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Background: Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD.Study Design and Methods: PG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273-point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS).Results: In five patients, 12 autologous blood collections were performed; median 3 (range 1-3) per patient, and 26 PG applications were performed; median 6 (range 2-8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%-47.3%), and median NIH OMS total score for 27.3% (range 20.0%-50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%-100%). No side effects were observed.Conclusion: Application of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment. [ABSTRACT FROM AUTHOR]

The field of immunotherapy in cancer treatments has been accelerating over recent years and has entered the forefront as a leading area of ongoing research and promising therapies that have changed the treatment landscape for a variety of solid malignancies. Prior to its designation as the Science Breakthrough of the Year in 2013, cancer immunotherapy was active in the treatment of hematologic malignancies. This review provides a broad overview of the past, present, and potential future of immunotherapy in hematologic malignancies. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the effects of acupuncture treatment for persistent hiccups in cancer patients. Design: The study design was a retrospective case series. Settings/location: The study setting was the Clinical Research Center of the National Institutes of Health. Subjects: The subjects were 16 adult male patients ages 27–71 with cancer, with persistent hiccups. Interventions: There were one to three acupuncture sessions over a 1–7-day period. Outcome measures: Treatment efficacy was measured using a hiccup assessment instrument pre- and post-treatment. The effects of acupuncture on common symptoms reported by all patients were also evaluated. Results: Thirteen (13) patients experienced complete remission of persistent hiccups ( p < 0.0001); 3 patients experienced decreased hiccups severity. Significant improvement was observed in discomfort ( p < 0.0001), distress ( p < 0.0001), and fatigue ( p = 0.0078). Conclusions: This case series demonstrates that acupuncture may be a clinically useful, safe, and low-cost therapy for persistent hiccups in patients with cancer. [ABSTRACT FROM AUTHOR]

The authors discuss the effectivity of interleukin-2 (IL-2) in the treatment of patients with chronic graft-versus-host disease (cGVHD). They concluded that increasing the amount of regulatory T cells (Tregs) and natural killer (NK) cells may result into reversal of cGVHD manifestations and progression reduction by IL-2.

The authors discuss aspects of the study "Targeting Syk-activated B cells in murine and human chronic graftversus-host disease," by R. Flynn and colleagues which focuses on the development of clinical trials regarding the effect of spleen tyrosine kinase (Syk) inhibition for the treatment of chronic graft-versus-host disease (cGVHD). Topics include the understanding of cGVHD biology, identification of Syk signaling in B cells as a mediator of cGVHD, and tyrosine kinase inhibitor (TKI) therapy.

Highlights • cGVHD remains a serious complication of cell transplantation. • Available options on SR-cGVHD vary in both cost and effectiveness. • Attention to economic issues when treating SR-cGVHD can help guide how treatments should be sequenced. Abstract Given the increasing incidence of chronic graft-versus-host disease (cGVHD) and its rapidly escalating costs due to many lines of drug treatments, we aimed to perform a meta-analysis to assess the comparative effectiveness of various treatment options. Using these results, we then conducted a cost-effectiveness analysis for the frequently utilized agents in steroid-refractory cGVHD. We searched for studies examining tacrolimus, sirolimus, rituximab, ruxolitinib, hydroxychloroquine, imatinib, bortezomib, ibrutinib, extracorporeal photopheresis, pomalidomide, and methotrexate. Studies with a median follow-up period shorter than 6 months and enrolling fewer than 5 patients were excluded. Meta-analysis for overall and organ system–specific GVHD response (overall response [ORR], complete response [CR], and partial response [PR]) was conducted for each intervention. Cost per CR and cost per CR + PR were calculated as the quotient of the 6-month direct treatment cost by CR and CR + PR. Forty-one studies involving 1047 patients were included. CR rates ranged from 7% to 30% with rituximab and methotrexate, respectively, and ORR ranged from 30% to 85% with tacrolimus and ruxolitinib, respectively. Cost per CR ranged from US$1,187,657 with ruxolitinib to US$680 with methotrexate. Cost per ORR ranged from US$453 for methotrexate to US$242,236 for ibrutinib. The most cost-effective strategy was methotrexate for all of the organ systems. Pomalidomide was found to be the least cost-effective treatment for eye, gastrointestinal, fascia/joint, skin, and oral GVHD, and imatinib was found to be the least cost-effective treatment for liver and extracorporeal photopheresis for lung GVHD. We observed huge cost-effectiveness differences among available agents. Attention to economic issues when treating cGVHD is important to recommend how treatments should be sequenced, knowing that many patients will cycle through available agents. [ABSTRACT FROM AUTHOR]

Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. cGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures that could represent clinically useful and reproducible predictive characteristics. We analyzed 227 previously treated patients most with moderate (n = 54) or severe (n = 170) cGVHD defined by NIH criteria who were prospectively enrolled in a natural history protocol (NCT00092235). Patients received a median of 4 prior systemic therapy regimens and were seen at the NIH for a single time-point visit and were then monitored for survival and ability to discontinue cGVHD systemic therapy. With a median follow-up of 71.1 months, the cumulative incidence of systemic therapy discontinuation was 9.5% (95% confidence interval, 6.0% to 13.9%) at 2 years and 27.7% (95% confidence interval, 20.9% to 34.8%) by 5 years after the initial visit. Factors associated with a higher incidence of immunosuppression discontinuation included lower NIH global severity ( P  = .019) and lung ( P  = .030) scores and less extensive deep sclerosis (<37% body surface area, P  = .024 ). Lower patient- and clinician-reported 0 to 10 severity NIH scores and noncyclosporine prophylaxis regimens were also associated with higher incidence of immunosuppression discontinuation ( P  <   .05). In conclusion, we found low success rates for immune suppression discontinuation in previously treated patients who were severely affected with cGVHD. NIH scoring and clinical measures provide new standardized disease-specific tools to predict discontinuation of systemic therapy. [ABSTRACT FROM AUTHOR]

Aim To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). Methods 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. Results Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P = 0.043), had lower Karnofsky performance status (P = 0.028), and had a higher B-cell number (P = 0.005), platelet count (P = 0.022), and total protein (P = 0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P = 0.001), higher intensity of immunosuppressive treatment (P = 0.020), and total body irradiation conditioning (P = 0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). Conclusion These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported. [ABSTRACT FROM AUTHOR]

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study ( NCT01307462 ). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM. [ABSTRACT FROM AUTHOR]

Aim To investigate the ability of two standard quality of life (QOL) questionnaires-The Short Form (36-item) Health Survey (SF-36) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) to evaluate QOL in patients with chronic graft-vs-host disease (cGVHD) graded according to National Institutes of Health (NIH) consensus criteria. Methods In this cross-sectional study, QOL was assessed in patients who underwent allogeneic stem cell transplantation (allo-SCT) at the University Hospital Centre Zagreb and were alive and in complete remission for more than one year after allo-SCT. Results The study included 58 patients, 38 patients with cGVHD and 20 controls, patients without cGVHD. Patients with cGVHD scored according to the NIH criteria had significantly lower scores of global health status and lower QOL on all SF-36 subscales and most of QLQ C30 functional subscales (P < 0.050 for all comparisons). Furthermore, patients with active cGVHD had significantly lower QOL scores than patients with inactive cGVHD, and this difference was most evident in physical functioning subscale of SF-36 (P = 0.0007) and social functioning subscale of QLQ C30 (P = 0.009). Conclusion cGVHD scored according to the NIH criteria is correlated with patient-reported QOL, particularly in the physical domains as detected by SF-36. QLQ C30 questionnaire adds more information on social functioning and should be used as a valuable tool in the evaluation of social domains in cGVHD patients. [ABSTRACT FROM AUTHOR]

The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence. [ABSTRACT FROM AUTHOR]

Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients. [ABSTRACT FROM AUTHOR]

The authors reflect on the challenges and opportunities for chronic graft versus host disease (GVHD) in 2016. They explain thay chronic GVHD can impact a patient's medical, social, and quality of life, with added problems in terms of health-related costs and health care management. The authors think that allogeneic hematopoietic stem cell transplantation (alloHSCT) still remains the only curative option for chronic GVHD despite other advances in the treatment of hematological diseases.

Abstract: Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials. [Copyright &y& Elsevier]