No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients

Background: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. Patients and methods: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. Results: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). Conclusions: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocol

Update on extracorporeal photochemotherapy for graft-versus-host disease treatment

Pediatric experience with extracorporeal photochemotherapy (ECP) for graft-versus-host disease (GvHD) has mainly been reported by Italian and French groups. Data concerning 41 children with acute GvHD and 63 children affected by chronic GvHD are available. In 73 and 63% of them, respectively, improvement was observed, with addition of ECP to their immunosuppressive regimen. Treatment with ECP was associated with minimal side effects, even in the smallest of patients. In all responded pediatric patients, both with acute and chronic GvHD, ECP allowed progressive reduction or discontinuation of the concomitant pharmacological immunosuppressive therapy without an increase in GvHD activity. These data show that ECP is a useful therapy for children affected by GvHD resistant to conventional treatment and can be safely used

Allogeneic bone marrow transplant or second autograft in patients with acute leukemia who relapse after an autograft. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Among 2752 patients with acute leukemia who had recurrent leukemia after autograft in remission and were reported to the EBMT, 94 underwent an allogeneic bone marrow transplant and 74 received a second autograft. Recipients of HLA-mismatched related or unrelated bone marrow had an increased transplant-related mortality (TRM, P = 0.017) and a decreased leukemia-free survival (LFS, P = 0.03), compared to recipients of HLA matched related or unrelated bone marrow. Outcome in recipients of HLA-compatible related or unrelated bone marrow was compared to those receiving a second autograft. TRM at 2 years was 51 +/- 8% in recipients of matched allografts and 26 +/- 6% following a 2nd autograft (P 25 years of age (P < 0.01), if the interval from first autograft to relapse was 8 months or less (P < 0.01) and if TBI was used at first autograft (P < 0.05)

Extracorporeal photochemotherapy induces arginase 1 in patients with graft versus host disease

International audienceThe benefits of extracorporeal photochemotherapy (ECP; psoralen and UVA exposure of blood mononuclear cells) in graft-versus-host-disease (GVHD) are well-recognized, but the mechanisms of action remain elusive. As the metabolism of L-arginine in immune cells is known to play a role in immune tolerance, we investigated the effect of ECP on arginine metabolism, and the influence of extracellular L-arginine concentration on the response to ECP in cells from patients on therapy by ECP for a GVHD and healthy donors cultured before and after ECP in the presence of different concentrations of arginine (0, 50, 100, 200 and 1000 μmol/l). At baseline arginine was not metabolized through the same pathway in patients and donors. When cells were exposed to ECP, the production of ornithine but not NO° was enhanced, while mRNA of arginase 1 was up-regulated but not INOS. In GVHD patients, increasing arginine concentration resulted in down-regulation of IFNγ and TNFα mRNA expression, whereas IL10 was up-regulated especially at physiological plasma levels (between 0 and 100 μM). Overall, our study shows that ECP orients the metabolism of arginine toward the arginase pathway together with shifting the cytokine profile toward IL-10, providing new insights into the enigmatic mechanism of action of ECP

Allogeneic Bone-marrow Transplantation Following a Busulfan-based Conditioning Regimen in Young-children With Acute Lymphoblastic-leukemia - a Cooperative Study of the Societe-francaise-de-greffe-de-moelle

A subgroup of children with ALL remains at high risk of relapse despite the administration of intensive chemotherapeutic protocols and may benefit from allogeneic BMT. The cytoreductive regimen used most often combines TBI with cyclophosphamide. Nevertheless, miscellaneous long-term sequelae have been consequent upon radiotherapy, especially in young children. This retrospective multicentric study analyzes the outcome of children with ALL under 4 years of age receiving an HLA-genoidentical BMT following a radiation-free preparative regimen. A busulfan-based regimen with cyclophosphamide or melphalan +/- etoposide +/- cytarabine was given to 21 children (median age: 28 months, range 6-48). Sixteen patients with initial poor prognostic factors were transplanted in first complete response (CR) and five patients in relapse or second CR. With a median follow-up of 47 months, the results show an overall 4-year DFS of 61.1%. Leukemic recurrence was observed in eight patients. The preparative regimen was well-tolerated and there were no transplant-related deaths. A busulfan-based BMT preparative regimen may be a therapeutic alternative to TBI-containing regimens in young children. Efforts are currently aimed at reducing the relapse rate in these children by optimizing the tumoricidal potential of chemotherapy and the graft-versus-leukemia effect of allogeneic BMT