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Biomedical subjects

Y Takaue

Publications and source records attributed to Y Takaue.

At least 127 records · Page 7Linked to original sources
PubMed1993

[Evaluation of the benefits of sodium 2-mercaptoethane sulfonate (MESNA) therapy for children undergoing high-dose chemotherapy].

Preventive effects of hemorrhagic cystitis by the use of sodium 2-mercaptoethane sulfonate (MESNA) was evaluated in 40 children undergoing peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy which included high-dose cyclophosphamide (CY, 50mg/kg x 2). Fifteen patients received MESNA (group A) and 25 did not (group B), and all received concomitant hyperhydration (3,000ml/m2/day). No renal dysfunction or toxicity attributed to the use of MESNA was observed in either group of patients. Transient hemorrhagic cystitis developed in one of the 15 group A (6.7%) and 3 of 25 (12.0%) group B patients but there was no statistical significance. Although the results may suggest that MESNA is a controversial agent in preventing hemorrhagic cystitis caused by CY when hyperhydration protocol is used, further observation with a larger number of patients is required to establish a firm conclusion.

Adolescent↗
PubMed1993

[Results of the CCLSG high risk ALL 874 protocol in childhood acute lymphoblastic leukemia. Children's Cancer and Leukemia Study Group].

One hundred and eighty eight children with acute lymphoblastic leukemia (ALL) were treated in a Children's Cancer and Leukemia Study Group high-risk ALL 874 study from April, 1987 to September, 1991. These patients received a four-drug induction regimen followed by the early consolidation regimen, cranial irradiation at 6 months of remission and three years of continuation therapy with rotational administration of four drugs. The patients were randomized into two regimens. In regimen A, the consolidation chemotherapy consisted of the intermediate dose cytosine arabinoside (Ara-C), cyclophosphamide (CPM) plus 6MP, and in regimen B, it consisted of high-dose Ara-C plus CPM. Regimen A was given to 106 patients and 82 patients received regimen B. The complete remission induction rate for regimen A and B was 89.4% (93/104) and 98.7% (78/79), respectively. The 3-year event-free-survival (EFS) rate was 70.6% for regimen A, which was higher than the 56.7% for regimen B. The 3-year EFS rate was 44.4% for the 53 patients with an initial leukocyte count > or = 10 x 10(4)/microliters and 72.2% for 132 patients with a leukocyte count < 10 x 10(4)/microliter. We considered that Ara-C plus L-asp, added to the conventional high-risk ALL 811 protocol, improved the prognosis of the high risk ALL patients. However, further intensive chemotherapy was required for improvement of the outcome of the patients with hyperleukocytosis (> or = 10 x 10(4)/microliters).

Adolescent↗
PubMed1992

Combination of recombinant cytokines fails to produce ex vivo expansion of human blood hematopoietic progenitor cells.

The concept of ex vivo expansion of the human progenitor cell population was tested in this study. In the presence of interleukin-3 and -6 we compared the abilities of various liquid culture conditions of human blood-derived hematopoietic progenitor cells to yield a suitable condition for the expansion of blood progenitor cells. Although the best result was obtained in the gastpermeable bag culture system, the enhancement effect (maximum of 3.8-fold for granulocyte/macrophage colony-forming units and 3.0-fold for erythroid burst-forming units) lasted for only a short period (less than 6 d). The results of this study are disappointing for clinical use, and attempts with currently available technology appear to be limited in their potential.

Adolescent↗
PubMed1992

Kawasaki-like disease in early course of acute monocytic leukaemia.

We report a rare occurrence of Kawasaki-like disease in an 11-year-old boy with acute monocytic leukaemia (AML). After 1 week of induction therapy with daunorubicin, etoposide, and cytosine arabinoside, the patient sequentially developed persistent fever, lymphadenopathy, conjunctival injection, exanthema, redness of the lips, and desquamation of the hands. Chest roentgenology showed cardiomegaly and an echocardiogram revealed a dilation of the left coronary artery. The patient was treated with high doses of gamma globulin and steroids. All symptoms except the coronary artery dilation improved. The symptoms did not recur on reinstatement of the original antileukaemia drugs.

Child↗
PubMed1992

Successful autograft with peripheral blood stem cells in a child with T-lymphoblastic leukemia.

Peripheral blood stem cells (PBSC) were collected by two leukaphereses and cryopreserved in a 3-year-old girl with T-lymphoblastic leukemia; this was after remission was induced by an investigative regimen when she failed to respond to a first-line induction therapy. The patient received marrow-ablative chemotherapy 4.5 months after the diagnosis; this was followed by the infusion of thawed PBSC (203 x 10(4) CFU-GM/kg). The peripheral granulocyte count reached 0.5 x 10(9)/L by day +7 and the platelet count reached 20 x 10(9)/L by day + 9. Thereafter, the leukocyte count increased to 38 x 10(9)/L by day +14, with a gradual decline to normal levels. She has remained in unmaintained, complete remission 47 months after the autograft, with full school activity. This case illustrates the PBSC autograft is useful as an alternative to bone-marrow transplantation in a selected patient population, and extends the application of cure-oriented therapy to refractory childhood leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Suspected distinct activation pathways of human lymphocytes induced by antilymphocyte globulin and anti-CD3 monoclonal antibody result in different secretion of hematopoietic colony-stimulating activities.

We evaluated the activation sequence of peripheral blood lymphocytes from healthy donors using different mitogens, including antilymphocyte globulin (ALG), anti-CD3 monoclonal antibody (OKT3), and phytohemagglutinin (PHA). Blood mononuclear cells stimulated by ALG, OKT3 and PHA incorporated 3H-thymidine in the same way. When enriched T cells were tested in the presence of interleukin-1 alpha (0 to 100 U/ml, incorporation of 3H-thymidine was greater in those cells stimulated by ALG than by PHA. OKT3 did not activate enriched T cells. Thymidine incorporation was reduced to less than 50% of maximum concentrations by the addition of 10(-7) mol/1,25-dihydroxyvitamin D3 (vit D3) in PHA- or OKT3-activated cells. However, the inhibitory effect of vit D3 was not apparent in ALG-activated cells. Production of granulocyte-macrophage colony-stimulating factor and interleukin-3 by lymphocytes upon activation was consistently higher when cells were treated with ALG or PHA than with OKT3. Taken together, the data indicate that there appear to be distinct functional mechanisms between ALG- and OKT3-induced lymphocyte activation that lead to characteristic immunohematologic events.

Antibodies, Monoclonal↗
PubMed1992

Effect of chemotherapy on colony-forming unit-granulocyte macrophage from bone marrow and peripheral blood in patients with lung cancer.

The effects of chemotherapy on the growth of colony forming unit-granulocyte macrophage (CFU-GM) from the bone marrow (BM) and peripheral blood (PB) of 8 patients with lung cancer were studied by using recombinant interleukin-3, granulocyte macrophage-colony stimulating factor, and granulocyte-colony stimulating factor. After chemotherapy, the kinetics of CFU-GM depend on the type of chemotherapeutic regimens used: a rebound overshoot of CFU-GM in the PB was seen in the 4 patients treated with cisplatin plus etoposide (PVP) but not in the 4 patients treated with cisplatin plus mitomycin plus vindesine (CMV). In the BM, the recovery of CFU-GM was more retarded in patients treated with CMV relative to that seen in patients treated with PVP. The results obtained in simultaneous cultures revealed the differences between CMV and PVP in the kinetics of chemotherapy-induced myelosuppression. Determination of the optimal timing of in vivo use of hematopoietic growth factors after cytoreductive chemotherapy requires careful experimental design.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Recovery of hematopoiesis after high-dose chemotherapy and peripheral blood stem cell autografts in children].

Hematopoietic recovery kinetics were evaluated in 34 children with therapy-refractory malignant tumors who underwent a total of 35 peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy without total body irradiation. A negative correlation was found between the numbers of colony-forming units of granulocyte-macrophage (CFU-GM) infused per kilogram of the patients' body weight and the time of achieving an absolute granulocyte count (AGC) of 0.5 x 10(9)/l or a platelet count of 50 x 10(9)/l (granulocyte: r = -0.631, p less than 0.001, platelet: r = -0.590, p less than 0.001). The patients were classified into three groups; 14 patients who received less than 1 x 10(5) CFU-GM/kg (group A), 7 patients who received 1-3 x 10(5) CFU-GM/kg (group B), and 14 patients who received greater than or equal to 3 x 10(5) CFU-GM/kg (group C). The AGC recovered to 0.5 x 10(9)/l by 21 day in group A, 14 day in group B, and 10 day in group C. The platelet count recovered to 50 x 10(9)/l 102 in group A, 23 in group B, and 16 day in group C patients. The final platelet infusion was on day 60 in group A, day 12 in group B, and day 12 in group C. Transient decrease in the blood cell count developed in all patients 3 to 7 weeks after transplantation, and two cases developed reversible ITP. In the remaining patients, the recovered hematopoietic function was sustained for 1-48 months after transplant action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Experience with peripheral blood stem cell collection for autografts in children with active cancer.

This report examines laboratory and clinical experience with peripheral blood stem/progenitor cell harvest for autografts in 71 consecutively referred children with various types of cancer from one institution. The age of the patients ranged from 7 months to 17 years with a median of 8 years. Ten of the 71 referred children were removed from the collection procedure because of failure to induce clinical remission (nine) or deteriorating chemotherapy-induced liver failure (one). A total of 215 aphereses were performed on a CS 3000 cell separator in 61 patients, including 18 children aged 4 years or less. The methylcellulose progenitor assay was used as an index of stem cell collection. A minimum of greater than or equal to 3 x 10(5) colony-forming units-granulocyte/macrophage (CFU-GM)/kg body weight were collected in 31 of 71 children (44%) with a mean of 3.1 (range, 1-5) aphereses, and greater than or equal to 1 x 10(5) CFU-GM/kg in 46 children (65%). The incidence of serious morbidity was low. When apheresis or chemotherapy was repeated, the progenitor yields decreased rapidly. By multivariate analysis, the age of the patients was the only significant predictor of CFU-GM yield (p = 0.009). In our experience with 12 children with acute leukemia or non-Hodgkin's lymphoma, regimens containing high-dose cytarabine (2.0 g/m2 x 10) were effective for mobilization. Our results extend the earlier findings that harvesting PBSCs for autografts in children with active cancer is a safe and reliable procedure with a low incidence of serious morbidity.

Adolescent↗
PubMed1992

[Varicella-zoster virus infection after peripheral blood stem cell autografts in children with leukemia or non-Hodgkin's lymphoma].

Thirty-two patients with leukemia or non-Hodgkin's lymphoma (NHL) who underwent high-dose chemotherapy without total body irradiation (TBI) and peripheral blood stem cell autografts (PBSCT) were evaluated for the occurrence of clinically manifested varicella-zoster virus infection (VZV). In a minimum follow-up of 3 mo, there were 14 cases with VZV; 12 patients were treated with intravenous acyclovir and 2 patients received additional intravenous VZV hyperimmune immunoglobulin preparations. History of previous varicella-zoster at some time before PBSCT was the only significant risk factor for the development of VZV. Furthermore, a significant association between VZV and higher disease-free survival rate after PBSCT was proved. Development of minor and reversible VZV is rather common event after high-dose chemotherapy without TBI and PBSCT. VZV appears to be one of the factors which reflects basic physiologic mechanism preventing relapse of leukemias or NHL after PBSCT.

Adolescent↗
PubMed1992

Production of interleukin 3 and granulocyte-macrophage colony-stimulating factor from stimulated blood mononuclear cells in patients with aplastic anemia.

Blood cells from patients with aplastic anemia (AA) were evaluated for the ability to produce interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on stimulation with phytohemagglutinin (PHA) or antilymphocyte globulin (ALG) by the use of an IL-3-dependent cell-line, TF-1, and the GM-CSF-IRMA kit. The IL-3 levels in patients with active AA were significantly lower, both in PHA-stimulated conditioned medium (CM) and in ALG-CM, than those of normal healthy donors (HD; p < 0.01). The degree of reduced IL-3 production in AA patients correlated well with the severity of neutropenia; the level of IL-3 returned to normal after successful treatment with ALG plus methylprednisolone (ALG therapy). On the other hand, GM-CSF production in AA patients varied widely and was only significant in remission patients in PHA-CM; in this case production was higher than that in active AA patients (p < 0.05) or in HD (p < 0.01). Sensitivity to PHA or ALG stimulation was evaluated by the ratio of IL-3 concentrations in ALG-CM versus PHA-CM (ALG/PHA index). The index varied widely from < 0.1 to > 10 in AA patients, contrasting to the clustered values in HD. Seven of the eight patients who had an ALG/PHA index of > 1.0 showed a good clinical response to ALG therapy. However, 12 of the 14 patients who had a lower index (< 1.0) failed to respond. The ALG/PHA index might have an ability to predict the response to ALG therapy.

Adolescent↗
PubMed1992

[Clinical toxicity at the infusion of cryopreserved and thawed peripheral blood stem cell grafts in children].

To test the safety of infusing cryopreserved and thawed peripheral blood stem cells (PBSC) in children, toxicity assessment was made at 36 infusions in 33 children with various types of cancer. The mean volume of PBSC graft infused was 224 ml (range, 46-500 ml) or 8.0 ml/kg (1.7-23.8 ml/kg), in containing 10% dimethylsulfoxide (DMSO). Vomiting was the only toxic feature related to the amount of DMSO. However, eight patients developed transient shock, but recovered shortly afterward with or without supportive therapy. Attention should be drawn to increased risk in children receiving thawed blood cell grafts.

Blood Preservation↗
PubMed1991

Synergistic effect of recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic progenitors.

Purified peripheral blood hematopoietic progenitors from children in early remission from cancer respond to recombinant human interleukin-3 (IL-3), but not to granulocyte colony-stimulating factor (G-CSF). With these purified cells as a target, we studied the effect of recombinant human interferon-gamma (IFN-gamma) on progenitor growth, using both liquid-suspension limiting dilution assay (LDA) and regular methylcellulose culture of progenitors. We found that in LDA with IL-3, IFN-gamma directly stimulated the growth of blood progenitors in a dose-dependent manner with single-hit kinetics, whereas IFN-gamma suppressed the growth of G-CSF-supported progenitors obtained from bone marrow. The stimulatory effect was also observed in methylcellulose culture, but the addition of antibodies for G-CSF, granulocyte-macrophage CSF, IL-1 alpha, IL-1 beta, IL-6, or tumor necrosis factor did not result in a decrease of the colony number, supporting further the possible direct effect of IFN-gamma on progenitor growth. These results suggest that the inhibitory effect of IFN-gamma on hematopoietic progenitors is limited to those in an advanced stage of maturation. IFN-gamma may be one of the essential lymphokines upregulating the growth of human hematopoietic progenitor cells.

Blood Component Removal↗
PubMed1991

Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autografts treatment of childhood acute leukemia/lymphoma with high-risk features.

Clinical and pharmacokinetic studies were performed regarding the toxicity of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) with other drugs, in conjunction with a peripheral blood stem cell autograft (PBSCT), for treating 26 children with acute leukemia or lymphoma associated with high-risk features. In the early phase of the study, MCNU (300 to 500 mg/m2) was administered with cytosine arabinoside (Ara-C) (1.6 to 16 g/m2), etoposide (VP-16) (0.8 to 1.6 g/m2), cyclophosphamide (CY) (100 to 200 mg/kg), or busulfan (16 mg/kg). No acute toxicity was noticed after this high-dose therapy. The dose-limiting factor of the regimens was significant but reversible interstitial pneumonitis (IP). In a subsequent trial with an MCNU/VP-16/Ara-C/CY (MCVAC) regimen in which the dose of MCNU was reduced, the risk of IP diminished. This study is still in progress, but the clinical response has so far been encouraging. Fifteen of 26 children are alive and well in unmaintained complete remission (CR) with a median follow-up period of 11 months (range, 3 to 34 months) after transplantation. This MCNU-based regimen without total body irradiation (TBI) is especially important in children to avoid the serious sequelae of irradiation. Our results justify a broader clinical trial to evaluate the effects of the MCVAC regimen followed by PBSCT.

Adolescent↗
PubMed1991

A simplified and rapid limiting dilution assay of T lymphocytes.

We report here the development of an alternative limiting dilution assay (LDA) of T lymphocytes (T cells). Blood mononuclear cells were first stimulated for 60 hr with PHA and then cultured in microwells in the presence of recombinant interleukin-2 without feeder cells. After 4 days of culture, wells were scored for proliferation. Clonal expansion of T cells followed the single-hit model of the Poisson distribution. The progenitor frequency (f) in the mononuclear cells and E-rosette-positive cells from normal donors were 0.082 +/- 0.025 (n = 12) and 0.236 +/- 0.029 (n = 5), respectively, but this was markedly decreased in patients who underwent marrow-ablative chemotherapy and autografts with blood hematopoietic stem cells. This LDA system should be of value in routine use for the evaluation of T cell proliferative activities.

Bone Marrow Transplantation↗
PubMed1991

Impaired production of burst promoting activity by blood mononuclear cells from chronic uremic patients.

The ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P less than 0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units x3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU-E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patients.

Adult↗
PubMed1991

Early infectious complications after peripheral blood stem cell autografts in children.

Seventeen children underwent marrow-ablative high-dose chemotherapy with peripheral blood stem cell autografts and were studied retrospectively to determine the type, frequency, and outcomes associated with infectious complications 3 months postgraft. The patients were kept in isolated rooms with a laminar air flow facility, but no decontamination procedures, such as gut sterilization with nonabsorbable antibiotics, nonmicrobial diet, and skin cleansing, were used. They were under their mothers' daily care to maintain good psychological conditions. After the completion of marrow-ablative chemotherapy and the infusion of stem cells, the absolute granulocyte count exceeded 0.5 x 10(9)/liter with a mean of 17.9 days (range 6-65 days). Fifteen patients developed a total of 16 febrile episodes during the first 4 week period, and the confirmed diagnoses were mucositis (12), enterocolitis (nine), septicemia (four), central venous catheter-associated infection (three), pneumonia (one), perianal abscess (one), and possible invasive fungal infection (one). All episodes were successfully treated with parenteral antibiotic therapy, and no patient died of infectious complications. The observations suggest that high-dose chemotherapy can be performed safely with simple and efficient patient management protocol followed by peripheral blood stem cell autografts.

Adolescent↗