Bone Marrow Transplantation (2019) 54:53–62 https://doi.org/10.1038/s41409-018-0212-7 ARTICLE Favorable immune recovery and low rate of GvHD in children transplanted with partially T cell-depleted PBSC grafts Christian Martin Seitz 1 ● Matthias Eyrich 2 ● Johann Greil 3 ● Patrick Schlegel 1 ● Tobias Feuchtinger 4 ● Peter Bader 5 ● Martin Ebinger 1 ● Carl Philipp Schwarze 1 ● Paul Gerhardt Schlegel 2 ● Michael Schumm 1 ● Rupert Handgretinger 1 ● Peter Lang 1 Received: 1 September 2017 / Revised: 9 April 2018 / Accepted: 16 April 2018 / Published online: 24 May 2018 © Macmillan Publishers Limited, part of Springer Nature 2018 Abstract Transplantation of peripheral blood stem cells (PBSC) from matched unrelated donors (MUD) is still associated with a significant risk for graft vs. host disease (GvHD), especially in pediatric patients receiving grafts from adult donors containing high amounts of T cells. Here, we present long-term follow-up results on 25 pediatric patients, (acute leukemia n = 15, NHL n = 3, CML n = 3, MDS n = 5), transplanted with CD34 or CD133 positively selected PBSC from MUDs supplemented with an add-back of 1 × 10 7 /kg body weight (kgBW) unselected T cells resulting in a median T-cell depletion (TCD) of 1.97 log. A total of 24/25 (96%) patients had primary engraftment. Early T-cell recovery was significantly improved compared to patients receiving CD34-selected grafts without T-cell add-back and similar to patients receiving unmanipulated bone marrow. GvHD incidence was low with 8/4% aGvHD grade II/III, no grade IV and 13% limited cGvHD. In total, 16/25 (64%) patients are alive after a median follow-up of 10 years. Five-year event-free survival (EFS) was 68%, relapse probability 24% and transplantation-related mortality (TRM) 12%. Thus, in PBSC allotransplants from MUD, partial TCD with serotherapy and CSA/MTX prophylaxis, can effectively reduce GvHD without hampering engraftment and immune reconstitution. Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) from matched unrelated donors (MUD) has become a well-established and routinely performed treatment strategy in various malignant and non-malignant hematolo- gical disorders [1]. Early post-transplant T-cell recovery and function is likely to be beneficial in alloHSCT due to sup- pression of graft rejection, reduction of infectious complica- tions and mediation of a graft-vs.-leukemia effect [2–4]. In contrast, subsets of donor T cells are essentially linked to the pathogenesis of graft-vs.-host disease (GvHD), which remains a major cause of morbidity and mortality in alloHSCT [5–7]. The risk for GvHD is positively correlated with the amount of T cells infused [8–11]. Especially in the setting of young pediatric patients with low BW and adult MUDs, grafts with high numbers of stem cells may inevitably contain consider- able numbers of T cells, potentially raising the risk for acute GvHD (aGvHD) and chronic GvHD (cGvHD). Several groups have shown that ex vivo T-cell depletion (TCD) can substantially reduce the incidence of GvHD in children [12– 14]. However, this benefit was counterbalanced by an increased risk for graft failure, delayed immune reconstitution, and consecutively higher risk for life-threatening viral and fungal infections and malignant relapse [12, 13, 15–17]. In an attempt to counteract these shortcomings of TCD, add-backs of unselected CD3 + T cells at various dose levels have been transplanted with the graft, demonstrating improvements [14, 18]. However, important questions, such as the optimal dosage of T cells, whether immunosuppression should be * Peter Lang peter.lang@med.uni-tuebingen.de 1 Department of General Pediatrics, Hematology/Oncology, University Children’s Hospital, Tuebingen 72076, Germany 2 Department of Hematology, Oncology and Stem Cell- Transplantation, University Children’s Hospital, Wuerzburg 97080, Germany 3 Department of Hematology/Oncology, University Children’s Hospital, Heidelberg 69120, Germany 4 Department of Hematology, Oncology and Stem Cell Transplantation, Dr. von Haunersches Kinderspital, Muenchen 80337, Germany 5 Division for Stem Cell Transplantation and Immunology, University Children’s Hospital, Frankfurt 60590, Germany 1234567890();,: 1234567890();,: