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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre- and post-transplant bone marrow samples from 20 patients with aplastic anemia were studied. Morphologic evidence of marrow reconstitution was noted in 18 patients one to three weeks following transplantation. In most instances the engrafted marrow elements in early weeks appeared as small clusters of erythroid or myeloid precursors. Bone marrow biopsy or clot sections obtained four to eight weeks after transplantation were more cellular with larger clusters of hematopoietic cells, which were most often composed of mixed cellular elements, including megakaryocytes. Two patients with morphologic evidence of engraftment died shortly after transplantation and were excluded from further analysis. In four of the remaining 16 patients grafts were "rejected" three to eight weeks after transplant. A fifth patient who received a marrow graft from his identical twin showed a transient increase in marrow cellularity without clinical improvement. However, the second marrow transplantation in this patient using the same donor after conditioning with cyclophosphamide resulted in moderate clinical improvement. In four of the five patients developing graft "rejection" or failure there was an increase in marrow mast cells in pre- and post-transplant marrow samples. In contrast, only two of 11 patients with successful engraftment had an increase in mast cells. Although the pathophysiologic role of mast cells in marrow transplantation is unclear, the present study suggests a possible inverse correlation between the numbers of marrow mast cells and the likelihood of successful engraftment. Bone marrow samples in patients with graft versus host disease displayed a slight increase in the number of eosinophils, lymphocytes, and plasma cells.
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PMID:Morphologic aspects of bone marrow transplantation in patients with aplastic anemia. 2 34

Lymphocytes from mice of strain CBA are strongly MLC-responsive to lymphocytes from the H-2-compatible but M-antigen-incompatible strain C3H. This strong reactivity disappears after infusion of CBA mice with C3H lymphocytes. This study shows that the host-versus-graft reactivity (swelling of local lymph node after antigen injection) is specifically reduced after injection of CBA mice with C3H times CBA spleen cells. However, lymphocytes from such mice showed a specifically increased GVH reactivity (inhibition of erythroid cell growth) compared with lymphocytes from unimmunized mice. Lymphocytes from normal CBA mice showed a high proliferative rate in the spleens of irradiated C3H times CBA mice. Such 'educated' cells showed strongly increased specific GVH reactivity. Lymphocytes from CBA mice previously injected with C3H times CBA cells showed reduced capacity to proliferate when injected into irradiated C3H times CBA hybrids and a poor capacity to develop new 'effector' cells reactive against C3H times CBA bone marrow target cells. The results indicate that the presence of specifically 'MLC-responsive' lymphocytes in a lymphoid cell population is a prerequisite of its production of 'effector' cells able to respond in this GVH assay.
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PMID:Reduced capacity to produce specific 'effector' cells after injection of CBA mice with C3H cells. 24 Nov 16

The cell composition of peripheral blood, bone marrow and spleen of CBA mice after the transplantation ca. 20.10(6) lymph node cells of a Wistar rat, sensitized against mouse liver antigens 10--15 days prior to the transplantation, during first 24 hrs after birth was studied. The runt disease developed in 100% recipients and was characterized by sharp disturbances of the formation of immuno- and hemopoietic systems. All runting animals suffered from aplastic anemia, leukopenia with predominance of hyperlobular neutrophils and histio-monocytes in the peripheral blood. The total number of cells in bone marrow decreased almost 15 times. The elimination of erythroid line was coupled with relative augmentation of undifferentiated myeloid and monocytoid cells. The cellular pool of spleen increased twice and more. The intensive proliferation of histio-monocytes and macrophages was accompanied by the destruction and depletion of lymphatic structures. A suggestion is put forward to the effect that the incorporation of "not-self" genetic information, such as non-syngeneic lymphocytes, during the early postnatal period may not only induced some genuine immunological effects, but inhibit the normal way of differentiation in proliferating cell systems due to the lack of their mutual adaptation as well.
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PMID:[Disorders in the formation of the hematologic status of mice following rat lymph node transplantation during the early postnatal period]. 105 39

Hematopoietic growth factors were found as factors stimulating hematopoietic colony formation in in vitro culture system using bone marrow cells as a source of hematopoietic progenitor cells. Erythropoietin, a growth factor stimulating erythroid lineage has now been clinically used as an therapeutic agent for anemia of chronic renal failure. Macrophage colony-stimulating factor (M-CSF), a growth factor stimulating the production of leukocytes including monocytes and neutrophils has been clinically used as an agent for leukopenic patients after anti-cancer therapy. M-CSF improves a survival rate after bone marrow transplantation (BMT) through the reduction of mortality rate associated with BMT such as bleeding, engraftment failure and GVHD. M-CSF accelerated platelet production when injected to thrombopenic patients with solid tumor after anticancer therapy. Granulocyte CSF (G-CSF) is a most powerful agent for various kinds of neutropenia such as neutropenia after anti cancer therapy, neutropenia after BMT, aplastic anemia, chronic neutropenia of children and myelodysplastic syndrome. However, since G-CSF stimulates growth of leukemic cells in vitro, careful observations should be required when clinically used on leukemic patients. Clinical studies of granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3) are now in progress, in which a promoting activity of leukocyte production of these factors is evaluated.
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PMID:[Clinical application of hematopoietic growth factor (IL-3, G-CSF, GM-CSF, and EPO)]. 127 40

We have previously reported the successful development of hematopoietic chimerism after the in utero transplantation of fetal hematopoietic stem cells (HSC) in rhesus monkeys (Macaca mulatta). These animals exhibit sustained engraftment without immunosuppression or graft-versus-host disease (GVHD). To assess the functional response of the donor-derived erythropoietic population, we assayed the relative expression of donor and recipient hematopoietic progenitors in chimeric monkeys before and after anemic stress. Anemia in our chimeric animals resulted in increased erythropoietin (EPO) production comparable to controls. This was accompanied by changes in erythroid progenitor profiles, again similar to controls. Chimeric animals demonstrated normal reticulocytosis and reconstituted their hematocrit after hemorrhage at the same rate as controls. The donor-derived erythropoietic population exhibited normal responses to recipient regulatory signals and did not seem to expand at the expense of other hematopoietic lineages. Thus the proportions of engraftment for the myeloid and erythroid precursors in bone marrow and for blood lymphocytes remained stable. Our results demonstrate that the in utero transplantation of fetal HSC results in stable engraftment of donor erythropoietic progenitors, which appear to be fully integrated within the recipient's regulatory system. The abnormalities reported in the postnatal transplantation setting can then be attributed to immunologic reactions requiring conditioning myeloablative regimens. Fetal transplantation bypasses all these factors.
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PMID:Effect of erythropoietic stress on donor hematopoietic cell expression in chimeric rhesus monkeys transplanted in utero. 134 81

To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR-->CBA). T-cell-depleted B10.BR marrow (10(7) cells) was transplanted into CBA recipients prepared with TBI doses ranging from 4 to 14 Gy. Selected animals also received 10(4) (0.1%) and 10(5) (1.0%) measured B10.BR T lymphocytes. The extent of donor marrow engraftment was determined from hemoglobin and carbonic anhydrase phenotyping of peripheral blood at 3 months posttransplant. Toxicity was assessed from breathing-rate measurements, histopathology, and animal survival. Addition of T cells had a profound effect on survival related to radiation dose. The TBI doses resulting in an LD50 at 12 weeks were 6.9 Gy, 9.3 Gy, and 13.0 Gy for animals receiving 10(5), 10(4), and no T cells, respectively. Mortality was associated with pulmonary dysfunction as measured by an elevation of breathing rates. Autopsy and histological analysis revealed extensive damage to the lung parenchyma. In contrast to the toxicity data, addition of T cells to the donor marrow had no effect on the TBI dose required for equivalent erythroid engraftment. These results demonstrate that in combination with TBI small numbers of T cells in the transplanted marrow do not aid engraftment but do significantly increase the risk of pulmonary toxicity.
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PMID:The effect of donor T lymphocytes and total-body irradiation on hemopoietic engraftment and pulmonary toxicity following experimental allogeneic bone marrow transplantation. 135 84

Delayed erythroid recovery is common after bone marrow transplantation (BMT), with some patients continuing to require red blood cell (RBC) transfusion support for as long as 1 year. While the etiology is multifactorial, inadequate stimulation of erythroid progenitors by the erythroid growth factor, erythropoietin, may play a role. In this study, the erythropoietin response to anemia of 70 consecutive patients undergoing BMT at the Johns Hopkins Oncology Center was compared with the erythropoietin response in uncomplicated iron deficiency anemia. Erythropoietin levels were elevated for the degree of anemia early after BMT; however, at the time of marrow recovery, erythropoietin levels were significantly suppressed in both allogeneic and autologous BMT patients compared with the iron-deficient patients. Patients with acute graft-versus-host disease (GVHD) had a more marked suppression of the erythropoietin response to anemia. In the patients who remained anemic for extended periods of time (up to 12 months after BMT), an inadequate erythropoietin response to anemia persisted. Delayed erythroid recovery after BMT is associated with inadequate erythropoietin levels. Therefore, recombinant human erythropoietin may be useful in the treatment of the anemia associated with both autologous and allogeneic BMT.
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PMID:Impaired erythropoietin response to anemia after bone marrow transplantation. 142 81

To characterize immune suppressive and hematopoietic features of enriched subsets of human marrow cells, we separated these cells on Percoll density gradients. CD4+ and CD8+ T cells (CD3+) were enriched in the high-density marrow cell fractions and reduced in low-density fractions. CD4-CD8- (CD3+) T cells expressing the alpha beta T-cell antigen receptor were at least 10 times less numerous than the CD4+ and CD8+ T cells in all fractions. Purified populations of the CD4-CD8- alpha beta + T cells obtained by flow cytometry suppressed the mixed leukocyte reaction (MLR). Another population of suppressor cells that expressed neither T-cell (CD3) nor natural killer cell (CD16) surface markers was also identified. The latter cells had the phenotypic and functional characteristics of "natural suppressor" cells. Suppressor cell activity was enriched in the low-density fractions along with hematopoietic progenitors (colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid). The progenitor and suppressor cell activities were depleted in high-density fractions. The latter fractions made vigorous responses in the MLR. The low-density fractions, which accounted for less than 10% of the input marrow cells, suppressed the MLR and did not respond. Further evaluation of the low-density fractions may be of value in allogeneic bone marrow transplantation due to the reduction of CD4+ and CD8+ T cells and the enrichment of hematopoietic progenitors as well as immune suppressor cells that may inhibit graft-versus-host disease.
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PMID:T-cell subsets and suppressor cells in human bone marrow. 146 27

Erythroid regeneration is an important and separate element in the engraftment process in allogeneic and autologous bone marrow transplantation (alloBMT, autoBMT). Qualitative visual reticulocyte counting has proved inadequate in the evaluation of erythropoiesis after BMT but automated flow cytometry now allows the reliable quantitation of reticulocytes even to very low levels. Reticulocyte counts and highly fluorescent reticulocyte (HFR) counts (very early reticulocytes) were estimated daily in recipients of 22 autoBMT and 14 alloBMT using a Sysmex R-1000 automated reticulocyte counter. Marrow ablation caused an immediate and rapid fall in both the reticulocyte count and the HFR. Measurable numbers of reticulocytes persisted throughout the hypoplastic period, but HFR fell to zero in the majority of both the autoBMT and alloBMT. HFR rose significantly after a median time of 14 d post-autoBMT, and 12 d post-alloBMT. Attainment of 15 x 10(9)/l reticulocytes and 0.5 x 10(9)/l HFR at day 21 post-transplant was associated with ultimate engraftment in 100% cases. Inadequate engraftment was seen in the majority of patients whose responses fell below these levels. Graft-versus-host disease was associated with a transient slight reduction in reticulocyte count. Neither episodes of infection nor blood transfusions had any significant impact on trends of reticulocytes or HFR. Automated flow cytometric reticulocyte counting has been shown to provide an accessible measure of erythroid activity which may be of predictive value in the management of patients following bone marrow transplantation.
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PMID:Evaluation of erythropoiesis after bone marrow transplantation: quantitative reticulocyte counting. 152 Jun 10

The authors report an 18-year-old female who developed severe hemolytic reaction and delayed neutrophil recovery after bone marrow transplantation (BMT) for aplastic anemia from her HLA-identical sibling. She had received much transfusion (61 units of red blood cells including 4 units of fresh whole blood from her parents and 350 units of platelets) for 12 years before BMT. To prevent graft rejection, she received an intensified preparative regimen consisted of cyclophosphamide 200 mg/kg followed by 5 Gy total body irradiation and 5 Gy total lymphoid irradiation. Prophylaxis for GVHD was short term methotrexate and cyclosporin-A. Despite of the removal of the red cells from the marrow, marked hemolytic reaction caused by antibodies directed to rh" (E) and hr' (c) red cell antigens was observed when rh" (E) and hr' (c) positive donor erythroid began to recover. The recovery of neutrophils, especially the fraction of segmented cells was also delayed. Flow cytometry showed that the serially collected patient's sera reacted to neutrophils derived from both patient's blood on the 64th post-transplant day and the donor's blood. The reactivity was strongest in pre-BMT sera. We conclude that residual antibodies sensitized before BMT are a major cause of these hematological problems.
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PMID:[A case report of multiple-transfused aplastic anemia complicated by hemolysis and delayed neutrophil recovery after bone marrow transplantation]. 157 36


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