scholarly journals Mixed hematopoietic chimerism after allogeneic transplantation with lymphocyte-depleted bone marrow is not associated with a higher incidence of relapse

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1367-1372 ◽  
Author(s):  
A Schattenberg ◽  
T De Witte ◽  
M Salden ◽  
J Vet ◽  
B Van Dijk ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Allogeneic Bone Marrow Transplantation ◽  
High Sensitivity ◽  
Lymphocyte Culture ◽  
Mixed Chimerism ◽  
Allogeneic Bone ◽  
Red Cell ◽  
Marrow Graft ◽  
Mixed Chimeras

Abstract Using red cell phenotyping, cytogenetic analysis of blood lymphocytes, chromosome studies of bone marrow cells, and restriction fragment length polymorphism (RFLP) studies of peripheral blood cells, we demonstrated a high number of mixed chimeras after allogeneic bone marrow transplantation (BMT). Donor marrow from HLA-A, -B, and -DR identical, mixed lymphocyte culture (MLC) nonreactive siblings was depleted of 98% of lymphocytes using counterflow centrifugation. Thirty- two of 48 recipients (67%) appeared to be mixed chimeras at 6 months after transplantation. The high number of mixed chimeras is probably a result of lymphocyte depletion of the marrow graft and the high sensitivity of red cell phenotyping for the demonstration of minor cell populations (at levels as low as 0.01%). The probability of relapse- free survival from 6 months to 4 years after BMT was 85% for the mixed chimeras and 65% for the complete donor chimeras. We conclude that in this study, mixed chimerism is not associated with a higher incidence of relapse.

scholarly journals Mixed hematopoietic chimerism after allogeneic transplantation with lymphocyte-depleted bone marrow is not associated with a higher incidence of relapse

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1367-1372 ◽  
Author(s):  
A Schattenberg ◽  
T De Witte ◽  
M Salden ◽  
J Vet ◽  
B Van Dijk ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Allogeneic Bone Marrow Transplantation ◽  
High Sensitivity ◽  
Lymphocyte Culture ◽  
Mixed Chimerism ◽  
Allogeneic Bone ◽  
Red Cell ◽  
Marrow Graft ◽  
Mixed Chimeras

Using red cell phenotyping, cytogenetic analysis of blood lymphocytes, chromosome studies of bone marrow cells, and restriction fragment length polymorphism (RFLP) studies of peripheral blood cells, we demonstrated a high number of mixed chimeras after allogeneic bone marrow transplantation (BMT). Donor marrow from HLA-A, -B, and -DR identical, mixed lymphocyte culture (MLC) nonreactive siblings was depleted of 98% of lymphocytes using counterflow centrifugation. Thirty- two of 48 recipients (67%) appeared to be mixed chimeras at 6 months after transplantation. The high number of mixed chimeras is probably a result of lymphocyte depletion of the marrow graft and the high sensitivity of red cell phenotyping for the demonstration of minor cell populations (at levels as low as 0.01%). The probability of relapse- free survival from 6 months to 4 years after BMT was 85% for the mixed chimeras and 65% for the complete donor chimeras. We conclude that in this study, mixed chimerism is not associated with a higher incidence of relapse.

scholarly journals Influence of cell dose and graft-versus-host reactivity on rejection rates after allogeneic bone marrow transplantation

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1612-1621 ◽  
Author(s):  
L Uharek ◽  
W Gassmann ◽  
B Glass ◽  
J Steinmann ◽  
H Loeffler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Marrow Graft ◽  
Graft Versus Host ◽  
Mhc Antigens ◽  
Number Of Cells ◽  
Rejection Rates ◽  
Marrow Cells

Abstract The number of cells transplanted and their capacity to induce graft- versus-host reactivity (GvHR) are two factors that are suspected to influence the engraftment of allogeneic bone marrow. We have investigated their impact on graft rejection rates in busulfan-treated LEW rats. In a series of experiments, we varied (1) the number of marrow cells transferred (1, 5, 10, 20, 30, and 40 x 10(7)), (2) the degree of pretransplant immunosuppression (1.5, 3.0, and 4.5 Gy of total body irradiation [TBI]; 0, 30, 60, 90, 120, and 180 mg/kg cyclophosphamide), and (3) the ability of the marrow graft to induce classical GvHR against major histocompatibility complex (MHC) antigens [semiallogeneic (CAP x LEW)F1 or CAP rats as marrow donors]. Reducing either the immunosuppressive pretreatment or the number of cells transplanted resulted in a stepwise increase in rejection rates. However, every reduction in the size of the marrow inoculum was compensated by increased immunosuppression and vice versa. While 60 mg/kg cyclophosphamide was sufficient to prevent rejections after grafting of 40 x 10(7) cells, 90 mg/kg was necessary to ensure 100% engraftment after transplantation of 20 x 10(7) cells, 120 mg/kg after 10 x 10(7) cells, and 180 mg/kg after 1 x 10(7) cells. Since CAP marrow leads to GvHR-mediated immunosuppression in LEW recipients, in contrast to (CAP x LEW)F1 marrow, we had supposed that lower cell numbers or cyclophosphamide doses are sufficient to achieve engraftment of CAP marrow. Although severe GvHR was present in all animals receiving escalating doses of CAP cells, the rejection rates were the same as for (CAP x LEW)F1 marrow. In conclusion, we have demonstrated that there is a sensitive balance between the immunosuppression of the host and the number of marrow cells transferred. We were not able to number of marrow cells transferred. We were not able to detect a beneficial effect of classical GvHR against MHC antigens on the engraftment of allogeneic marrow. Thus, our results do not support the hypothesis that the loss of GvHR-mediated immunosuppression is responsible for higher rejection rates following transplantation of T-cell-depleted bone marrow.

scholarly journals Mixed T-lymphoid chimerism after allogeneic bone marrow transplantation for hematologic malignancies of children is not correlated with relapse

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1921-1928 ◽  
Author(s):  
JE van Leeuwen ◽  
MJ van Tol ◽  
AM Joosten ◽  
JT Wijnen ◽  
PM Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Cell Lineage ◽  
Hematologic Malignancies ◽  
Mixed Chimerism ◽  
Cell Populations ◽  
Allogeneic Bone ◽  
Leukemia Relapse

Abstract We performed polymerase chain reaction-variable number of tandem repeats analysis of flow-sorted peripheral blood T-, B-, natural killer- , and myeloid cell populations (van Leeuwen et al, Br J Haematol 79:218, 1991) in 32 children following allogeneic bone marrow transplantation (BMT) for leukemia to evaluate the relationship between mixed lymphoid chimerism and leukemia relapse. Five patients showed a stable mixed chimerism pattern characterized by the presence of both recipient as well as donor type cells in all cell populations up to 1 year posttransplantation. Five others showed transient mixed chimerism in the T-lymphoid cell lineage. In one patient, host T cells persisted until leukemia relapse. The remaining 21 patients showed a complete chimerism throughout the period of investigation. Twenty-five of these patients were classified according to the presence (n = 10) or absence (n = 15) of recipient type T cells. Statistical analysis did not show significant differences in the distribution of a number of clinical variables between the two groups, nor in the actuarial survival (P = .11) and leukemia-free interval (P = .97). Therefore, these results suggest that persistence of recipient type T lymphoid cells after allogeneic BMT for hematologic malignancies is not correlated with leukemia relapse. In addition, we observed that persistence of host cells within the original leukemia cell lineage and at the correct maturational stage was predictive for leukemia relapse in one case.

scholarly journals Constitutive Expression of a CD44 Variant Isoform on T Cells Facilitates Regaining of Immunocompetence in Allogeneic Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 873-885 ◽  
Author(s):  
Margot Zöller ◽  
Annette Schmidt ◽  
Angela Denzel ◽  
Jürgen Moll
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Bone Marrow Cells ◽  
Allogeneic Bone Marrow Transplantation ◽  
Constitutive Expression ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Cd44 Variant

Abstract Constitutive expression of a rat CD44 variant isoform, rCD44v4-v7, on murine T cells accelerates immune responsiveness. Because prolonged immunodeficiency can be a major drawback in allogeneic bone marrow transplantation, we considered it of special interest to see whether repopulation of lethally irradiated syngeneic and allogeneic mice may be influenced by constitutive expression of the rCD44v4-v7 transgene. When lethally irradiated syngeneic and allogeneic mice were reconstituted with bone marrow cells (BMC) from rCD44v4-v7 transgenic (TG) or nontransgenic (NTG) mice, the former had a clear repopulation advantage: thymocytes expanded earlier after reconstitution and, as a consequence, higher numbers of lymphocytes were recovered from spleen and lymph nodes. Lymphocytes also displayed functional activity in advance to those from mice reconstituted with BMC from NTG mice. Most importantly, after the transfer of BMC from TG mice into an allogeneic host, the frequency of host-reactive T cells decreased rapidly. Apparently, this was due to accelerated induction of tolerance. Because these effects were counterregulated by an rCD44v6-specific antibody, it is likely that they could be attributed to the rCD44v4-v7 TG product. Thus, expression of a CD44 variant isoform at high levels facilitated reconstitution with allogeneic BMC by accelerated establishment of tolerance and the regaining of immunocompetence.

Mixed Chimerism of Erythro- and Megakaryopoiesis following Allogeneic Bone Marrow Transplantation

2003 ◽  
Vol 109 (4) ◽  
pp. 176-183 ◽  
Author(s):  
J. Thiele ◽  
C. Wickenhauser ◽  
H.M. Kvasnicka ◽  
E. Varus ◽  
C. Schneider ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Mixed Chimerism ◽  
Allogeneic Bone

Subtyping of erythrocyte phosphoglucomutase-1 as a genetic marker for bone-marrow engraftment and hematopoietic chimerism after allogeneic bone-marrow transplantation in a patient with acute lymphoblastic leukemia.

1988 ◽  
Vol 34 (12) ◽  
pp. 2586-2588 ◽  
Author(s):  
B Grahovac ◽  
B Labar ◽  
A Stavijenić
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Genetic Marker ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Marrow Graft

Abstract We report an effective follow-up of the establishment of bone-marrow function after an allogeneic bone-marrow transplantation in a patient with acute lymphoblastic leukemia, by means of a suitable genetic marker, phosphoglucomutase-1 (EC 5.4.2.2) isoenzyme. A patient with acute lymphoblastic leukemia received allogeneic bone-marrow graft from a sibling who was of the same sex and blood group, HLA-identical, and mixed-lymphocyte-culture nonreactive. To monitor the bone-marrow engraftment and the type and degree of chimerism established, we used a genetic marker, the phosphoglucomutase-1 isoenzyme system, to reveal the difference between the bone-marrow host and donor. We did phosphoglucomutase-1 isoenzyme subtyping of the host's and donor's erythrocytes before transplantation, and isoenzyme phenotyping of the host's erythrocytes during a year after transplantation. Establishment of bone-marrow graft function, a period of temporary mixed chimerism with a population of both host's and donor's erythrocytes, a period of the exclusive presence of donor's erythrocytes, and the resumed appearance of host's erythrocytes after eight months, with no signs of relapse of leukemia, were all observed by analysis of phenotypes. These isoenzymes served as a significant and practical genetic marker, which could be successfully used in studies on bone-marrow transplantation.

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