Correspondence

Predictors of Acute Graft-versus-Host Disease in Bone Marrow Transplantation between HLA-Identical Siblings

N Engl J Med 1993; 328:1497-1498May 20, 1993

Article

To the Editor:

The informative paper by Theobald et al. on the prediction of acute graft-versus-host disease (GVHD) in bone marrow transplantation between HLA-identical siblings (Dec. 3 issue) states, “No practical test is currently available to identify . . . patients who are at risk for serious acute GVHD”1.

In their discussion the authors refer to several studies2-4 that have attempted to predict acute GVHD, with success. All these studies were based on knowledge of the in vitro allogeneic T-cell response, including activation, proliferation, differentiation, and effector functions. All were pilot studies that followed about 80 to 90 patients prospectively. All the studies1-4 were able to predict the risk of acute GVHD in transplantations between siblings.

None of these studies claim to explain the pathogenesis of acute GVHD, but the most important conclusion now is that they have confirmed one another. They provide the background for the conclusion that in vitro donor alloreactivity may be a risk factor for acute GVHD. Several risk factors have been described, many controversial, but the most likely seem to be pretransplantation variables related to pathogenesis1-4.

Hans E. Johnsen, M.D., Dr.Med.Sci.
Herlev Hospital, DK-2730, Herlev, Denmark

4 References

1. 1

   Theobald M, Nierle T, Bunjes D, Arnold R, Heimpel H. Host-specific interleukin-2-secreting donor T-cell precursors as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings. N Engl J Med 1992;327:1613-1617
   Full Text | Web of Science | Medline

2. 2

   Delmonte L, O'Reilly RJ, Kirkpatrick D, Kapoor N. In vitro model for detection of alloreactivity between HLA-matched donor-host pairs: preliminary evaluation as a predictor of graft-versus-host disease. Transplantation 1982;34:100-103
   CrossRef | Web of Science | Medline

3. 3

   Vogelsang GB, Hess AD, Berkman AW, et al. An in vitro predictive test for graft versus host disease in patients with genotypic HLA-identical bone marrow transplants. N Engl J Med 1985;313:645-650
   Full Text | Web of Science | Medline

4. 4

   Johnsen HE, Mickelson EM, Beatty PG, Hansen JA. Donor alloreactivity may predict acute graft-versus-host disease in patients receiving marrow transplants from HLA identical siblings. Bone Marrow Transplant 1992;9:91-96
   Web of Science | Medline

Author/Editor Response

Dr. Theobald replies:

To the Editor: Dr. Johnsen comments on the practicability of various in vitro assays that have been used to predict acute GVHD in bone marrow transplantation between HLA-identical siblings. It is our understanding that a clinically practical in vitro test for the prediction of GVHD has to be simple, timesaving, sensitive, and specific.

As discussed in our paper, the in vitro models described by Delmonte et al.1 and Vogelsang et al.2 had a reasonable predictive value but failed to meet the other criteria of practicability and thus did not have broad clinical application. The in vitro test described by Johnsen et al. measures overall donor T-cell alloreactivity rather than a specific donor anti-host T-cell response. The results seem to be statistically significant only if this assay is used in a population of patients with low-risk acute or chronic leukemias in first remission or chronic phase3.

Limiting-dilution analysis of host-specific donor T cells certainly meets the criteria of clinical practicability. Both the predictive value and the clinical practicability of frequency analysis of host-specific, interleukin-2-secreting donor T-cell precursors have been confirmed4. The quantitative assessment of these precursor T cells in the post-transplantation period also supports our conclusion that host-reactive interleukin-2-secreting donor T cells are critically involved in the pathogenesis of GVHD5.

Surely, prospective cooperative studies would be helpful in the search for the most clinically practical assay to predict GVHD in bone marrow transplantation between HLA-identical siblings.

Matthias Theobald, M.D.
The Scripps Research Institute, La Jolla, CA 92037

5 References

1. 1

   Delmonte L, O'Reilly RJ, Kirkpatrick D, Kapoor N. In vitro model for detection of alloreactivity between HLA-matched donor-host pairs: preliminary evaluation as a predictor of graft-versus-host disease. Transplantation 1982;34:100-103
   CrossRef | Web of Science | Medline

2. 2

   Vogelsang GB, Hess AD, Berkman AW, et al. An in vitro predictive test for graft versus host disease in patients with genotypic HLA-identical bone marrow transplants. N Engl J Med 1985;313:645-650
   Full Text | Web of Science | Medline

3. 3

   Johnsen HE, Bostrom L, Moller J, Jorgensen JA, Jensen L, Ringden O. A study of donor alloreactivity, which may predict acute graft-versus-host disease in HLA identical bone marrow transplantations for early leukaemia. Scand J Immunol 1992;35:353-360
   CrossRef | Web of Science | Medline

4. 4

   Schwarer AP, Jiang YZ, Brookes PA, et al. Frequency of anti-recipient alloreactive helper T-cell precursors in donor blood and graft-versus-host disease after HLA-identical sibling bone-marrow transplantation. Lancet 1993;341:203-205
   CrossRef | Web of Science | Medline

5. 5

   Nierle T, Bunjes D, Arnold R, Heimpel H, Theobald M. Quantitative assessment of posttransplant host-specific interleukin-2-secreting T-helper cell precursors in patients with and without acute graft-versus-host disease after allogeneic HLA-identical sibling bone marrow transplantation. Blood 1993;81:841-848
   Web of Science | Medline