Malnutrition risk prior to hematopoietic stem cell transplantation predicts mortality in adults.

Patients with hematological malignancies have a high risk of developing malnutrition. Few data are currently available that illustrate the impact of the patients' nutritional status prior to HSCT on their outcome. The aim of this study was to investigate the association between the patients' malnutrition status prior to receiving autologous or allogeneic HSCT and mortality in adults with hematological malignancies. We conducted a retrospective cohort study including 341 patients. Survival curves and Cox proportional-hazards models were used to reveal whether malnutrition risk served as a predictor for the overall mortality and non-relapse mortality. The survival curves revealed that patients with malnutrition risk prior to HSCT had an increased risk of death during the 1-year follow-up period (overall mortality as well as non-relapse mortality). This result was confirmed by the Cox regression models, which showed a mortality risk that is more than two times higher in patients at risk of malnutrition. In allogeneic transplant patients, the impact of malnutrition risk on mortality was even higher. Our conclusions presuppose that nutrition is an important factor during the holistic treatment of HSCT patients by all healthcare professionals involved in the care of this patient group. Future studies should be carried out to examine how and whether different nutritional interventions effectively improve the nutritional status of this patient group.

Immunohistochemistry for c-myc and bcl-2 overexpression improves risk stratification in primary central nervous system lymphoma.

Overexpression of bcl-2 and c-myc are defining features of double-expressor-lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Here, we first describe the relationship between DEL biology, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), treatment response, disease progression, and mortality in PCNSL. In this study, we determined c-myc and bcl-2 status immunohistochemically in samples of 48 patients with newly diagnosed PCNSL and followed these patients for a median interval of 6.2 years. Twelve, 18, and 17 patients harbored none, one, or both DEL features. Corresponding overall response rates after first-line therapy were strongly associated with DEL biology (100%, 42%, and 44% in patients with 0, 1, or 2 DEL features). Patients with one or both DEL features had a 5-fold and 13-fold higher 5-year risk of progression and/or death than patients without DEL features. These associations prevailed after adjusting for the NCCN-IPI. DEL improved the discriminatory capability of the NCCN-IPI (P = .0001). Furthermore, we could show that addition of DEL biology to the NCCN-IPI significantly improved the score's discriminatory potential both toward progression-free survival (increase in Harell's c = 0.15, P = .005) and overall survival (increase in Harell's c = 0.11, P = .029). In conclusion, DEL biology is a strong and simple-to-use predictor of adverse outcome in PCNSL. Addition of DEL to the NCCN-IPI improves its prognostic potential. Disease progression from PCNSL harboring both DEL features is invariably fatal. This defines a novel PCNSL patient subset with a great unmet need for improved therapy.

Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation.

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.

UV treatment of chronic skin graft-versus-host disease--focus on UVA1 and extracorporeal photopheresis.

Chronic graft-versus-host disease (GVHD) is a serious and life-threatening complication after allogeneic hematopoietic stem cell transplantation. Cutaneous manifestations such as lichenoid or sclerotictype skin changes have been frequently observed in these patients. UVA1 phototherapy appears as a very effective treatment option for treatment-refractory lichenoid and sclerodermatous GVHD. Substantial improvements can often be achieved within 8-12 weeks of treatment allowing for subsequent reduction or withdrawal of immunosuppressive medications. UVA1 treatment acts via a local effect and is therefore only indicated for cutaneous manifestations of GVHD. In patients with multiorgan involvement by chronic GVHD, extracorporeal photopheresis is an efficacious and safe secondline therapy for steroid-refractory disease in both pediatric as well as adult patients. Besides high response rates in cutaneous and extracutaneous manifestations of chronic GVHD, a substantial corticosteroid-sparing effect and improved survival rates have been reported in patients given extracorporeal photopheresis treatment.

Effects of extracorporeal photoimmunotherapy on soluble IL-2Ralpha, TNF-RI, and CD8 in patients with steroid-resistant acute graft-versus-host disease.

Extracorporeal photoimmunotherapy (ECP) has been successfully used as adjunct treatment for steroid-resistant graft-versus-host disease (GvHD) after allogeneic stem cell transplantation. We serially investigated serum levels of soluble interleukin-2 receptor-alpha (sIL-2Ralpha), soluble tumor necrosis factor receptor I (sTNF-RI), and soluble CD8 (sCD8) in 19 patients with steroid-resistant acute GvHD before and after each ECP treatment. Highest levels of sIL-2Ralpha and sTNF-RI correlated with severe acute GvHD and infections. Despite an immediate sIL-2Ralpha and sTNF-RI decrease after each treatment cycle, a mean surge of sTNF-RI>sIL-2Ralpha during the first three ECP cycles was observed in infections. A delayed surge, i.e., after the third ECP cycle, of sIL-2Ralpha and elevated post-ECP sCD8 levels was observed in patients developing chronic GvHD. While levels of sIL-2Ralpha and sTNF-RI correlate with the severity of acute GvHD and infections during the early ECP treatment period, the recurring increase of post-ECP sCD8 possibly may serve as parameter for developing chronic GvHD.