Statement of current majority practices in graft-versus-host disease prophylaxis and treatment in children.

Great variations exist in the prophylaxis and treatment of GVHD in children undergoing allogeneic stem cell transplantation (SCT). The EBMT Working Party Paediatric Diseases (EBMT-WP PD) and the International BFM Study Group--Subcommittee Bone Marrow Transplantation (IBFM-SG), aimed at evaluating current local standards in the prevention and treatment of GVHD and steps which can be taken to achieve a uniform policy for the individual methods. Several conferences with their members assessed practices which are mainly applied or under investigation in children and identified where additional information is needed. For prevention of GVHD, the majority of the paediatric centres prefer CsA +/- MTX. Addition of folinic acid to MTX was considered for reduction of side-effects. During treatment of acute GVHD most centres administer prednisolone and whole blood level-adjusted CsA as medications of first choice. In cases of poor or no response to this therapy, additional immunosuppressive agents such as ATG, mycophenolate-mofetile and tacrolimus are being increasingly used. The treatment of chronic GVHD usually consists of various combinations of prednisolone and CsA. In severe cases, extracorporeal photopheresis, psoralene-UVA (PUVA) and thalidomide are administered

Bone marrow transplantation (BMT) in Europe for primary immunodeficiencies other than severe combined immunodeficieny: a report from the European Group for BMT and the European Group for Immunodeficiency

Bone marrow (BM) transplantations performed between 1977 and 1991 at 13 European centers in 149 patients with 11 different primary immunodeficiency (ID) diseases (excluding severe combined immunodeficiency) were analyzed retrospectively. Overall survival among recipients of HLA genetically identical BM (n = 56) was 66%. Since October 1985, the date of a previous survey, a significant improvement in survival has been achieved in most ID diseases (overall survival, 81.5% v 51.7%; P < .01), primarily because of a decrease in the frequency of infectious complications. In long-term survivors, disease correction is excellent, with minimal sequelae in most patients. In 22 patients who received closely matched BM (ie, from phenotypically identical related donors, matched unrelated donors, or one HLA-ag-mismatched related donors), the survival rate (45.5%) was not significantly better than among 71 recipients of BM with 2 or 3 mismatched HLA antigens (38%). In the latter group, favorable outcome was associated with younger age, with transplantation since October 1985 (47% v 25%; P < .0001), and with a diagnosis of leukocyte adhesion deficiency. The improvement in outcome was mainly because of a higher engraftment rate and a decrease in the frequency of infections, although Epstein-Barr virus-induced B-lymphocyte proliferative disorders occurred in 16 patients (mainly those with Wiskott-Aldrich syndrome), 10 of whom died. The improvement in engraftment corresponded to the introduction of treatment in vivo with anti-LFA-1 antibody to prevent rejection of T-cell-depleted grafts (74% engraftment and 45% survival in 38 treated patients versus 37.5% and 21%, respectively, in 24 untreated patients

Comparisons of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukaemia

In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]: 0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P <.07). In conclusion, the use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor

Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation

Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multicenter study, we analyzed the results of this approach using HLA-matched unrelated bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characteristics before and after transplant were provided by the European group blood and marrow transplant registry and were analyzed in collaboration with the European Fanconi Anemia Registry. The 3-year probability of survival was 33%. Extensive malformations, a positive recipient cytomegalovirus serology, the use of androgens before transplant, and female donors were associated with a worse outcome. Primary graft failures were observed more frequently when female donors were used, mainly because the grafts contained lower nucleated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus-host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminases before transplantation; limb, urogenital tract, or nephrologic malformations; and non-T-cell-depleted grafts were predictors of severe acute GVHD. This study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated donors. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure