ArticlesOutcomes of transplantation with matched-sibling and unrelateddonor bone marrow in children with leukaemia
Introduction
Allogeneic bone-marrow transplantation is effective against many childhood leukaemias that respond poorly to conventional therapies. However, fewer than a third of patients who might benefit from this procedure have an HLA-identical sibling-traditionally the donor of choice. For the remaining patients, use of a closely HLA-matched unrelated donor is an option, though its associated mortality rate (30–50% in many series) is higher than for procedures that rely on matched siblings.1, 2, 3, 4 For most conditions amenable to transplantation, marrow grafts from unrelated donors have resulted in lower disease-free survival, partly owing to higher frequencies of graft rejection,5 graft-versus-host disease (GvHD),6 and severe infections,7 many of which are viral.8 Consequently, allogeneic bone-marrow transplantation tends to be reserved for patients with high-risk features; others are excluded because of a perceived increase in the risk of transplant-related complications.
During the past few years, modifications of transplantation with matched unrelated-donor bone marrow have made the procedure more viable. These modifications include improvements in GvHD prophylaxis;9, 10 molecular techniques for donor-recipient histocompatibility matching;11 the development of regimens to prevent cytomegalovirus;12, 13 and Epstein- Barr virus14, 15 infections, both of which are leading viral causes of death after bone-marrow transplantation from matched unrelated donors. To assess the clinical impact of these innovations, we compared the result of transplantation with either matched-unrelated-donor or matched-sibling bone marrow for a large series of leukaemia patients treated at St Jude Children's Research Hospital (Memphis, TN, USA).
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Patients and methods
We studied 103 consecutive patients who received matchedsibling (n=52) or matched-untreated-donor (n=51) marrow grafts for leukaemia between May, 1990, and March, 1996. This number represented all patients with leukaemia who received transplantation from a matched sibling or matched-unrelateddonor, with the exception of six recipients of matched-sibling marrow who had been treated on a protocol that yielded an excessive incidence of GvHD; they were excluded from analysis and reported separately.
Results
Patients in the two transplant groups were closely matched for age, sex, and risk factors (table 1). Of the 51 patients who received marrow from an unrelated donor, 32 (63%) had a six/six HLA antigen match with DRβ1 identity by molecular typing, whereas 19 (37%) had a five/six HLA antigen match. There were four mismatches at the HLA-A locus, eight at HLA-B, and seven DRB1 mismatches. All sibling recipients were fully matched at all six HLA loci.
The course of transplantation in patients
Discussion
Our analysis supports the perception that advances in HLA typing, GvHD prevention, and antiviral prophylaxis have improved the results of allogeneic bone-marrow transplantation for patients without an HLA-identical sibling.9, 11, 22, 23, 24, 25 Apart from platelet engraftment, which was delayed by 12 days in the unrelated donor group, the endpoints of our study-engraftment, frequency of acute or chronic GvHD, leukaemic relapse rate, performance status, and disease-free survival-were unaffected
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