Phase II study of FK 506 for allogeneic bone marrow transplantation.
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Acute Disease↗
Biomedical subjects
A Kanamaru
Publications and source records attributed to A Kanamaru.
Stromal fibroblastic and hematopoietic progenitors in patients with graft-versus-host disease (GVHD).
We cultured bone marrow cells from patients receiving bone marrow transplantation (BMT) to assay bone marrow fibroblast colony-forming cells (CFU-F) and hematopoietic progenitors (CFU-mix, CFU-C, BFU-E and CFU-E), and compared the mean values obtained from patients with and without graft-versus-host disease (GVHD). The value of CFU-F colonies from 15 patients was always less in patients with acute GVHD Grade II,III than in those with Grade 0,I over the period 30 to 110 days after BMT. The CFU-F colonies from patients with Grade 0,I consisted of approximately the same number of small and large colonies, whereas virtually all CFU-F colonies from patients with Grade II,III were small. Fibroblasts collected from bone marrow cells cultured for 2-3 weeks were incubated with IL-1 (50 U/ml) for 24 h. The concentrations of G-CSF in the culture supernatants from patients with Grade II,III were higher than in those with Grade 0,I. The results of assays of hematopoietic progenitors from 48 patients showed that the number of hematopoietic progenitors decreased as the severity of acute GVHD increased. These results suggest that the myelosuppression seen in GVHD may be associated with reduced numbers of CFU-F in bone marrow.
Bone Marrow↗
Androgen in the treatment of refractory anemia.
We retrospectively evaluated the efficacy of androgen in the treatment of refractory anemia (RA) and compared patient characteristics and the probability of survival in androgen-responder and nonresponder groups. Forty patients with RA were treated in our hospital between 1975-1989, and 27 were treated with various derivatives of androgen. Eleven of the latter responded effectively to androgen therapy, representing an efficacy rate of 40.7%, higher than that of any other treatments thus far reported. The probability of 10-year survival estimated by the Kaplan-Meier method was 75.0% for the responder group and 41.3% for nonresponders, with a median follow-up of 1202 and 1272 days, respectively. In addition, the percent probability of transformation-free survival was higher among androgen-responders than among nonresponders, though the difference was not significant. Transformation from RA to RAEB or overt leukemia was seen in only one case among the former group, but in six among the latter. With respect to patient characteristics, only the percentage of marrow myeloblasts differed significantly between the groups.
Adolescent↗
[An evaluation of combination antibiotic therapy in infections with hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders].
A clinical study was undertaken to determine the effects of combination antibiotic therapy in 104 patients with infections associated with hematological disorders. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) plus an aminoglycoside as an empiric therapy for fever. The overall efficacy rate of the therapy was 63.5%. Efficacy rates were 61.2% and 71.9% when initial neutrophil counts were less than 500/mm3 and over 500/mm3, respectively. No significant difference was found between the cases in which initially used antibiotics were continued (efficacy rate 62.5%) and those in which antibiotics were switched during the course of therapy (65.6%). Antibiotic therapy with SBT/CPZ plus an aminoglycoside provides adequate antibiotic coverage against infections associated with hematological disorders. This combination was highly effective even in the neutropenic periods of febrile patients.
Adult↗
[Multiple discriminant analysis for prognosis of refractory anemia].
Forty-eight patients with refractory anemia (RA) were retrospectively analyzed for their prognosis and subclassified into three groups: 12 patients with hematological improvement (A), 23 patients with no changes (B), and 13 patients with progression to RAEB or acute leukemia (C). For all patients, the median survival were 49.2 months, and the rate of leukemic transformation was 16%. The median survivals were 60.6, 32.1, and 17.9 months, respectively, for groups A, B and C. The factors indicating poor prognosis were low reticulocyte counts, low neutrophil alkaline phosphatase activity, low% red cell utilization, high M/E ratio, high blast percentage in the bone marrow and cytological abnormalities in the granulocyte and megakaryocyte series. By using multiple discriminant analysis, we obtained a formula for the prognostic estimation with a discrimination probability of 62.5%. This formula could predict either the patients with good (Y greater than 0.85) or poor (Y less than 0.59) prognosis, and might be useful to select the treatment for this intractable anemia at the time of diagnosis.
Adolescent↗
[Coombs negative autoimmune hemolytic anemia in a patient with myelodysplastic syndrome].
A 29 year-old-man who had been diagnosed as having myelodysplastic syndrome (MDS) in August 1985 was re-admitted to our hospital because of fever and palpitation. His peripheral blood showed severe pancytopenia and bone marrow findings remained to be compatible with MDS (refractory anemia), but karyotype of bone marrow cells revealed 7 monosomy in 17 of 20 metaphases examined. Other laboratory findings revealed decreased serum haptoglobin, positive urine hemosiderin and the normal resistance of red cell membrane. In addition, both Ham test and sugar water test were negative. The titer of cold agglutinin was low, Donath-Landsteiner antibody was not detected. These findings suggested the association of autoimmune hemolytic anemia (AIHA), although both direct and indirect Coombs' test were negative. After administration of 50mg of prednisolone daily, the frequency of red cell transfusion was markedly decreased and transfused red cell life span was prolonged from 10.4 days to 27 days. Afterward, his hematological status rapidly transformed into that of acute nonlymphocytic leukemia about 13 months after admission and he died of gastrointestinal bleeding and cerebral bleeding. Cases of MDS with immunological disorder have been reported. This is, however, the first case of MDS associated with Coombs negative AIHA.
Adult↗
Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia.
Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.
Acute Disease↗
Pre-inspiratory burst in the caudal medulla of rabbits.
The activity of 48 respiratory units in the paraolivary region from the middle to the rostral end of the hypoglossal cranial nerve root, and the effect of electrical stimulation and L-glutamate applied to the region on phrenic nerve activity was investigated in 14 rabbits. Electrical stimulation (50 Hz, 0.2 ms current pulses at intensities 5-20 microA) and L-glutamate (30-100 ng) shortened the expiratory time and increased the respiratory rhythm with no change in tidal phrenic nerve activity. Rhythmic activity preceding the phrenic nerve activity (pre-inspiratory burst) was recorded in the paraolivary region. The temporal relationship between the pre-inspiratory (pre-I) burst and the phrenic activity remained constant even when the respiratory frequency was altered by passive lung inflation. These results suggest that structures in the paraolivary region may influence the respiratory rhythm in rabbits and that pre-I burst neurons may play a role in triggering periodic phrenic activity.
Action Potentials↗
Membrane expression of decay-accelerating factor on neutrophils from normal individuals and patients with paroxysmal nocturnal hemoglobinuria.
Decay-accelerating factor (DAF), a complement-regulating glycoprotein, was found to be a maturational protein for normal neutrophils, and a remarkable correlation was found between the DAF level and alkaline phosphatase activity in neutrophils. We studied the relationship between the amount of DAF on the membrane and cell maturity in total nucleated bone marrow (BM) cells, mature BM and peripheral blood (PB) neutrophils from normal subjects, and patients with paroxysmal nocturnal hemoglobinuria (PNH) using a fluorescence-activated cell sorter with anti-DAF monoclonal antibodies. Percentage distributions of differentiating neutrophils from normal total nucleated BM cells showed that the proportion of immature cells (myeloblasts plus promyelocytes) decreased, while that of mature ones (bands plus segmented forms) increased as the fluorescence intensity increased. For PB neutrophils, no apparent correlation was found between DAF expression and cell maturity. This may have resulted from margination of the fully matured neutrophils with a high amount of DAF. In PNH patients who have low levels of DAF, this study showed that DAF expression in their neutrophils differs from that in normal subjects, and abnormalities occur in PNH cells from a very early stem-cell stage.
Alkaline Phosphatase↗
Expression of decay-accelerating factor on hematopoietic progenitors and their progeny cells grown in cultures with fractionated bone marrow cells from normal individuals and patients with paroxysmal nocturnal hemoglobinuria.
Decay-accelerating factor (DAF), a complement-regulating glycoprotein, has been shown to be expressed on hematopoietic progenitors and their progeny cells in normal individuals but not on abnormal cells in patients with paroxysmal nocturnal hemoglobinuria (PNH). Fluorescence histograms of bone marrow cells showed the heterogeneity of DAF expression on their cell membranes, suggesting mixed hematopoietic cell populations in PNH. We have previously shown that DAF is a maturational protein expressed on normal hematopoietic cells. In order to elucidate the relationship between DAF expression and cell maturity in PNH, we fractionated bone marrow cells according to amount of DAF and cultured these cells in methylcellulose for clonal assay of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM), followed by reanalysis of DAF expression on their progeny. The matured cells from the bursts/colonies in cultures with DAF-negative PNH marrow cells had no or little DAF, but those grown from DAF-positive PNH progenitors showed nearly as much of this factor as those grown from normal progenitors. These results clearly indicate that there are at least two distinct populations of hematopoietic progenitors with respect to the membrane expression of DAF and that abnormalities occur at the level of the stem cell in PNH.
Bone Marrow↗
Randomized trial of combination antibiotic therapy in patients with hematological disorders. Hanshin Study Group of Hematopoietic Disorders and Infection.
A 3 arm prospective randomized trial was designed to compare the effectiveness of aztreonam (AZT) + clindamycin (CLDM), amikacin (AMK) + AZT and CLDM + AMK as antibiotic therapy for fever in patients with hematological disorders. Between July 1987 and June 1988, one hundred and sixty of the 199 febrile episodes entered in this study were evaluated for response. Underlying diseases were hematological malignancies in 88.8% of the subjects, and there was no statistically significant differences in incidences of the diseases among the 3 groups. Efficacy rates were 64.2% in the AZT + CLDM group, 52.8% in the AMK + AZT group and 35.2% in the CLDM + AMK group. Efficacy rates in those with neutrophil counts was less than 500/microliters before starting the antibiotics were 53.3%, 43.8% and 25.0%, respectively, in the 3 groups. The combination of AZT + CLDM was found to be the most effective even in the treatment of infections associated with febrile neutropenic patients.
Adolescent↗
[Complications classified under clinical stages following bone marrow transplantation].
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Bone Marrow Transplantation↗
[Bone marrow transplantation for MDS].
Five patients with myelodysplastic syndrome (RA: 4 cases, RAEB in T: 1 case) were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Median age was 20-y-o (11-31-y-o). All patients were prepared with cyclophosphamide and total body irradiation. Engraftment was documented in all patients. One patients (case 4, 31-y-o female) died of brain hemorrhage due to the thrombocytopenia refractory to platelet transfusion because of anti-platelet antibody in 34 days after BMT. A patient with RAEB in T was also died of respiratory failure from interstitial pneumonia on Day 173. One patient (case 1, 22-y-o, female) progressively became granulocytopenic and thrombocytopenic status after BMT. She suffered from life-threatening infection and then received a second bone marrow cell infusion from the same donor without any preparative conditioning. These results suggest that BMT could be the treatment of choice for MDS, especially for the patients with RA who have poor prognostic factors including life-threatening cytopenia and or cytogenetical abnormalities.
Adolescent↗
[Mixed blast crisis with the cytogenetic evidence of three clonal evolutions].
A 46-year-old man was diagnosed as having chronic myelogenous leukemia (CML) in chronic phase in Dec. 1985. In Dec. 1987, anemia and leukocytopenia progressed, and the percentage of blast cells increased in the bone marrow. The blast cells were lymphoblastoid and positive for TdT. It was treated as a lymphoid crisis with vincristine and prednisolone, and complete remission was achieved. However, the blasts (11%) were observed in the bone marrow in Mar. 1988, and the chromosomal analysis revealed 46, XY, t (2q-; 11q+), t (9q+; 22q-) in 13 out of 20 cells. In June, the percentage of the blasts increased again, but chromosomal analysis showed a different karyotype, 46, XY, t(2p-; 11p+), t(9q+; 22q-) which was observed in 9 out of 10 cells. Then, myeloblastoid cells increased rapidly in spite of the chemotherapy in Dec. 1988. The chromosomal analysis showed 46, XY, 2p-, 7q-, 9q+, 11p+, 22q- in all analyzed cells. The rearrangement of the bcr gene could be detected by the Southern blotting. The blasts were positive for CD7, CD11, CD13, CD33, CD36, CD41 and CD42, suggesting that the blasts had the surface phenotypes of both myeloid and megakaryocytoid-lineage. This is a case with the mixed blast crisis that changed from the lymphoid to the myelo-megakaryocytoid in nature, in which three clonal evolutions were observed during the clinical course.
Antigens, CD↗
Angioimmunoblastic lymphadenopathy. Review of 44 patients with emphasis on prognostic behavior.
In order to investigate the relationship between histologic findings and clinical behavior in angioimmunoblastic lymphadenopathy (AILD), 44 patients with AILD were reviewed. These patients comprised 24 men and 20 women with age range from 25 to 84 years of age (median, 64 years). Lymphadenopathy was observed in all patients, systemic in 37, and localized in seven. Polyclonal hypergammaglobulinemia was present in 64% of patients. Histologically clear cells or convoluted cells were observed in 36% and 48% of the patients, respectively. Univariate analysis (log-rank test) for prognostic factors revealed age, appetite, presence of clear cells, or convoluted cells were important factors. However, multivariate analysis revealed that there were no independent factors for prognosis. The presence of clear cells and/or convoluted cells were histologic signs for poor prognosis; autopsy showed that patients with the clear cells with or without convoluted cells mostly died of active disease of AILD with two cases progressing to non-Hodgkin's lymphomas and those with convoluted cells alone died of lung infection. From these findings, AILD could be divided into three groups: AILD with (1) clear cells with or without convoluted cells, (2) convoluted cells alone, or (3) neither cells. The first two groups showed poor prognosis, and the last a favorable prognosis.
Adult↗
Recombinant human granulocyte colony-stimulating factor in allogeneic bone marrow transplantation.
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Adolescent↗
[Clinical evaluation of monotherapy with ceftazidime for severe infections complicating hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders].
Clinical effects of the monotherapy with ceftazidime (CAZ) were evaluated in patients with severe infections associated with febrile granulocytopenia in hematological disorders in 10 institutions. CAZ (4-6g/day) was administered intravenously by drip infusion divided into 2 to 4 doses. 83% of the underlying diseases were hematological malignancies. Infections mainly consisted of documented sepsis (10%), presumed sepsis (60%). Overall efficacy rate was 65%, and that of septic patients was 83.3%. Adverse reactions were minimal, and this study revealed safety of CAZ.
Adolescent↗
Inhibition against CFU-C and CFU-E colony formation by soluble factor(s) derived from hairy cells.
The inhibitory effect by hairy cell conditioned medium (HCCM) on the growth of granulocyte and erythrocyte colony forming cells was studied in vitro. The percent inhibition of CFU-C formation by HCCM from four hairy cell leukemia (HCL) patients ranged from 36% to 76%, while no inhibition was observed with conditioned medium (CM) obtained from three B-cell chronic lymphocytic leukemia (B-CLL) patients nor from two normal controls. HCCM inhibited specially the growth of rG-CSF responding stem cells. The hairy cell-derived colony inhibitory factor from HCCM was nondialyzable, fairly stable to heat treatment, and trypsin sensitive. Its maximal inhibitory activity against granulopoiesis was observed in the fractions of 5,000 to 6,000 daltons. Moreover HCCM inhibited CFU-E colony formation but not BFU-E. These results indicate that hairy cells produce a factor that inhibits granulopoiesis and erythropoiesis in vitro. This factor may play a role in neutropenia and anemia observed in HCL.
Culture Media↗