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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to analyze the homing and progression patterns of childhood acute lymphoblastic leukemias (ALL) in mice with severe combined immunodeficiency (SCID). Upon intraperitoneal (IP) transfer, cells from relapse samples of three children with T-lineage ALL spread hematogenously and infiltrated the non-lymphoid and/or lymphoid organs with a pattern reminiscent of the human clinical disease. These mice either died or were killed in extremis at a mean of 9 weeks. Moreover, cell lines established in vitro from two of these samples manifested identical homing and progression in the SCID mouse as compared with the original patients' cells. Thus, long-term culture of the primary leukemic T cells did not alter their invasive potential and migration pattern. When engrafted IP, three cell lines established from pre-B-ALL cases displayed primarily a lymphatic spread with induction of local tumor masses and kidney/liver nodules. Mice were killed at 11 to 13 weeks, but had not developed imminently fatal leukemia. However, when transferred intravenously, one pre-B ALL cell line was able to spread hematogenously and to infiltrate both lymphoid and non-lymphoid tissues. Overall, these data demonstrate that the SCID mouse provides an efficient and reproducible model to study the pathogenesis of childhood ALL, and may be a suitable system for evaluating therapy.
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PMID:Homing and progression patterns of childhood acute lymphoblastic leukemias in severe combined immunodeficiency mice. 203 29

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.
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PMID:Status of allogeneic bone marrow transplantation in childhood in the GDR. 248 Feb 79

Animal models of AIDS are essential for understanding the pathogenesis of retrovirus-induced immune deficiency and encephalopathy and for development and testing of new therapies and vaccines. AIDS and related disorders are etiologically linked to members of the lentivirus subfamily of retroviruses; these lymphocytopathic lentiviruses are designated human immuno-deficiency virus type 1 (HIV-1) and human immuno-deficiency virus type 2 (HIV-2). The only animals susceptible to experimental HIV-1 infection are the chimpanzee, gibbon ape, and rabbit but AIDS-like disease has not yet been reported in these species. Macaques can be persistently infected with some strains of HIV-2 but no AIDS-like disease has resulted. It is not yet clear how suitable HIV-infected SCID-hu mice will be as a model for AIDS. Several subfamilies of naturally occurring cytopathic retroviruses cause immune suppression, including fatal immunodeficiency syndromes in chickens, mice, cats, and monkeys. Domestic cats suffer immunosuppression from both an onco-virus, feline leukemia virus, and a member of the lentivirus subfamily, feline immunodeficiency virus (FIV). Asian macaques are susceptible to fatal simian AIDS from a type D retrovirus, indigenous in macaques, and from a lentivirus, simian immunodeficiency virus (SIV), which is indigenous to healthy African monkeys. SIV is the animal lentivirus most closely related to HIV. Of these animal models, the lentivirus infections of cats (FIV) and macaques (SIV) appear to bear the closest similarity in their pathogenesis to HIV infection and AIDS. This review will summarize these various animal model systems for AIDS and illustrate their usefulness for antiviral therapy and vaccinology.
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PMID:Animal models of AIDS. 255 12

A human acute lymphoblastic leukemia (ALL) cell line that was transplanted into immune-deficient SCID mice proliferated in the hematopoietic tissues, invaded various organs, and led to the death of the mice. The distribution of leukemic cells in SCID mice was similar to the course of the disease in children. A-1 cells marked with a retrovirus vector showed clonal evolution after the transplant. SCID mice that were injected with bone marrow from three patients with non-T ALL had leukemic cells in their bone marrow and spleen. This in vivo model of human leukemia is an approach to understanding leukemic growth and progression and is a novel system for testing new treatment strategies.
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PMID:A model of human acute lymphoblastic leukemia in immune-deficient SCID mice. 259 71

The mouse monoclonal antibody 25-3 specific for the alpha subunit of LFA-1 (CD11a) has been infused to children undergoing HLA non-identical bone marrow transplantation because of lethal inherited diseases or of leukemia in order to prevent graft failure. We have assessed the serum concentrations of the antibody infused according to two regimens: 0.1 mg/kg five times, every alternate day (eight patients) or 0.2 mg/kg daily for 10 days (30 patients). Serum trough levels of 25-3 antibody in the first group were constantly found to be low (less than 0.6 micrograms/ml) while 25-3 serum concentration in the second group rose progressively to a mean value of 2.2 micrograms/ml. Serum antibody concentrations were significantly lower in patients with greater antigenic mass, i.e. with splenomegaly, or non conditioned. The engraftment rate was slightly higher in patients treated by the daily infusion of 25-3 for 10 days. No immunization against 25-3 antibody occurred. One patient who subsequently received other mouse anti-B cell antibodies eventually produced anti-isotype antibodies. The consequences of 25-3 infusion on leukocyte counts has been evaluated in the group of patients (n = 6) with severe combined immunodeficiency who did not receive any chemotherapy and in one who was treated with 25-3 because of acute graft-versus-host disease. In none of the cases did 25-3 antibody infusion modify blood leukocyte counts. In addition, it was shown that saturation of LFA-1 on leukocytes was a transient phenomenon, since it could not be found 24 h following infusion of 25-3 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo infusion of anti LFA-1 antibody in HLA non-identical bone marrow transplantation in children: serum concentrations and biological effects. 267 57

Adenosine deaminase (ADA) deficiency is associated with a fatal severe combined immunodeficiency. Because most patients do not have a suitable marrow donor, the introduction of a normal ADA gene into the patient's marrow cells is a potentially useful alternative therapy. To identify vectors that provide optimal gene expression in human hematopoietic cells, we investigated retroviral vectors containing the ADA gene under the transcriptional control of the promoter/enhancers of Moloney murine leukemia virus, the simian virus 40 early region, the cytomegalovirus immediate-early gene, the lymphotropic papovavirus, and the human beta-globin gene. ADA expression from these vectors was monitored in the ADA- human histiocytic lymphoma cell line DHL-9, and in the multipotential chronic myeloid leukemia cell line K562. ADA expression in infected K562 cells was also measured after induction of megakaryoblastic differentiation by phorbol ester, and after induction of erythroid differentiation by sodium n-butyrate or hemin. In these hematopoietic cell lines, the vectors that contained ADA controlled by either the Moloney murine leukemia virus promoter (LASN) or the cytomegalovirus promoter (LNCA) expressed ADA at much higher levels than the other vectors tested. Furthermore, in K562 cells infected with LASN and LNCA vectors, induction of terminal differentiation resulted in the same or higher level expression of ADA. These cell lines have permitted the evaluation of transduced gene expression in proliferating and differentiating hematopoietic cells that provide a model for bone marrow-targeted gene therapy.
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PMID:Expression of human adenosine deaminase from various strong promoters after gene transfer into human hematopoietic cell lines. 275 48

A 4 1/2-year-old boy with acute myelomonocytic leukemia developed fever, neutropenia, and a prolonged respiratory illness while receiving maintenance chemotherapy. An open lung biopsy specimen demonstrated a giant cell pneumonia with intracytoplasmic and probable intranuclear viral inclusions of the paramyxovirus type. Serologic studies demonstrated convincing evidence of a parainfluenza type 3 infection. Although parainfluenza type 3-induced giant cell pneumonia has been reported in infants with the severe combined immunodeficiency syndrome, to our knowledge, this is the first reported case of this complication in a patient with leukemia.
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PMID:Giant cell pneumonia caused by parainfluenza type 3 in a patient with acute myelomonocytic leukemia. 303 89

Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation.
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PMID:Transient increase of serum IgD levels after allogeneic bone-marrow transplantation. 304 51

The human thymus leukemia-like antigens (CD1a-c) consist of three similar glycoproteins found on subpopulations of normal thymocytes, T cell acute leukemias, and cutaneous dendritic cells. The CD1c antigen recognized by the M241 monoclonal antibody was detected on the circulating mononuclear cells of three children with severe combined immunodeficiency disease (SCID). Two-color immunofluorescence analysis demonstrated that M241 expression (43 to 95%) was limited to cells expressing the B cell-restricted antigens B4 (CD19), B1 (CD20), and surface immunoglobulin. To confirm M241 expression on normal cells of the B lineage rather than aberrant expression limited to SCID B cells, its expression was demonstrated serologically and biochemically on purified B cells from spleen, tonsil, and peripheral blood. Parallel analyses with monoclonal antibodies NA1/34 and 4A76 demonstrated that the CD1a and CD1b molecules were negative on all B cells that were studied. It has been hypothesized that the CD1 molecules represent the human counterpart of the murine thymus leukemia antigens due to their similar size, limited tissue distribution, and association with beta 2-microglobulin. This study suggests that a subset of CD1 antigens detected by M241 (CD1c) may represent a human analog of a murine Qa antigen due to its extended distribution on normal peripheral B cells.
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PMID:M241 (CD1) expression on B lymphocytes. 310 92

A child born with severe combined immunodeficiency, who was immunoreconstituted by a fetal liver and thymus transplant, developed acute lymphoblastic leukaemia in the donor cell line. During remission she contracted acute Q fever, which gave rise to unexpected complications. Early treatment of the Q fever might have altered the subsequent events and prevented her death.
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PMID:Severe combined immunodeficiency syndrome, tissue transplant, leukaemia, and Q fever. 327 27


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