Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients

Kolb, Hans Jochem; Mittermüller, J.; Clemm, Ch.; Holler, Ernst; Ledderose, Georg; Brehm, G.; Heim, M. U.; Wilmanns, W.

doi:10.1182/blood.v76.12.2462.2462

Cited by 1,387 publications

(306 citation statements)

References 20 publications

Supporting

Mentioning

294

Contrasting

Unclassified

Order By: Relevance

“…Especially in patients with a relapse from CML after BMT, treatment with infusion of lymphocytes from the original marrow donor may induce second complete remission (Cullis et al, 1992;Drobyski et al, 1992;Kolb et al, 1990Kolb et al, , 1995. 11 patients who relapsed from CML-CP1 were treated with lymphocyte infusions from the donor and nine patients (82%) responded.…”

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Problems associated with DLI, including GVHD or delayed response (usually 4 weeks), prompted mHag researchers to test the effects of adoptive immunotherapy with mHag-specific CTL clones against recurrent leukemia. (3) A protocol to generate HA-1 H and HA-2 V specific T-cell lines from mHag-negative donors was proposed for adoptive immunotherapy. (15) Another adoptive immunotherapy trial using CTL clones that lyse hematopoietic cells but not dermal fibroblasts has been performed in the Fred Hutchinson Cancer Research Center, (50) where a dramatic decline of cytomegalovirus (CMV)-related disease has already been demonstrated by adoptive transfer of CMV-specific CTL clones.…”

Section: Clinical Application Of Mhagmentioning

confidence: 99%

Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions

et al. 2007

View full text Add to dashboard Cite

Minor histocompatibility antigens (mHag) were originally identified as antigens causing graft rejection or graft-versus-host disease in human leukocyte antigen (HLA)-matched allogeneic transplantation. Molecular identification has revealed most to be major histocompatibility complex (MHC)-bound short peptide fragments encoded by genes which are polymorphic due to single nucleotide polymorphisms (SNP). Genotypic disparity of SNP between transplantation donors and recipients gives rise to mHag as non-self antigens for both the donor and the recipient. Subsequently, mHag have been explored as immunotherapeutic antigens for use against recurring hematological malignancies after allogeneic hematopoietic cell transplantation (HCT), because mHag expressed only on hematopoietic cells are considered to augment graft-versusleukemia/lymphoma (GVL) effects without increasing the risk of life-threatening graft-versus-host disease (GVHD). Accumulating evidence suggests that T-cell responses to mHag aberrantly expressed on solid tumor cells are also involved in the eradication of sensitive tumors such as renal cell carcinomas following HCT. Over the past decade, the number of putative GVL-directed mHag has increased to a level that covers more than 30% of the Japanese patient population, so that clinical trials may now be executed in the setting of either vaccination or adoptive immunotherapy. As it is expected that immune responses to alloantigens are more powerful than to tumor antigens mostly derived from overexpressed selfproteins, mHag-based immunotherapy may lead to a new treatment modality for high-risk malignancies following allogeneic HCT.

show abstract

“…Recently, it has been shown that the administration of donor leucocytes given at the time of leukaemic relapse after allogeneic BMT can produce haematological and cytogenetic remissions ( Jiang et al, 1993;Kolb et al, 1990;Porter et al, 1994;Szer et al, 1993). However, the high incidence of severe GVHD and prolonged periods of pancytopenia induced by the infusion of immunocompetent T lymphocytes represent major obstacles to the success of this therapy.…”

Section: Gvhdmentioning

confidence: 99%

Allogeneic MHC‐mismatched activated natural killer cells administered after bone marrow transplantation provide a strong graft‐versus‐leukaemia effect in mice

et al. 1997

View full text Add to dashboard Cite

Summary. Allogeneic lymphocytes administered with an unmanipulated bone marrow transplant provide a strong antileukaemic effect, the so-called graft-versus-leukaemia (GVL) effect. On the other hand, T-cell-mediated graftversus-host-disease (GVHD) observed after transplantation of unmanipulated BM graft causes substantial morbidity and mortality. The aim of the present study was to determine the antileukaemic potential of enriched IL-2 activated NK cells administered 2 h after BMT. Balb/c (H-2 d ) mice were given a dose of A20 (H-2 d , B-cell leukaemia) cells 2 d prior to lethal total body irradiation (TBI) and transplantation of either syngeneic or allogeneic anti-Thy1.2 (CD90) depleted bone marrow cells. Either syngeneic (Balb/c, H-2 d ) or allogeneic (C57BL/6, H-2 b ) enriched and IL-2 (200 U/ml for 24 h) activated NK cells were given 2 h after BMT. Injection of A20 leukaemia into normal Balb/c recipients led to death after a median of 14 d. A lethal dose of TBI followed by either syngeneic or allogeneic Thy1.2-depleted BMT resulted in a modest antileukaemic effect. The adoptive transfer of syngeneic enriched and IL-2 preincubated NK cells given at time of BMT exerted a significantly better GVL effect. However, the infusion of allogeneic enriched NK cells resulted in a stronger GVL effect. These results clearly demonstrate that allogeneic NK cells are superior to syngeneic NK cells in their potential to eradicate residual leukaemia cells after BMT without mediating clinical overt GVHD. This experimental setting may offer a strategy for treatment of haematological malignancies in a phase of minimal residual disease.

show abstract

Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients

Cited by 1,387 publications

References 20 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

Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions

Allogeneic MHC‐mismatched activated natural killer cells administered after bone marrow transplantation provide a strong graft‐versus‐leukaemia effect in mice

Contact Info

Product

Resources

About