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Hodgkin's disease (HD) is a disorder with a better prognosis than non-Hodgkin's lymphoma and it predominantly affects young persons. In association with the aging of the population, however, HD has been increasing among persons aged 65 years and over in recent years. We used the COP-BLAM regimen to treat elderly patients with HD, and responses and adverse reactions were investigated. A total of 14 patients with HD treated at our department between April 1987 and December 1997 were included in this study. The patients were 8 men and 6 women aged 65 years or older, with a median age of 68 years. Five patients with clinical stage I or II disease, who had factors indicating a poor prognosis, received 3 courses of the COP-BLAM regimen with additional regional therapy of the involved field (IF). Six courses of COP-BLAM were administered to 9 patients with stage III or IV disease. The treatment was evaluable in all patients. Treatment achieved a complete remission (CR) in 12 (85.7%) of the 14 patients and a partial remission in 2 (14.3%). The CR rate was 100% for stage I or II and 77.8% for stage III or IV. The overall 5-year survival rate was 76.2% and overall disease-free 5-year survival rate was 75.7%. Adverse reactions included grade 3 or higher leukopenia in 35.7% and grade 3 or higher thrombocytopenia in 7.1%. Grade 3 or higher non-hematological toxicity included stomatitis and peripheral neuropathy in one patient each. From these results, we concluded that the COP-BLAM regimen was safe for elderly patients with HD and could achieve prolongation of survival.

123I-metaiodobenzylguanidine (MIBG) myocardial single photon emission computed tomography (SPECT), 123I-beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECT, and holter ECG recording were performed in patients with non-Hodgkin's lymphoma who underwent chemotherapy including pirarubicin (THP), in an attempt at early detection of cardiac toxicity from THP. Twenty-six patients with untreated non-Hodgkin's lymphoma who received THP-COPBLM therapy were studied. For THP-COPBLM therapy. THP was administered at a dose of 40 mg/m2 every 21 days and the total dose was 250 mg/m2 on average (40 approximately 400 mg/m2). 1) The washout rate (WR) correlated with the total THP dose, and was considered to be a useful index of cardiac sympathetic nervous dysfunction. 2) The left ventricular ejection fraction (LVEF) correlated negatively with the total dose of THP. 3) The total dose of THP showed a correlated positively with the extent score and severity score determined by BMIPP. 4) The WR correlated with the frequency of premature ventricular contraction. Animal studies have indicated that THP has less cardiac toxicity than doxorubicin, but the present study showed that cardiac toxicity occurred at a total THP dose of about 360 mg/m2 in elderly patients. Accordingly, when THP is used to treat elderly patients, multimodal evaluation of cardiac is necessary to detect cardiotoxicity and to determine the optimal dosage.

The study group comprised 10 patients who were referred between 1992 and 1996 with non-Hodgkin's lymphoma arising in the thyroid gland. There were three men and seven women, with a median age of 75 years, and seven of the group had a history of Hashimoto's disease. All 10 patients had hypothyroidism; anti-microsomal antibody was positive in six. The lymphoma was of the diffuse type in all patients (B cell, 9; T cell, 1). Five patients had stage I and five had stage II. Generally, four courses of COP-BLAM therapy were given, followed by radiotherapy (30 Gy). Complete remission was achieved in all patients, and they remained alive and disease-free for a median period of 40 months. Ultrasonography revealed diffuse, an-or hypoechoic confluent nodules, and there was intensification of the posterior acoustic enhancement in most patients. With early diagnosis non-Hodgkin's lymphoma arising in the thyroid of elderly patients, mainly women, can be cured with chemotherapy and radiotherapy.

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.

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.

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.

An epidemiological study on 173 consecutive elderly malignant lymphoma patients age 65 years or over was performed and the clinical outcome of chemotherapy is reported. Of there, 131 patients (75.7%) had non-Hodgkin's lymphoma (NHL) and 21 patients had Hodgkin's disease (HD). As for clinical staging, 58.9% of patients were in stage 3 or 4. The initial sites were nodal in 61.8% of the patients the most common sites of involvement in superficial lymph nodes being cervical, inguinal and axillar. The most frequent site of extranodal involvement was the gastrointestinal tract. The cases were treated with CHOP/COPP, BACOP or COP-BLAM combination chemotherapy. The clinical efficacy of these modalities was similar, with complete remission rates being about 50%. However, the total response rate (CR+partial remission) by the COP-BLAM regimen were 88.1%. The median survival time of cases achieving CR, was longer than 47 months. The most frequent cause of death was infection, especially pneumonia and septicemia. Many elderly ML patients were found and diagnosed when the disease developed to an advanced stage. Therefore it is necessary to make efforts to find early ML patients by screening apparently healthy elderly people. Improvement of the complete remission rate should be obtained if vigorous and intensive chemotherapy is carried out with careful supportive therapy concerning the general condition and complications in patients.

COP-BLAM therapy with concomitant G-CSF was performed in patients 65 years of age of older with non-Hodgkin's lymphoma (NHL) and the therapeutic effects and its adverse effects were compared with those in a group not given G-CSF concomitantly. The subjects were 64 patients with NHL, divided into 36 in the G-CSF group and 28 in the non-G-CSF group. In the G-CSF group, complete remission (CR) was achieved in 88.9% and the efficacy rate was 94.5%. In the non-G-CSF group, 89.3% achieved CR, and there was no significant difference between the G-CSF and non-G-CSF groups. The survival time and duration of remission also showed no significant differences between the G-CSF and non-G-CSF groups. The frequency of granulocytopenia as an adverse effects was significantly reduced in the G-CSF group, but the other adverse effects showed no intergroup differences. The occurrence rates of fever of at least 37.5 degrees C and documented infection were significantly less in the G-CSF group. These results indicate that COP-BLAM therapy with concomitant G-CSF achieved a high remission rate, showed few severe adverse effects, especially infections, and can be safely performed in elderly patients.

We studied the usefulness of bronchoscopy in the diagnosis of pulmonary complications in elderly patients with non-Hodgkin's lymphoma (NHL). The subjects were 12 patients 65 or older with NHL. Two of these patients underwent transbronchial lung biopsies (TBLB), all of them underwent bronchiolavage (BAL) and 2 with tumors underwent transbronchial biopsies of the tumors. Diagnosis was obtained in 8 out of 12 patients (66.7%). Two patients showed infiltration of lymphoma cells, 2 had cytomegalovirus (CMV) infection, 1 had pneumocystosis (P. carinii), 2 had fungal infections and 1 had a bacterial infection. TBLB was performed in 2 patients with platelet counts of over 5 x 10(4)/microliters. Lymphoma cell infiltration was diagnosed in one of these patients and a fungal infection in the other. BAL was performed on all patients. CMV was detected in 2 cases by the PCR method, P. carinii was detected in 1 case and aspergillus in 1 case. Klebsiella pneumonia was diagnosed in 1 patient. Since respiratory tract complications are often serious in NHL and the prognosis depends on early diagnosis and treatment, it is important to perform bronchoscopy on elderly patients and obtain a definitive diagnosis.

VCAP chemotherapy combined with natural interferon-alpha (HBLI) was performed on elderly patients over 65 year with multiple myeloma (MM), and its clinical effects were compared with those of VCAP chemotherapy without HLBI on elderly MM and also with those of HLBI-VCAP and VCAP combination therapy on non-elderly MM. Sixteen elderly and 21 non-elderly patients received HLBI-VCAP combination therapy, whereas 12 elderly and 21 non-elderly patients were treated with VCAP chemotherapy alone. The remission rate (CR+PR) was 81% for the elderly HLBI-VCAP group, 58% for the elderly VCAP group, 90% for the non-elderly HLBI-VCAP group, and 76% for the non-elderly VCAP group. While the median survival time was 54 months for the elderly HLBI-VCAP group and 13.5 months for the elderly VCAP group, it was 70 months for non-elderly HLBI-VCAP group and 34.5 months for the non-elderly VCAP group. The survival time in the elderly HLBI-VCAP group was significantly longer than that in the elderly VCAP group. Therefore, improvement of survival in cases treated by interferon was much better in the elderly group than in the non-elderly group. These results indicate that HLBI-VCAP combination therapy is beneficial for the treatment of elderly MM.

Chemotherapy and radiotherapy were performed on patients over 70 years of age with malignant lymphoma of the thyroid gland and complete remission (CR) was achieved in three patients who are reported here. Case 1: An 87-year-old woman who had been treated for Hashimoto's disease for 10 years as an outpatient was diagnosed as having a diffuse-small cell, B-cell type lymphoma by an aspiration biopsy of the tumor in the left thyroid. COP-BLAM chemotherapy followed by radiotherapy achieved CR. Case 2: A 71-year-old woman was referred to our department because of a right cervical tumor. A biopsy of the tumor revealed a diffuse medium-sized, B-cell type lymphoma. She also has been proved to have hypothyroidism. She entered CR after COP-BLAM chemotherapy combined with a radiotherapy. Case 3: A 76-year-old male patients with Hashimoto's disease who had been treated for 12 years at another outpatient clinic, presented with a right cervical tumor. Aspiration biopsy of the tumor yielded a diagnosis of B-cell lymphoma. COP-BLAM chemotherapy combined with radiotherapy achieved a CR. All three patients entered CR after chemotherapy combined with radiotherapy. Moreover, the microsome test and thyroid test also became negative after the combined modality therapy. In the future, there will probably be increases in the incidence of malignant lymphoma of the thyroid gland, due to the aging of society, and it will be necessary to establish methods of diagnosis and treatment for this disease.

We investigated pulmonary function and bronchoalveolar lavage fluid (BALF) before and after COP-BLAM III therapy in elderly patients with non-Hodgkin's lymphoma (NHL). The patients consisted of 8 men and 5 women, over 60 years of age, with previously untreated NHL. The PaO2 averaged 86.5 +/- 7.6 mmHg before treatment, and 69.3 +/- 9.2 mmHg after treatment. Six Patients showed a decrease in PaO2 to less than 20 mmHg. Percent (%) carbon monoxide diffusion capacity was 91.4 +/- 7.1% before treatment and 69.6 +/- 11.5% after-treatment, and 8 patients showed a decrease of at least 20%, whereas there were no definite changes in percent vital capacity or the percent of forced expiratory volume in one second. After BALF collection, the total cell count was slightly increased and the lymphocyte count was also increased after treatment, whereas there were no significant changes in neutrophil or eosinophil counts. There were no significant changes in T-cell or B-cell counts after treatment. The CD4/CD8 was 0.51 before treatment and 1.65 after treatment in patients without pulmonary complications, showing a tendency to increase, while the low ratio before treatment, 0.24, was nearly unchanged after treatment in those who developed pneumonia during their course. Considerable attention should be paid to pulmonary complications. As a result of chemotherapy, lymphocytic infiltration was observed subclinically in the lung, suggesting that changes in the local pulmonary immune system may be involved in the occurrence of pulmonary complications.

A case of therapy-related acute non-lymphocytic leukemia (t-ANLL) in a 70-year-old female patient is reported. An operation for lung cancer was performed in February 1991, and she was treated with etoposide (VP-16), a topoisomerase II inhibitor. Nineteen months after the start of chemotherapy, she complained of palpitations, and anemia and thrombocytopenia developed. The myelogram revealed 41.2% leukemic cells, and a diagnosis of t-ANLL induced by VP-16 was made. The karyotype of bone marrow cells showed 46, XX, t(7;11) (p13;p15), 16p+. She obtained complete remission (CR) by treatment with low dose cytosine arabinoside (Ara-C) and cytarabine ocfosfate (SPAC). Karyotype with t-ANLL induced by alkylate agents frequently shows unbalanced abnormalities. The difference of cytogenetic findings suggest the difference of mechanisms. Detailed chromosomal analysis make clear the oncogenesis of t-ANLL. It is reported that the prognosis of patients with t-ANLL treated by conventional chemotherapy is poor. Considering that elderly cases of acute leukemia have a lower probability of achieving CR than non-elderly cases, because of complications and side effects of chemotherapy such as bone marrow suppression, treatment with low dose Ara-C and SPAC is thought to be indicated in elderly patients with t-ANLL.

An 87-year-old woman, who had been suffering from hypothyroidism and had been treated as an outpatient at our department since 1982, noticed left cervical swelling toward the end of November 1992. Because ultrasonic examination revealed a mass in her thyroid gland, she was admitted for a closer examination and additional treatment. Biopsy of thyroid gland revealed non-Hodgkin's lymphoma (NHL; the diffuse small cell type, B-cell origin). A part from the swelling of thyroid gland and the left cervical lymph node, performance of various examinations did not detected any other NHL lesions. Therefore, it was classified as stage II NHL according to the Ann Arbor classification. Laboratory data on admission were as follows; WBC 4,400/microliters, Hb 13.6 g/dl, platelet count 10.1 x 10(4)/microliters, GOT 51 IU/l, GPT 31 IU/l, TSH 1.17, free-T4 1.03, free-T3 2.04, and microsome test 1,600 x. Those data indicated marked hypothyroidism. In addition, stage IIa and IIc gastric cancers were detected by the examination with gastric endoscopy performed for stage classification. Both were adenocarcinomas. Because polyps were found in her sigmoid colon with colonoscopy, polypectomy was performed. The polyps were diagnose histologically as moderately differentiated adenocarcinoma. On July 20, COP-BLAM therapy was started (CPM 600 mg div, VCR 1.2 mg iv, ADR 30 mg iv on day 1, PDN 40 mg p.o and PCZ 100 mg p.o. on days 1-10, BLM 7.5 mg div on day 14). Subsequently, the left cervical lymph node swelling disappeared, and shrinkage of the mass in the thyroid gland was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Although the third generation regimens for the treatment of malignant lymphoma are used more predominantly than those of other generations in recent years, a number of elderly patients die due to the toxicity of those treatments. We treated elderly patients with non-Hodgkin's lymphoma (NHL) with COP-BLAM III, and compared its therapeutic and adverse effects on elderly NHL patients (more than 65 years of age) with those in non-elderly patients. Nine previously untreated elderly NHL patients (4 males and 5 females, with a median age of 71 years) and 13 previously untreated NHL non-elderly patients (6 males and 7 females, with a median age of 43 years) were treated with COP-BLAM III. According to the Ann Arbor staging rules for malignant lymphoma, 4 and 6 elderly patients were classified in stage III and IV, respectively, while 6 and 7 non-elderly patients were in stage III and IV, respectively. There were 5 elderly patients with diffuse large cell type lymphoma (D. large), 3 with diffuse medium-sized cell type (D. medium) and one with diffuse mixed-cell type (D. mixed), while there were 6 non-elderly patients with D. large, 6 with D. medium and one with D. mixed. The COP-BLAM III regimen consisting of portion A with continuous infusion of the drugs and portion B with intravenous bolus administration of drugs was identical to that used by Boyd et al. Portion A and portion B were repeated every 3 weeks alternatingly. The administration of granulocyte-colony stimulating factor (G-CSF) was started, when the granulocyte count fell to below 1,000/microliters.(ABSTRACT TRUNCATED AT 250 WORDS)

A 66-year-old woman visited a local hospital complaining of left brachial tumor in June 1988. She was diagnosed as having non-Hodgkin's lymphoma (diffuse medium-sized type) by biopsy of the tumor. No other lesions were detected at any site. The disease was classified as stage IA and radiotherapy was carried out resulting in complete remission (CR). Because a tumor was observed at the same site again she was admitted to our hospital. Under a diagnosis of recurrence, she received 2 courses of COP-BLAM therapy, and achieved CR. Subsequently she was treated with chemotherapy as an outpatient. As another tumor developed at the same site in June 1992, the patient was readmitted. The re-evaluation of clinical stage revealed no other lesions. Under a diagnosis of second recurrence, still in stage I, she underwent both chemotherapy (IMV-triple P therapy) and radiotherapy, and CR was achieved again. She is now being treated as an outpatient. Malignant lymphoma originating from soft tissue, particularly the skeletal muscle, is rare. The present case was considered to be rare because the tumor was a non-Hodgkin's lymphoma originating from the left brachial soft tissue, in which the tumor recurred twice at the same site.