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A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34 + selection, CD3 + CD19 + depletion, TCRαβ + CD19 + depletion or CD45RA + depletion, added to CD34 + selection for GvHD prophylaxis. The PBSCs were the only source in patients

Summary:In this study we analysed the incidence and clinical impact of the persistence of host haemopoiesis (mixed chimaerism, MC) after allogeneic BMT in 35 consecutive patients with haematologic malignancies using a total CD4؉ cell-depleted graft with an adjusted dose of CD8 ؉ cells (1 ؋ 10 8 /kg). Chimaerism was assessed by PCR amplification of VNTRs in 30 evaluable patients: 19 non-CML and 11 CML cases which were also evaluated for the BCR-ABL transcript by RT-PCR. All but one had complete engraftment with a donor profile early post-BMT. At the end of the study period, 12 of 30 patients displayed MC (40%). The overall diseasefree survival for MC patients was clearly unfavourable when compared to those who exhibited a donor profile (24.7% vs 100%, P = 0.005). However, we found that only two of five patients with MC in the non-CML group relapsed, whereas a clear correlation could be made between MC and relapse in CML (seven showed MC, preceding cytogenetic or haematological relapse in six of them, which displayed a prior BCR-ABL mRNA positivity). In addition, a quantitative-PCR approach enabled us to demonstrate that increasing amounts of MC are invariably associated with subsequent relapse, whereas a low stable level of host or complete donor haemopoiesis is consistent with clinical complete remission. Although these results suggest that the clinical impact of MC may depend on the underlying disease, it is compatible with the concept that the graftversus-leukaemia effect against CML is mainly exerted by donor CD4 ؉ lymphocytes. Elimination of this cellular subset may be responsible for the inability of the graft to prevent a progressive increase in the tumor cell burden. Keywords: MC; BMT; T cell depletion; relapse Bone marrow transplantation (BMT) is the treatment of choice for many patients with haematologic malignancies. malignant clone by the conditioning regimen followed by the infusion of healthy donor marrow cells which re-establish normal haematologic and immune functions. However, the differences in post-transplant relapses between allogeneic and autologous or syngeneic BMT, 2,3 and especially between in vitro T cell-depleted and unmanipulated allogeneic BMT, [3][4][5] indicate that allogeneic donor T cells play a pivotal role in the eradication of malignant cells, the socalled graft-versus-leukaemia (GVL) effect, and may be crucial for the development of complete donor haematopoiesis. Furthermore, graft failure and development of mixed chimaerism (MC, the coexistence of recipient and donor haematopoiesis) are more common after T cell-depleted BMT when compared with conventional transplants. 6-8The true incidence and significance of the detection of MC post-BMT remain unclear.6-10 However, with the use of increasingly sensitive molecular techniques for the detection of residual recipient cells, MC is frequently observed post-allogeneic BMT, 6-13 although more important than simple documentation of the incidence of MC is an assessment of its relevance in relation to clinical outcome, particularly any ...

Objective Describe the GETH haploidentical stem cell transplantation (haplo‐HSCT) activity in non‐malignant disease (NMDs). Methods We retrospectively analyzed data from children with NMDs who underwent haplo‐HSCT. Results From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo‐HSCT through ex vivo T cell‐depleted (TCD) graft platforms or post‐transplantation cyclophosphamide (PT‐Cy) at 7 Spanish centers. Five cases employed unmanipulated PT‐Cy haplo‐HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+CD19+ depletion, TCRαβ+CD19+ selection or naive CD45RA+ T‐cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo‐HSCT, and bone marrow was the source for one PT‐Cy haplo‐HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1‐year cumulative incidence of graft failure was 27.4%. The 1‐year III‐IV acute graft‐versus‐host disease (GvHD) and 1‐year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2‐year overall survival was 44.9% for PIDs, and the 2‐year graft‐versus‐host disease‐free and relapse‐free survival rate was 37.6% for the other NMDs. The transplantation‐related mortality at day 100 was 30.8%. Conclusion Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise.

Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7–66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years’ survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.