Clinical application of all-trans retinoic acid (tretinoin) for adult T-cell leukaemia.
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Biomedical subjects
Publications and source records attributed to A Kanamaru.
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The present study investigated fecal flora changes in 20 patients who received either the nonabsorbable antifungal agent amphotericin B, or the absorbable antifungal agent fluconazole, with tobramycin and vancomycin as preparation for undergoing allogeneic bone marrow transplantation (BMT). The oral antibiotic regimen consisted of tobramycin (540 mg/day, three times a day), vancomycin (1,500 mg/day, three times a day) and either amphotericin B (2,400 mg/day, twice a day) (AMPH group) or fluconazole (400 mg/day, twice a day) (FLCZ group) and was designed to prevent infections from microorganisms in the gut. Aerobic bacterial colonies were not detected on the day of BMT or 1 week after BMT, except in 1 case unable to take the full antibiotic regimen due to nausea and vomiting. Anaerobic bacterial colonies were not detected on the day of BMT except in this single case. Furthermore, there were no episodes of bacterial infection. In both groups, Candida colonies were detected in some case. Candida colonies were also detected in the pharynx and urine. However, there were no fungal infections. The present report suggests that amphotericin B and fluconazole administrations, with tobramycin and vancomycin, are equally effective for protection against bacterial and fungal infections in BMT recipients.
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To investigate the pathogenesis of immunological abnormalities (IA) in myelodysplastic syndrome (MDS), we examined B cells for their ability to produce cytokine and their X chromosome inactivation pattern (XCIP). An IA was defined as being positive for at least one autoimmune laboratory test (e.g. antinuclear antibody, rheumatoid factor). Seventy-three MDS patients [65 with refractory anemia (RA), 3 with RA with excess blasts (RAEB), and 5 with RAEB in transformation] were examined; 47 had IA and 26 had no IA. To examine the function of B cells in MDS, the production of interleukin (IL)-6 and IL-10 was measured in cultures of purified B cells with or without stimulators. Both IL-6 and IL-10 production rates in patients with IA were significantly higher than in patients without IA and normal controls. The skewing of XCIP of B cells was analyzed by using the polymerase chain reaction, and the skewing rate of B cell XCIP was quantitatively assayed by compared to control T lymphocytes. The skewing rate of B cells was higher in patients with IA than in those without IA and normal controls. Therefore, a small population of B cells in patients with IA might be derived from MDS clones, and be associated with the induction of IA.
Central nervous system disorders are an important complication of bone marrow transplantation (BMT). We have recently performed cerebral angiography to examine central nervous system dysfunction in a 22-year-old woman with acute lymphoblastic leukaemia who had undergone BMT. Angiography demonstrated multiple stenoses and occlusions in the peripheral branches of the anterior and middle cerebral arteries, a pattern similar to that seen in vasculitis. She was thought to most likely have cytomegalovirus (CMV) vasculitis, but other forms of vasculitis, such as angiitis-like-syndrome-associated graft-versus-host disease could not be excluded. This case suggests that CMV vasculitis may cause central nervous system dysfunction after BMT and that imaging studies may provide useful information about central nervous system disorders in these patients.
Although the occurrence of marrow fibrosis in acute myeloid leukemia has been described, there have been no reports of acute promyelocytic leukemia (APL) associated with marrow fibrosis. Here we describe an APL patient with severe marrow fibrosis at initial presentation. He had the typical manifestations of APL, except for marrow fibrosis. Complete remission was achieved by treatment with all-trans retinoic acid plus chemotherapy, and his marrow fibrosis gradually improved concomitantly with the decrease in leukemic cells. To clarify the mechanism of marrow fibrosis in this patient, we investigated the expression of genes for several cytokines promoting fibrosis by the reverse transcriptase polymerase chain reaction methods. An overexpression of transforming growth factor-beta(1) was noted in his leukemic cells at initial presentation, whereas no increase in expression was observed at the time of relapse when he no longer had marrow fibrosis. These findings suggest that overexpression of transforming growth factor-beta(1) was involved in the development of marrow fibrosis in this APL patient.
A tumor marker, CA125, is known to increase in the serum or other body fluids in various malignancies such as ovarian cancer. Here we present a case of progressive systemic sclerosis (PSS) with massive pleural effusion, in which CA125 in the serum and pleural fluid were elevated. The serum level of CA125 decreased in accordance with the change of the pleural effusion. CA125 level may be an indicator for the activity of serositis in some cases with collagen vascular diseases.
Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adult-onset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.
Effects of perineural capsaicin (CAPS) treatment on compound action potentials of the superior laryngeal nerve (SLN) afferents were studied in 6 sevoflurane-anesthetized dogs. Perineural CAPS (100 microg/ml) to the bilateral SLNs reduced (P<0.01) the peak and integral amplitudes of the C-wave of the compound action potential. By contrast, the perineural CAPS had no effect on the A-wave component (P>0.05). Removal of the perineural CAPS recovered the C-wave to pretreatment level. The perineural CAPS treatment selectively blocks C-wave compound action potentials of the SLN afferents, providing a useful tool for studies of laryngeal C-fibers in respiratory physiology.
The aim of this study was to determine the effect of perineural capsaicin (CAPS) treatment on cardiopulmonary reflexes elicited by topical laryngeal instillation of CAPS and distilled water (DW) in sevoflurane-anesthetized dogs. Cardiopulmonary reflexes elicited by CAPS (10 microg/ml, 10 ml) were attenuated by perineural CAPS treatment to the superior laryngeal nerves (SLNs) (P<0.05), whereas those by DW (10 ml) remained unaffected (P>0.05). The reflex responses to DW that remained even after the perineural CAPS treatment were eliminated by laryngeal anesthesia with lidocaine. These results suggest that cardiopulmonary reflexes from the laryngeal mucosa elicited by CAPS instillation can be blocked by perineural CAPS treatment to the SLNs, which may result from inhibition of the laryngeal CAPS-sensitive C-fiber afferents.
OBJECTIVE: To characterize and determine the sensory innervation of respiratory reflexes elicited by nasal administration of halothane to dogs. ANIMALS: 10 healthy Beagles. PROCEDURE: Dogs underwent permanent tracheostomy and, 2 to 3 weeks later, were anesthetized with thiopental and alpha-chloralose administered IV. The nasal passages were functionally isolated so that halothane could be administered to the nasal passages while dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of halothane at concentrations of 1.25, 1.75, and 2.5 times the minimum alveolar concentration (MAC), and 5% (administered in 100% O2 at a flow rate of 5 L/min) were recorded. Reflexes in response to administration of 5% halothane were also recorded following transection of the infraorbital nerve, transection of the caudal nasal nerve, and nasal administration of lidocaine. RESULTS: Nasal administration of halothane induced an inhibition of breathing characterized by a dose-dependent increase in expiratory time and a resultant decrease in expired volume per unit time. Effects were noticeable immediately after the onset of halothane administration and lasted until its cessation. Reflex responses to halothane administration were attenuated by transection of the caudal nasal nerve and by nasal administration of lidocaine, but transection of the infraorbital nerve had no effect. CONCLUSIONS AND CLINICAL RELEVANCE: Nasal administration of halothane at concentrations generally used for mask induction of anesthesia induces reflex inhibition of breathing. Afferent fibers in the caudal nasal nerve appear to play an important role in the reflex inhibition of breathing induced by halothane administration.
A myeloid cell line (YM711) was established by transfecting exogenous PML/RARalpha cDNA into peripheral blood stem cells. The cells were positive for CD33, CD34, CD38, CD13, CD14, and CD11b. Cytochemical examination revealed YM711 cells to be positive for peroxidase, alpha-naphtyl butyrate esterase, and acid phosphatase as well. Karyotypic analysis showed them to be nearly tetraploid (92 XXYY). Reverse-transcription polymerase chain reaction showed that, although PML/RARalpha mRNA was detected in YM711, these cells could not be differentiated by all-trans retinoic acid (ATRA). We therefore designated the YM711 cell line as being ATRA resistant. Because YM711 expressed multi drug resistance 1 (MDR-1) mRNA and p-glycoprotein cell surface protein, we assessed whether verapamil and ATRA would induce the differentiation of YM711 cells; they did not. An increased expression of cellular retinoic acid-binding protein (CRABP)-II was also detected on YM711 cells compared with that of HL-60. These results suggest that high level of expression of CRABP-II may contribute to be the mechanism of ATRA resistance. This cell line may be useful in evaluating the mechanism of resistance to retinoid.
The earthquake that struck the Hanshin-Awaji district on January 17, 1995, was one of the most destructive to occur in Japan. We analyzed the changes in microorganisms isolated from patients with hematological disorders in relation to this earthquake. We reviewed a total of 4137 microbial cultures obtained over 1-year periods before and after the earthquake. There were 123 neutropenic patients admitted during the study period (54 before the earthquake and 69 afterwards). No significant differences in clinical characteristics and underlying diseases were found between the 2 groups. Polynomial analysis revealed a significant increase in the isolation of Candida albicans, Candida glabrata, and Pseudomonas aeruginosa from sputum and stool cultures after the earthquake. These microorganisms increased markedly in patients from severe earthquake-damaged areas. In neutropenic patients with hematological disorders, microbial isolates changed significantly after the Hanshin-Awaji earthquake. These changes may have been related to physical and emotional stress, as well as to the deterioration of environmental factors such as food, air, and water.
We report a patient with acute monocytic leukemia (AMoL; M5) who received a second bone marrow transplantation (BMT) with graft-versus-leukemia (GVL) effect on relapsed leukemia cutis, which had been refractory to intensive chemotherapy and donor lymphocyte transfusions (DLTs). A 21-year-old woman was diagnosed with AMoL and achieved complete remission after intensive chemotherapy. The patient received a nonmanipulated allogeneic BMT from her HLA-identical father. Skin tumors developed in her upper extremities, chest, and thigh 11 months after BMT. Leukemia cutis was confirmed by skin biopsy. There was no evidence of relapse in bone marrow. The patient received several courses of chemotherapy and DLTs for the skin relapse, but the skin tumors persisted. The patient then received a second BMT from the same donor. On day 80, grade II acute graft-versus-host disease developed, and the remaining skin tumors were eradicated on day 98, most probably because of GVL effect.
We report herein the clinical results of a multicenter trial of the Japan Adult Leukemia Study Group for cases of newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy (JALSG AML-92 study). Of 196 evaluable patients, 173 (88%) achieved complete remission (CR). Multivariate analysis showed that no or minor purpura at diagnosis and age less than 30 years were favorable factors for achievement of CR. There was a significant difference in the 4-year event-free survival between the AML-92 study (54%) and both the AML-87 (32%) and AML-89 (32%) studies which consisted of intensive chemotherapy. Since prognosis in patients with APL largely depends on chemotherapy, it is important to consider more effective chemotherapy during induction and consolidation therapy.
Forty-nine adult patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia that progressed from MDS were registered for the multicenter study of the Japan Adult Leukemia Study Group. Forty-three patients were evaluable for the analysis. Idarubicin 12 mg/m2 per day for 3 days and continuous cytosine arabinoside 100 mg/m2 per day for 7 days were given as induction therapy, followed by postremission chemotherapy after complete remission (CR). Because elderly patients and those with hypoplastic marrow usually have complications after intensive chemotherapy, often causing early death, the treatment dose was reduced to 60% or 80% according to the presence of 3 risk factors: age 60 years or older, performance status 2 or more, or presence of hypoplastic bone marrow. Of the 43 evaluable patients (median age, 58 years), 26 (60%) achieved CR. Two patients (5%) died within 2 months of completion of induction therapy. The CR rates for patients treated with 100%, 80%, and 60% of the chemotherapy dose were 55% (12 of 22), 63% (10 of 16), and 80% (4 of 5), respectively, indicating that the risk factor-adjusted dose attenuation was appropriately applied to those who might have had problems with the original dose, thus reducing regimen-related mortality rate. The median overall survival of the 43 patients was 8 months.
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BACKGROUND: Adult respiratory distress syndrome-like respiratory disorders are a serious, but uncommon, complication of bone marrow transplantation. METHODS: We measured various cytokines in 2 patients with respiratory disorders and 11 patients without respiratory problems after allogeneic bone marrow transplantation. RESULTS: The patients with respiratory disorders had elevated levels of interferon-gamma and interleukin-2 in the aplastic phase, and elevation of tumor necrosis factor-alpha, intercellular adhesion molecule-1, and interleukin-8 at the time of leukocyte recovery. Both patients with respiratory disorders developed fever during the aplastic phase, whereas none of the patients without fever had respiratory disorders. Among patients who had fever during the aplastic phase but no respiratory disorders, there was no elevation of cytokines from the aplastic phase to the recovery phase. CONCLUSIONS: Respiratory disorders may occur after bone marrow transplantation when an inflammatory response during the aplastic phase stimulates cytokines that cause vascular endothelial damage and increases the levels of chemokines and adhesive molecules along with elevation of the leukocyte count.