patient-reported quality-of-life and injury-history measures among adolescent athletes at different sport-specialization levels and to compare these measures between those who did and those who did not report participating in club sports., Design: Cross-sectional study., Setting: High school athletic facility., Patients or Other Participants: High school student athletes 13 to 18 years of age were recruited and tested during their annual preseason athletic physical examinations., Main Outcome Measure(s): Our primary grouping variables were sport-specialization level (classified as low, moderate, or high) and club sport participation (organized sport outside of traditional school athletics). Our outcome variables were the Patient-Reported Outcome Measurement Information System Pediatric Profile-37 rating, Severity Measure for Depression-Child score, and injury history., Results: A total of 97 individuals participated (mean age = 15.2 ± 1.1 years; 38% female). Relatively similar proportions of individuals reported participating at each level of sport specialization (low = 34%, moderate = 40%, high = 26%). Forty-six (48%) participants stated they participated in club sports. No differences were evident in quality of life ( P values = .15-.92 across domains), depression ( P = .60), or injury history ( P > .70) among the specialization groups. Those who described participating in club sports had a higher proportion of time-loss musculoskeletal injuries (63% versus 29%; P = .002) and of injuries requiring imaging, injection, a cast, a brace, or crutches (72% versus 46%; P = .013) than those who did not., Conclusions: Although no injury-history differences were found among the sport-specialization groups, a higher proportion of club sport athletes than nonclub sport athletes reported a history of injury. Club sports are generally seen as more competitive, and the higher number of injuries seen in this setting could be related to a higher level of play among club sport athletes.

Objective: To identify clinically significant postural control measures capable of distinguishing the performance of adolescents with concussion from uninjured controls., Approach: Fifteen adolescents with concussion (67% female; median age  =  16.3 years; tested 8  ±  4 d post-injury) and 31 controls (45% female; median age  =  15.2 years) completed a single/dual-task gait evaluation with a smartphone affixed to their lumbar spine, modified balance error scoring system (mBESS), and single/dual-task tandem gait test. Outcome measures were obtained via smartphone (single/dual-task gait speed, cadence, step length), mBESS (double/single/tandem errors), and tandem gait (single/dual-task time). We calculated area under the curve (AUC) values for each measure that demonstrated a significant difference between groups independently, and calculated a comprehensive AUC value for all measures combined., Main Results: The concussion group walked significantly slower (mean  =  0.89  ±  0.15 versus 1.05  ±  0.15 m s -1 ; p   =  0.002) and with significantly fewer steps per minute (median  =  103 [interquartile range  =  94-108] versus 116 [104-118] steps/minute; p   =  0.002) than the control group under single-task conditions. They also completed single-task (median  =  22.0 [16.6-24.2] versus 14.5 [12.4-15.5] s; p   <  0.001) and dual-task (median  =  30.0 [24.0-35.2] versus 18.6 [16.1-21.7] s; p   <  0.001) tandem gait tests significantly slower than controls. The AUC value for single-task gait velocity, single-task cadence, single-task tandem gait time, and dual-task tandem gait time indicated an excellent ability to distinguish between concussion and control groups (AUC  =  0.91, 95% CI  =  0.80-0.99)., Significance: Smartphone-obtained gait measures and tandem gait times allowed for an excellent differentiation between adolescents with concussion versus control participants. This reinforces the need for multimodal approaches to postural control impairment recognition among adolescents with concussion.

Objective: To determine the relationship between low back pain (LBP), flexibility, and individual demographic characteristics in competitive adolescent female gymnasts., Design: Cross-sectional observational study., Setting: Gymnastics facilities in Colorado., Participants: Six- to 18-year-old gymnasts who participate in the USA Gymnastics Women's Artistic Junior Olympic Program levels 3 to 10., Independent Variables: Demographic data included height, weight, menstrual status, gymnastics level, and participation hours per week. Flexibility measurements were obtained on the gymnasts. Gymnasts also completed a questionnaire documenting LBP in the past 12 months. Univariable (t test and χ) analyses were used to assess between-group differences; multivariable logistic regression model was used to assess the association between LBP, flexibility, and demographics/injury history., Main Outcome Measures: Low back pain within the past 12 months., Results: Thirty (45%) of 67 gymnasts reported LBP within the past year. Those who reported LBP were older (11.7 vs 13.7 years, P = 0.005), heavier (37.5 vs 43.4 kg, P = 0.049), and participated in gymnastics more often (19.1 vs 22.4 h/wk, P = 0.017). A greater proportion of gymnasts with LBP had experienced menarche compared with those without LBP (47% vs 16%; P = 0.008). On multivariable analysis, gymnasts with LBP were less likely to have left Iliotibial (IT) band tightness compared with those without LBP [adjusted odds ratio (aOR) = 0.186; 95% confidence interval (CI), 0.04-0.82] and more likely to have experienced menarche (aOR = 8.0; 95% CI, 1.2-50.9)., Conclusions: Low back pain is more common in gymnasts who experienced menarche, whereas limited joint flexibility does not seem to be associated with LBP in this population.

Objective: The goal of this study was to determine which variables assessed during an initial clinical evaluation for concussion are independently associated with time until symptom resolution among pediatric patients., Methods: Data collected from a prospective clinical registry of pediatric patients with concussion were analyzed. The primary outcome variable was time from injury until symptom resolution. Predictor variables assessed within 10 days after injury included preinjury factors, Health and Behavior Inventory scores, headache severity, and balance, vestibular, and oculomotor test performances. The researchers used univariate Cox proportional models to identify potential predictors of symptom resolution time and constructed a multivariate Cox proportional hazards model in which total duration of concussion symptoms remained the outcome variable., Results: The sample consisted of 351 patients (33% female, mean age 14.6 ± 2.2 years, evaluated 5.6 ± 2.6 days after concussion). Univariate Cox proportional hazards models indicated that several variables were associated with a longer duration of symptoms, including headache severity (hazard ratio [HR] 0.90 [95% CI 0.85-0.96]), headache frequency (HR 0.83 [95% CI 0.71-0.96]), confusion (HR 0.79 [95% CI 0.69-0.92]), forgetfulness (HR 0.79 [95% CI 0.68-0.92]), attention difficulties (HR 0.83 [95% CI 0.72-0.96]), trouble remembering (HR 0.84 [95% CI 0.72-0.98]), getting tired often (HR 0.86 [95% CI 0.76-0.97]), getting tired easily (HR 0.86 [95% CI 0.76-0.98]), dizziness (HR 0.86 [95% CI 0.75-0.99]), and abnormal performance on the Romberg test (HR 0.59 [95% CI 0.40-0.85]). A multivariate Cox proportional hazards model indicated that an abnormal performance on the Romberg test was independently associated with a longer duration of symptoms (HR 0.65 [95% CI 0.44-0.98]; p = 0.038)., Conclusions: For children and adolescents evaluated within 10 days after receiving a concussion, abnormal performance on the Romberg test was independently associated with a longer duration of symptoms during recovery. In line with findings of other recent studies investigating predictors of symptom resolution, postural stability tests may provide useful prognostic information for sports medicine clinicians.

Objectives: To determine the scores of gymnasts with low back pain (LBP) on two functional pain scales: the Micheli Functional Scale (MFS) and the Oswestry Low Back Pain Disability Questionnaire (ODQ)., Design: Cross-sectional study., Setting: Gymnastics facilities., Participants: Female gymnasts aged 7-18 years., Main Outcome Measures: We grouped gymnasts into those having pain affecting gymnastics and those with pain not affecting gymnastics and then compared MFS and ODQ scores for various activities., Results: Eleven of the 29 participants (38%) endorsed LBP during gymnastics and 18 had LBP not affecting gymnastics. There were no demographic differences between the two groups. A significantly greater proportion of gymnasts who had pain during gymnastics reported pain with jumping (N = 11, 100% vs N = 8, 44%, p = 0.003) and lifting weights (N = 4, 36% vs N = 0, p = 0.016) compared to those not having pain during gymnastics. There were no significant differences between the two groups for pain with spine flexion or extension or for hip flexibility., Conclusions: Although gymnastics requires extreme flexion and extension of the spine, gymnasts whose pain affects them during gymnastics do not endorse more pain with these movements. Gymnasts with LBP during gymnastics are more likely to have pain with jumping and with lifting weights., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

HLA matching at an allelic-level resolution for volunteer unrelated donor (VUD) hematopoietic cell transplantation (HCT) results in improved survival and fewer post-transplant complications. Limitations in typing technologies used for the hyperpolymorphic HLA genes have meant that variations outside of the antigen recognition domain (ARD) have not been previously characterized in HCT. Our aim was to explore the extent of diversity outside of the ARD and determine the impact of this diversity on transplant outcome. Eight hundred ninety-one VUD-HCT donors and their recipients transplanted for a hematologic malignancy in the United Kingdom were retrospectively HLA typed at an ultra-high resolution (UHR) for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 using next-generation sequencing technology. Matching was determined at full gene level for HLA class I and at a coding DNA sequence level for HLA class II genes. The HLA matching status changed in 29.1% of pairs after UHR HLA typing. The 12/12 UHR HLA matched patients had significantly improved 5-year overall survival when compared with those believed to be 12/12 HLA matches based on their original HLA typing but were found to be mismatched after UHR HLA typing (54.8% versus 30.1%, P = .022). Survival was also significantly better in 12/12 UHR HLA-matched patients when compared with those with any degree of mismatch at this level of resolution (55.1% versus 40.1%, P = .005). This study shows that better HLA matching, found when typing is done at UHR that includes exons outside of the ARD, introns, and untranslated regions, can significantly improve outcomes for recipients of a VUD-HCT for a hematologic malignancy and should be prospectively performed at donor selection., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Acute and overuse injuries are a common experience for artistic gymnasts; however, this population has unique needs when returning to their sport after an injury due to the technical demands imposed during gymnastics. We reviewed the current literature regarding return to play (RTP) in artistic gymnasts and developed four goals: 1) to define the guiding principles used to determine RTP in sports, 2) to identify factors that affect recovery progression among gymnasts, 3) to determine how different injury types affect RTP protocols, and 4) to create structured RTP protocols specific to gymnasts based on sex and body part injured. By establishing these guidelines, we hope to provide guidance to medical providers through a standardized approach for returning gymnasts to their sport.

Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1.22, 95% confidence interval (CI) 1.2-1.5, P=0.033 for 1 mismatch and RR 1.46, 95% CI 1.1-1.9, P=0.009 for >1 mismatch) and CMV mismatching (RR 1.37, 95% CI 1.2-1.6, P<0.001) were significantly associated with inferior survival. Donors aged <30 years showed a trend towards better survival. The multivariate model for mortality, combining CMV and HLA-match status, found an RR of 1.36 (95% CI 1.1-1.7, P=0.003) for HLA matched/CMV mismatched, an RR of 1.22 (95% CI 0.99-1.5, P=0.062) for HLA mismatched/CMV matched and an RR of 1.81 (95% CI 1.4-2.3, P=<0.001) for HLA/ CMV mismatched, compared with the HLA/CMV-matched recipients. These data suggest that HLA and CMV matching status should be considered when selecting unrelated donors and that CMV matching may abrogate the effect of an HLA mismatch.

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology, the British Society for Bone Marrow Transplantation and the UK Clinical Virology Network has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with haematological malignancies or those undergoing haematopoietic stem cell transplantation. This guideline includes recommendations for the diagnosis, prevention and treatment of respiratory viral infections in adults and children. The suggestions and recommendations are primarily intended for physicians practising in the United Kingdom., (© 2016 John Wiley & Sons Ltd.)

Transforming growth factor β-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, 'p001', showed significantly reduced overall survival (5-year overall survival 30.7% for p001/p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year non-relapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04-2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06-2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor β-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor β-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms., (Copyright© Ferrata Storti Foundation.)

Background: The introduction of central venous catheters has advanced medical care, particularly in hemato-oncology. However these can be associated with an increased thrombotic risk. Previous studies have compared the rate of thrombotic events between peripherally- inserted (PICCs) and long term skin tunneled catheters (LTSTCs) noting fewer complications associated with the latter, though this has rarely translated into clinical practice. The objectives of our study was to compare the cumulative incidence of thrombotic events between peripherally-inserted and long term skin tunneled venous catheters., Patients/methods: We performed a retrospective, single center cohort analysis of patients with hematological malignancies who had either a PICC or LTSTC line inserted between January 2010 through January 2013. Cumulative incidences of thrombotic events were compared between the two groups, and post-thrombotic complications were also examined., Results: 346 patients had a PICC inserted with cumulative incidence of symptomatic thrombosis of 5.8%, while 237 patients had a LTSTC inserted with a cumulative incidence of 1.7% (p = 0.003). Post-thrombotic complication rates, particularly infection, were higher in the PICC group compared to the LTSTC group (p = 0.597)., Conclusions: Our study showed that the incidence of thrombotic events in hemato-oncology patients was significantly lower in those who had a LTSTC compared to PICC line. As the use of central venous lines increases in hemato-oncology patient care, a randomized trial comparing PICCs and LTSTCs is necessary to address which venous access is most appropriate in this cohort of patients, with minimal risk of morbidity and mortality.

This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen-identical sibling or human leukocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=0.04) and was associated with lower relapse incidence (HR=0.5; P=0.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitor administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=0.002) and overall survival (HR=0.42; P=0.004), and a lower relapse incidence (HR=0.40; P=0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long-term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post-transplant setting., (Copyright© Ferrata Storti Foundation.)

Discrepancies exist between the care of unrelated donors (UDs) and related donors (RDs), particularly regarding medical suitability criteria, consenting procedures and donor follow-up. Changes to the most recent JACIE standards have addressed these issues. We studied 208 RDs who underwent PBSC or BM donation in a single centre during 2004-2013 to determine the impact of regulatory changes on donor care, and assessed the safety and efficacy of stem cell donation in donors not meeting UD medical suitability criteria. We observed significant improvements in donor consenting procedures (P=0.003) and donor follow-up (P=0.007) after stipulations in these areas were introduced. We saw a higher incidence of serious adverse events (SAEs) in RDs not meeting UD suitability criteria (P=0.018), and a higher incidence of SAEs in donors ⩾60 years (P=0.020). Haematopoietic progenitor cell donation is less safe in RDs who do not meet UD criteria for medical suitability. Although changes to JACIE standards have improved practice, development of specific medical suitability for RDs and guidelines around 'grey areas' where risks to a donor are unclear or theoretical, will be important in improving RD safety and standardising practice.

There are few prospective studies evaluating the role of extracorporeal photopheresis (ECP) in chronic GVHD (cGVHD) and only occasional reports of the effect of ECP on patients' quality of life (QoL). We report a single-centre prospective study of patients undergoing fortnightly ECP for moderate or severe cGVHD. Response was assessed after 6 months of treatment using NIH scoring criteria and reduction in immunosuppression. QoL assessments were undertaken at baseline and at 6 months using the chronic GVHD symptom scale (cGVHD SS) and dermatology life quality index (DLQI). An intention-to-treat analysis showed that 19/38 (50%) of patients had a complete or partial response. Twenty-seven out of 38 patients completed 6 months of ECP treatment and 70% (19/27) had a complete or partial response. Eighty per cent of patients who completed 6 months of ECP treatment had a reduction in immunosuppression dose. A subset of patients completed QoL questionnaires. Seventeen out of 18 patients (94%) showed an improvement in scores. The mean cGVHD SS and mean DLQI score were both significantly lower after 6 months of ECP (22 compared with 36, P=0.012 and 3.4 compared with 6.9, P=0.009, respectively). This study confirms that ECP can lead to objective clinical responses and, in addition, may lead to an improvement in QoL in cGVHD.

The presence of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) has been associated with adverse outcomes in AML patients treated with chemotherapy alone, but its impact in the setting of allogeneic hematopoietic SCT (HSCT) is less clear. We studied 88 patients who underwent myeloablative (MA) or reduced-intensity conditioned allogeneic HSCT for AML in first or subsequent remission at our center. MRD status was determined using three-color MFC on pre-HSCT BM aspirates, and patients were stratified by MRD status into MRD-negative, low-level MRD-positive (<1%) or high-level MRD-positive groups (1-4.9%). Two-year survival estimates in these groups were 66.8%, 51% and 30%, respectively (P=0.012), and 2-year estimates of relapse were 7.6, 37 and 70% (P<0.001). Pre-HSCT MRD was related to disease characteristics including secondary AML (P=0.002) and primary induction failure (P=0.005), but, despite these strong correlations, MRD remained independently associated with poorer survival in multivariate analysis (hazard ratio, 1.92; P=0.014). Pre-HSCT MRD is associated with adverse clinical outcomes in AML patients undergoing reduced-intensity or MA HSCT in first or subsequent remission and should be integrated into transplant strategies for patients with AML.

Diagnosis: It is recommended that the diagnosis of veno-occlusive disease (sinusoidal obstruction syndrome) [VOD (SOS)] be based primarily on established clinical criteria (modified Seattle or Baltimore criteria) (1A). Ultrasound imaging may be helpful in the exclusion of other disorders in patients with suspected VOD (SOS) (1C). It is recommended that liver biopsy be reserved for patients in whom the diagnosis of VOD (SOS) is unclear and there is a need to exclude other diagnoses (1C). It is recommended that liver biopsies are undertaken using the transjugular approach in order to reduce the risks associated with the procedure (1C). It is suggested that the role of plasminogen activator inhibitor 1 levels remains an area for further research but that these levels should not form part of the routine diagnostic work-up for VOD (SOS) at present (2C)., Risk Factors: It is recommended that patients are assessed for risk factors for VOD (SOS) and that these risk factors are addressed prior to haematopoietic stem cell transplantation (1A)., Prophylaxis: Defibrotide is recommended at a dose of 6.25 mg/kg intravenously four times daily for the prevention of VOD (SOS) in children undergoing allogeneic stem cell transplantation with the following risk factors: pre-existing hepatic disease, second myeloablative transplant, allogeneic transplant for leukaemia beyond second relapse, conditioning with busulfan-containing regimens, prior treatment with gemtuzumab ozogamicin, diagnosis of primary haemophagocytic lymphohistiocytosis, adrenoleucodystrophy or osteopetrosis (1A). Defibrotide is suggested at a dose of 6.25 mg/kg intravenously four times daily for the prevention of VOD (SOS) in adults undergoing allogeneic stem cell transplantation with the following risk factors: pre-existing hepatic disease, second myeloablative transplant, allogeneic transplant for leukaemia beyond second relapse, conditioning with busulfan-containing regimens, prior treatment with gemtuzumab ozogamicin, diagnosis of primary haemophagocytic lymphohistiocytosis, adrenoleucodystrophy or osteopetrosis (2B). Prostaglandin E1 is not recommended in the prophylaxis of VOD (SOS) due to lack of efficacy and toxicity (1B). Pentoxifylline is not recommended in the prophylaxis of VOD (SOS) due to lack of efficacy (1A). Ursodeoxycholic acid is suggested for use in the prophylaxis of VOD (SOS) (2C). Heparin (unfractionated and low molecular weight) is not suggested for use in the prophylaxis of VOD (SOS) due to the risk of increased toxicity (2B). Antithrombin is not suggested for the prophylaxis of VOD (SOS) due to lack of efficacy (2B)., Treatment: Defibrotide is recommended in the treatment of VOD (SOS) in adults and children (1B). Tissue plasminogen activator is not recommended for use in the treatment of VOD (SOS) due to the associated risk of haemorrhage (1B). N-acetylcysteine is not routinely recommended for use in the treatment of veno-occlusive disease due to lack of efficacy (1A). Methylprednisolone may be considered for use in the treatment of veno-occlusive disease with the appropriate caveats of caution regarding infection (2C). Judicious clinical care, particularly in the management of fluid balance, is recommended in the management of VOD (SOS) (1C). Early discussion with critical care specialists and a specialist hepatology unit is recommended in the management of VOD (SOS) and other treatment options including transjugular intrahepatic portosystemic shunt or hepatic transplantation may be considered (1C)., Summary: A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Blood and Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of veno-occlusive disease of the liver following haematopoietic stem cell transplantation (HSCT). This guideline includes recommendations for both prophylaxis and treatment of the condition and includes recommendations for children and adults undergoing HSCT., (© 2013 John Wiley & Sons Ltd.)

Myeloablative allo-SCT decreases relapse incidence (RI) in ALL. Reduced intensity conditioning (RIC) may extend allo-SCT to older and less fit patients. Sixty-nine ALL patients reported to the BSBMT underwent fludarabine-based RIC allo-SCT, 38 from unrelated donors (UD). Forty-four patients received alemtuzumab. ALL was in CR in 64 patients (93%). This was a second or third SCT in 23 patients. Two-year OS and PFS were 36% and 32%, respectively. In multivariate analysis male recipients demonstrated better OS and PFS (hazard ratio (HR) = 0.42, P = 0.008 and HR = 0.45, P = 0.012, respectively). Two-year TRM was 29%: higher with younger age (HR = 0.97/year, P = 0.041), female recipient (HR = 2.55, P = 0.049) and increasing grade of acute GVHD (HR = 1.87, P = 0.001). Two-year RI was 38% and was lower in patients with acute and chronic GVHD (HR = 0.62 per increasing grade, P = 0.035 and HR = 0.52, P = 0.025, respectively). Long-term ALL-free survival is achievable following fludarabine-based RIC allo-SCT. The association between GVHD and decreased RI suggests the presence of a GVL effect.

Graft-versus-host disease (GvHD) is a common complication following haematopoietic stem cell transplant but little is published about the impact of this condition on hospital readmission rates. We report a retrospective analysis of readmission rates and associated costs in 187 consecutive allogeneic transplant patients to assess the impact of GvHD. The overall readmission rate was higher in patients with GvHD (86% (101/118) vs. 59% (41/69), p < 0.001). The readmission rate was higher both in the first 100 d from transplant (p = 0.02) and in the first year following transplant (p < 0.001). 151/455 (33%) of all readmission episodes occurred within 100 d of transplant. The mean number of inpatient days was significantly higher in patients with grade III/IV acute GvHD (101 d) compared with those with grade I/II GvHD (70 d; p = 0.003). The mean cost of readmission was higher in patients with GvHD (£28 860) than in non-GvHD patients (£13 405; p = 0.002) and in patients with grade III/IV GvHD (£40 012) compared with those patients with grade I/II GvHD (£24 560; p = 0.038). Survival was higher in those with grade I/II GvHD (55%) compared to grade III/IV GvHD (14%; p < 0.001). This study shows the high economic burden and poor overall survival associated with grade III/IV GvHD., (© 2012 John Wiley & Sons A/S.)

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology and the British Society for Bone Marrow Transplantation has reviewed the available literature and made recommendations for the supportive care and management of organ-specific complications of chronic graft-versus-host disease (cGvHD). This guideline includes recommendations for the specific therapy of skin, oral, liver, gut, lung, ocular and genital manifestations of cGvHD and for the supportive care of these patients, including vaccinations and prophylaxis against infection. The goal of treatment should be effective control of GvHD while minimizing the risk of toxicity and relapse., (© 2012 Blackwell Publishing Ltd.)

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of acute graft-versus-host disease. This guideline includes recommendations for the diagnosis and grading of acute graft-versus-host disease as well as primary treatment and options for patients with steroid-refractory disease. The goal of treatment should be effective control of graft-versus-host disease while minimizing risk of toxicity and relapse., (© 2012 Blackwell Publishing Ltd.)

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of chronic graft-versus-host disease (GvHD). This guideline includes recommendations for the diagnosis and staging of chronic GvHD as well as primary treatment and options for patients with steroid-refractory disease. The goal of treatment should be the effective control of GvHD while minimizing the risk of toxicity and relapse., (© 2012 Blackwell Publishing Ltd.)

Extracorporeal photopheresis (ECP) has become a recognised treatment for steroid-refractory chronic GVHD (cGVHD), but the optimal frequency and duration of treatment are yet to be established. We report on 82 consecutive patients with mucocutaneous cGVHD who received a bimonthly regimen of ECP treatment for two consecutive days, which could be subsequently tapered to a monthly regimen depending on response. Patients were steroid-refractory, steroid-dependent or steroid-intolerant, and 29 (35%) had multiorgan involvement. The median duration of treatment was 330 days (42-987). The median number of ECP cycles was 15 (1.5-32). Response was assessed by clinical assessment and reduction in immunosuppression after 6 months. 69/82 (84%) had completed 6 months of ECP and 65/69 (94%) had ≥ 50% improvement in symptoms and signs of cGVHD. A total of 77% of patients who completed 6 months of ECP had a reduction in immunosuppression dose and 80% had decreased their steroid dose (27.5% stopped, 30% had ≥ 75% reduction, 17.5% had ≥ 50% reduction and 25% had <50% reduction). OS at 3 years from the start of ECP was 69%. This study reports the largest series of patients receiving bimonthly ECP treatment for cGVHD, and confirms that ECP allows successful reduction of immunosuppression.

The clinical course of 2009 H1N1 influenza in Allo-SCT patients is unknown. Data were collected in the UK from October 2009 to April 2010 on laboratory-confirmed cases of H1N1 influenza in Allo-SCT recipients. H1N1 infection was diagnosed in 60 patients, median age 42 years, at a median of 10 months post-SCT. Twenty-one patients (35%) developed pneumonia and nine (15%) required admission to intensive care units. Actuarial mortality was 7% at 28 days and 19% 4 months post-diagnosis of 2009 H1N1 influenza. Increasing age and pre-existing lung disease were risk factors for pneumonia (P=0.006 and 0.037, respectively); older age was a risk factor for death (P=0.012). Morbidity and mortality from 2009 H1N1 influenza in SCT patients exceeds that of immunocompetent patients, but parallels that in other critically ill hospitalised cohorts; the elderly and those with chronic pulmonary disease are at greatest risk.