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Biomedical subjects

N Niitsu

Publications and source records attributed to N Niitsu.

At least 55 records · Page 3Linked to original sources
PubMed1997

Induction of differentiation of human myeloid leukemia cells by 2'-deoxycoformycin in combination with 2'-deoxyadenosine.

2'-Deoxycoformycin (dCF), a specific and potent inhibitor of adenosine deaminase, has demonstrated significant antitumor effect on lymphoid malignancies. The drug induced functional and morphologic differentiation of myeloid leukemia cells in combination with 2'-deoxyadenosine (dAd), but not dCF alone. NB4, a cell line derived from a patient with t(15; 17) acute promyelocytic leukemia (APL) underwent granulocytic differentiation when treated with all-trans retinoic acid (ATRA) or dCF plus dAd, but not with cytosine arabinoside. Pre-exposure of NB4 cells to ATRA greatly potentiated differentiation induced by dCF plus dAd, but pretreatment with dCF plus dAd before exposure to ATRA was less effective. Differentiation of NB4 cells was effectively induced by clinically applicable concentrations of dCF in combination with dAd. These findings may provide useful information about induction of differentiation in vivo.

Antibiotics, Antineoplastic↗
PubMed1997

Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991-96.

Twenty cases of interstitial pneumonia secondary to treatment with granulocyte colony-stimulating factor (G-CSF) were reviewed. Their interstitial pneumonia had the following features: (a) it occurred predominantly in patients aged 60 years or older; (b) it was prevalent among patients with haematological malignancies, particularly non-Hodgkin's lymphoma; (c) in all patients G-CSF was given after anti-cancer agents with potential to affect the lungs; (d) at the onset, many patients had symptoms such as dyspnoea and fever; and (e) the leucocyte (neutrophil) count as well as lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were usually higher than normal at the onset. These findings indicate that, when G-CSF is used in combination with pneumotoxic anti-cancer agents, respiratory function should be monitored before and during treatment. If the leucocyte (or neutrophil) count and/or LDH and CRP increase suddenly in association with dyspnoea and fever during administration of G-CSF, interstitial pneumonia should be suspected. Accordingly, a chest radiograph and pulmonary functional tests should be performed promptly. If a diagnosis of interstitial pneumonia is made, steroid pulse therapy should be commenced immediately.

Adult↗
PubMed1997

THP-COPBLM (pirarubicin, cyclophosphamide, vincristine, prednisone, bleomycin and procarbazine) regimen combined with granulocyte colony-stimulating factor (G-CSF) for non-Hodgkin's lymphoma in elderly patients: a prospective study.

THP-COPBLM including pirarubicin (THP), which is thought to be less toxic than doxorubicin, was used to treat non-Hodgkin's lymphoma (NHL) and the remission rate and adverse effects were studied in 26 patients older than 70 years. Complete remission (CR) was achieved in 19 patients (73.1%) and partial remission in three (11.5%). Classified by stages, CR was achieved in seven out of nine stage II patients and 12 out of 17 stage III, IV patients. The 2-year survival rate was 60.3%. Grade 3 or higher adverse effects included leukopenia in eight patients (30.8%), anemia in three (11.5%), thrombocytopenia in two (7.7%) and nausea/vomiting in 1 (3.8%). The THP-COPBLM regimen appears useful for the treatment of NHL in elderly patients. The regimen was seldom associated with gastrointestinal symptoms and cardiotoxicity. Despite the administration of granulocyte colony-stimulating factor (G-CSF), however, the white blood cell count decreased in many patients, suggesting the necessity for further study of this regimen to modify the dose of THP.

Aged↗
PubMed1997

Evaluation of long-term daily administration of oral low-dose etoposide in elderly patients with relapsing or refractory non-Hodgkin's lymphoma.

Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.

Administration, Oral↗
PubMed1997

Prognostic factors in elderly patients with non-Hodgkin's lymphoma treated with cyclophosphamide, vincristine, prednisone, bleomycin, Adriamycin, procarbazine (COP-BLAM) therapy.

Elderly patients with non-Hodgkin's lymphoma (NHL) were treated with cyclophosphamide, vincristine, prednisone, bleomycin, Adriamycin, procarbazine (COP-BLAM) therapy at our institution. Prognostic factors were analyzed in 62 patients with untreated NHL aged 65 years or older. Of these patients, 47 (75.8%) achieved a complete remission and 11 (17.7%) partial remission. The overall response rate was 93.5%, with a 5-year survival rate of 70%. Factors with prognostic significance included age, performance status, albumin, stage, B symptoms, and histologic type according to the International Working Formulation. Of the 62 patients, 26 were alive at the time of writing. Of the 36 patients who died, 30 died due to progression of NHL or treatment-related disorders, and 6 died from disease other than NHL. Some of the prognostic factors identified in these elderly patients are not included among the prognostic factors reported for younger patients, suggesting the need to individualize chemotherapy for NHLs of different types, which can be defined by prognostic factors. Prognostic factors other than age should be taken into account, particularly when doses and dosing intervals are determined.

Aged↗
PubMed1997

[Effectiveness of prolonged oral therapy with low-dose etoposide in patients aged 85 years and over with non-Hodgkin's lymphoma].

Individualizing the doses of cancer chemotherapy agents and progress in supportive therapy have improved the prognosis for elderly patients with non-Hodgkin's lymphoma. Prolonged hospitalization elderly patients has adverse effects, which include dementia, difficulty in walking, and depression. We treated 10 elderly patients (> or = 85 years) with non-Hodgkin's lymphoma as outpatients with oral etoposide, 25 mg or 50 mg daily for as long as possible, or until the white blood cell count decreased to < or = 2,000/microliter or the platelet count decreased to < or = 5 x 10(4)/microliter. Complete remission was achieved in 4 patients and partial remission in 4; the median duration of survival was 19 months. Adverse effects included leukopenia in 1 patient (< or = 1,000 cells/microliter), thrombocytopenia in 1 patient (< or = 5 x 10(4) cells/microliter), and anorexia in 1 patient. These results indicate that prolonged oral administration of low-dose etoposide is effective and safe for the treatment of non-Hodgkin's lymphoma in elderly patients. This outpatient chemotherapy caused no serious adverse reactions.

Administration, Oral↗
PubMed1997

[Doxorubicin-induced myocardial damage in elderly patients with hematologic malignancies].

Cardiac function was evaluated in 53 elderly patients with hematologic malignancies who were being treated with doxorubicin (DXR). The left ventricular ejection fraction was measured by radionuclide angiocardiography, the washout rate by 123I-MIBG myocardial SPECT, the extent and severity scores by 123I-BMIPP myocardial SPECT, and the frequency of premature ventricular contractions by Holter electrocardiography. 1) In some patients, both the washout rate and the extent and severity scores were abnormally high before treatment. 2) Because the washout rate correlated with the total dose of DXR, it may be an early indicator of cardiac sympathetic nervous dysfunction. 3) The left ventricular ejection fraction correlated with the extent and severity scores, but not with the washout rate or with the frequency of premature ventricular contractions. 4) The washout rate correlated with the frequency of premature ventricular contractions. These data show that elderly patients had abnormal cardiac function even before treatment with DXR; that cardiac sympathetic dysfunction and cardiac mitochondrial dysfunction developed at total DXR doses of 250 to 300 mg/m2 or higher; and that the left ventricular ejection fraction was less than or equal to 50% in many patients. Consequently, when DXR is used to treat elderly patients, multimodal evaluation of cardiac function is necessary to detect cardiotoxicity and to determine the optimal total dose and the optimal dosage.

Aged↗
PubMed1997

[Usefulness of THP-COPBLM therapy in elderly patients with non-Hodgkin's lymphoma].

We studied the remission rate and adverse effects in THP-COPBLM therapy consisting of pirarubicin (THP), which is said to be less cardiotoxic than doxorubicin. Subjects were 21 non-Hodgkin's lymphoma (NHL) patients older than 70 years of age. Of 21 patients, complete remission (CR) was achieved in 16 patients (76.2%) and partial remission in 2 patients (9.5%). Classified by stages, CR was achieved in 5 out of 6 patients in stage II, 7 out of 8 in stage III and 4 out of 7 in stage IV. Two-year survival rate was 61.5%. Adverse effects were observed in 7 patients (33.3%) with grade 3 or above leukocytopenia, 2 (9.5%) with thrombocytopenia and 1 (4.8%) with gastrointestinal symptoms. However, no abnormality in EKG was found, and the left ventricular ejection fraction in echocardiography did not differ before and after therapy. One patient each developed pneumonia and sepsis when they had granulocytopenia. THP-COPBLM therapy seemed useful in treatment of elderly patients with NHL. There were few adverse effects such as gastrointestinal symptoms or cardiotoxicity. However, leukocytopenia was observed in many patients despite combined use of G-CSF, suggesting the dose and administration method of THP should be studied further.

Aged↗
PubMed1997

AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells.

AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages, because a significant level of the AML1 gene is expressed in these cells. We overexpressed AML1a (without the transcription-activating domain) and AML1b (with the domain) proteins in K562 leukemia cells, which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes. The AML1a-transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers, such as hemin, 1-beta-D-arabinofuranosylcytosine, and herbimycin A. The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate. On the other hand, AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone. AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester. These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation.

Antigens, CD↗
PubMed1997

[Prognostic factors of follicular lymphoma treated with combination chemotherapy].

This study investigated 72 patients (12.4%) with follicular lymphoma among 582 patients with non-Hodgkin's lymphoma admitted to our department. Treatment achieved complete remission (CR) in 83.3% of the follicular lymphoma patients, with an overall 5-year survival rate of 63.7%. The 5-year survival rate was 76.9% for the 60 patients who achieved CR, and this rate was significantly higher than that for patients who achieved only partial remission (PR) (p < 0.01). The 5-year survival rate was 40% with the CHOP regimen and 74.3% with the COP-BLAM regimen. The 3-year survival rate for biweekly COP-BLAM was 88.4%. The 5-year disease free survival rate for patients who achieved CR was 80.5%. The rate reached a plateau after 42 months, and the same survival was maintained for more than 10 years. These results suggest that intensive chemotherapy is effective even against follicular lymphoma. The 5-year survival rate for patients who achieved PR, suggesting the importance of the response to initial chemotherapy.

Adult↗
PubMed1997

[Non-Hodgkin's lymphoma associated with cold agglutinin disease].

Autoimmune hemolytic anemia (AIHA) complicated with non-Hodgkin's lymphoma (NHL) is not unusual. Two cases of NHL associated with cold agglutinin disease were reported. Case 1: A 38-year-old man had diffuse medium-sized cell NHL diagnosed by cervical lymph node biopsy. The Hb was 7.6 g/dl with a cold agglutinin titer of 32,768, and the IgM level was 890 mg/dl (I-specific), so cold agglutinin disease (CAD) was suspected. After administration of COP-BLAM therapy, complete remission (CR) was achieved along with a decrease in the cold agglutinin titer and improvement of anemia. Case 2: A 68-year-old woman had follicular mixed NHL diagnosed by inguinal lymph node biopsy. The Hb was 8.2 g/dl with a cold agglutinin titer of 51,200, and an IgM level of 920 mg/dl (I specific), thus concurrent CAD was suspected. Biweekly COP-BLAM therapy was administered and CR was achieved along with a decrease in the cold agglutinin titer and improvement of her anemia. In both patients, the cold agglutinin titer decreased after CR was achieved suggesting that production of anti-erythrocyte autoantibody was due to disturbance of the antibody system by NHL.

Adult↗
PubMed1997

Neplanocin A, a potent inhibitor of S-adenosylhomocysteine hydrolase, potentiates granulocytic differentiation of acute promyelocytic leukemia cells induced by all-trans retinoic acid.

Several neplanocin A analogs were synthesized and their growth-inhibiting and differentiation-inducing activities on myelogenous leukemia cells were examined. An adenosine kinase-ineffective analog of neplanocin A was effective in inducing differentiation, suggesting that phosphorylation of the nucleoside is not essential for inducing the differentiation of leukemia cells. Neplanocin A induced functional and morphological differentiation of HL-60 cells, but did not effectively induce differentiation of NB4, a cell line derived from a leukemia patient with t(15;17). However, these cells have been known to undergo granulocytic differentiation upon treatment with all-trans retinoic acid (ATRA), and are used as a model for differentiation therapy in acute promyelocytic leukemia. Preexposure of NB4 cells to low concentrations of neplanocin A greatly enhanced the ATRA-induced differentiation of the cells, whereas representative antileukemic drugs such as cytosine arabinoside and daunomycin did not enhance this differentiation. A clinical strategy that combines intermittent treatment with neplanocin A analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.

Adenosine↗
PubMed1996

Biweekly COP-BLAM (cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin and procarbazine) regimen combined with granulocyte colony stimulating factor (G-CSF) for intermediate-grade non-Hodgkin's lymphoma.

We evaluated the efficacy and adverse effects of biweekly COP-BLAM (cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin and procarbazine) therapy combined with granulocyte colony-stimulating factor (G-CSF) for treating non-Hodgkin's lymphoma (NHL). A complete remission was achieved in 65 (90.3%) of the 72 patients. THe median follow-up period was 28 months, and 64 patients were alive at the time of writing. Treatment was delivered as scheduled to 61 patients. G-CSF made it possible to shorten the interval between courses of chemotherapy. One of the 72 patients died of granulocytopenia and pneumonia; no other severe infections were noted. Further studies regarding adverse effects on organs other than the bone marrow are required to improve the long-term results of combination therapy on NHL.

Adult↗
PubMed1996

Salvage chemotherapy for relapsed or refractory non-Hodgkin's lymphoma with a combination of ACES (high-dose Ara C, carboplatin, etoposide and steroids) therapy.

ACES (Ara-C, carboplatin, etoposide, steroids) therapy using granulocyte-colony stimulating factor (G-CSF) was designed for relapsed or refractory non-Hodgkin's lymphoma (NHL), and the therapeutic effects and adverse reactions were studied. The subjects were 40 patients, including 19 relapsed cases and 21 refractory cases, subjected to chemotherapy using anthracycline type agents. The ACES therapy consisted of carboplatin at 100 mg/m2 and etoposide at 80 mg/m2 for 4 d from the first day, Ara-C at 2 g/m2 on the fifth day, solumedrol at 500 mg for 5 d from the first day and G-CSF at 2 micrograms/kg from the seventh day. This therapy was performed every 3 weeks, in principle. The doses were reduced to 70% of the above values for patients aged 70 yr or older. Among the 40 patients, complete remission (CR) was achieved in 14 (35%) and partial remission (PR) in 14 (35%) for a response of 70%. The 50% survival period was 526 d, and the 2-yr disease-free survival rate was 58.3%. Adverse reactions of grade 3 or higher included granulocytopenia in 62.5%, anemia in 17.5% and thrombocytopenia in 50%, but there was no death related to treatment. Four patients underwent transplantation of hematopoietic stem cells and have survived for long periods. This treatment was effective against relapsed NHL and could be performed safely with few adverse reactions.

Adolescent↗
PubMed1996

Evaluation of cytosine arabinoside, carboplatin and etoposide chemotherapy in the treatment of relapsing and refractory non-Hodgkin's lymphoma.

Twenty-eight patients (14 with relapsing and 14 with refractory non-Hodgkin's lymphoma; NHL) were treated with a combination of CACE chemotherapy (cytosine arabinoside, carboplatin, and etoposide) and recombinant granulocyte colony-stimulating factor (G-CSF) to investigate the efficacy and adverse effects of this regimen. Twenty-eight NHL patients (16 men and 12 women, median age 52 years) received intravenous infusions of cytosine arabinoside (100 mg/m2) on days 1-7, carboplatin (250 mg/m2) on day 1, and etoposide (70 mg/m2) on days 1-3, as well as the subcutaneous administration of G-CSF (2 micrograms/kg) beginning on day 9. Eleven of 28 (39.3%) patients achieved complete remission (CR) and 10 patients (35.7%) partial remission (PR). Therefore, a total response rate of 75% was achieved. Nine patients with relapsing disease and 2 with refractory NHL achieved CR. Of the 28 patients 51.5% were alive at 3 years, while the 3-year survival rate for those who achieved CR was 87.5%. The 50% disease-free survival duration was 20.8 months. Adverse effects included leukopenia (2 x 10(9)/l) in 4 patients (14.2%) and thrombocytopenia (50 x 10(9)/l) in 18 patients (64.3%). Although the efficacy of the CACE regimen was demonstrated for treatment of relapsing NHL, the efficacy of CACE was not satisfactory for the treatment of refractory NHL. Further study is required to determine the value of the CACE regimen as therapy for the refractory NHL.

Adult↗
PubMed1996

[Double cancer in elderly patients with hematologic malignancies].

The occurrence of multiple malignancy was studied in 674 patients with hematologic malignancies who were admitted to this department during the past 10 years. Of the 674 patients, 205 were aged 65 years or older, and 56 (8.3%) had another cancer. The frequency of multiple malignancy was significantly higher in older patients than in younger patients: 44 (21.5%) vs. 12 (2.6%). The major hematologic conditions in patients with multiple malignancy were multiple myeloma, myelodysplastic syndromes, non-Hodgkin's lymphoma, and chronic myelogenous leukemia. The major sites of cancers other than hematological malignancies were the stomach, colon, breast, and esophagus. Many of the older patients had gastric cancer or colon cancer, and gastric cancer was common in the younger patients. The multiple malignant neoplasms were synchronous in as many as 20 of the 44 older patients. There was only one such case among the younger patients. Of the 56 patients, nine had received alkylating agents, and one has received etoposide. In brief, elderly patients with hematologic malignancies are likely to have multiple malignant neoplasms. If they are synchronous, the patient's prognosis may be adversely affected, because simultaneous management of multiple malignant neoplasms is not easy.

Aged↗
PubMed1996

[Clinical usefulness of 123I-BMIPP (beta-methyl iodophenyl pentadecanoic (acid) myocardial SPECT in patients with hematological malignancies with adriamycin-induced cardiomyopathy].

In order to investigate myocardial lipid metabolism in patients receiving chemotherapy regimens containing adriamycin (ADR) for hematological malignancies, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial SPECT was performed. Thirty-two patients with hematological malignancies received a mean total ADR dose of 245 mg/m2 (range: 0-550 mg/m2). A polar map based on data from 8 normal individuals was used to calculate the extent score (representing the area of decreased uptake) and the severity score (representing the severity of defects) in the patients given ADR. 1) There was a significant association between the total ADR dose and the extent and severity scores. 2) The left ventricular ejection fraction was significantly associated with the extent and severity scores. 3) The two scores were also significantly associated with the washout rate of 123I-metaiodobenzylguanidine (MIBG). These results suggest that 123I-BMIPP myocardial scintigraphy reflects dysfunction of the myocardial mitochondria and serves as a guide for determining whether administration of ADR should be discontinued or the dose reduced.

Antibiotics, Antineoplastic↗