Analysis of Rejection in HLA Matched T-Depleted Bone Marrow Transplants

Patterson, J.; Prentice, HG; Gilmore, M. J. M. L.; Blacklock, Hilary; Brenner, Malcolm K.; Jánossy, G.; Skeggs, D.; Ivory, Kamal; Av, Hoffbrand; Apperley, J.F.; Goldman, John M.; Burnett, Alan Kenneth; Gribben, JG; Alcorn, M.; Pearson, C.; McVickers, I.; Hann, Ian; Reid, C. D. L.; Wardle, D.; Bacigalupo, Andrea; Robertson, Anne S.

doi:10.1007/978-3-662-40457-7_93

Cited by 4 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pan-T cell depletion of donor marrow with immunotoxins greatly reduces the risk of GVHD in BMT patients (Blazar et al, 1987;Filipovich et al, 1987;Cobb & LeMaistre, 1992). However, the broad elimination of virtually all T cells contributes to two major problems: (1) allograft rejection by the recipient (O'Reilly et al, 1985;Patterson et al, 1985;Hale & Waldmann, 1986;Martin et al, 1988), and (2) greater likelihood of relapse owing to loss of the graft-versus-leukemia (GVL) effect (Apperley et al, 1986(Apperley et al, , 1988Martin et al, 1988;Pollard et al, 1986). …”

Section: Current Challenges In Allogeneic Bone Marrow Transplantationmentioning

confidence: 99%

Allograft and Autograft Purging Using Immunotoxins in Clinical Bone Marrow Transplantation for Hematologic Malignancies

Uckun¹,

Myers²

1993

Journal of Hematotherapy

View full text Add to dashboard Cite

Bone marrow manipulation is an essential procedure when bone marrow transplantation (BMT) is used to improve the chances of survival among high risk patients with hematologic malignancies. Ex vivo purging of donor T cells effectively prevents a fatal reaction known as graft-versus-host disease in allogeneic BMT. Ex vivo purging of residual leukemia cells from autologous marrow can virtually eliminate the risk of autograft contamination. Immunotoxins are powerful and selective reagents for these tasks. However, ex vivo purging may be insufficient by itself to overcome the high risk of relapse that confronts many patients undergoing autologous BMT. Bone marrow manipulation may even present problems of its own, such as loss of the graft-versus-leukemia effect when allogeneic marrow is T cell depleted. We are currently evaluating immunotoxins containing pokeweed antiviral protein in clinical trials as in vivo purging reagents that may reduce the risk of relapse for BMT patients.

show abstract

Section: Current Challenges In Allogeneic Bone Marrow Transplantationmentioning

confidence: 99%

Allograft and Autograft Purging Using Immunotoxins in Clinical Bone Marrow Transplantation for Hematologic Malignancies

Uckun¹,

Myers²

1993

Journal of Hematotherapy

View full text Add to dashboard Cite

show abstract

“…Rejection is rare when BMT is undertaken for leukaemia but occurs in 25% or more of patients transplanted for aplastic anaemia or thalassaemia [5]. Following the introduction of T-cell depletion, an unexpectedly high rejection rate was encountered [6], and it seems likely that infused donor T lymphocytes interact with the recipient immune system to block graft resistance/rejection. The implication of this is that if the donor marrow is T-depleted then the reci pient must receive more intensive or more immuno suppressive conditioning.…”

Section: Graft-versus-host Diseasementioning

confidence: 99%

Bone Marrow Transplantation in Acute or Chronic Leukaemia

Hg¹,

Brenner²

1987

Acta Haematol

View full text Add to dashboard Cite

Using T-depleted BM from HLA-identical sibling donors we have performed 36 BMTs since 5/83 in first remission (CR1) of acute leukaemia (AL). Standard conditioning for BMT consisted of Cy 60 mg/kg×2 and 7.5 Gy single fraction TBI (n = 27). Six patients received Ara-C 3 g/m²×6, Cy 45 mg/kg×2 and 7.5 Gy, while 3 received Cy 60 mg/kg×2 and 8 Gy radiation. T lymphocytes were depleted in vitro with 2 murine McAbs (MBG6 + RFT8, n= 17; or RFT8 + RFT12, n= 13; or RFT2, RFT8 + RFT12, n=6) plus rabbit C’-mediated lysis. No immunosuppressive therapy was given in the absence of graft-versus-host disease (GvHD). Of 34 patients evaluable for aGvHD, 4 had grade I, 2 grade II and 1 grade III. Chronic GvHD occurred in 3 of 22 evaluable patients ( > 150 days). There have been 13 deaths but only 1 from leukaemic relapse (CNS). The mean KS of surviving patients is 86% and actuarial disease-free survival is 53% at 40 months or 65% in those having ‘standard conditioning’. The previous major problems of GvHD and leukaemic relapse appear to have been largely overcome. The major risk factor now is infection, particularly pneumonitis, and this problem is surmountable

show abstract

Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation

Witte

Hoogenhout

Pauw

et al. 1986

Blood

View full text Add to dashboard Cite

Bone marrow from 22 histocompatible siblings was depleted of 98% of the lymphocytes using a combination of density flotation centrifugation followed by counterflow elutriation. Even with the marrow suppressive influence of methotrexate (MTX), the viability of the hematopoietic stem cells was not affected, as indicated by the normal repopulation after grafting in the evaluable patients. One patient (UPN 9) showed a primary graft failure, possibly resulting from persisting septicemia and long-term antibiotic therapy. Two patients have persistent host lymphocytes, one of whom was examined during relapse; the other remains in remission. Two patients did not receive immunosuppression after bone marrow transplantation (BMT), and acute graft-v-host disease (GVHD) developed in both. Nine patients received MTX as immunosuppression following BMT. GVHD did not develop in any of them, but fatal infections in the immediate posttransplant period developed in five patients. Eleven patients received cyclosporine (CsA) after transplantation. Beginning in week 5 after BMT, CsA was gradually replaced by MTX. Acute GVHD, substantial chronic GVHD, or fatal infections did not develop in any of these patients. Removal of 98% of the lymphocytes by counterflow centrifugation prevents development of acute GVHD, provided that immunosuppression is administered after BMT. Graft rejection was not observed, but the number of evaluable patients is limited at present.

show abstract

Analysis of Rejection in HLA Matched T-Depleted Bone Marrow Transplants

Cited by 4 publications

References 0 publications

Allograft and Autograft Purging Using Immunotoxins in Clinical Bone Marrow Transplantation for Hematologic Malignancies

Allograft and Autograft Purging Using Immunotoxins in Clinical Bone Marrow Transplantation for Hematologic Malignancies

Bone Marrow Transplantation in Acute or Chronic Leukaemia

Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation

Contact Info

Product

Resources

About