Immunoglobulin Therapy for Hematopoietic Stem Cell Transplant Recipients
Abstract & Commentary
Synopsis: Prophylactic administration of immunoglobin failed to demonstrate any benefit among recipients of an allogeneic hematopoietic stem cell transplant from HLA-identical sibling donors.
Source: Cordonnier C, et al. Should immunoglobulin therapy be used in allogeneic stem-cell transplantation? A randomized, double-blind, dose effect, placebo-controlled, multicenter trial. Ann Intern Med. 2003;139:8-18.
The European Blood and Marrow Transplantation (EBMT) group reported that more than half the participating centers admitted to giving immunoglobulin prophylactically to prevent post-transplant infections. However, the evidence supporting this practice was meager and unconvincing. This motivated Cordonnier and associates to conduct a randomized, double-blind, dose-effect placebo-controlled trial to assess the role and the dose-effect relationship of immunoglobulin to prevent infectious complications after allogeneic hematopoietic stem cell transplantation. Between 1998 and 2000, 19 centers in France recruited 200 patients who had allogeneic stem cell transplantation from HLA-identical sibling donors. Patients were randomly allocated to receive weekly, from 1 week before transplant through 100 days after, either placebo or 1 of 3 doses of immunoglobulin, namely 50 mg/kg, 250 mg/kg, or 500 mg/kg. The principal outcome measure was the cumulative incidence of infection during the first 6 months after transplant, which was 45 of 50 given placebo (90%), 49 of 53 (94%) given 50 mg/kg, 42 of 49 (86%) given 250 mg/kg, and 45 of 48 (94%) given 500 mg/kg. The cumulative incidences of the secondary outcome measures, interstitial pneumonia, graft-vs-host disease, and transplantation-related mortality were similar between the treatment groups, as was the overall survival, and there was no apparent dose-effect relationships with the possible exception of severe veno-occlusive disease, which occurred more frequently as the immunoglobulin dose increased.
Comment by J. Peter Donnelly, PhD
This study, the first of its kind to be reported, came some 2 decades after prophylactic immunoglobulin had been adopted and showed there to be no obvious benefit. However, we all know that lack of evidence is rarely of itself sufficient to change practice. Cordonnier et al anticipate this and point out that at the time hematopoietic stem cell transplantation was introduced, measures to prevent fungal infection and cytomegalovirus (CMV) infection were woefully inadequate. This has certainly changed for CMV as preemptive strategies that rely on early detection of virus activity and prompt administration of ganciclovir are well established. Dealing with fungal infection lags some way behind, but there are more agents available and early diagnosis is almost a reality. Moreover, giving immunoglobulin in this fashion is not without potential adverse effect. Hence, there is no need for using a blunderbuss approach without its problems since 7 (5%) of the 150 patients given immunoglobulin died of veno-occlusive disease, while none of the 50 given the placebo did. Thus, more patients were harmed than helped. The results will disappoint believers and confirm the views of those who have long regarded the strategy to be one of wishful thinking. It will be interesting indeed for the EBMT group to repeat their survey in a few months to see whether this evidence results in a change of practice.
Dr. Donnelly is Clinical Microbiologist University Hospital Nijmegen, The Netherlands Section Editor, Microbiology.
Prophylactic administration of immunoglobin failed to demonstrate any benefit among recipients of an allogeneic hematopoietic stem cell transplant from HLA-identical sibling donors.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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