[Autologous peripheral blood stem cell transplantation--an evaluation in adults].
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Adolescent↗
Biomedical subjects
K Akashi
Publications and source records attributed to K Akashi.
Cytotoxic drug and cytotoxic drug/G-CSF mobilization of peripheral blood stem cells and their use for autografting.
We analysed 99 courses of leukapheresis after the use of cytotoxic drugs or cytotoxic drugs plus G-CSF (cytotoxic/G-CSF) to mobilize peripheral blood stem cells (PBSC) in 68 patients with hematologic or solid malignancies. Mean yields of granulocyte-macrophage progenitor cells (CFU-GM) with cytotoxic/G-CSF mobilization were significantly higher than those with cytotoxic mobilization (18.6 vs 8.40 x 10(4)/kg). The optimal timing of collection was different between these two mobilizations; the mean number of days to a peak level of circulating CFU-GM after cytotoxic/G-CSF mobilization was less than that after cytotoxic mobilization (24.2 vs 27.7 days). The leukocyte level on the day of peak CFU-GM was significantly higher in cytotoxic/G-CSF mobilization than that in cytotoxic mobilization (mean 12.8 vs 2.7 x 10(9)/l), whereas the platelet level was not different (mean 132 vs 125 x 10(9)/l). Increasing patient age was not a major adverse factor for PBSC collection. Synchronous recovery of both leukocytes and platelets was critical for achieving a high CFU-GM yield in these two mobilizations. Following PBSC autotransplantation, the rate of trilineage hematologic reconstitution showed a significant correlation with the infused dose of CFU-GM, whether they were collected with cytotoxic or cytotoxic/G-CSF mobilization. These results suggest that G-CSF can expand the PBSC pool and that CFU-GM yield after cytotoxic/G-CSF mobilization may predict trilineage hemopoietic reconstitution after ABSCT, as well as cytotoxic mobilization.
Adolescent↗
[Immunophenotypic analysis in acute leukemia].
Acute leukemias have been classified on French-American-British (FAB) criteria depending on the morphocytochemical features of blasts. Immunophenotyping and clonal rearrangement analysis of lineage-associated genes can decide a frozen stage of the hematopoietic differentiation process in blasts from acute leukemias. B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL are systematically classified according to the sequential expression of differentiation-associated antigens. In acute myelogenous leukemia (AML), several new entities are proposed: AML-M0 is an AML without cytologic maturation, in which the myeloid commitment should be demonstrated by myeloperoxidase-positive microgranule on immunohistochemical staining or electron-microscopy, or by positive reaction for CD13 or CD33 antigens. CD7-positive AML is considered to be one of immature subtypes of AML, rather than hybrid leukemia. Thus, immunological studies on blasts enable us to discriminate a subgroup of leukemias, which will perhaps contribute to the improvement of treatment approach.
Acute Disease↗
[i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML].
A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF-dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated.
Adult↗
Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia.
We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34-positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL-6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3-dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML.
Adolescent↗
Simultaneous occurrence of myelomonocytic leukemia and multiple myeloma: involvement of common leukemic progenitors and their developmental abnormality of "lineage infidelity".
We investigated the origin of leukemic progenitors in a case of the simultaneous occurrence of myelomonocytic leukemia and multiple myeloma (IgG-kappa). At presentation, myeloperoxidase and nonspecific esterase-positive myelomonocytic cells had proliferated up to 12.2 x 10(9)/liter in the peripheral blood. Bone marrow cell differentials revealed the coexistence of myelomonocytic cells (30%) and atypical plasmacytoid cells (26%). Myelomonocytic cells in peripheral blood expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33) and T/B-lymphoid antigens (CD2, CD4, CD5, CD7, CD10, PCA-1). Bone marrow mononuclear cells (BMMC) could be divided into PCA-1 strongly positive and PCA-1 weakly positive populations, which were considered to represent myeloma cells and myelomonocytic cells, respectively; the former were CD2-positive (CD2+), CD14-, and CD15-, whereas the latter were CD2+, CD14+, and CD15+. Immunohistochemical analysis revealed that, in addition to plasmacytoid cells, a minority of myelomonocytic cells showed a positive reaction for IgG staining, and production of IgG was observed in the culture supernatant of CD14+ myelomonocytic cells in peripheral blood. Southern blot analysis revealed the presence of two identical rearrangement bands of immunoglobulin heavy chain gene in both BMMC containing myeloma cells and myelomonocytic cells and CD14+ myelomonocytic cells in peripheral blood. In a long-term methylcellulose assay, peripheral blood mononuclear cells produced large compact colonies consisting of macrophages and IgG+ plasmacytoid cells (M phi/P colonies), while BMMC produced a different type of colonies consisting of CD14+ myelomonoblasts, macrophages, and IgG+ plasma cells (Mb/M phi/P colonies) in addition to M phi/P colonies. Recloning experiments showed that primary Mb/M phi/P colonies gave rise to both secondary M phi/P and Mb/M phi/P colonies. These observations strongly suggest that common leukemic progenitors provide both myeloma and myelomonocytic leukemia cells, and the mechanism of "lineage infidelity" is probably involved in the development of their "bilineal" differentiation.
Antigens, CD↗
Colonic motility and transit in health and ulcerative colitis.
Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.
Adult↗
Characterization of leukaemic basophil progenitors from chronic myelogenous leukaemia.
We describe the unique characteristics of leukaemic basophils from a patient with chronic myelogenous leukaemia (CML). The leukaemic cells were immature basophil-like blasts and expressed CD4, CD7 and HLA-DR in addition to CD13 and CD33. Both immunoglobulin and T cell receptor genes were retained in germline configurations. Interleukin-1 (IL-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as IL-3 or IL-4 enhanced the proliferation and differentiation of leukaemic cells and only basophils were generated from in vitro culture. These results suggest that basophil progenitors expressing CD4, CD7 and HLA-DR may be involved in the development of basophilic crisis of CML and that both IL-1 and GM-CSF may act on basophil progenitors as well as IL-3 or IL-4.
Antigens, CD↗
Folinic acid did not expand the peripheral blood stem cell pool during recovery from consolidation chemotherapy.
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Acute Disease↗
Role of interleukin-4 in the negative regulation of proliferation of chronic myelomonocytic leukemia cells.
We studied the effects of interleukin-4 (IL-4) on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro to clarify whether IL-4 can act as a negative regulator of hematopoiesis. The results clearly show that IL-4 suppressed spontaneous DNA synthesis and colony formation by CMMoL cells in vitro. Colony formation by CMMoL cells was substantially suppressed by adding either an anti-IL-6 or anti-GM-CSF antibody to the colony assay system. This suppression was abrogated by the treatment of IL-4 with an anti-IL-4 antibody. Furthermore, the production of IL-6 or GM-CSF was markedly inhibited by adding IL-4 to the culture system. These observations indicate that IL-4 can act as a negative regulator for the autocrine growth of CMMoL cells by inhibiting their production of IL-6 and/or GM-CSF.
Aged↗
Human recombinant granulocyte colony-stimulating factor for the treatment of autoimmune neutropenia.
We have recently treated a case of autoimmune neutropenia in a 57-year-old male. Because neutropenia persisted despite the administration of prednisolone for 30 days, daily subcutaneous injection of human recombinant granulocyte colony-stimulating factor (rhG-CSF) at a dosage of 100 micrograms was started. Neutrophil count increased gradually and reached a plateau of 5,000/microliters by day 25 after administration of rhG-CSF. This observation suggests that rhG-CSF is effective for the treatment of autoimmune neutropenia.
Autoimmune Diseases↗
Interleukin 4 suppresses the spontaneous growth of chronic myelomonocytic leukemia cells.
We studied the effects of IL-4 on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro. IL-4 (100 U/ml) suppressed the spontaneous DNA synthesis by approximately 50% in 5 of 8 cases examined. IL-4 (100 U/ml) also inhibited the spontaneous colony formation by CMMoL cells in a methylcellulose culture by 50-97% in all of the 10 cases in which spontaneous colonies were formed. This IL-4-mediated suppression of the growth of CMMoL cells was completely abolished by the addition of anti-IL-4 neutralizing antibodies. The spontaneous CMMoL colonies were substantially suppressed by the addition of either anti-IL-6 or anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies to the colony assay system: the addition of both anti-IL-6 and anti-GM-CSF antibodies resulted in greater than 80% inhibition of the colony formation by CMMoL cells. On the other hand, none of anti-IL-1-beta, anti-granulocyte-CSF, anti-macrophage-CSF, or anti-tumor necrosis factor-alpha antibodies affected the CMMoL colony formation. In the supernatants from 24-h cultures of CMMoL cells, high levels of IL-6 and GM-CSF were demonstrated in 9 of 9 and 2 of 9 cases examined, respectively. IL-4 (100 U/ml) almost completely inhibited the secretion of IL-6 and GM-CSF by CMMoL cells. These observations suggest that IL-4 suppresses the spontaneous proliferation of CMMoL cells by inhibiting their production of IL-6 and/or GM-CSF, both of which could act in vitro as an autocrine growth factor for CMMoL cells.
Adult↗
Human urinary proteinase inhibitor in the treatment of P carinii pneumonia.
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Glycoproteins↗
A simplified method for cryopreservation of peripheral blood stem cells at -80 degrees C without rate-controlled freezing.
A simplified method was established for cryopreservation of peripheral blood stem cells (PBSCs) using hydroxyethyl starch (HES) and dimethylsulfoxide (DMSO) as a cryoprotective agent at -80 degrees C without rate-controlled freezing. The data indicate that a cryoprotective solution consisting of 6% HES and 5% DMSO produced the highest recovery rates for nucleated cells (92.0 +/- 3.5%), CFU-GM (73.8 +/- 4.1%) and BFU-E (82.2 +/- 6.9%), and the highest trypan blue viability (88.4 +/- 3.6%). For long-term cryopreservation of PBSCs, CFU-GM recovery rates remained almost unchanged during 5-18 months; the mean CFU-GM recovery rate after 18 months of cryopreservation was 70 +/- 11%. When large-scale samples of PBSCs in 100-ml freezing bags were cryopreserved for clinical use, cell and CFU-GM recoveries were similar. Using this method, 10 patients with hematological malignancy received PBSC transplants after marrow-ablative chemotherapy. All demonstrated early engraftment; seven are now alive in unmaintained complete remission for 3.5-15 months after PBSC transplant. This simple and inexpensive method will be useful for the wider application of PBSC transplant as a therapeutic alternative in the treatment of malignant diseases.
Acute Disease↗
[A case of Kearns-Sayre syndrome with impaired respiratory regulation].
We reported a case of Kearns-Sayre syndrome with impaired respiratory regulation. A 55-year-old male was admitted to our hospital complaining of chronic progressive external ophthalmoplegia, limb muscle weakness and dyspnea. On admission, because arterial blood gas analysis showed marked alveolar hypoventilation, ventilatory response was measured and diminished chemosensitivity to both hypoxia and hypercapnia was found. His vital capacity and forced expiratory volume in 1 second were slightly decreased, and a chest X-ray film revealed a moderate degree of elevation of the bilateral diaphragm. Therefore, we considered that the diminished response to hypoxia and hypercapnia in this case was caused by an impairment of the respiratory center, as well as chemoreceptors and also the presence of respiratory muscular weakness.
Chemoreceptor Cells↗
[A case of bronchial artery aneurysm demonstrating a mass shadow on chest X-ray film].
A 66-year-old woman was admitted on May 13, 1989, because of an abnormal round shadow in the right hilum on chest X-ray film. Bronchoscopy revealed a stenosis of the right B8 caused by a bulging lesion. An aortogram showed a large meandering bronchial artery and a saccular aneurysm. The aneurysm was about 25 mm in diameter and associated with a bronchopulmonary anastomosis. It was surgically removed by right lower lobectomy. Pathological examination proved that the resected lesion was an arterial aneurysm. Patchy arteriosclerotic change was present in the intima of the aneurysm, but there was no evidence of inflammatory change in the arterial wall and the adjacent alveoli and bronchi. Twenty-six cases of bronchial artery aneurysm have been previously reported in the literature, but this is the first case that appeared as a solitary nodule on conventional chest X-ray.
Aneurysm↗
Central nervous system involvement in adult T-cell leukemia/lymphoma.
Central nervous system (CNS) involvement was reviewed in 99 patients with adult T-cell leukemia/lymphoma (ATLL). Fifteen episodes of CNS involvement developed in ten of 99 patients (10.1%); nine had leptomeningeal involvement, whereas two developed intracerebral invasion, one developed cord involvement, and one developed both. CNS involvement was more frequent in the lymphoma type than in the other types of ATLL. Nuchal rigidity was not common (33%) and a syndrome of inappropriate secretion of antidiuretic hormone (ADH) occurred in association with CNS involvement (40%). Three episodes of marked hypoglycorrhachia also were noticed. The systemic progression of ATLL was the most common setting of CNS involvement (80%) and the major cause of death (80%). As for the acute and lymphoma types of ATLL, no significant difference was observed in survival between patients with and those without CNS involvement. These results indicate that CNS involvement is not an essential prognostic factor of ATLL and that it should be treated with systemic chemotherapy coupled with intrathecal chemotherapy. The control of systemic ATLL is important for the prophylaxis of CNS involvement.
Adult↗
Clinical characteristics of hybrid leukemia: report of five cases.
We studied clinical and biological features of five cases of hybrid leukemia. Three of the five patients were classified as biphenotypic leukemia because of the coexpression of myeloid/B lymphoid markers in patients 1 (FAB M2) and 2 (FAB CMMoL) and myeloid/T lymphoid markers in patient 3 (FAB M4). Patient 4 was identified as bilineal-biphenotypic leukemia because acute myelogenous leukemia (AML) (FAB M4) and acute lymphoblastic leukemia (ALL) (FAB L1) coexisted and each population coexpressed myeloid and T lymphoid markers. Patient 5 was identified as bilineal leukemia due to the conversion from AML (FAB M1) to ALL (FAB L1) at an interval of 3 months. The Philadelphia (Ph1) chromosome was negative in all cases. A leukemic blast colony formation using cell line 5637 conditioned medium as a stimulator was obtained in all four patients examined. Three of the five patients had been suffering from so-called stem cell disorders such as aplastic anemia in patient 2, trilineage myelodysplasia in patient 4 and refractory anemia with excess of blasts in transformation in patient 5. The pre-existing impairment of pluripotent stem cell was probably the background of these hybrid leukemia. Hybrid leukemia appears to have an inferior prognosis: an AML-directed chemotherapy resulted in a low remission rate (2/5) with a short duration of relapse free survival (1/2) and an ALL-directed chemotherapy produced no remission (0/3). Chronological phenotypic analysis revealed that hybrid features of leukemic blasts disappeared at the time of relapse in patient 1 and progression to AML in patient 2. Monitoring of lineage-associated markers should be required for the management of hybrid leukemia.
Adult↗