Matched, Unrelated Bone Marrow Transplants Prove Equivalent for Patients with Chronic Phase CML
Matched, Unrelated Bone Marrow Transplants Prove Equivalent for Patients with Chronic Phase CML
ABSTRACT & COMMENTARY
Synopsis: Transplantation of bone marrow from unrelated but matched donors has been previously reported to be associated with less favorable clinical outcomes when compared to those from matched sibling donors. In this report from the transplant program at the University of Minnesota, the data from 141 consecutively treated chronic myelogenous leukemia patients were examined to determine if there was a difference in outcome for those receiving unrelated marrow. This was a retrospective, uncontrolled review, but the data suggest comparable clinical outcomes for recipients of matched, unrelated bone marrow.
Source: Davies SM, et al. Am J Med. 2001;110:
404-405.
The purpose of the report from the transplantation program at the University of Minnesota was to examine their accumulated experience with allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) with regard to the clinical outcomes using matched but unrelated donors compared with matched, related donors. The experience between 1983 through 1997 of 141 (96 matched, sibling donor and 45 matched, unrelated donor) transplants for chronic phase CML was reviewed. All were HLA-A,B/DRB1 matched. The median age of matched sibling donor recipients was 38 years (range, 8-56) and of unrelated donor recipients was 35 years (range, 3-53), and the median range of follow-up was 6 years (range, 1-15) in matched sibling donor recipients and 5 years (range, 2-10) in unrelated donor recipients.
There was no significant difference in the 5-year survival rates of matched sibling donor recipients (58%; 95% confidence interval [CI], 48-68%) and unrelated donor (53%; 95% CI, 39-67%; P = .4). Among people who underwent transplant within 1 year after diagnosis, the 5-year survival rate of matched sibling donor recipients (76%; 95% CI, 65-87%) was not significantly different (P = .5) from that of unrelated donor recipients (70%; 95% CI, 52-88%). In multiple regression analysis, longer time from diagnosis to transplantation, T-cell depletion, and grades III or IV graft vs. host disease were independently associated with poorer survival. Transplantation of unrelated donor bone marrow was not associated with increased mortality (relative risk, 1.1; 95% CI, 0.6-2.1; P = .7).
COMMENT by William B. Ershler, MD
This is a retrospective review of 2 groups of early-phase transplanted CML patients; one with matched sibling donors, and the other with matched, unrelated donors. Although there are inherent difficulties in an analysis such as this, it was heartening to note the apparent success of recipients of unrelated donor transplants, comparable to those with sibling donors. The data are in contrast to earlier reports in which complications were greater and survival less for recipients of unrelated marrow,1 but is similar to a more recent series of CML patients treated with unrelated bone marrow grafts2 in which the survival rate at 5 years was 57% for those transplanted during early chronic phase. Presumably, the improved clinical outcomes with unrelated donors resulted from more precise methods of matching and more successful prevention and/or management of graft vs. host disease, graft failure, and late infections.
Thus, it is apparent that transplantation of bone marrow from a matched sibling donor or an HLA-A,B/DRB1-matched unrelated donor produces comparable outcomes in patients with CML, particularly if the transplant takes place within the first year. With the expansion of the national and international bone marrow transplant registries, there are now more than 6 million registered donors, and the likelihood of identifying at least one 6-antigen-matched donor is approximately 75%. Consequently, marrow transplantation during early phase CML is a reasonable, and increasingly available, treatment option.
Alternatives, of course include chemotherapies, such as hydroxyurea or busulfan, which may successfully control symptoms, but offer no curative potential and may not even prolong survival.3,4 Interferon-alpha, administered early and in sufficient doses, has resulted in complete cytogenetic remissions, and for these patients survival is likely to be enhanced. Interferon treatment, however, may reduce the success of subsequent transplantation.5 Patients and oncologists are anxious to hear more about the tyrosine kinase inhibitor STI 571, an oral agent that inhibits the Bcr-Abl transcript and has led to complete cytogenetic responses in many patients, particularly those in chronic phase.6 Just where this agent will fit in the management of CML, particularly in the context of the potentially curative transplantation schemes, is yet to be established, but no doubt will be the subject of future intensive research.
In the meantime, it is reassuring to know that transplantation with unrelated marrow is producing good results. Hopefully, such will also be the case for unrelated donor transplants for other diseases, such as lymphoma and acute leukemia.
References
1. Kernan NA, et al. N Engl J Med. 1993;328:593-602.
2. Hansen JA, et al. N Engl J Med. 1998;338:962-968.
3. Hehlmann R, et al. Blood. 1994;84:4064-4077.
4. Hasford J, et al. Blood. 1996;87:5384-5391.
5. Beelan DW, et al. Blood. 1995;85:2981-2990.
6. Talpaz M, et al. Blood. 2000;96:49A.
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