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CORRESPONDENCE Acute graft-versus-host disease (AGVHD) complicates donor
lymphocyte infusion (DLI) treatment in 40% to 60% of
cases.1,2 Although factors predictive of GVHD after
allogeneic stem cell transplantation (SCT) could also be valid after
DLI, patients receiving DLI are a select group, having survived the
GVHD after transplantation and relapsed. We therefore investigated the
role of possible factors in the development of AGVHD after DLI. Sixty-three consecutive patients with BCR-ABL-positive chronic
myeloid leukemia (CML) who relapsed after allogeneic SCT (31 from their
respective HLA-identical siblings and 32 from volunteer-matched unrelated donors) were started on treatment with DLI between August 1990 and April 1999. At the time of DLI, 7 patients were in molecular relapse, 15 were in cytogenetic relapse, and 26 were in hematologic relapse (19 in chronic phase, 7 in accelerated phase). Twenty-seven patients received a single infusion of donor lymphocytes (bulk-dose regimen [BDR]), and 36 patients received lymphocytes according to our
escalating-dose regimen (EDR).3 Molecular remission was
defined as the absence of detectable BCR-ABL transcripts by reverse
transcriptase-polymerase chain reaction (RT-PCR) analysis of
peripheral blood on 2 consecutive occasions.4 AGVHD was graded according to the Glucksberg criteria.5 Grades II to IV were deemed of clinical significance. Forty-five patients (71%) treated with DLI achieved molecular
remission. Fifteen patients (24%) developed grade II to IV AGVHD, 48 patients (76%) showed no or minimal AGVHD. Results of the univariate analyses are presented in Table 1. No
association was found between AGVHD after DLI and AGVHD after
transplantation. The vast majority of patients who developed AGVHD
following DLI treatment did not have a history of AGVHD after their
original transplantation. Recipient-donor sex mismatch, patient-donor
CMV seropositivity, and increasing patient age (> 35 years) were found
to be significantly associated with AGVHD in the DLI setting. In accord
with previous observations,1,2 patients who received
T-cell-replete allografts suffered less AGVHD after DLI compared to
those who received a T-cell-depleted stem cell preparation. We did not
observe any association between achievement of complete remission and
development of AGVHD. This finding contrasts with the results reported
by other groups, whereby 89% of the responders suffered
AGVHD.6 Such a difference may be attributed to the high
proportion of patients receiving DLI according to an EDR in our study.
In fact, the influence of method of administration was highly
significant. In a multivariate logistic analysis, any positive
patient-donor CMV serostatus (relative risk [RR] = 19.5,
P = .013), BDR (RR = 9.4, P = .008),
and T-cell depletion (TCD) at transplantation (RR = 21.9,
P = .011) were found to be independent predictors of GVHD
after DLI. Although there is more AGVHD associated with patient-donor sex mismatch, in the mismatch-only group
there is considerably more AGVHD associated with the use of BDR than
with EDR (9 of 16 patients vs 2 of 11 patients, P = .048);
this explains why sex mismatch is not significant in the multivariate
analysis.
Our findings demonstrate that most of the factors known to be associated with AGVHD after allogeneic SCT are not predictive of AGVHD following DLI. Our data reinforce the notion that DLI can be safe if the effective cell dose is administered late after transplantation3,7; this has important practical implications for the use of DLI in the context of reduced-intensity conditioning SCT.
Francesco Dazzi, Richard M. Szydlo, Jane F. Apperley, and John M. Goldman
References
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Kolb HJ, Schattenberg A, Goldman JM, et al.
Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients: European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia.
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1995;86:2041-2050
2.
Sehn LH, Alyea EP, Weller E, et al.
Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion.
J Clin Oncol.
1999;17:561-568
3.
Dazzi F, Szydlo RM, Craddock C, et al.
Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia.
Blood.
2000;95:67-71
4.
Dazzi F, Szydlo RM, Cross NC, et al.
Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.
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2000;96:2712-2716 5. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295-304[Medline] [Order article via Infotrieve]. 6. Porter DL, Collins RH Jr, Shpilberg O, et al. Long-term follow-up of patients who achieved complete remission after donor leukocyte infusions. Biol Blood Marrow Transplant. 1999;5:253-261[CrossRef][Medline] [Order article via Infotrieve].
7.
Johnson BD, Truitt RL.
Delayed infusion of immunocompetent donor cells after bone marrow transplantation breaks graft-host tolerance allows for persistent antileukemic reactivity without severe graft-versus-host disease.
Blood.
1995;85:3302-3312   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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