NK cells expressing killer cell inhibitory receptors after allogeneic bone marrow transplantation.
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Bone Marrow Transplantation↗
Biomedical subjects
S Hashino
Publications and source records attributed to S Hashino.
FK 506 inhibits severe graft-versus-host disease without mediating cytokine balance and/or cytotoxic molecules.
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Animals↗
Effect of granulocyte colony-stimulating factor administered before bone marrow transplantation on hematopoietic recovery.
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Animals↗
Increased adhesion molecule expression during graft-versus-host disease.
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Acute Disease↗
Alterations in binding activity of T cell transcription factor CD28 responsive element binding complex (CD28RC) following allogeneic bone marrow transplantation.
The CD28 responsive element binding complex (CD28RC) has an important role in transducing CD28/B7 costimulatory signals. Using electrophoretic mobility-shift assay (EMSA), we have analyzed the binding activity of CD28RC in the mixed lymphocyte culture (MLC) using peripheral blood mononuclear cells (PBMC) obtained from the patients before and after allogeneic bone marrow transplantation (allo-BMT). The binding activity of CD28RC was low in MLCs using PBMC from patients without acute GVHD and it was also low in MLCs using PBMC from patients without chronic GVHD (cGVHD). In contrast, this activity in patients with cGVHD was estimated to be high. The relative values of CD28RC in comparison with third party MLCs were significantly higher in MLCs using PBMC from patients with cGVHD than those in MLCs using PBMC from patients without GVHD (0.55+/-0.31 versus 0.23+/-0.12, respectively, n = 10, p = 0.05). IL-2 concentrations in the MLC medium from patients without GVHD were undetectable; however, a detectable level of IL-2 was present in MLC medium from a patient with extensive cGVHD. These data were interpreted to suggest that the CD28 costimulatory pathway was specifically activated against recipient antigen in allo-BMT patients with GVHD. In other words, it was suggested that the CD28 costimulatory pathway was specifically suppressed in allo-BMT patients without GVHD, and this suppression might contribute immunological tolerance after allo-BMT.
Adult↗
Expression of HLA-C-specific natural killer cell receptors (CD158a and CD158b) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation.
We investigated the expression of natural killer cell receptors (NKRs) for HLA-C on peripheral blood mononuclear cells (PBMCs) in 23 allogeneic bone marrow transplantation (allo-BMT) patients to analyse the role of NKRs in alloresponse concerning graft-versus-host disease (GVHD). CD158a expression was low and there was little change in the expression after allo-BMT. Also, there was no difference in the proportion of CD158a+/CD3- after allo-BMT. In contrast, the proportion of CD158b+/CD3- cells, mainly NK cells, increased in the early stage (< 2 months) after allo-BMT and then gradually decreased (3.3 +/- 2.6% before BMT vs. 15.4 +/- 8. 6% in the early stage after BMT, 8.5 +/- 4.9% during the period 3-6 months after BMT and 7.0 +/- 3.0% > 6 months after BMT; P < 0.05). However, CD158b expression on CD3+ T cells increased 3 months after allo-BMT (1.1 +/- 1.1% before BMT vs. 5.1 +/- 7.7% during the period 3-6 months after BMT and 3.0 +/- 2.4% > 6 months after BMT, P < 0. 05). The highest percentages of CD158 expression in patients without chronic GVHD (cGVHD) and those with cGVHD were compared. The percentage of CD158b+/CD3+ cells and also that of CD158b+/CD8+ cells were significantly increased in patients with cGVHD compared with those in patients without cGVHD (2.6 +/- 2.0% vs. 8.0 +/- 11.2% and 2.3 +/- 1.5% vs. 8.3 +/- 11.7% respectively; P < 0.05). The exact clinical relevance of these CD158b-expressing cells is not clear. However, there is an interesting possibility that CD158b-expressing cells play some role in the regulation of GVHD after allo-BMT.
Bone Marrow Transplantation↗
Evolution to acute myeloblastic leukemia from chronic neutrophilic leukemia with dysplastic features in granulocytic lineage.
We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.
Aged↗
Proliferation of CD4+ lymphocytes in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation.
Expansion of donor-derived lymphocytes after allogeneic stem cell transplantation is a serious and sometimes fatal complication. Lymphoproliferative disorders are reportedly caused mainly by reactivation of Epstein-Barr virus (EBV) and non-EBV-associated secondary lymphoma or leukemia. In this paper, we report massive proliferation of CD4+ lymphocytes in peripheral blood of a patient with chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (alloBMT) from an HLA-identical sibling donor. The abnormal lymphocytes showed CD3low, CD4+, CD8-, CD2+, CD5+, CD7+, CD25-, CD19-, CD20-, CD21-, CD16-, CD56low, T-cell receptor (TCR)-alpha/beta- and TCR-gamma/delta- phenotypes, and no rearrangement of either TCR-C beta 1 or IG(H)JH was detected from the lymphocytes by Southern blot analysis. EBV was not found in the nuclei of lymphocytes by an immunofluorescence antibody. The lymphoproliferation was resistant against immunosuppressive drugs, administered for the treatment of chronic GVHD, and it effectively inhibited aggravation of the chronic GVHD. Although antithymocyte globulin and cytosine arabinoside were administered later, the patient died of respiratory failure with bilateral pleural effusion and interstitial pneumonia. Because we found no evidence of monoclonality of the abnormal lymphocytes, we could not conclude that this patient had suffered from malignant lymphoproliferation. To our knowledge, this is the first case report of proliferation of CD4+ lymphocytes in a patient with chronic GVHD following alloBMT. In this paper, we discuss the possible pathophysiology of the patient.
Adult↗
Immunophenotype of peripheral blood mononuclear cells and NK cell activity after allogeneic bone marrow transplantation using recombinant human granulocyte colony-stimulating factor.
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Antigens, CD↗
Possible role of granulocyte colony-stimulating factor in increased serum soluble interleukin-2 receptor-alpha levels after allogeneic bone marrow transplantation.
Serum soluble interleukin-2 receptor - alpha (sIL-2R) levels markedly increased at the engraftment period in patients who underwent allogeneic bone marrow transplantation (BMT). Since serum G-CSF levels increased during G-CSF administration and decreased after the cessation, increased sIL-2R levels appeared to be induced by G-CSF administration. There was no increase in sIL-2R levels in a patient given macrophage colony-stimulating factor (M-CSF). The sIL-2R levels at the engraftment period and the onset of acute graft-versus-host disease (GVHD) were higher in patients who developed acute GVHD during G-CSF administration than in those who developed acute GVHD after G-CSF cessation. This finding suggests that G-CSF administration may possibly augment acute GVHD. However, it appears to be unlikely, because in the entire population, 18 of 35 patients had acute GVHD while only 6 of 17 patients had acute GVHD during G-CSF administration. Further analysis is still needed in order to draw definite conclusions. Preconditioning regimens did not appear to affect the sIL-2R levels, when the variable frequencies of methotrexate (MTX) administration were compared.
Adolescent↗
Bone marrow infarction due to acute graft-versus-host disease in an acute lymphoblastic leukemia patient after unrelated bone marrow transplantation.
We report a case of bone marrow infarction in a 20-year-old woman with acute lymphocytic leukemia (ALL) who underwent unrelated bone marrow transplantation (BMT). Hematopoietic engraftment occurred on day 9 and, thereafter, the patient developed acute dermal and hepatic graft-versus-host disease (GVHD). She also experienced severe arthralgia in her knee joints on day 21. Immunosuppressive therapy with prednisolone (PSL) for acute GVHD was given, and the arthralgia improved rapidly, correlating with the improvement in dermal and hepatic GVHD. Based on the laboratory findings and analysis of magnetic resonance images, she was diagnosed as having bone marrow infarction. The cause of the bone marrow infarction was thought to be acute GVHD-related microangiopathy.
Adult↗
Bone marrow dysplasia with basophilic cells in a patient with angiocentric lymphoma.
We report a 46-year-old man suffering from angiocentric lymphoma of the skin. On admission, he had atypical cells rich in basophilic granules in the bone marrow and peripheral blood, in addition to skin eruptions and bone marrow dysplasia. Immediately after diagnosis, the patient was treated with multidrug combination chemotherapy. At first, the chemotherapy markedly relieved the skin eruption and bone marrow dysplasia, and atypical cells in the bone marrow and peripheral blood disappeared rapidly. However, the disease gradually became resistant to chemotherapy, resulting in a gradual deterioration of the skin eruption and bone marrow dysplasia, and reappearance of atypical cells. The levels of serum cytokines such as interleukin-4 and interleukin-6, and of soluble interleukin-2 receptor correlated well with the disease states. These results suggest that the lymphoma cells directly or indirectly induce the production of these cytokines and that a dysregulated cytokine network, which might be caused by lymphoma cells, induces an increase in atypical cells.
Bone Marrow↗
The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease.
We have investigated cytokine mRNA expression in the peripheral blood mononuclear cells of 20 patients who received allogeneic hematopoietic stem cell transplants to assess the cytokine network after transplantation. IL-4 mRNA expression decreased in five of five (100%) patients with > or = grade III (severe) acute GVHD and increased in 10 of 22 (45%) patients without severe GVHD. In contrast, IL-12 mRNA expression increased in two of two (100%) patients with severe GVHD, but increased in only six of 18 (33%) patients without severe GVHD. Furthermore, IL-10 and/or IL-13 mRNA expression increased in 19 of 22 (86%) patients without severe GVHD, but increased in only one of three (33%) patients with severe GVHD. In patients with allogeneic PBSCT who had severe acute GVHD, the cytokine mRNA expression in patients with allogeneic PBSCT, who had no severe GVHD, showed a similar pattern to that in patients with allogeneic BMT. IL-4 mRNA expression increased in three of five (60%) patients and IL-10 and/or IL-13 mRNA expression increased in five of five (100%) patients. In contrast, IL-12 mRNA expression increased in only one of three (33%) patients. Serum IL-4 concentration in allogeneic PBSCT patients in the early engraftment phase was relatively high, while serum IL-12 concentration was low. These findings suggest that severe GVHD may be related to the cytokine imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells.
Adult↗
Inhaled vancomycin-induced allergic reaction in decontamination of respiratory tracts for allogeneic bone marrow transplantation.
A 34-year-old male suffered from an allergic reaction after inhalation of decontaminating drugs for BMT. Clinical challenge tests were undertaken to determine the causal drug. It was found that vancomycin hydrochloride (VCM) repeatedly induced dyspnea, fever, hypoxia, eosinophilia, and elevation of CRP. Therefore, clindamycin (CLDM) was used instead of VCM for decontamination of patient respiratory tract. Although complete decontamination of the respiratory tract was not achieved during the leukocytopenic period, BMT was successful, and there were no life-threatening infectious complications. Although inhaled VCM-induced allergic reaction may be a very rare complication in the BMT setting, careful clinical attention should be paid to such patients.
Administration, Inhalation↗
Invasive pulmonary aspergillosis complicated by subclavian artery occlusion following allogeneic stem cell transplantation.
We describe an unusual case of invasive pulmonary aspergillosis (IPA) complicated by subclavian artery occlusion in a 32-year-old man with severe aplastic anemia, who underwent allogeneic stem cell transplantation. He was severely neutropenic after the conditioning for transplantation, but he had no history of fungal infection. Five days after the transplantation, he developed IPA in the left upper lung, complicated by left subclavian artery occlusion. Extensive chronic graft-versus-host disease, which required the administration of potent immunosuppressants for a long period of time, interfered with the resolution of the IPA.
Adult↗
Clinical relevance of serum soluble interleukin-2 receptor levels in acute and chronic graft-versus-host disease.
Soluble interleukin-2 receptor (sIL-2R) levels were analyzed in the sera from 27 patients who underwent allogeneic bone marrow transplantation (BMT) in order to to examine whether there was any correlation between sIL-2R levels and graft-versus-host disease (GVHD). The sIL-2R levels markedly increased at the engraftment period, mainly due to cytokine administration shortly after BMT. Although the sIL-2R levels increased at the onset of acute GVHD, the subsequent development of GVHD could not be predicted by the sIL-2R levels documented before acute GVHD. As acute GVHD improved, the sIL-2R levels decreased, thus showing that the sIL-2R levels correlated with the disease status. In patients without acute GVHD, the sIL-2R levels gradually decreased with time and returned to the pretransplant levels after about 12 weeks post BMT. The sIL-2R levels were higher in unrelated allogeneic BMT patients with acute GVHD when compared with related allogeneic BMT patients. There was a significant increase in the sIL-2R levels at the engraftment period and at the onset of acute GVHD. At the onset of chronic GVHD, the sIL-2R levels once again increased and then decreased as chronic GVHD improved. Prolonged increase in sIL-2R levels was followed by subsequent development of chronic GVHD. Patients with a poor prognosis had higher sIL-2R levels than those with a good prognosis. Therefore, it seems that sIL-2R is a useful marker for monitoring the disease status of acute and chronic GVHD.
Adolescent↗
A translocation t(8;14) and c-myc gene rearrangement associated with the histological transformation of B-cell acute lymphocytic leukemia (FAB-L2) into Burkitt's type (FAB-L3) leukemia.
We report a case of B-cell acute lymphocytic leukemia which showed histological transformation from an FAB-L2 into a Burkitt's type (FAB-L3). Both leukemias had identical immunoglobulin heavy-chain joining gene and kappa light-chain joining gene rearrangements, indicating the clonal identity of the two leukemias. A chromosomal analysis of leukemia cells on the onset indicated normal karyotype, whereas that of the transformed FAB-L3 showed t(8;14)(q24;q32). Furthermore, the proto-oncogene c-myc was in the germline configuration in the initial leukemia but in the rearranged configuration after transformation. Presence of t(8;14)(q24;q32) and the c-myc gene rearrangement after transformation suggested that the chromosomal translocation followed by the activation of the c-myc proto-oncogene might be involved in the Burkitt's type transformation of the FAB-L2 leukemic clone, but not in the leukemogenesis of the initial FAB-L2 leukemia.
Adolescent↗
Low levels of serum soluble c-kit relates to delayed engraftment after bone marrow transplantation.
Serum soluble c-kit concentrations were measured in 28 patients undergoing bone marrow transplantation (BMT). The c-kit levels in patients with delayed engraftment (time to leukocyte recovery > 1.0 x 10(9)/L being more than 20 days after BMT) were significantly lower than those in patients with early engraftment (time to leukocyte recovery being less than 19 days after BMT) from the start of conditioning until day 100 after BMT. The data from this study indicates that the measurement of serum soluble c-kit concentrations may be a useful indicator of engraftment.
Adolescent↗