Depletion of T Lymphocytes in Donor Marrow Prevents Significant Graft-Versus-Host Disease in Matched Allogeneic Leukaemic Marrow Transplant Recipients

Prentice, HG; Jánossy, G.; Price-Jones, L.; Trejdosiewicz, Ludwik K.; Panjwani, D.; Graphakos, Stelios; Ivory, Kamal; Blacklock, Hilary; Gilmore, M. J. M. L.; Tidman, N; Skeggs, D.; Ball, Sarah E.; Patterson, J.; Hoffbrand, A. V.

doi:10.1016/s0140-6736(84)92848-4

Cited by 333 publications

(85 citation statements)

References 28 publications

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“…The 5-year probability of chronic GVHD and its extensive manifestation is in the same range of HLA-identical T-celldepleted transplants in other studies (Blaise et al, 1993;Filipovich et al, 1982;Maraninchi et al, 1987;Marmont et al, 1991;Martelli & Aversa, 1993;Mitsuyasu et al, 1986;Naparstek et al, 1995;Prentice et al, 1984). In multivariate analysis we observed a relationship between the T-cell dose and the probability of developing chronic GVHD.…”

Section: Discussionsupporting

confidence: 75%

“…T-cell depletion is an effective prevention of GVHD as has been shown in experimental animal models and in man (Marmont et al, 1991;Prentice et al, 1984;van Bekkum, 1985). In the present analysis the probability of acute GVHD 5 grade 2 at day 100 after BMT compares favourably with the actuarial incidence of 40-80% in recipients of HLAidentical unmanipulated grafts and is comparable with figures from other studies on T-cell-depleted marrow Butturini & Gale, 1988;Goldman et al, 1988;Maraninchi et al, 1987;Marmont et al, 1991;Martelli & Aversa, 1993;Naparstek et al, 1995).…”

Section: Discussionmentioning

confidence: 94%

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Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Schaap¹,

Schattenberg²,

Bär³

et al. 1997

Br J Haematol

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Summary.One hundred and eighty-one consecutive patients with standard-risk leukaemia were transplanted with HLAidentical sibling grafts depleted of lymphocytes using counterflow centrifugation. In 116 patients, standard conditioning was intensified by the addition of anthracyclines.Multivariate analysis revealed significantly more acute GVHD 5 grade 2 and a trend towards more chronic GVHD in patients conditioned with the addition of anthracyclines. For all patients the risk for chronic GVHD, but not for acute GVHD, increased with a higher number of T cells in the graft. The projected 5-year probability of relapse was significantly lower in the group of patients conditioned with anthracyclines; 26% versus 52% (P ¼ 0 . 015). In multivariate analysis the addition of anthracyclines to the conditioning regimen was the only significant factor contributing to a lower probability of relapse. The projected 5-year probability of leukaemia-free survival [LFS] in the patients conditioned with and without the addition of anthracyclines was 56% and 36%, respectively (P ¼ 0 . 004). In multivariate analysis the addition of anthracyclines to the conditioning regimen correlated significantly with a lower number of mixed chimaeras in patients at 6 and 12 months after BMT. Mixed chimaerism at 6 months after transplantation did not significantly correlate with a higher incidence of relapse in further follow-up. In contrast, mixed chimaerism at 12 months after BMT was significantly associated with higher relapse rate.We conclude that the addition of anthracyclines to the conditioning regimen improves outcome of BMT using Tcell-depleted grafts.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 94%

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Schaap¹,

Schattenberg²,

Bär³

et al. 1997

Br J Haematol

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“…T lymphocyte depletion was performed on marrows from mismatched family members or matched unrelated donors using antibodies to CD3 in the presence of complement until March 1992, and antibodies to CD6 and CD8 in the presence of complement thereafter. [20][21][22][23] Surveillance cultures for viral pathogens from the throat, nasopharynx, blood and rectum were obtained twice weekly during hospitalization. Tracheal and conjunctival culture specimens were obtained when clinically indicated.…”

Section: Methodsmentioning

confidence: 99%

Adenovirus infection after pediatric bone marrow transplantation

Hale

Heslop

Krance

et al. 1999

Bone Marrow Transplant

241

209

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Summary:Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow transplants (BMT) at St Jude Children's Research Hospital between November 1990 and December 1994 identified 6% (seven male, six female) with adenovirus infection. The affected patients had a median age of 7.9 years (range 3-24 years) at time of transplantation. Although transplants were performed for hematologic malignancies, solid tumors or nonmalignant conditions, only patients with hematologic malignancies had adenoviral infections. Adenovirus was first detected at a median of 54 days (range ؊4 to ؉333) after BMT. Adenovirus developed in eight of 69 (11.6%) patients receiving grafts from matched unrelated or mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched siblings, and in one of 93 (1.1%) receiving autografts. The most common manifestation of adenovirus infection was hemorrhagic cystitis, followed by gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus infection in pediatric BMT patients at our institution is similar to that reported in adult patients. Using univariate analysis, use of total body irradiation and type of bone marrow graft were significant risk factors for adenovirus infection. Only use of total body irradiation remained as a factor on multiple logistic regression analysis.

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“…Male and female C57BL/10SnJ (1110, H-2 6 , KbIbSbDb), B10 .D2/nSn (1110.132, H-2d, KdIdSdDd), and A/J (H-2a, KIIISdDd) mice were obtained from The Jackson Laboratory Bar Harbor, ME, or from the Frederick Cancer Research Facility ofthe National Cancer Institute .…”

Section: Methodsmentioning

confidence: 99%

In vivo administration of interleukin 2 plus T cell-depleted syngeneic marrow prevents graft-versus-host disease mortality and permits alloengraftment.

Sykes

Romick

Hoyles

et al. 1990

The Journal of Experimental Medicine

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Avoiding graft-vs .-host disease (GVHD)' while retaining the engraftment-promoting and antileukemic effects of T cells in allogeneic marrow remains a major challenge in the field of bone marrow transplantation (BMT). While T cell depletion reduces the incidence of GVHD, it is associated with an increased probability ofengraftment failure (1-6) and a greater risk ofleukemic relapse (4, 5, 7). Previous work from this laboratory has demonstrated that the GVHD-related mortality of lethally irradiated, bone marrow-reconstituted mice can be delayed by the coadministration of T cell-depleted (TCD) syngeneic marrow (8). Although this result was encouraging, we have found the magnitude ofthe protection from acute GVHD mortality to be limited, and no protection from chronic GVHD mortality has been apparent (8). We therefore sought a method of augmenting this protective effect of TCD syngeneic marrow. We have previously demonstrated that TCD syngeneic marrow is responsible for most of the natural suppressor (NS) activity arising in spleens of lethally irradiated mice reconstituted with a mixture of allogeneic plus syngeneic marrow, and have hypothesized that such cells might be responsible for the anti-GVHD effect of TCD syngeneic marrow (9). Since cell lines with in vitro NS activity and in vivo anti-GVHD effects have been successfully cultured in IL-2 (10, 11; Sykes M., K. A. Hoyles, M. L. Romick, and D. H. Sachs, manuscript in preparation), we wished to address the possibility that the administration of IL-2 in vivo to lethally irradiated, bone marrow-transplanted mice might increase the anti-GVHD effect of TCD syngeneic bone marrow. Our results indicate that IL-2 provides significant protection against GVHD mortality from allogeneic lymphocytes while permitting complete repopulation by allogeneic bone marrow cells (BMC). When suboptimal amounts of IL-2 were given, maximal protection was achieved when TCD syngeneic marrow was also administered . Survivors protected in this manner similarly demonstrated complete allogeneic reconstitution .

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Depletion of T Lymphocytes in Donor Marrow Prevents Significant Graft-Versus-Host Disease in Matched Allogeneic Leukaemic Marrow Transplant Recipients

Cited by 333 publications

References 28 publications

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Adenovirus infection after pediatric bone marrow transplantation

In vivo administration of interleukin 2 plus T cell-depleted syngeneic marrow prevents graft-versus-host disease mortality and permits alloengraftment.

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