scholarly journals Monoclonal antibody T-cell-depleted HLA-haploidentical bone marrow transplantation for Wiskott-Aldrich syndrome

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1031-1035
Author(s):  
SL Rumelhart ◽  
ME Trigg ◽  
SD Horowitz ◽  
R Hong
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
T Cell ◽  
Marrow Transplantation ◽  
Cell Function ◽  
Chronically Ill ◽  
Good Health ◽  
Wiskott Aldrich Syndrome ◽  
Gvhd Prophylaxis ◽  
Number Of Patients

Four patients with Wiskott-Aldrich syndrome received bone marrow transplants (BMT) using monoclonal antibody T cell-depleted HLA- haploidentical marrow from a family member donor. The patients did not receive a significantly larger inoculum of mature T cells than other recipients of T cell-depleted marrow transplants. All four patients achieved quick engraftment, and three of the four patients are alive and well today. The three living patients have all had a complete return of normal T-cell and B-cell function. Infectious complications in the surviving patients were minimal; however, all three experienced some degree of graft-versus-host disease (GVHD). Two of these three patients received GVHD prophylaxis. The patient not receiving GVHD prophylaxis experienced severe GVHD and had a difficult posttransplant course. The patient who did not survive was chronically ill before BMT, whereas the other patients were in relatively good health at the time of BMT. Since the majority of individuals with this disease lack a matched bone marrow donor, our results using partially matched donors suggest that a greater number of patients can be successfully treated for Wiskott-Aldrich syndrome and that outcome is related to control of GVHD and state of health before BMT. Marrow transplantation should be offered earlier in the disease course before the onset of major infectious problems.

scholarly journals Monoclonal antibody T-cell-depleted HLA-haploidentical bone marrow transplantation for Wiskott-Aldrich syndrome

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1031-1035 ◽  
Author(s):  
SL Rumelhart ◽  
ME Trigg ◽  
SD Horowitz ◽  
R Hong
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
T Cell ◽  
Marrow Transplantation ◽  
Cell Function ◽  
Chronically Ill ◽  
Good Health ◽  
Wiskott Aldrich Syndrome ◽  
Gvhd Prophylaxis ◽  
Number Of Patients

Abstract Four patients with Wiskott-Aldrich syndrome received bone marrow transplants (BMT) using monoclonal antibody T cell-depleted HLA- haploidentical marrow from a family member donor. The patients did not receive a significantly larger inoculum of mature T cells than other recipients of T cell-depleted marrow transplants. All four patients achieved quick engraftment, and three of the four patients are alive and well today. The three living patients have all had a complete return of normal T-cell and B-cell function. Infectious complications in the surviving patients were minimal; however, all three experienced some degree of graft-versus-host disease (GVHD). Two of these three patients received GVHD prophylaxis. The patient not receiving GVHD prophylaxis experienced severe GVHD and had a difficult posttransplant course. The patient who did not survive was chronically ill before BMT, whereas the other patients were in relatively good health at the time of BMT. Since the majority of individuals with this disease lack a matched bone marrow donor, our results using partially matched donors suggest that a greater number of patients can be successfully treated for Wiskott-Aldrich syndrome and that outcome is related to control of GVHD and state of health before BMT. Marrow transplantation should be offered earlier in the disease course before the onset of major infectious problems.

Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4336-4343 ◽  
Author(s):  
Josef Kurtz ◽  
Juanita Shaffer ◽  
Ariadne Lie ◽  
Natalie Anosova ◽  
Gilles Benichou ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Cd4 T Cells ◽  
Marrow Transplantation ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance

Abstract Anti-CD154 (CD40L) monoclonal antibody (mAb) plus bone marrow transplantation (BMT) in mice receiving CD8 cell-depleting mAb leads to long-term mixed hematopoietic chimerism and systemic donor-specific tolerance through peripheral and central deletional mechanisms. However, CD4+ T-cell tolerance is demonstrable in vitro and in vivo rapidly following BMT, before deletion of donor-reactive CD4 cells is complete, suggesting the involvement of other mechanisms. We examined these mechanisms in more detail. Spot enzyme-linked immunosorbent (ELISPOT) analysis revealed specific tolerization (within 4 to 15 days) of both T helper 1 (Th1) and Th2 cytokine responses to the donor, with no evidence for cytokine deviation. Tolerant lymphocytes did not significantly down-regulate rejection by naive donor-reactive T cells in adoptive transfer experiments. No evidence for linked suppression was obtained when skin expressing donor alloantigens in association with third-party alloantigens was grafted. T-cell receptor (TCR) transgenic mixing studies revealed that specific peripheral deletion of alloreactive CD4 T cells occurs over the first 4 weeks following BMT with anti-CD154. In contrast to models involving anti-CD154 without BMT, BMT with anti-CD154 leads to the rapid induction of anergy, followed by deletion of pre-existing donor-reactive peripheral CD4+ T cells; the rapid deletion of these cells obviates the need for a regulatory cell population to suppress CD4 cell-mediated alloreactivity. (Blood. 2004;103:4336-4343)

scholarly journals Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 249-256 ◽  
Author(s):  
A Fischer ◽  
W Friedrich ◽  
A Fasth ◽  
S Blanche ◽  
F Le Deist ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Graft Failure ◽  
Cell Functions ◽  
Fanconi's Anemia ◽  
Fanconi’S Anemia ◽  
European Group

Abstract Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti- LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus- induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.

Reconstitution of the T-Cell Compartment After Bone Marrow Transplantation: Restoration of the Repertoire by Thymic Emigrants

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4464-4471 ◽  
Author(s):  
Florence Dumont-Girard ◽  
Etienne Roux ◽  
René A. van Lier ◽  
Geoff Hale ◽  
Claudine Helg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Cd4 T Cells ◽  
Marrow Transplantation ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Cell Compartment ◽  
Gvhd Prophylaxis

We have studied the reconstitution of the T-cell compartment after bone marrow transplantation (BMT) in five patients who received a graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate, cyclosporin, and 10 daily injections (day −4 to day +5) of Campath-1G. This treatment eliminated virtually all T cells (7 ± 8 T cells/μL at day 14) which facilitated the analysis of the thymus-dependent and independent pathways of T-cell regeneration. During the first 6 months, the peripheral T-cell pool was repopulated exclusively through expansion of residual T cells with all CD4+ T cells expressing the CD45RO-memory marker. In two patients, the expansion was extensive and within 2 months, the total number of T cells (CD8>>CD4) exceeded 1,000/μL. In the other three patients, T cells remained low (87 ± 64 T cells/μL at 6 months) and remained below normal values during the 2 years of the study. In all patients, the first CD4+CD45RA+RO− T cells appeared after 6 months and accumulated thereafter. In the youngest patient (age 13), the increase was relatively fast and naive CD4+ T cells reached normal levels (600 T cells/μL) 1 year later. In the four adult patients (age 25 ± 5), the levels reached at that time-point were significantly lower (71 ± 50 T cells/μL). In all patients, the T-cell repertoire that had been very limited, diversified with the advent of the CD4+CD45RA+RO− T cells. Cell sorting experiments showed that this could be attributed to the complexity of the T-cell repertoire of the CD4+CD45RA+RO− T cells that was comparable to that of a normal individual and that, therefore, it is likely that these cells are thymic emigrants. We conclude that after BMT, the thymus is essential for the restoration of the T-cell repertoire. Because the thymic activity is restored with a lag time of approximately 6 months, this might explain why, in particular in recipients of a T-cell–depleted graft, immune recovery is delayed.

scholarly journals Effects of anti-CD3 monoclonal antibody on engraftment of T-cell- depleted bone marrow allografts in mice: host T-cell suppression, growth factors, and space

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 3050-3058 ◽  
Author(s):  
K Hiruma ◽  
R Hirsch ◽  
M Patchen ◽  
JA Bluestone ◽  
RE Gress
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
T Cell ◽  
Cell Function ◽  
Bone Marrow Cells ◽  
Flow Cytometric Analysis ◽  
Peripheral Blood Lymphocytes ◽  
Serum Factors ◽  
T Cell Function ◽  
Allogeneic Marrow

Abstract To investigate the role of CD3-positive T cells in allogeneic marrow rejection in mice and to examine the effects of anti-CD3 monoclonal antibody (MoAb) on allogeneic marrow engraftment, a hamster MoAb, 145- 2C11, with specificity for the CD3 epsilon portion of the murine T-cell receptor complex was administered to B6 (H-2b) mice that had been sublethally irradiated with 626 cGy and injected with 10 x 10(6) T-cell- depleted B6C3F1 (H-2b/k) bone marrow cells. Lymphoid chimerism status was assessed by flow cytometric analysis of peripheral blood lymphocytes using H-2k-specific MoAb 5 to 6 weeks after bone marrow transplantation. When hosts were treated with 400 micrograms of anti- CD3 MoAb at the time of marrow injection, the percentage of donor-type cells was 75.2% +/- 15.0%, while it was 1.9% +/- 1.2% in untreated mice. It was demonstrated that anti-CD3 MoAb not only suppressed T-cell function but also induced colony-stimulating factors in host mice, and that enhancement of marrow engraftment in anti-CD3 MoAb-treated mice was associated with factor release as well as suppression of host T- cell function. Results were consistent with engraftment being enhanced by a differential response of donor (rather than host) marrow to serum factors in association with host T-cell immunocompromise.

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