Elsevier

The Lancet

Volume 350, Issue 9080, 13 September 1997, Pages 767-771
The Lancet

Articles
Outcomes of transplantation with matched-sibling and unrelateddonor bone marrow in children with leukaemia

https://doi.org/10.1016/S0140-6736(97)03098-5Get rights and content

Summary

Background

For most conditions amenable to bone-marrow transplantation, grafts from HLA-matched but unrelated donors have yielded poorer results than those obtained from matched-sibling donors. We assessed this pattern in the light of improvements in donor selection and posttransplant supportive care.

Methods

We reviewed transplant outcome in 103 consecutive patients with childhood leukaemia who underwent allogeneic bone-marrow transplantation with HLA-matched sibling marrow (n=52) or matched unrelated donor marrow (n=51) between May, 1990, and March, 1996, at St Jude Children's Research Hospital.

Findings

Analysis of engraftment, frequency of procedurerelated complications, and disease-free survival revealed no advantage from use of matched-sibling marrow. The 2-year disease-free survival estimate for standard-risk recipients of matched-sibling marrow was 81 [8·1]% compared with 73 [12·1]% in the unrelated donor marrow group (p=0·77). In the high-risk category, patients with a matched-sibling donor had a 2-year disease-free survival of 31 [11·6]%, compared with 32 [15·1]% among recipients of matched unrelated donor marrow (p=0·87).

Interpretation

We believe this improved result with unrelated donor marrow is a consequence of recent innovations in histocompatibility matching, prevention of graft-versus-host disease (GvHD), and antiviral prophylaxis. We suggest that such grafts can now be used in patients at both standard and high risk without compromising treatment outcome.

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).

Section snippets

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

References (35)

  • AM Marmont et al.

    T-cell depletion of HLA-identical transplants in leukemia

    Blood

    (1991)
  • K Lucas et al.

    The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation

    Blood

    (1996)
  • JE Wagner et al.

    Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease

    Blood

    (1996)
  • F Aversa et al.

    Successful engraftment of T-cell depleted haploidentical “three loci” incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow incoculum

    Blood

    (1994)
  • PG Beatty et al.

    Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies

    Transplantation

    (1991)
  • MR Howard et al.

    Unrelated donor marrow transplantation between 1997 and 1987 at four centers in the United Kingdom

    Transplantation

    (1990)
  • R Szydlo et al.

    Results of allogeneic bone marrow transplants for leukemia using donors other than HLA identical siblings

    J Clin Oncol

    (1997)
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