scholarly journals Evidence for engraftment of donor-type multipotent CD34+ cells in a patient with selective T-lymphocyte reconstitution after bone marrow transplantation for B-SCID

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3584-3589 ◽  
Author(s):  
GE Tjonnfjord ◽  
R Steen ◽  
OP Veiby ◽  
W Friedrich ◽  
T Egeland
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocyte ◽  
Marrow Transplantation ◽  
B Lymphocyte ◽  
B Lymphopoiesis ◽  
Type B ◽  
Cd34 Cells ◽  
Donor Type

Abstract Severe combined immunodeficiencies (SCID), a heterogeneous group of disorders of infancy, are fatal without treatment directed at immunologic reconstitution. Allogeneic bone marrow transplantation (BMT), which is such a treatment presents some unique features in SCID, especially when T-lymphocyte-depleted HLA haploidentical allografts are used. Donor-type T lymphopoiesis, less often B lymphopoiesis, develops, whereas myelopoiesis remains the recipient-type. Little is known about the engrafting cells in this peculiar lymphohematopoietic chimerism and the pathophysiology of the frequent failure of B-lymphocyte reconstitution. To address these issues, we purified CD34+ BM cells from a patient with selective T-lymphocyte reconstitution after HLA haploidentical BMT for B-SCID. Phenotypic analysis of CD34+ cells was performed by flow cytometry, and functional studies of donor- and recipient-type CD34+ cells were performed in vitro. Donor-type CD34+ cells, constituting approximately 2% of the CD34+ cells, were detected; both CD34+ HLA-DR- cells and CD34+ cells coexpressing B-(CD10 and CD19) and T-(CD2 and CD7) lymphocyte-associated cell surface molecules. Donor- type CD34+ cells coexpressing myeloid-associated molecules (CD13, CD14, CD15, and CD33) were undetectable. However, donor-type CD34+ myeloid progenitors could be shown in functional assays. Recipient-type CD34+ cells coexpressing B- and T-lymphocyte- as well as myeloid-associated molecules were detected, but recipient-type CD34+ cells could not be driven into T-lymphocyte differentiation in vitro. These findings provide evidence for engraftment of multipotent stem cells in our patient with B-SCID. Furthermore, the failure of B-lymphocyte reconstitution cannot be explained by lack of donor-type B-lymphocyte progenitors. Donor-type B lymphopoiesis and myelopoiesis are prevented by an unidentified mechanism.

scholarly journals Evidence for engraftment of donor-type multipotent CD34+ cells in a patient with selective T-lymphocyte reconstitution after bone marrow transplantation for B-SCID

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3584-3589 ◽  
Author(s):  
GE Tjonnfjord ◽  
R Steen ◽  
OP Veiby ◽  
W Friedrich ◽  
T Egeland
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocyte ◽  
Marrow Transplantation ◽  
B Lymphocyte ◽  
B Lymphopoiesis ◽  
Type B ◽  
Cd34 Cells ◽  
Donor Type

Severe combined immunodeficiencies (SCID), a heterogeneous group of disorders of infancy, are fatal without treatment directed at immunologic reconstitution. Allogeneic bone marrow transplantation (BMT), which is such a treatment presents some unique features in SCID, especially when T-lymphocyte-depleted HLA haploidentical allografts are used. Donor-type T lymphopoiesis, less often B lymphopoiesis, develops, whereas myelopoiesis remains the recipient-type. Little is known about the engrafting cells in this peculiar lymphohematopoietic chimerism and the pathophysiology of the frequent failure of B-lymphocyte reconstitution. To address these issues, we purified CD34+ BM cells from a patient with selective T-lymphocyte reconstitution after HLA haploidentical BMT for B-SCID. Phenotypic analysis of CD34+ cells was performed by flow cytometry, and functional studies of donor- and recipient-type CD34+ cells were performed in vitro. Donor-type CD34+ cells, constituting approximately 2% of the CD34+ cells, were detected; both CD34+ HLA-DR- cells and CD34+ cells coexpressing B-(CD10 and CD19) and T-(CD2 and CD7) lymphocyte-associated cell surface molecules. Donor- type CD34+ cells coexpressing myeloid-associated molecules (CD13, CD14, CD15, and CD33) were undetectable. However, donor-type CD34+ myeloid progenitors could be shown in functional assays. Recipient-type CD34+ cells coexpressing B- and T-lymphocyte- as well as myeloid-associated molecules were detected, but recipient-type CD34+ cells could not be driven into T-lymphocyte differentiation in vitro. These findings provide evidence for engraftment of multipotent stem cells in our patient with B-SCID. Furthermore, the failure of B-lymphocyte reconstitution cannot be explained by lack of donor-type B-lymphocyte progenitors. Donor-type B lymphopoiesis and myelopoiesis are prevented by an unidentified mechanism.

scholarly journals Persistence of myeloid progenitor cells expressing BCR-ABL mRNA after allogeneic bone marrow transplantation for chronic myelogenous leukemia

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2109-2114
Author(s):  
G Pichert ◽  
EP Alyea ◽  
RJ Soiffer ◽  
DC Roy ◽  
J Ritz
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Progenitor Cell ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Myeloid Differentiation ◽  
Allogeneic Bone

Previous studies have shown that tumor-specific bcr-abl mRNA can often be detected by polymerase chain reaction. (PCR) for months to years after allogeneic bone marrow transplantation (BMT) for chronic myelocytic leukemia (CML). Nevertheless, the presence of bcr-abl mRNA by itself does not invariably predict for clinical relapse post-BMT. This has led to the hypothesis that bcr-abl mRNA might be expressed in cells that have lost either proliferative or myeloid differentiation potential. To directly characterize the cells detected by PCR in patients with CML after allogeneic BMT, we first identified five individuals in whom PCR-positive cells could be detected at multiple times post-BMT. Bone marrow samples from these individuals were cultured in vitro and single erythroid, granulocytic, and macrophage colonies, each containing 50 to 100 cells, were examined for the presence of bcr-abl mRNA by PCR. PCR-positive myeloid colonies could be detected in four of five individuals in marrow samples obtained 5 to 56 months post-BMT. Overall, 7 of 135 progenitor cell colonies (5.2%) were found to be PCR-positive. The expression of bcr-abl mRNA appeared to be equally distributed among committed erythroid, macrophage, and granulocyte progenitors. These patients have now been followed-up for an additional 20 to 33 months from the time of progenitor cell PCR analysis but only one of these individuals has been found to have cytogenetic evidence of recurrent Ph+ cells. These results show that long-term persistence of PCR-detectable bcr-abl mRNA after allogeneic BMT can be caused by the persistence of CML-derived clonogenic myeloid precursors that have survived the BMT preparative regimen. These cells continue to have both proliferative and myeloid differentiation capacity in vitro. Nevertheless, these PCR-positive cells do not appear to either expand or differentiate in vivo for prolonged periods, suggesting the presence of mechanisms for suppression of residual clonogenic leukemia cells in vivo.

scholarly journals Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1043-1046
Author(s):  
GD Goss ◽  
MA Wittwer ◽  
WR Bezwoda ◽  
J Herman ◽  
A Rabson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Cell Activity ◽  
High Dose

Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.

Clinical Consequences and Treatment of Primary Immunodeficiency Syndromes Characterized by Functional T and B Lymphocyte Anomalies (Combined Immune Deficiency)

PEDIATRICS ◽  
1994 ◽  
Vol 93 (2) ◽  
pp. 265-270 ◽  
Author(s):  
Françoise Berthet ◽  
Françoise Le Deist ◽  
Anne Marie Duliege ◽  
Claude Griscelli ◽  
Alan Fischer
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
B Lymphocyte ◽  
Severe Combined Immunodeficiency ◽  
Clinical Manifestations ◽  
Immunodeficiency Syndrome ◽  
Immunodeficiency Syndromes

Objective. To review the clinical presentation and outcome of patients with an unusual primary T + B lymphocyte immunodeficiency syndrome, characterized by the presence of T lymphocytes with no detectable gross phenotypic anomaly, but which are not activated in vitro or in vivo in response to antigens, although they do respond to mitogens. Methods. A retrospective analysis of clinical and immunological data recorded in 25 cases. Acquired immunodeficiencies and known primary T cell immunodeficiency syndromes (severe combined immunodeficiency syndrome, Di-George syndrome, Wiskott-Aldrich syndrome, cartilage hair hypoplasia, Omenn's syndrome, ataxia telangiectasia, defective expression of major histocompatability complex class II molecules, and defective expression of the CD3/T cell receptor complex) were excluded. Results. The patients had severe and particularly protracted infections, mainly of the respiratory tract and gut. Severe viral infections, generally due to herpes viruses, occurred in nearly two-thirds of the patients, with a median follow-up of 54 months. Autoimmune manifestations are frequent (60%), targetting mainly marrow-derived cells, and were characterized by a tendency to relapse and by a dependence on immunosuppressive therapy. Allergic manifestations were also frequent (48% of cases). Eight of the 19 patients who had not undergone bone marrow transplantation died. All but one of the 11 survivors had moderate to severe sequelae. Bone marrow transplantation seemed to be the treatment of choice, because four of six recipients of HLA-identical (n = 2) or nonidentical (n = 4) marrow are alive and the immune deficiency has been corrected. Conclusion. Early recognition of these life-threatening syndromes may improve the chances of cure. Despite common clinical manifestations and prognosis, these functional immunodeficiencies appear heterogeneous regarding inheritance pattern and at least existence of a B cell immunodeficiency.

T Lymphocyte Reconstitution Following Bone Marrow Transplantation

1985 ◽  
pp. 79-79
Author(s):  
P. Myrenfors ◽  
O. Ringdén ◽  
U. Persson ◽  
P. Larsson ◽  
B. Sundberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocyte ◽  
Marrow Transplantation

Recipient immune-competent T lymphocytes can survive intensive conditioning for bone marrow transplantation

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 954-956 ◽  
Author(s):  
A Butturini ◽  
RC Seeger ◽  
RP Gale
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Interleukin 2 ◽  
Marrow Transplant ◽  
Effector Cells ◽  
And Function

Abstract Bone marrow transplantation is usually preceded by intensive chemotherapy and radiation therapy designed to completely eliminate recipient immune-competent cells that might reject the donor bone marrow. We show that seven of 14 bone marrow transplant recipients who received intensive conditioning retained circulating T lymphocytes that proliferate after incubation with interleukin 2 and phytohemagglutinin and function as effector cells in an in vitro model of graft rejection. These T cells may mediate graft rejection.

scholarly journals Prolonged impairment of hematopoiesis after high-dose therapy followed by autologous bone marrow transplantation

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3320-3327 ◽  
Author(s):  
J Domenech ◽  
C Linassier ◽  
E Gihana ◽  
A Dayan ◽  
D Truglio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
High Dose Therapy ◽  
Colony Forming Unit ◽  
Hematopoietic Reconstitution

Hematopoietic reconstitution has been studied in 180 patients after autologous bone marrow transplantation based on peripheral blood cell (PBC) recovery time and marrow progenitor counts sequentially tested for up to 4 years. Several factors that could influence hematopoietic reconstitution have been analyzed including sex, age, diagnosis, disease status, conditioning regimen, graft progenitor content, graft in vitro purging, and postgrafting administration of growth factors. Before transplantation, marrow progenitor values were normal only for colony-forming unit granulocyte macrophage (CFU-GM) in contrast to colony-forming unit-erythroid (CFU-E), burst-forming unit-erythroid (BFU-E), and colony-forming unit-megakaryocyte (CFU-Meg). After transplantation, as described with allogenic grafts, these values remained low for several years, although PBC counts were nearly normalized within a few weeks. Pregraft values were reached after 2 years for CFU-GM and BFU-E, and after 4 years for CFU-E, while CFU-Meg failed to reach pregraft values after this time. Normal levels were reached after 4 years only by CFU-GM. On univariate and multivariate analysis, the following factors appeared to delay both PBC and marrow progenitor reconstitution: underlying disease (particularly acute myeloid leukemias), graft characteristics such as low stem cell content and in vitro purging, conditioning regimens with total body irradiation or busulfan, and lack of postgraft administration of growth factors. In conclusion, high-dose therapy followed by bone marrow transplantation induces a deep and prolonged impairment of hematopoiesis irrespective of any alloimmune reaction or postgraft immunosuppressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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