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Teltschik, Heiko-Manuel; Heinzelmann, Frank; Gruhn, Bernd; Feuchtinger, Tobias; Schlegel, Patrick; Schumm, Michael; Kremens, Bernhard; Müller, Ingo; Ebinger, Martin; Schwarze, Carl Philipp; Ottinger, Hellmut; Zips, Daniel; Handgretinger, Rupert; Lang, Peter (2016): Treatment of graft failure with TNI-based reconditioning and haploidentical stem cells in paediatric patients. In: British Journal of Haematology, Vol. 175, No. 1: pp. 115-122
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Abstract

Graft failure is a life-threatening complication after allogeneic haematopoietic stem cell transplantation (HSCT). We report a cohort of 19 consecutive patients (median age: 85years) with acute leukaemias (n=14) and non-malignant diseases (n=5) who experienced graft failure after previous HSCT from matched (n=3) or haploidentical donors (n=16) between 2003 and 2012. After total nodal irradiation (TNI)-based reconditioning combined with fludarabine, thiotepa and anti-T cell serotherapy, all patients received T cell-depleted peripheral blood stem cell grafts from a second, haploidentical donor. Median time between graft failure and retransplantation was 14d (range 7-40). Sustained engraftment (median: 10d, range 9-32) and complete donor chimerism was observed in all evaluable patients. 5 patients additionally received donor lymphocyte infusions. Graft-versus-host disease (GvHD) grade II and III occurred in 1 patient each (22%);no GvHD grade IV was observed. 2 patients had transient chronic GvHD. The regimen was well tolerated with transient interstitial pneumonitis in one patient. Treatment-related mortality after one year was 11%. Event-free survival and overall survival 3years after retransplantation were 63% and 68%. Thus, a TNI-based reconditioning regimen followed by transplantation of haploidentical stem cells is an option to rescue patients with graft failure within a short time span and with low toxicity.