The depletion of T cells from haematopoietic stem cell transplants

Slaper‐Cortenbach, Ineke; Bois, M.; Rossen, A. de Vries-van; Borst, H. P. E.; Lelie, Hans van der; Heugten, Hans G. van; Verdonck, LF; Wulffraat, N. M.; Hoogerbrugge, Peter M.

doi:10.1093/rheumatology/38.8.751

Cited by 29 publications

(21 citation statements)

References 7 publications

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“…In this regard, the present approach is superior to those methods which rely purely on ex vivo means, such as magnetic beads, for removing donor T cells. 20,25 As with most clinical studies of stem cell transplantation, there are never sufficient patients to allow prospective randomized trials for comparing different treatments. Instead, we are obliged to rely on historical comparisons and a registry style of statistical analysis to elucidate significant trends.…”

Section: Discussionmentioning

confidence: 99%

CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells

Hale

Jacobs²,

Wood³

et al. 2000

Bone Marrow Transplant

154

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Summary:Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transplantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T cell depletion increases the risk of graft rejection. In this study, two strategies are used to overcome rejection: (1) use of high doses of stem cells obtained from peripheral blood (PBSC), (2) admixture with a CD52 monoclonal antibody in order to deplete both donor and residual recipient lymphocytes. Two antibodies are compared: CAMPATH-1G (rat IgG2b) and its humanized equivalent CAMPATH-1H (human IgG1). A total of 187 consecutive patients at six centers received PBSC transplants from HLA-matched siblings between 1997 and 1999. A wide spectrum of diseases, both malignant and non-malignant, was included. The recovery of CD34 + cells after antibody treatment was close to 100%. The risk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH-1G group and 4% in the CAMPATH-1H group (P = NS). The risk of chronic GVHD (any grade) was 11% in the CAMPATH-1G group and 24% in the CAMPATH-1H group (P = 0.03) but the risk of extensive chronic GVHD was only 2%. The overall risk of graft failure/rejection was 2%, not significantly different between the two antibodies. Antibody treatment was equally effective at concentrations between 10 g/ml and 120 g/ml and it made no significant difference to the outcome whether the patients received post-transplant immunosuppression or not (87% did not). Transplant-related mortality in this heterogenous group of patients (including high-risk and advanced disease) was 22% at 12 months. It is proposed that treatment of peripheral blood stem cells with CAMPATH-1H is a simple and effective method for depleting T cells which may be applicable to both autologous and allogeneic

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Section: Discussionmentioning

confidence: 99%

CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells

Hale

Jacobs²,

Wood³

et al. 2000

Bone Marrow Transplant

154

View full text Add to dashboard Cite

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“…In case of mismatching, T-cell depletion was performed by immunorosetting. 21 Peripheral blood stem cells from mismatched (related) donors were T-cell-depleted by CD34 purification (CliniMACS; Miltenyi Biotec, Auburn, CA, USA) and administered without CsA. GvHD was graded according to Glucksberg.…”

Section: Inclusion Of Patientsmentioning

confidence: 99%

Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation

et al. 2010

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Relapse of pediatric acute lymphoblastic leukemia (ALL) remains the main cause of treatment failure after allogeneic stem cell transplantation (alloSCT). A high level of minimal residual disease (MRD) before alloSCT has been shown to predict these relapses. Patients at risk might benefit from a preemptive alloimmune intervention. In this first prospective, MRD-guided intervention study, 48 patients were stratified according to pre-SCT MRD level. Eighteen children with MRD level X1 Â 10 À4 were eligible for intervention, consisting of early cyclosporine A tapering followed by consecutive, incremental donor lymphocyte infusions (n ¼ 1-4). The intervention was associated with graft versus host disease Xgrade II in only 23% of patients. Event-free survival in the intervention group was 19%. However, in contrast with the usual early recurrence of leukemia, relapses were delayed up to 3 years after SCT. In addition, several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence. In 8 out of 11 evaluable patients, relapse was preceded by MRD recurrence (median 9 weeks, range 0-30). We conclude that in children with high-risk ALL, immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells.

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“…8 The immunorosette depletion technique (CD2/3) was performed as described by Slaper-Cortenbach et al 9 In short, tetrameric complexes (CLB, Amsterdam, The Netherlands) were formed by addition of crosslinking RaMIgG1 Mabs to a mixture of murine IgG1 Mabs, one directed against glycophorin A in the membrane of human erythrocytes and another against T cell-specific antigens (CD2 or CD3). These complexes were then bound to donor erythrocytes (in the case of a MUD transplant obtained from a healthy O rhesus-negative donor from the blood bank) and the coated erythrocytes were washed.…”

Section: T and B Cell Depletionmentioning

confidence: 99%

Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique

Meijer

Slaper‐Cortenbach

Thijsen

et al. 2002

Bone Marrow Transplant

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The depletion of T cells from haematopoietic stem cell transplants

Abstract: Our own immunorosette depletion technique and the two tested CD34 selection methods for stem cell transplants both resulted in a very efficient T-cell depletion with the recovery of 40-60% of the CD34 haematopoietic stem cells present in the transplant.

Cited by 29 publications

References 7 publications

CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells

CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells

Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation

Increased incidence of EBV-associated lymphoproliferative disorders after allogeneic stem cell transplantation from matched unrelated donors due to a change of T cell depletion technique

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