title: Treatment of graft failure with TNI-based reconditioning and haploidentical stem cells in paediatric patients.
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: 8·5 years) 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 14 d (range 7-40). Sustained engraftment (median: 10 d, 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 3 years 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.
authors.affiliation: Children's University Hospital, University Hospital (UH) of Tuebingen, Tuebingen, Germany.
authors.forename: Heiko-Manuel
authors.initials: HM
authors.lastname: Teltschik
authors.affiliation: Department of Radiation Oncology, UH of Tuebingen, Tuebingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Heinzelmann
authors.affiliation: Children's University Hospital, UH of Jena, Jena, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
authors.affiliation: Dr. von Hauner'sches Kinderspital, Ludwig-Maximilians-Universität Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: Children's University Hospital, University Hospital (UH) of Tuebingen, Tuebingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schlegel
authors.affiliation: Children's University Hospital, University Hospital (UH) of Tuebingen, Tuebingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.affiliation: Children's University Hospital, UH of Essen, Essen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kremens
authors.affiliation: Clinic for Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
authors.affiliation: Children's University Hospital, University Hospital (UH) of Tuebingen, Tuebingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ebinger
authors.affiliation: Children's University Hospital, University Hospital (UH) of Tuebingen, Tuebingen, Germany.
authors.forename: Carl Philipp
authors.initials: CP
authors.lastname: Schwarze
authors.affiliation: Department of Bone Marrow Transplantation, UH of Essen, Essen, Germany.
authors.forename: Hellmut
authors.initials: H
authors.lastname: Ottinger
authors.affiliation: Department of Radiation Oncology, UH of Tuebingen, Tuebingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: Children's University Hospital, University Hospital (UH) of Tuebingen, Tuebingen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Children's University Hospital, University Hospital (UH) of Tuebingen, Tuebingen, Germany. peter.lang@med.uni-tuebingen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000401:mortality / Q000628:therapy*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006402:Hematologic Diseases / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D019233:Retreatment; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens
keywords: Haploidentical; T cell depletion; children; graft failure; stem cell transplantation