A Self-Help Manual for Psychological Distress and Quality of Life During a Haemopoietic Stem-Cell Transplant: An Effectiveness and Acceptability Pilot.

Haemopoietic stem-cell transplantation (HSCT) can be a highly distressing procedure that negatively impacts quality of life (QoL). Self-help interventions can help improve psychopathology and wellbeing in patients with physical illness, but have rarely been trialled with HSCT recipients. This study aimed to pilot the utility of a self-help manual intervention during the acute phase of HSCT. Forty autologous and allogeneic HSCT candidates were randomly assigned to a self-help manual intervention or treatment as usual (TAU). Psychological distress (BSI-18) and QoL (FACT-BMT-Vs4) were measured pre-, 2-3 weeks and 3 months post-HSCT. Linear mixed-effects analyses showed no significant group-time interaction for global QoL (p = .199) or global distress (p = .624). However, highlighting a protective role during admission, manual participants showed minimal QoL or somatic distress change at 2-3 weeks post-transplant compared with moderate-large effects for reduced QoL (d = 0.62) and increased somatic distress (d = - 0.81) for TAU patients. Thematic analysis suggests the manual helped prepare patients for transplant and provided strategies to improve distress and QoL. This pilot provides preliminary evidence for the benefit of a self-help manual during hospitalisation for a HSCT. More intensive, recovery-focussed care, however, may be needed to improve psychological health in the post-hospital period. Retrospectively registered trial (ANZCTR No. 12620001165976, 6th November 2020).

Preventing the adverse cardiovascular consequences of allogeneic stem cell transplantation with a multi-faceted exercise intervention: the ALLO-Active trial protocol.

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) is a potentially lifesaving treatment for high-risk hematological malignancy, but survivors experience markedly elevated rates of cardiovascular disease and associated functional impairment. Mounting evidence suggests regular exercise, combined with a reduction in sedentary time through replacement with light exercise may be a useful therapeutic strategy for the prevention of cardiovascular comorbidities. However, this type of intervention has yet to be evaluated in patients undergoing allo-SCT. The ALLO-Active study will evaluate the efficacy of a ~ 4 month multi-faceted exercise intervention, commenced upon admission for allo-SCT, to preserve peak oxygen uptake (VO2peak) and peak cardiac output, compared with usual care. The study will also evaluate the effect of the intervention on functional independence, quality of life, and symptoms of fatigue. METHODS: Sixty adults with hematological malignancy scheduled for allo-SCT will be randomly assigned to usual care (n = 30) or the exercise and sedentary behaviour intervention (n = 30). Participants assigned to the intervention will complete a thrice weekly aerobic and progressive resistance training program and concomitantly aim to reduce daily sedentary time by 30 min with short, frequent, light-intensity exercise bouts. Participants will undergo testing prior to, immediately after inpatient discharge, and 12 weeks after discharge. To address aim 1, VO2peak and peak cardiac output (multiple primary outcomes, p < 0.025) will be assessed via cardiopulmonary exercise testing and exercise cardiac magnetic resonance imaging, respectively. Secondary outcomes include functional independence (defined as VO2peak ≥ 18.mL.kg-1.min-1), quality of life, and fatigue (assessed via validated questionnaire). Exploratory outcomes will include indices of resting cardiac, vascular, and skeletal muscle structure and function, cardiovascular biomarkers, anxiety and depression, transplant outcomes (e.g., engraftment, graft-versus-host disease), and habitual physical activity, sedentary time, and sleep. DISCUSSION: Multi-faceted exercise programs are a promising approach for ameliorating the cardiovascular consequences of allo-SCT. If this intervention proves to be effective, it will contribute to the development of evidence-based exercise guidelines for patients undergoing allo-SCT and assist with optimising the balance between acute cancer management and long-term health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ID: 12619000741189 . Registered 17 May 2019.

Altered Immune Reconstitution in Allogeneic Stem Cell Transplant Recipients With Human Immunodeficiency Virus (HIV).

BACKGROUND: Persons living with human immunodeficiency virus (HIV) are at elevated risk of developing the malignant diseases that require allogeneic stem cell transplantation (ASCT). Recent data suggest that these individuals are also at an elevated risk of certain complications post-ASCT. This risk may result from preexisting HIV-related factors affecting dynamics of immune reconstitution post-ASCT. However, to date, there has been little work describing the dynamics of immune reconstitution post-ASCT in persons with HIV and none comparing these data to controls without HIV. METHODS: We assessed T-cell reconstitution in 6 ASCT with HIV recipients (HIV+ASCT) compared to a control population of 21 ASCT without HIV recipients. In a subset of HIV+ASCT recipients we performed additional flow cytometry profiling of CD8+ T-cell subsets and antigen specificity of reconstituting CD4+ and CD8+ T cells. RESULTS: We observe no difference in post-ASCT CD4+ T cells between HIV+ASCT and HIV-negative ASCT recipients, despite much lower pre-ASCT CD4+ T-cell counts in the HIV+ASCT group. In contrast, we observed significantly higher CD8+ T-cell numbers in the HIV+ASCT group post-ASCT. The reconstituting CD8+ T-cells were predominantly CD45RO+, whereas homing markers and antigen specificity of these cells varied between participants. CONCLUSION: This study represents the most extensive characterization of immune-reconstitution post-ASCT in persons with HIV, and the first to our knowledge to compare these data to ASCT controls without HIV. The results indicate that immune reconstitution in this group can be affected by preexisting HIV infection and post-ASCT antigen exposure.

Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of response to therapy and patient outcomes.

PURPOSE: Defibrotide is an agent used to treat sinusoidal obstruction syndrome (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim of this study was to evaluate the effectiveness of defibrotide used within institutional guidelines for the treatment of SOS/VOD in patients undergoing haemopoietic stem cell transplantation (HSCT). METHODS: Data for 23 patients was retrospectively reviewed to evaluate the effectiveness of defibrotide and the utility of response criteria to direct therapy as specified within institution guidelines. Patients met institutional criteria for a diagnosis of SOS/VOD based on predominantly Baltimore criteria and received defibrotide. Stabilisation or improvement in symptoms and biochemical markers was required for continuation of therapy with defibrotide. RESULTS: Overall, 14 patients responded to therapy. Survival at day 100 post HSCT was 70%. Median serum (total) bilirubin concentrations in all evaluable patients had decreased at days 5 and 10 (p < 0.001). There was a proportional reduction in median weight of 4% by day 5 and 6.6% by day 10 (p < 0.001). On cessation of defibrotide, there was a decrease in the proportion of patients exhibiting hepatomegaly (p = 0.02), ascites (p < 0.01) and requiring oxygen supplementation (p < 0.01), with 70% survival at day 100 post HSCT. CONCLUSION: Defibrotide to treat SOS/VOD and continued based on attainment of early response was effective management of this condition. Defibrotide should be considered in any consensus protocol providing guidance on the management of SOS/VOD, with future studies considered to assess appropriate time points for response to therapy during treatment.

Dapsone and azole interactions: A clinical perspective.

An understanding of the clinical significance of dapsone-drug interactions is essential for optimal use of this agent. This review aims to provide clinicians with an overview of this topic.

Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML.

Phosphoinositide signaling regulates diverse cellular functions. Phosphoinositide-3 kinase (PI3K) generates PtdIns(3,4,5)P3 and PtdIns(3,4)P2, leading to the activation of proliferative and anti-apoptotic signaling pathways. Termination of phosphoinositide signaling requires hydrolysis of inositol ring phosphate groups through the actions of PtdIns(3,4,5)P3 3-phosphatase (PTEN), PtdIns(3,4,5)P3 5-phosphatases (eg, SHIP), and PtdIns(3,4)P2 4-phosphatases (eg, INPP4B). The biological relevance of most of these phosphoinositide phosphatases in acute myeloid leukemia (AML) remains poorly understood. Mass spectrometry-based gene expression profiling of 3-, 4- and 5-phosphatases in human AML revealed significant overexpression of INPP4B. Analysis of an expanded panel of 205 AML cases at diagnosis revealed INPP4B overexpression in association with reduced responses to chemotherapy, early relapse, and poor overall survival, independent of other risk factors. Ectopic overexpression of INPP4B conferred leukemic resistance to cytosine arabinoside (ara-C), daunorubicin, and etoposide. Expression of a phosphatase inert variant (INPP4B C842A) failed to abrogate resistance of AML cells to chemotherapy in vitro or in vivo. In contrast, targeted suppression of endogenously overexpressed INPP4B by RNA interference sensitized AML cell lines and primary AML to chemotherapy. These findings demonstrate a previously unsuspected and clinically relevant role for INPP4B gain of function as a mediator of chemoresistance and poor survival outcome in AML independent of its phosphoinositide phosphatase function.

Cost-effectiveness of a lifestyle modification program in long-term survivors of hemopoietic stem cell transplantation.

To evaluate the cost-effectiveness of a lifestyle modification program targeting long-term survivors of hematological malignancy treated with hemopoietic stem cell transplantation, a multistate life table Markov model was used to calculate health outcomes for both the intervention and no intervention. Cost per health-adjusted life year (HALY) saved was reported for four scenarios: all participants with/without standard weight regain, and participants who at baseline were overweight with/without standard weight regain. The program recruited 53 participants and was associated with reductions in body weight of 2.2 kg and BMI 0.8 units on intervention completion (12 months) at a cost of $1233/participant. These adipose reductions were sustained and remained significant at 24 months. The incremental cost-effectiveness ratios varied from $118 418 per HALY to dominant, depending on the weight regain assumption. The program may be cost-effective in transplant survivors, with the results most sensitive to the weight regain assumption and intervention cost.

Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia.

In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0-25 mg, days 5-25) in combination with azacitidine (50-75 mg/m(2) , days 1-5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age ≥60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50% at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17-39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration.

Comparison of biosimilar filgrastim with originator filgrastim for peripheral blood stem cell mobilization and engraftment in patients with multiple myeloma undergoing autologous stem cell transplantation.

BACKGROUND: Nivestim is a biosimilar approved for the same indications as Neupogen including the mobilization of autologous peripheral blood stem cells (PBSCs). The clinical efficacy and safety of Nivestim for this use have not been formally assessed in clinical trials. STUDY DESIGN AND METHODS: In our retrospective single-center study we compared variables of PBSC mobilization and engraftment of 60 patients mobilized with Nivestim to that of 38 patients mobilized with Neupogen. RESULTS: We found no difference between Nivestim and Neupogen in peripheral blood CD34+ at first leukapheresis (47 × 10(6) cells/L vs. 60 × 10(6) cells/L, p = 0.48) nor the total CD34+ collected (5.37 × 10(6)/kg vs. 4.59 × 10(6) /kg, p = 0.22). However, a difference in the median number of leukapheresis procedures (one vs. two, p = 0.0007) was observed. Eighty-one patients (51 Nivestim and 30 Neupogen mobilized) went on to transplantation. Median time to neutrophil engraftment (15 days vs. 13.5 days, p = 0.09) and platelet (PLT) engraftment (20 days vs. 18 days, p = 0.01) was longer in the Nivestim group. The significant delay in PLT engraftment did not, however, translate to increased PLT transfusions (two vs. three, p = 0.2) or impact significantly on hospitalization time for admissions within 30 days posttransplant (20 days vs. 18 days, p = .17). CONCLUSION: Nivestim is as effective as Neupogen for PBSC mobilization; however, its use was associated with a delay in PLT recovery. A prospective study should be conducted to confirm our findings.

A prospective study of the relationship between sense of coherence, depression, anxiety, and quality of life of haematopoietic stem cell transplant patients over time.

OBJECTIVES: The primary aim of this study was to examine the impact of patient sense of coherence (SOC) on anxiety and depressive symptoms, and quality of life (QoL) dimensions in the acute phase of haematopoietic stem cell transplantation (HSCT). A secondary aim was to determine if SOC measured pre-transplant was predictive of psychological distress and QoL post-transplantation, after controlling for physical wellbeing. METHOD: A series of measures was completed by 60 HSCT patients prior to transplantation. Follow-up data were collected at 2-3 weeks and 3 months post-transplantation. Measures administered included the Brief Symptom Inventory-18, Orientation to Life Questionnaire, and Functional Assessment of Cancer Therapy-Bone Marrow Transplantation. RESULTS: When compared across the three time points, depression levels, and physical and functional wellbeing were worst at 2-3 weeks post-transplantation. SOC was positively associated with physical wellbeing prior to HSCT but not after transplantation. Weaker SOC predicted higher levels of depression, and poorer social, emotional, and functional wellbeing at both follow-up points, after accounting for physical wellbeing. CONCLUSIONS: Given that SOC was related to depression and QoL dimensions post-transplantation, it may be important for health care professionals to conduct psychosocial assessments to determine patient SOC. This would enable provision of tailored psychological support prior to and following stem cell transplantation.

Psychosocial factors associated with quality of life in allogeneic stem cell transplant patients prior to transplant.

OBJECTIVES: The primary aim of this retrospective study was to determine levels of psychological distress and quality of life (QoL) immediately prior to allogeneic stem cell transplantation. The secondary aim was to examine the demographic, medical and psychosocial factors that were correlated with various QoL domains at this stage of treatment. METHODS: A series of measures was completed by 122 allograft patients as part of routine psychological assessment at the treating hospital prior to undergoing the transplant. These included the Mental Adjustment to Cancer Scale, the Brief Symptom Inventory-18 and the World Health Organisation Quality of Life-BREF. Demographic and medical data were also extracted. RESULTS: In this study, 12% and 14% of the sample experienced significant levels of depressive and anxiety symptoms, respectively. Half of the sample reported impaired physical QoL, whereas approximately 40% reported poor psychological and social QoL. Besides relationship status, the limited number of demographic (age and gender) and medical factors (disease status) tested did not contribute significantly to reported QoL. After controlling for medical and demographic factors, weaker Fighting Spirit and higher levels of depression (trend towards significance) were associated with poorer physical and social QoL. CONCLUSIONS: The association among psychological distress, coping responses and QoL indicates that poor psychosocial functioning pre-transplant renders an increased likelihood of experiencing impaired QoL across various dimensions. It thus seems important that psychologically vulnerable patients are identified early in the treatment process. If psychosocial adjustment were improved, patients may experience better QoL pre-transplant with a potential subsequent influence on post-transplant outcomes.

Psychosocial factors predicting survival after allogeneic stem cell transplant.

PURPOSE: A primary aim was to assess the relative contribution of psychological factors, such as anxiety, depression and mental adjustment to cancer, to overall survival outcomes at a median follow-up of 2 years following allogeneic haematopoietic stem cell transplant (HSCT). A secondary aim was to ascertain if demographic, medical and psychosocial factors assessed prior to transplantation were predictors of survival for patients after accounting for post-transplant events. METHOD: Between 2005 and 2011, 130 allograft patients completed the Mental Adjustment to Cancer Scale and Brief Symptom Inventory-18 as part of routine psychological assessment before undergoing transplantation. Survival status data were obtained, and predictors of survival status assessed and analysed using Cox-regression models. RESULTS: Thirteen percent experienced clinical levels of distress pre-transplant. None of the psychological factors predicted post-HSCT survival. In contrast, hierarchical multivariate analysis indicated that post-transplant factors (acute graft-versus-host disease and relapse post-transplant) predicted survival (Chi-square change, p < 0.001). The addition of a series of pre-transplant psychosocial and medical variables further improved the prediction of survival (Chi-square change, p = 0.01). In particular, relationship status (being single) (p = 0.04) and increased somatic symptoms (p = 0.02) pre-transplant were associated with shorter survival. Both variables were not associated with medical factors but were related to increased severity of anxiety and depressive symptoms as well as greater use of helpless-hopelessness and reduced fighting spirit adjustment response. CONCLUSIONS: Despite the significant influence of acute post-transplant factors in predicting survival following allogeneic HSCT, multidisciplinary pre-transplant assessments are important in identifying patients who are likely to experience poorer survival outcomes.

Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts.

The influence of cell dose and human leukocyte antigen (HLA) match on double-unit cord blood (CB) engraftment is not established. Therefore, we analyzed the impact of cell dose and high-resolution HLA match on neutrophil engraftment in 84 double-unit CB transplant recipients. The 94% sustained engraftment rate was accounted for by 1 unit in nearly all patients. Higher CD3(+) cell doses (P = .04) and percentage of CD34(+) cell viability (P = .008) were associated with unit dominance. After myeloablative conditioning, higher dominant unit total nucleated cell (TNC), CD34(+) cell, and colony-forming unit doses were associated with higher sustained engraftment and faster neutrophil recovery (P = .07, P = .0008, and P < .0001, respectively). Total infused TNC (P = .0007) and CD3(+) cell doses (P = .001) also significantly influenced engraftment. At high-resolution extensive donor-recipient HLA disparity was frequent, but had no influence on engraftment (P = .66), or unit dominance (P = .13). Although the unit-unit HLA match also did not affect sustained engraftment (P = 1.0), recipients of units closely (7-10 to 10-10) HLA-matched to each other were more likely to demonstrate initial engraftment of both units (P < .0001). Our findings have important implications for unit selection and provide further insight into double-unit biology.

Vascular Aging Is Accelerated in Hematological Cancer Survivors Who Undergo Allogeneic Stem Cell Transplant.

BACKGROUND: Survivors of allogeneic stem cell transplant (SCT) receive intensive cancer treatments that are associated with cardiovascular dysfunction. Markers of vascular age can indicate early signs of adverse (cardio)vascular changes; however, the impact of SCT on these makers is unknown. We aimed to determine the short (3 months) and longer-term (≥2 years) effect of SCT on markers of vascular age in hematologic cancer survivors compared with an age-matched noncancer control group. METHODS: The short-term effects of SCT, markers of vascular age (aortic compliance, arterial elastance, and ventricular-vascular coupling) were assessed via cardiac magnetic resonance imaging (cardiac and aortic volumes) before and ≈3 months post-SCT in 13 short-term survivors and compared with 11 controls. The longer-term impact was assessed by comparing 14 long-term survivors (6.5 [2-20] years post-SCT) to the short-term survivors (post-SCT) and controls (n=16). RESULTS: The groups were similar for age and body mass index. In the short-term survivors, no significant group-by-time interactions were observed for any markers of vascular aging from pretransplant to posttransplant (net difference for change in compliance between groups -0.07 [95% CI, -1.49 to 1.35]). For the time-course analysis, aortic compliance was significantly lower in both SCT groups (overall P=0.007) compared with controls, whereas ventricular-vascular coupling was higher in both survivor groups as was arterial elastance in long-term SCT survivors (ie, worse; P<0.01 for all). CONCLUSION: This study provides evidence of an accelerated vascular aging phenotype in allogeneic SCT survivors and provides insight into the increased burden of cardiovascular disease among hematologic cancer survivors.

Reduced cardiovascular reserve capacity in long-term allogeneic stem cell transplant survivors.

Premature cardiovascular mortality is increased in long-term allogeneic stem cell transplant (allo-SCT) survivors, but little information exists regarding subclinical cardiovascular dysfunction in this population. We compared peak oxygen uptake ([Formula: see text]O2peak), a prognostic cardiovascular marker, and its determinants between long-term allo-SCT survivors and non-cancer controls. Fourteen allo-SCT survivors (mean ± SD, 44 ± 15 years, 50% male, median time since allo-SCT: 6.5 years [range 2-20]) and 14 age- and sex-matched controls (46 ± 13 years, 50% male) underwent cardiopulmonary exercise testing to quantify [Formula: see text]O2peak. Resting echocardiography (left-ventricular ejection fraction and strain), exercise cardiac MRI (peak cardiac and stroke volume index [CIpeak, SVIpeak]), biochemistry (hemoglobin, troponin-I, B-natriuretic peptide), dual-energy x-ray absorptiometry (lean [LM] and fat [FM] mass, percent body fat [%BF]) and Fick-principal calculation (arteriovenous oxygen difference) were also performed. Survivors exhibited impaired [Formula: see text]O2peak as compared with controls (25.9 ± 5.1 vs. 33.7 ± 6.5 ml kg-1 min-1, p = 0.002), which coincided with reduced CIpeak (6.6 ± 0.8 vs. 8.6 ± 1.9 L min-1 m-2; p = 0.001) secondary to reduced SVIpeak (48 ± 4 vs. 61 ± 8 ml m-2; p < 0.001) rather than chronotropic impairment, and higher %BF (difference, 7.9%, p = 0.007) due to greater FM (5.8 kg; p = 0.069) and lower LM (4.3 kg, p = 0.25). All other measures were similar between groups. Despite comparable resting cardiac function and biomarker profiles, survivors exhibited reduced [Formula: see text]O2peak and exercise cardiac function and increased %BF relative to controls. These results highlight potential therapeutic avenues and the utility of exercise-based cardiovascular assessment in unmasking cardiovascular dysfunction in allo-SCT survivors.

Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity.

Objectives: Influenza causes significant morbidity and mortality, especially in high-risk populations. Although current vaccination regimens are the best method to combat annual influenza disease, vaccine efficacy can be low in high-risk groups, such as haematopoietic stem cell transplant (HSCT) recipients. Methods: We comprehensively assessed humoral immunity, antibody landscapes, systems serology and influenza-specific B-cell responses, together with their phenotypes and isotypes, to the inactivated influenza vaccine (IIV) in HSCT recipients in comparison to healthy controls. Results: Inactivated influenza vaccine significantly increased haemagglutination inhibition (HAI) titres in HSCT recipients, similar to healthy controls. Systems serology revealed increased IgG1 and IgG3 antibody levels towards the haemagglutinin (HA) head, but not to neuraminidase, nucleoprotein or HA stem. IIV also increased frequencies of total, IgG class-switched and CD21loCD27+ influenza-specific B cells, determined by HA probes and flow cytometry. Strikingly, 40% of HSCT recipients had markedly higher antibody responses towards A/H3N2 vaccine strain than healthy controls and showed cross-reactivity to antigenically drifted A/H3N2 strains by antibody landscape analysis. These superior humoral responses were associated with a greater time interval after HSCT, while multivariant analyses revealed the importance of pre-existing immune memory. Conversely, in HSCT recipients who did not respond to the first dose, the second IIV dose did not greatly improve their humoral response, although 50% of second-dose patients reached a seroprotective HAI titre for at least one of vaccine strains. Conclusions: Our study demonstrates efficient, although time-dependent, immune responses to IIV in HSCT recipients, and provides insights into influenza vaccination strategies targeted to immunocompromised high-risk groups.

A meta-analysis of palifermin efficacy for the management of oral mucositis in patients with solid tumours and haematological malignancy.

BACKGROUND: Palifermin, a recombinant keratinocyte growth factor promotes thickening of the mucosa, minimising severity of mucositis caused by chemotherapy and radiotherapy. OBJECTIVE: To synthesise published literature on palifermin for the management of oral mucositis, in patients receiving chemotherapy and/or radiotherapy, aiming to ascertain recommendations for practice. METHODS: Databases searched were Medline, Embase, IPA and CIANHL. A meta-analysis included randomised controlled trials (RCT) for palifermin compared to placebo or no palifermin, with the key data extracted being number of events of severe mucositis (defined by WHO criteria grade 3 or 4). RESULTS: The meta-analysis included 10 RCT. Patients were treated for solid and haematological malignancy. Analysis suggested benefit of palifermin decreasing the incidence of severe mucositis in solid tumours RR0.76 [95%CI 0.63-0.92;p = 0.004], haematological malignancy RR0.63 [95 %CI 0.48-0.82;p = 0.0007] and overall RR0.69 [95 %CI 0.59-0.81;p < 0.0001]. CONCLUSION: Palifermin reduces the incidence of severe mucositis up to 30 % in patients receiving treatment with chemotherapy and/or radiotherapy.

Noninvasive Assessment of Acute Graft-Versus-Host Disease of the Gastrointestinal Tract After Allogeneic Hemopoietic Stem Cell Transplantation Using 18F-FDG PET.

Acute graft-versus-host disease of the gastrointestinal tract (acute GIT-GVHD) often complicates allogeneic hemopoietic stem cell transplantation (AHSCT). 18F-FDG PET/CT is known to detect active inflammation and may be a useful noninvasive test for acute GIT-GVHD. The objective of this study was to evaluate the diagnostic utility of 18F-FDG PET/CT to noninvasively assess patients with clinically suspected acute GIT-GVHD. Fifty-one AHSCT patients with clinically suspected acute GIT-GVHD prospectively underwent 18F-FDG PET/CT scanning followed by upper and lower GIT endoscopy within 7 d. Endoscopic biopsies of 4 upper GIT and 4 colonic segments were obtained for histology to compare with corresponding quantitative segmental 18F-FDG PET/CT SUVmax Receiver-operating-characteristic curve (ROC) analysis was performed to determine predictive capacity of 18F-FDG PET/CT SUVmax for acute GIT-GVHD. A separate qualitative visual 18F-FDG PET/CT analysis was also performed for comparison. Results: Twenty-three of 51 (45.1%) patients had biopsy-confirmed acute GIT-GVHD, with 19 of 23 (82.6%) having upper GIT and 22 of 22 (100%) colonic involvement. One of 23 patients did not undergo a colonoscopy. GVHD involved the entire colon contiguously in 21 of 22 patients. For quantitative analysis, histology from 4 upper GIT and 4 colonic segments were compared with 18F-FDG PET/CT SUVmax Colonic segments positive for GVHD had a higher SUVmax (4.1 [95% CI, 3.6-4.5]) than did normal colonic segments (2.3 [1.9-2.7], P = 0.006). No difference was demonstrated in upper GIT segments. Quantitative 18F-FDG PET/CT yielded a 69% sensitivity, 57% specificity, 73% negative predictive value, and 59% positive predictive value for the detection of GVHD compared with 70%, 76%, 76%, and 68%, respectively, for qualitative analysis. Conclusion: 18F-FDG PET is a useful noninvasive diagnostic test for acute GIT-GVHD, which when present always involves the colon and usually in its entirety, suggesting colonic biopsy obtained by sigmoidoscopy is adequate for histologic confirmation when acute GIT-GVHD is suspected. Of note, 18F-FDG PET cannot distinguish acute GIT-GVHD from non-GVHD inflammatory changes in the colon.

Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy.

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure for high-risk hematological malignancy; however, long-term survivors experience increased cardiovascular morbidity and mortality. It is unclear how allo-HCT impacts cardiovascular function in the short-term. Thus, this 3-month prospective study sought to evaluate the short-term cardiovascular impact of allo-HCT in hematological cancer patients, compared to an age-matched non-cancer control group. Methods: Before and ~3-months following allo-HCT, 17 hematological cancer patients (45 ± 18 years) underwent cardiopulmonary exercise testing to quantify peak oxygen uptake (VO2peak)-a measure of integrative cardiovascular function. Then, to determine the degree to which changes in VO2peak are mediated by cardiac vs. non-cardiac factors, participants underwent exercise cardiac MRI (cardiac reserve), resting echocardiography (left-ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), dual-energy x-ray absorptiometry (lean [LM] and fat mass [FM]), blood pressure (BP) assessment, hemoglobin sampling, and arteriovenous oxygen difference (a-vO2diff) estimation via the Fick equation. Twelve controls (43 ± 13 years) underwent identical testing at equivalent baseline and 3-month time intervals. Results: Significant group-by-time interactions were observed for absolute VO2peak (p = 0.006), bodyweight-indexed VO2peak (p = 0.015), LM (p = 0.001) and cardiac reserve (p = 0.019), which were driven by 26, 24, 6, and 26% reductions in the allo-HCT group (all p ≤ 0.001), respectively, as no significant changes were observed in the age-matched control group. No significant group-by-time interactions were observed for LVEF, GLS, FM, hemoglobin, BP or a-vO2diff, though a-vO2diff declined 12% in allo-HCT (p = 0.028). Conclusion: In summary, allo-HCT severely impairs VO2peak, reflecting central and peripheral dysfunction. These results indicate allo-HCT rapidly accelerates cardiovascular aging and reinforces the need for early preventive cardiovascular intervention in this high-risk group.