Polyclonal anti-T-cell globulin as part of the preparative regimen for pediatric allogeneic stem-cell transplantation.
To prevent graft rejection and graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation (ASCT), 56 children were given polyclonal anti-T-cell globulin (ATG) as part of the conditioning regimen. Of the 56 children in the cohort, 27 had a non-malignant disease and 29 had different hematological malignancies. Eight were in first remission of leukemia and the remainder in later stages. Donors were in 16 cases a human leucocyte antigen (HLA)-identical sibling and in 40 a matched unrelated donor (MUD). The control group comprised 16 patients with an HLA-identical donor; the children in this group were not treated with ATG. Side-effects related to the ATG treatment occurred in 63% of the patients and included fever, chills, headache, dyspnoea, nausea/vomiting, body pain, fall in blood pressure, and transient respiratory arrest. Engraftment occurred in 55 (98%) of the ATG-treated patients at a median of 17 (11-27) days after ASCT. One rejection occurred at 23 days post-SCT. The probabilities of acute graft-versus-host disease (GvHD) of grades II-IV were 6% for patients with an HLA-identical donor, 12% for controls, and 26% for the MUD group. Chronic GvHD occured in 20%, 50%, and 50% of patients in the three groups, respectively. Transplant-related mortality rates at 100 days were 6%, 6%, and 7%, respectively. The 5-yr survival rate was 94% and 81% using sibling donors, with and without ATG respectively, and 53% using unrelated donors (p = 0.002). Disregarding donor type, among the ATG-treated patients 5-yr survival rates were 46% in patients with a malignant disease and 77% in non-malignant disorders. Relapse and relapse-free survival rates were 42% and 46%, respectively. Five out of 12 patients who showed an early full donor chimerism in the T-cell lineage developed acute GvHD of grades II-IV, compared to none out of 13 patients being mixed chimeras (p = 0.01). Hence, the use of polyclonal ATG as part of conditioning prior to ASCT in children is safe and the survival rate encouraging.
Remberger
M
M
Center for allogeneic stem-cell transplantation, Department of Clinical Immunology, F79 Karolinska Institutet, Huddinge University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. Mats.Remberger@impi.ki.se
Mattsson
J
J
Ringdén
O
O
D000293:Adolescent; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D012307:Risk Factors; D018709:Statistics, Nonparametric; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents