Severely reduced physical performance is already present at the time of admission for stem cell transplantation.

Objectives: Paediatric patients with cancer undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) face a high risk for life-threatening infections and transplant-related complications. Therefore, these children should be in the best possible physical condition beforehand. The study aims to evaluate the fitness status before allo-HSCT and identify correlations between fitness, quality of life and fatigue, clinical data, and previous exercise sessions. Methods: Paediatric patients with cancer ≥4 years old, treated with allo-HSCT, were recruited for the ANIMAL trial ("Effects of a low vs. moderate intense exercise program on immune recovery during paediatric allo-HSCT.", DRKS ID:DRKS00019865). Assessed at admission for HSCT were (1) clinical and anthropometric data, (2) motor performance (strength, endurance and balance) and (3) psychological parameters. Values were compared with published reference values (normative data from the literature) of healthy children, and correlation analyses were conducted. Results: 22 paediatric patients undergoing pre-allo-HSCT (23% female, 9.4±4.5 years, 73% leukaemia) exhibited substantial reduced differences in all motor performance parameters, with up to -106%±98 (mean difference to reference value) in static stance, -37%±45 in sit-to-stand, -52%±16 in leg extension and -48%±22 in hand grip strength compared with reference values. Correlations were observed among age and fitness parameters, the number of inpatient days and fatigue, and many previous exercise sessions correlated with better hand grip strength. Conclusion: These results indicate a poorer fitness status in children before HSCT compared with healthy children, recommending the need for structured exercise programmes for children undergoing HSCT. Differently directed correlations between age/body mass index and endurance/strength and between exercise sessions and strength show the importance of individualised training recommendations and the effect of training.

Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors.

BACKGROUNDAdoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications.METHODSWe provide results of a personalized T cell manufacturing program evaluating donor, patient, T cell product, and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T lymphocyte (EBV-CTL) products from stem cell donors (SCDs), related third-party donors (TPDs), or unrelated TPDs from the allogeneic T cell donor registry (alloCELL) at Hannover Medical School were manufactured by immunomagnetic selection using a CliniMACS Plus or Prodigy device and the EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated, and patient outcome and side effects were retrieved by retrospective chart analysis.RESULTSForty clinical-grade EBV-CTL products from SCDs, related TPDs, or unrelated TPDs were generated for 37 patients with refractory EBV infections or EBV-associated malignancies with and without a history of transplantation, within 5 days (median) after donor identification. Thirty-four patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to a complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients' blood were detectable in 16 of 18 monitored patients (89%) after transfer, and their presence correlated with clinical response.CONCLUSIONPersonalized clinical-grade manufacture of EBV-CTL products via immunomagnetic selection from SCDs, related TPDs, or unrelated TPDs in a timely manner is feasible. Overall, EBV-CTLs were clinically effective and well tolerated. Our data suggest EBV-CTL transfer as a promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT, as well as patients with preexisting organ dysfunction.TRIAL REGISTRATIONNot applicable.FUNDINGThis study was funded in part by the German Research Foundation (DFG, 158989968/SFB 900), the Deutsche Kinderkrebsstiftung (DKS 2013.09), Wilhelm-Sander-Stiftung (reference 2015.097.1), Ellen-Schmidt-Program of Hannover Medical School, and German Federal Ministry of Education and Research (reference 01EO0802).