Music intervention in patients undergoing hematopoietic stem cell transplantation: A systematic review and meta-analysis.

AIMS: To explore whether music intervention improves the quality of life (QOL) of patients undergoing hematopoietic stem cell transplantation (HSCT) and to evaluate its impact on patients' symptoms of depression/anxiety and fatigue. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Cochrane CENTRAL, and EMBASE were searched from inception to September 30, 2022. The search strategy used a combination of the keywords "music" and "hematopoietic stem cell transplantation" or "HSCT." The outcomes assessed were QOL, depression and anxiety, and fatigue. Pooled standardized mean differences with 95% confidence intervals were calculated to compare the outcomes between the music intervention and control groups. Heterogeneity across the studies was assessed using a chi-square-based test, and the I2 and Q statistics. RESULTS: Meta-analysis of the included study population showed that music intervention for patients undergoing HSCT was associated with patients' improved QOL, and resulted in reduced depression/anxiety and fatigue compared to patients without music intervention. CONCLUSION: Music intervention benefits HSCT outcomes, including better QOL, less depression/anxiety, and less fatigue postoperatively. Future trials with larger samples are still warranted to strengthen the evidence supporting the benefits of music intervention in this patient population.

Window therapeutic of extraoral photobiomodulation for prevention of oral mucositis in HSCT patients: additional arm.

PURPOSE: This study aimed to evaluate the efficacy of 1W extraoral photobiomodulation (EOPBM) and to compare with our previous results of 2W EOPBM and intraoral photobiomodulation (IOPBM) protocols in the management of oral mucositis (OM) related to hematopoietic stem cell transplantation (HSCT). METHODS: A total of 30 patients underwent autologous or allogenic HSCT. Experimental protocol of 1W EOPBM was performed daily beginning in the first day of the conditioning regimen until 5 days after transplantation. The application areas included six points on the face and three points on the cervical area. Additional application of IOPBM was performed if patients had ulcered mucositis. Its severity was assessed daily according to WHO (World Health Organization) and NCI (National Cancer Institute) scales. Oral and oropharynx pains were scored daily by visual analogue scale (VAS). RESULTS: The 1W EOPBM protocol was well tolerated without any complaints. Of total, 13 patients were male and 17 were female and the mean age was 49.3 years old. Most patients (21 patients - 70%) received autologous HSCT, and 24 patients (80%) underwent myeloablative conditioning (MAC) regime and 6 patients (20%) reduced intensive conditioning regime. Nineteen patients (63.3%) developed OM according to WHO criteria, 3 patients grade I, 10 grade II and 6 grade III. NCI mucositis grades were similar to WHO grades. OM outcomes of 1W EOPBM were similar when compared to our previous groups and no significant differences were observed. No differences were found between pain and the protocols (1W EOPBM, IOPBM and 2W EOPBM). CONCLUSION: This 1W EOPBM protocol seemed to be as effective as IOPBM and 2W EOPBM in the prevention of OM in HSCT patients. In addition, we might assume that there is a window of application on EOPBM.

Novel Approaches to Treatment of Acute Myeloid Leukemia Relapse Post Allogeneic Stem Cell Transplantation.

The management of patients with acute myeloid leukemia (AML) relapsed post allogeneic hematopoietic stem cell transplantation (HSCT) remains a clinical challenge. Intensive treatment approaches are limited by severe toxicities in the early post-transplantation period. Therefore, hypomethylating agents (HMAs) have become the standard therapeutic approach due to favorable tolerability. Moreover, HMAs serve as a backbone for additional anti-leukemic agents. Despite discordant results, the addition of donor lymphocytes infusions (DLI) generally granted improved outcomes with manageable GvHD incidence. The recent introduction of novel targeted drugs in AML gives the opportunity to add a third element to salvage regimens. Those patients harboring targetable mutations might benefit from IDH1/2 inhibitors Ivosidenib and Enasidenib as well as FLT3 inhibitors Sorafenib and Gilteritinib in combination with HMA and DLI. Conversely, patients lacking targetable mutations actually benefit from the addition of Venetoclax. A second HSCT remains a valid option, especially for fit patients and for those who achieve a complete disease response with salvage regimens. Overall, across studies, higher response rates and longer survival were observed in cases of pre-emptive intervention for molecular relapse. Future perspectives currently rely on the development of adoptive immunotherapeutic strategies mainly represented by CAR-T cells.

Serum Electrolyte and Metabolic Changes During Conditioning of Autologous Hematopoietic Stem Cell Transplantation in Patients with Autoimmune Diseases: A Prospective Study in a Single Institution.

BACKGROUND AND OBJECTIVES: A hematopoietic stem cell transplant (HSCT) includes a conditioning regimen which may cause unwanted metabolic changes. We analyzed the changes in electrolytes, glucose, urea, and glomerular filtration rate in patients with multiple sclerosis (MS) who underwent an autologous HSCT employing the "Mexican method." PATIENTS AND METHODS: Serum and urinary electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were prospectively assessed on days -11, -9, and 0 in a group of 75 patients with MS receiving an autologous HSCT employing the "Mexican method," which includes high doses of both cyclophosphamide (Cy, 200 mg/kg) and rituximab (1000 mg). RESULTS: The median age of the patients was 46 years, with a range of 20-65. Baseline data were defined at day -11 of the HSCT. There were significant changes in serum and urinary electrolytes, which diminished substantially after the delivery of high-dose Cy; 12 patients (16%) developed hyponatremia and 2 had hyponatremia-induced seizures, which resulted in hospital admissions. A comparison of baseline blood metabolites with those obtained after the full Cy dosage (day 0) revealed a significant increase in blood glucose and uric acid levels with an associated decrease in serum calcium, sodium, and potassium levels. The salient findings were drug-induced hyponatremia and hyperglycemia. CONCLUSION: Significant changes in serum electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were observed in patients given autologous HSCT for MS employing high-dose Cy. Some of these changes may have clinical consequences, mainly those derived from iatrogenic hyponatremia. No evidence of damage to renal function was observed at day 0.

The Promise of Precision Nutrition for Modulation of the Gut Microbiota as a Novel Therapeutic Approach to Acute Graft-versus-host Disease.

Acute graft-versus-host disease (aGVHD) is a severe side effect of allogeneic hematopoietic stem cell transplantation (aHSCT) that has complex phenotypes and often unpredictable outcomes. The current management is not always able to prevent aGVHD. A neglected actor in the management of aGVHD is the gut microbiota. Gut microbiota dysbiosis after aHSCT is caused by many factors and may contribute to the development of aGVHD. Diet and nutritional status modify the gut microbiota and a wide range of products are now available to manipulate the gut microbiota (pro-, pre-, and postbiotics). New investigations are testing the effect of probiotics and nutritional supplements in both animal models and human studies, with encouraging results. In this review, we summarize the most recent literature about the probiotics and nutritional factors able to modulate the gut microbiota and we discuss the future perspective in developing new integrative therapeutic approaches to reducing the risk of graft-versus-host disease in patients undergoing aHSCT.

Feasibility of a New Model of Care for Allogeneic Stem Cell Transplantation Recipients Facilitated by eHealth: The MY-Medula Pilot Study.

The use of allogeneic stem cell transplantation (allo-SCT) for the treatment of hematologic diseases is steadily increasing; however, allo-SCT has the downside of causing considerable treatment-related morbidity and mortality. Mobile technology applied to healthcare (mHealth) has proven to be a cost-effective strategy to improve care and offer new services to people with multimorbidity, but there are little data on its usefulness in allo-SCT recipients. Here we describe a new integrated healthcare model facilitated by an mHealth platform, EMMASalud-MY-Medula, and to report the results of a feasibility and usability pilot study. The MY-Medula platform was developed in 4 phases. First, patient and healthcare professional needs were identified, and technological development and pretesting tests were conducted (phases 1 to 3, January 2016 to March 2021). Then a nonrandomized, prospective, observational, single-center pilot study was conducted (October 2021 to January 2022) at the adult SCT unit of a tertiary university hospital. Twenty-eight volunteer allo-SCT recipients were included in the pilot study, of whom one-half were outpatients in the first-year post-SCT and one-half were affected by steroid-dependent graft-versus-host disease (SR-GVHD). All patients used the MY-Medula app during the 2-month follow-up period, with a median number of visits to the app of 143 (range, 6 to 477). A total of 2067 self-monitoring records were created, and 205 text messages were received, most of them related to symptoms description (47%) and doubts about medication (21%). In 3.4% of the cases, drug dosage was adjusted by the pharmacist because of dosing errors or interactions. At the end of the study, a 6-question Likert-type questionnaire for patients and a 22-question test for healthcare professionals showed a high degree of satisfaction (95% and 100%, respectively) with the new healthcare pathway. Reengineering the follow-up of allo-SCT recipients into an integrated, multidisciplinary model of care facilitated by mHealth tools is feasible and has been associated with high usability and a high degree of satisfaction by patients and healthcare professionals. A randomized trial aiming to determine the cost-effectiveness of MY-Medula-based follow-up post-SCT is currently enrolling participants.

Pre-transplantation vitamin D deficiency increases acute graft-versus-host disease after hematopoietic stem cell transplantation in thalassemia major patients.

BACKGROUND: Although there are many studies on the role of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT), outcomes have often reported conflicting results because of the heterogeneity of the patients in the studies. METHODS: We investigated the association between VDD prior to HSCT and outcomes after HSCT in a relatively homogenous group of patients with thalassemia major (TM) who received identical treatment for TM before transplantation, and the same conditioning regimen and GVHD prophylaxis during and after transplantation. All patients, including the patients with normal vitamin D3 levels received 400 to 800 IU per day of vitamin D for the first 6 months after HSCT. RESULTS: Pre-HSCT VDD increased the frequency of aGVHD after transplantation, particularly in HSCTs performed with PBSC for the stem cell source. Pre-transplant low vitamin D3 levels had no association with transplant outcomes such as engraftment, viral infections, alloimmunization, chronic GvHD, total days of hospitalization, and success in terms of transfusion independence. CONCLUSIONS: Low vitamin D3 levels before HSCT carry a significant risk for aGVHD. All patients with TM should be screened for VDD before HSCT, and every effort should be made to supplement vitamin D before the transplant in VDD patients.

Treatment and outcomes of high-risk neuroblastoma in Southeast Asia: a single-institution experience and review of the literature.

Introduction: In Europe and North America, the majority of children with high-risk neuroblastoma survive the disease. Elsewhere, the treatment outcomes are poor. Methods: A retrospective review of children treated for high-risk neuroblastoma in a single institution in Singapore from 2007 to 2019 was carried out. Treatment consisted of intensive chemotherapy, surgery aimed at gross total resection of residual disease after chemotherapy, consolidation with high-dose therapy followed by autologous stem cell rescue, and radiotherapy to the primary and metastatic sites followed by maintenance treatment with either cis-retinoic acid or anti-disialoganglioside monoclonal antibody therapy. Survival data were examined on certain clinical and laboratory factors. Results: There were 57 children (32 male) treated for high-risk neuroblastoma. Their mean age was 3.9 (range 0.7-14.9) years. The median follow-up time was 5.5 (range 1.8-13.0) years for the surviving patients. There were 31 survivors, with 27 patients surviving in first remission, and the five-year overall survival and event-free survival rates were 52.5% and 47.4%, respectively. On log-rank testing, only the group of 17 patients who were exclusively treated at our centre had a survival advantage. Their five-year overall survival rate compared to patients whose initial chemotherapy was done elsewhere was 81.6% versus 41.1% (P = 0.011), and that of event-free survival was 69.7% versus 36.1% (P = 0.032). Published treatment results were obtained from four countries in Southeast Asia with five-year overall survival rates from 13.5% to 28.2%. Conclusion: Intensified medical and surgical treatment for high-risk neuroblastoma proved to be effective, with superior survival rates compared to previous data from Southeast Asia.

Treatment and outcomes of high-risk neuroblastoma in Southeast Asia: a single-institution experience and review of the literature

INTRODUCTION@#In Europe and North America, the majority of children with high-risk neuroblastoma survive the disease. Elsewhere, the treatment outcomes are poor.@*METHODS@#A retrospective review of children treated for high-risk neuroblastoma in a single institution in Singapore from 2007 to 2019 was carried out. Treatment consisted of intensive chemotherapy, surgery aimed at gross total resection of residual disease after chemotherapy, consolidation with high-dose therapy followed by autologous stem cell rescue, and radiotherapy to the primary and metastatic sites followed by maintenance treatment with either cis-retinoic acid or anti-disialoganglioside monoclonal antibody therapy. Survival data were examined on certain clinical and laboratory factors.@*RESULTS@#There were 57 children (32 male) treated for high-risk neuroblastoma. Their mean age was 3.9 (range 0.7-14.9) years. The median follow-up time was 5.5 (range 1.8-13.0) years for the surviving patients. There were 31 survivors, with 27 patients surviving in first remission, and the five-year overall survival and event-free survival rates were 52.5% and 47.4%, respectively. On log-rank testing, only the group of 17 patients who were exclusively treated at our centre had a survival advantage. Their five-year overall survival rate compared to patients whose initial chemotherapy was done elsewhere was 81.6% versus 41.1% (P = 0.011), and that of event-free survival was 69.7% versus 36.1% (P = 0.032). Published treatment results were obtained from four countries in Southeast Asia with five-year overall survival rates from 13.5% to 28.2%.@*CONCLUSION@#Intensified medical and surgical treatment for high-risk neuroblastoma proved to be effective, with superior survival rates compared to previous data from Southeast Asia.

BML-260 promotes the growth of cord blood and mobilized peripheral blood hematopoietic stem and progenitor cells with improved reconstitution ability.

Hematopoietic stem cells (HSCs), which are multipotent and have the ability to self-renew, are frequently used in the treatment of hematological diseases and cancer. Small molecules that target HSC quiescence regulators could be used for ex vivo expansion of both mobilized peripheral blood (mPB) and umbilical cord blood (UCB) hematopoietic stem and progenitor cells (HSPC). We identified and investigated 35 small molecules that target HSC quiescence factors. We looked at how they affected HSC activity, such as expansion, quiescence, multilineage capacity, cycling ability, metabolism, cytotoxicity, and genotoxicity. A transplantation study was carried out on immunocompromised mice to assess the expanded cells' repopulation and engraftment abilities. 4-[(5Z)-5-benzylidene-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzoic acid (BML)-260 and tosyl-l-arginine methyl ester (TAME) significantly increased both mPB and UCB-HSPC content and activated HSC re-entry into the cell cycle. The improved multilineage capacity was confirmed by the colony forming unit (CFU) assay. Furthermore, gene expression analysis revealed that BML-260 and TAME molecules aided HSC expansion by modulating cell cycle kinetics, such as p27, SKP2, and CDH1. In addition to these in vitro findings, we discovered that BML-260-expanded HSCs had a high hematopoietic reconstitution capacity with increased immune cell content after xenotransplantation into immunocompromised mice. In addition to the BML-260 molecule, a comparison study of serum-containing and serum-free chemically defined media, including various supplements, was performed. These in vitro and xenotransplantation results show that BML-260 molecules can be used for human HSC expansion and regulation of function. Furthermore, the medium composition discovered may be a novel platform for human HSPC expansion that could be used in clinical trials.

Inspiratory muscle training in addition to conventional physical rehabilitation in hospitalized patients undergoing hematopoietic stem cell transplantation: a randomized controlled trial.

PURPOSE: To investigate the effect of inspiratory muscle training (IMT) in addition to conventional physical rehabilitation on muscle strength, functional capacity, mobility, hemodynamics, fatigue, and quality of life in hospitalized patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: We conducted a randomized controlled trial in 57 inpatients with hematological diseases undergoing HSCT. Conventional inpatient physical rehabilitation was delivered to the IMT (n = 27) and control (CON; n = 30) groups according to usual care, and the first group additionally performed IMT. The IMT was prescribed according to clinical and laboratory parameters at 40% of maximal inspiratory pressure (MIP), 5 days/week throughout the hospitalization, in sessions of 10-20 min. The primary outcome was MIP and the secondary outcomes were maximal expiratory pressure (MEP), peripheral muscle strength (handgrip and sit-to-stand tests), functional capacity (6-min step test), mobility (timed up and go test), blood pressure, quality of life (EORTC-QLQ-C30), and fatigue (FACT-F) at admission and hospital discharge. RESULTS: The population was predominately autologous HSCT. The IMT group significantly increased the MIP (P < 0.01) and decreased both fatigue (P = 0.01) and blood pressure (P < 0.01) compared with control. No differences were found between admission and hospital discharge in peripheral and expiratory muscle strength, functional capacity, mobility, and quality of life in both groups (P > 0.05). CONCLUSIONS: Our results support the effectiveness of IMT as part of rehabilitation for HSCT inpatients, improving inspiratory muscle strength, and reducing fatigue and blood pressure. TRIAL REGISTRATION: NCT03373526 (clinicaltrials.gov).

Perspective: An International Fludarabine Shortage: Supply Chain Issues Impacting Transplantation and Immune Effector Cell Therapy Delivery.

Host immune depletion has been recognized as a necessary step for successful adoptive immune cell transfer in both the autologous and allogeneic settings. The chemotherapy agent fludarabine as an immune suppressive agent has a central role in multiple conditioning regimens for both transplantation and immune effector cell therapies. With the recent and sudden recognition of an imminent worldwide fludarabine shortage, novel approaches to overcome supply chain disruption are needed, including exploration of alternative therapies. The fludarabine shortage has highlighted the need to prioritize the development of institutional algorithms for maintaining ongoing clinical trials and standard of care procedures in the setting of critical drug shortages.

Examination of a nutritional treatment pathway according to pretreatment health status and stress levels of patients undergoing hematopoietic stem cell transplantation.

INTRODUCTION: This study aimed to validate hematopoietic stem cell transplantation (HSCT) treatment via a tailored nutritional pathway in myeloablative conditioning (MAC), determine its efficacy in terms of remission, and explore associations between clinical outcomes and nutritional indicators. METHODS: We included patients who underwent MAC for HSCT at the Shizuoka Cancer Center Stem Cell Transplantation between 2015 and 2019. We evaluated outcomes from the day before treatment initiation (transplant date: day 0) to day 42. RESULTS: Among the 40 MAC cases (participant characteristics: 20/40 males, mean age of 52 years, and mean body mass index of 21.9 kg/m2), we found that the percent loss of body weight and loss of skeletal muscle mass were correlated with the basal energy expenditure rate (BEE rate; r = 0.70, p<0.001 and r = 0.49, p<0.01, respectively). Based on the receiver operating characteristics curves, the cutoff value for the BEE rate in terms of weight loss was 1.1. Salivary amylase levels did not significantly change during the treatment course. Continuous variables, including oral caloric intake and performance status, showed statistically significant correlations with nutrition-related adverse events during treatment (r = -0.93, p<0.01 and r = 0.91, p<0.01, respectively). Skeletal muscle mass before treatment initiation was an independent predictive variable for reduced 2-year survival (p = 0.04). CONCLUSION: Our results support the validity of a safe nutritional pathway with a BEE rate of 1.1 for HSCT patients pretreated with MAC. Specifically, we found that this pathway could prevent weight loss in response to nutrition-related adverse events. Skeletal muscle mass before treatment was identified as an independent risk factor for reduced 2-year survival.

Quality of Life and Social and Psychological Outcomes in Adulthood Following Allogeneic HSCT in Childhood for Inborn Errors of Immunity.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) is well established as a corrective treatment for many inborn errors of immunity (IEIs) presenting in childhood. Due to improved techniques, more transplants are undertaken and patients are living longer. However, long-term complications can significantly affect future health and quality of life. Previous research has focused on short-term medical outcomes and little is known about health or psychosocial outcomes in adulthood. OBJECTIVE: This project aimed to ascertain the long-term social and psychological outcomes for adults who underwent HSCT for IEI during childhood. METHODS: Adult patients, who had all undergone HSCT for IEI during childhood at two specialist immunology services at least 5 years previously, were invited to participate in the study. Questionnaires and practical tasks assessed their current functioning and circumstances. Information was also gathered from medical notes. Data was compared with population norms and a control group of participant-nominated siblings or friends. RESULTS: Eighty-three patients and 46 matched controls participated in the study. Patients reported significantly better physical health-related quality of life than the general population norm, but significantly worse than matched controls. Patient's self-reported physical health status and the perceived impact of their physical health on everyday life were worse than matched controls and patients reported higher levels of anxiety and lower mood than the general population. For those where their IEI diagnosis was not associated with a learning disability, cognitive function was generally within the normal range. CONCLUSIONS: Patients who have had a HSCT in childhood report mixed psychosocial outcomes in adulthood. More research is needed to establish screening protocols and targeted interventions to maximize holistic outcomes. CLINICAL IMPLICATIONS: Screening for holistic needs and common mental health difficulties should be part of routine follow-up. Information should be provided to patients and families in order to support decision-making regarding progression to transplant and the early identification of any difficulties.

Effect of vitamin C on immune reconstitution after bone marrow transplantation.

BACKGROUND: Vitamin C is an essential nutrient for the adequate function and maturation of the immune system. In vitro studies show that the development, proliferation, and functioning of T cells requires vitamin C, especially for natural killer (NK) cells. Their deficiency during the acute phase post-transplantation could cause greater morbidity and mortality in these patients. A prospective clinical trial using high-dose vitamin C was performed to determine if vitamin C supplementation improves reconstitution of NK lymphocytes after hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: We enrolled 24 patients who underwent autologous HSCT for multiple myeloma and lymphoma. Patients were randomized to receive standard treatment or standard treatment plus 20 g vitamin C once daily (1 - 10 days) and 500 mg twice daily (11 - 100 days) after transplantation. RESULTS: NK and CD3+ lymphocytes showed an increase from days +30 to +100 only in the vitamin C-treated group. Patients in the vitamin C group had a lower frequency of infections. No severe adverse events were reported. CONCLUSION: Our results suggest that high-dose vitamin C supplementation is an effective and safe therapeutic option to decrease the frequency of infections and enhance immune reconstitution after HSCT.

Stem cell transplantation patients receiving a novel oral care protocol for oral mucositis prevention and treatment: patient-reported outcomes and quality of life.

BACKGROUND: Oral mucositis (OM) is one of the most debilitating effects of toxicity due to hematopoietic stem cell transplantation (HSCT) conditioning regimens. The aim of this secondary analysis of the data of a phase II study designed to assess the efficacy of a novel oral care protocol containing bovine colostrum and aloe vera to prevent oral mucositis was to compare outcomes reported by patients with those collected by healthcare professionals (HCPs). METHOD: Data on oral mucositis severity, duration, time of onset and related pain were collected from patients using the Oral Mucositis Daily Questionnaire (OMDQ). HCPs assessed the same outcomes using the World Health Organization oral mucositis scale and pain numerical rating scale. Quality of life was assessed with the 3-level EuroQol-5 dimensions. RESULTS: Fifty-nine autologous/allogeneic graft patients were recruited, 46 of whom (78.0%) experienced OM. Mean onset was 9.1 (SD ± 3.5) days after conditioning initiation, mean duration was 10.4 (SD ± 4.3) days, and the average maximum pain score was 3.7 (SD ± 2.7). Self-administration of the OMDQ detected oral symptoms at least 1 day sooner compared to objective assessments (p = 0.025). Significant differences were observed between the patient-reported and the HCP-assessment data on oral mucositis severity grading distribution (p < 0.0001) and highest pain score (p < 0.0001). Quality of life score variations were correlated with changes in oral mucositis severity during patients' hospital stay. CONCLUSIONS: Further studies are necessary to improve the understanding of these findings; a randomised controlled trial is being set up at our institution.

How to choose first salvage therapy in Hodgkin lymphoma: traditional chemotherapy vs novel agents.

Approximately 10% to 30% of patients with classical Hodgkin lymphoma (cHL) develop relapsed or refractory (R/R) disease. Of those patients, 50% to 60% show long-term progression-free survival after standard salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). In the past decade, novel therapies have been developed, such as the CD30-directed antibody-drug conjugate brentuximab vedotin and immune checkpoint inhibitors, which have greatly extended the treatment possibilities for patients with R/R cHL. Several phase 1/2 clinical trials have shown promising results of these new drugs as monotherapy or in combination with chemotherapy, but unfortunately, very few randomized phase 3 trials have been performed in this setting, making it difficult to give evidence-based recommendations for optimal treatment sequencing. Two important goals for the improvement in the treatment of R/R cHL can be identified: (1) increasing long-term progression-free and overall survival by optimizing risk-adapted treatment and (2) decreasing toxicity in patients with a low risk of relapse of disease by evaluating the need for HDCT/ASCT in these patients. In this review, we discuss treatment options for patients with R/R cHL in different settings: patients with a first relapse, primary refractory disease, and in patients who are ineligible or unfit for ASCT. Results of clinical trials investigating novel therapies or strategies published over the past 5 years are summarized.

Guided imagery relaxation in quality of life of patients undergoing hematopoietic stem cell transplantation: a quasi-experiment.

OBJECTIVE: The aim of this study was to evaluate the effects of the relaxation technique with guided imagery by means of virtual reality on health-related quality of life in patients undergoing hematopoietic stem cell transplantation. METHODS: A quasi-experiment conducted in a Bone Marrow Transplantation Service of a public hospital in southern Brazil. From October 2019 to October 2020, forty-two adult participants who underwent transplantation were included, 35 in the intervention group and seven in the control group. A guided imagery intervention, with audio guiding the relaxation associated with nature images in 360º, was performed during the hospitalization period. Data were collected on the first day of hospitalization, on the transplantation day, during the neutropenia stage, and at pre-hospital discharge. The Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Functional Assessment of Cancer Therapy-Neutropenia (FACT-N) were used to assess health-related quality of life, fatigue and neutropenia. Data were analyzed using the Generalized Linear Mixed Model for the evolution of the health-related quality of life assessments over time, considering the groups and stages. Pearson's correlation coefficient was adopted for the correlation analyses. RESULTS: Allogeneic transplantation was predominant: 28 (80%) in the intervention group and 5 (71.43%) in the control group. There were improvements in the health-related quality of life scores, although not significant. A significant difference was found among the stages (p <0.050) and a significant positive correlation (p <0.000) among the variables on general quality of life, additional concerns, fatigue and neutropenia in all stages. CONCLUSION: Patients undergoing hematopoietic stem cell transplantation suffer changes in their quality of life. Interventions based on integrative practices emerge as an option to minimize them. 
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HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis.

Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced-intensity regimens were analyzed separately. Among recipients of reduced-intensity regimens, 2-year graft failure (3% vs 11%), acute grades 2 to 4 GVHD (hazards ratio [HR], 0.70; P = .022), acute grades 3 and 4 GVHD (HR, 0.41; P = .016), and nonrelapse mortality (HR, 0.43; P = .0008) were lower after MUD than with Haplo donor transplantation. Consequently, disease-free (HR, 0.74; P = .008; 55% vs 41%) and overall (HR, 0.65; P = .001; 67% vs 54%) survival were higher with MUD than with Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% vs 88%) was higher and grades 3 and 4 acute (HR, 0.39; P = .07) and chronic GVHD (HR, 0.66; P = .05) were lower after MUD than with Haplo donor transplantation. There were no differences in graft failure, relapse, nonrelapse mortality, and disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced-intensity conditioning regimens.