PubMed Health⌕ Search

Biomedical subjects

K Sampi

Publications and source records attributed to K Sampi.

At least 55 records · Page 3Linked to original sources

Chromosome abnormalities in malignant lymphoma in patients from Saitama.

Clonal chromosome abnormalities were found in 89 (97%) of 92 patients with non-Hodgkin's malignant lymphoma including immunologically determined 34 B- and 25 T-lymphomas; only 3 of 19 T-lymphoma patients examined had serum adult T-cell leukemia/lymphoma-associated antigen antibody. Association of 8q24 translocations with small non-cleaved cell (P less than 0.01) and that of t(14;18) (q32;q21) with follicular histology (P = 0.03) were significant. Several other abnormalities were also found to be correlated with histological or immunological phenotypes: trisomy 5 with diffuse, mixed cell lymphoma (P = 0.03); a break at 3q21 with diffuse, large cell lymphoma (P = 0.04); gain of chromosome 18 or X and rearrangements of 13q with immunoblastic lymphoma (P = 0.02, 0.03, and 0.03, respectively); and rearrangements of 7q with diffuse large cell histology (P = 0.02) and T-cell phenotype (P = 0.02). Multiple clones were more frequently seen in T-cell lymphoma than in B-cell lymphoma (P = 0.01). Structural changes of the long arm of chromosome 4 or 15 and a break in 6p21 were also associated with T-lymphoma (P = 0.03, respectively). Since the frequency of T-lymphoma is significantly higher and that of t(14;18) is significantly lower in the adult T-cell leukemia/lymphoma nonendemic area of Saitama in Japan than in Minnesota in the United States (P less than 0.01), factors affecting the lymphoma-genesis may be different or operating in different intensities in different areas.

Adolescent↗

Differentiation of blasts from patients in myeloid crisis of chronic myelogenous leukemia by in-vivo and in-vitro plicamycin treatment.

Two cases in myeloid blast phase of chronic myelogenous leukemia (CML) responded to treatment with plicamycin alone. Their total white blood cell (WBC) count and immature myeloid cells fell in one case rapidly and in the other gradually. Approximately two to three weeks after initiation of plicamycin their total WBC count began to rise again, whereas the mature myeloid cells remained constant throughout the treatment. These results suggest that plicamycin may be effective in suppressing proliferation of blasts and promoting their maturation in the myeloid blast phase of CML, but that plicamycin alone may not be effective enough to sustain duration of response.

Adult↗

[Cefmenoxime or piperacillin plus amikacin. A prospective randomized comparison of empiric antibiotic therapy of febrile granulocytopenic cancer patients].

Cefmenoxime plus amikacin was compared in a prospective randomized trial with our standard regimen of piperacillin plus amikacin as an empiric therapy for fever in patients with granulocytopenia. Initial profound granulocytopenia (fewer than 100/mm3 mature granulocytes) was present in approximately 45% of the patients in trial of both treatment groups. Of 53 microbiologically and clinically documented infections treated with piperacillin plus amikacin, 36 (68%) showed improvement. Of 48 microbiologically and clinically documented infections treated with cefmenoxime plus amikacin, 23 (48%) showed improvement. The response rate for gram-negative infections treated with cefmenoxime plus amikacin was lower than that for infections treated with piperacillin plus amikacin. Toxicity was minimal, with an equivalent incidence of skin rash, diarrhea and hepatic dysfunction. Although clinical efficacy of the combination of piperacillin plus amikacin may be superior to cefmenoxime plus amikacin therapy, this study demonstrated no statistically significant differences.

Adolescent↗

[Cancer chemotherapy combined with a calcium antagonist in patients with hematologic malignancies and solid tumors resistant to standard chemotherapy].

Cancer chemotherapy combined with calcium-channel blockers was administered to seventeen evaluable patients with hematologic malignancy and solid tumor who became resistant to standard chemotherapies between November 1981 and June 1986 in Saitama Cancer Center. Nicardipine and diltiazem were used as the calcium-channel blockers, which were given orally or intravenously. Adriamycin and/or vinca alkaloids were mainly used as a cancer chemotherapy. Partial remission was attained in 3 of 6 patients with malignant lymphoma. Remission was attained in 2 of 7 patients with acute leukemia including acute transformation of chronic myelogenous leukemia (CML/BC), one complete remission with acute lymphocytic leukemia and one cytoreductive effect with CML/BC. One partial response and one minor response were obtained among 4 patients with solid tumor. The remission of these responders was of short duration. The most serious side effect caused by calcium-channel blockers was hypotension, which was dose-limiting and induced oliguria in 6 of 23 courses. In conclusion, the clinical impression obtained with regard to the effectiveness against chemotherapy-resistant malignancies of cancer chemotherapy combined with calcium-channel blockers was not good even though the overall remission rate was 41%.

Acute Disease↗

[Significance of tumor markers in the treatment of cancer: hematologic malignancy].

Hematologic malignancies, such as acute leukemia and malignant lymphoma. Respond well to cancer chemotherapy. Therefore, it is important to monitor the state of response to chemotherapy as well as to determine the complete disappearance of the tumor and to predict early detection of recurrence in routine clinical work by estimation of tumor marker levels. Although changes in the levels of paraprotein in multiple myeloma have been utilized for monitoring the responsiveness to chemotherapy, since the amounts of paraprotein are directly proportional to the number of myeloma cells, in other hematologic malignancies there are no tumor markers for monitoring the clinical course, for detecting the presence of minimal residual disease, or for predicting disease recurrence. In the future it is expected that developments in biotechnology create a large number of reagents including 'oncogene'-related markers or 'oncogene' products for application to the diagnosis and treatment of cancer patients.

Acute Disease↗

Aclacinomycin A and behenoyl arabinofuranosylcytosine combination chemotherapy for previously untreated acute leukemia.

Twenty-one patients with previously untreated acute leukemia were treated with a combination chemotherapy of 120-200 mg/m2 of aclacinomycin A (ACM-A) in five divided daily doses and behenoyl-arabinofuranosylcytosine (BH-AC) 200-250 mg/m2 for 7 days at Saitama Cancer Center between April 1980 and July 1983. Complete remission was obtained in 12 of 21 patients (57.1%; M1 0/1, M2 10/10, M3 0/2, M4 1/3, leukemic transformation from sideroblastic anemia 0/1, refractory anemia with excess of blasts in transformation 1/2, chronic myelomonocytic leukemia 0/1). Seven of 9 patients who failed to have complete remission were crossed over to a combination chemotherapy of daunorubicin (DNR) plus BH-AC or cytosine arabinoside (ara-C), or single DNR for patients with M3, yielding complete remission in 5 patients. Seven patients received a total cumulative dose of more than 600 mg/m2 of ACM-A. The maximum dose given was 2,000 mg/m2. No congestive heart failure has yet been experienced. The median survival time was 12 months. These results have demonstrated that a combination of ACM-A and BH-AC shows almost equivalent activity with that of a standard induction therapy consisting of DNR plus ara-C. In addition, it was suggested that ACM-A plus BH-AC could be incorporated into reinforcement therapy because of supposedly less cardiac toxicity.

Aclarubicin↗

[A phase II study of epirubicin in acute leukemia: a cooperative group study].

A new doxorubicin analogue, epirubicin (EPI), has been evaluated in 11 institutions throughout Japan in a phase II study in patients with acute leukemia. A total of 41 patients were entered into this study between January 1983 and July 1985, and 34 were considered evaluable. Two patients were added for evaluation of toxicity. There were 25 males and 9 females with a median age of 43 years. Of the 34 evaluable patients, 24 had previously been treated with intensive combination chemotherapy, 21 with anthracyclines. The remaining ten were previously untreated patients. Underlying diseases were acute lymphocytic leukemia (ALL) in 15, acute non-lymphocytic leukemia (ANLL) in 17 and blastic crisis of chronic myelogenous leukemia (CML/BC) in 2. EPI was administered intravenously in two schedules, a high-dose regimen consisting of 24 to 60 mg/m2/day for 3 to 5 days and a low-dose regimen involving 11-17 mg/m2/day for 5 to 8 days. Responses were obtained in 5 (33.3%) of 15 patients with ALL, 3 of these attaining complete remission, 2 (11.8%) of 17 patients with ANLL and one (50.0%) of 2 patients with CML/BC. Out of the 21 patients who had received previous anthracyclines, 4 (19.1%) attained responses. Also, responses were obtained in 23.5% with the higher doses as well as 24% with the lower doses. The remission duration of responders was 1, 1, 3, 3, 3, 16+, 17 and 26 weeks, respectively. The major non-hematologic toxicity was stomatitis which occurred in 15 patients, in 11 of whom the symptoms were severe (Grade 3 or 4). This stomatitis was thought to be the dose limiting factor. On the basis of the above observations, we concluded that EPI was active against acute leukemia, especially ALL. Stomatitis was considered to be the dose-limiting factor, especially in the high-dose regimen. Toxicity was tolerable in the low-dose regimen.

Acute Disease↗

[A phase II study of epirubicin in malignant lymphoma].

A new anthracycline analog, epirubicin (4'-epi-Adriamycin) was evaluated at eleven institutes in a phase II clinical study in patients with malignant lymphoma. Epirubicin was administered intravenously mainly with using the following two regimens; 50 to 60 mg/m2 every three weeks and 40 mg/m2 weekly. A total of 46 cases were entered into the study and 41 cases were evaluable. Clinical responses, complete plus partial remissions, were observed in 27 cases (65.9%) with 8 of these showing complete remission. There was no significant difference of response between the two regimens. Response rates taking into account previous chemotherapy were 90.9% (10/11) in previously nontreated cases, 61.9% (8/13) in cases previously treated with non-anthracyclines and 52.9% (9/17) in cases treated with anthracyclines. The major adverse effect was bone marrow suppression; leukopenia was observed in 83.8%, anemia in 60.5% and thrombocytopenia in 15.4%. Other adverse effects frequently observed were anorexia (59.0%), nausea-vomiting (48.8%) and alopecia (55.6%). These adverse effects seemed milder than those produced by doxorubicin. The results indicated that epirubicin seemed to be a markedly useful drug against malignant lymphoma.

Adult↗

[Phase II trial of mitoxantrone in patients with relapsed and refractory acute leukemia].

Mitoxantrone, a new anthracenedione, was administered to thirty-nine patients with relapsed and refractory acute leukemia and to 12 patients with blastic crisis of chronic myelogenous leukemia between August 1981 and September 1984. Eleven patients were not evaluable and 40 were analysed. There were 24 males and 16 females with a median age of 37 yrs (range 6-73 yrs). Three of these were less than 15 yrs and 7 more than 60 yrs. The initial dose employed was 1.9 mg/m2/day X 5. Although eventually a starting dose of 12.3 mg/m2/day X 5 was used, about one half of cases were given more than 5 mg/m2/day X 5 by i.v. bolus. Among 25 patients with acute non-lymphocytic leukemia, there were 4 complete and 6 partial remissions. Among 7 patients with acute lymphocytic leukemia there was one complete remission and one partial remission. All patients except one who attained remissions had received prior anthracyclines. One of 8 patients with blastic crisis of chronic myelogenous leukemia had a partial remission. The durations of complete remission were 1, 1, 5+, 13+ and 17 weeks, respectively. Side-effects showed expected bone marrow depression. Mucositis occurred in ten patients. Gastrointestinal symptoms were noted in approximately 50%, but were mostly mild. Mild alopecia occurred occasionally. The trials were too short to allow evaluation of possible cardiac toxicity. These data indicate that mitoxantrone is non-toxic but hematological and a promising single drug for use in treating relapsed and refractory acute leukemia and suggest that further study would be worthwhile in order to identify its role in the first-line therapy of acute leukemia.

Aclarubicin↗

[A comparative study of mitoxantrone and adriamycin in patients with non-Hodgkin's lymphoma: a preliminary result].

In order to compare the efficacy and toxicity of mitoxantrone and adriamycin in non-Hodgkin's lymphoma, a randomized trial has been conducted by a cooperative study group since June 1984. Previously untreated patients with non-Hodgkin's lymphoma of intermediate-grade-malignancy were allocated to either MCOP (a combination of mitoxantrone, cyclophosphamide, vincristine, and prednisolone) or CHOP (a combination of adriamycin, cyclophosphamide, vincristine, and prednisolone) regimens. Forty-four patients were entered and 43 of these were fully evaluated for tumor response and toxicity. The complete remission rate was 80% for 20 patients receiving MCOP compared to 61% for 23 patients treated with CHOP. Response duration and overall survival were similar for the two treatments. Toxicity was almost comparable for the two treatments. Only alopecia was significantly less frequent in patients given MCOP than in those receiving CHOP. Mitoxantrone thus appears to be as effective as adriamycin in the treatment of non-Hodgkin's lymphoma.

Adult↗

[Mitoxantrone-containing combination chemotherapy in patients with non-Hodgkin's lymphoma].

Thirty-one patients with advanced non-Hodgkin's lymphoma were entered in a trial of a four-drug combination of mitoxantrone, cyclophosphamide, vincristine, and prednisolone (MCOP). This trial was intended to test the efficacy of substituting mitoxantrone for adriamycin in the CHOP combination, and to evaluate tumor response in patients who had received anthracycline antibiotic therapy. Of 31 patients, 25 were fully evaluated for tumor response and toxicity. There were 7 responses (4 complete, 3 partial) among 9 patients who had received radiation alone or chemotherapy not containing anthracycline antibiotics, whereas there were 7 responses (3 complete, 4 partial) in 16 patients who had been given anthracycline-containing chemotherapy. Median duration of response was 11+ weeks (range; 5 to 43+ weeks). The major toxicity was myelosuppression, although patients tolerated this well. This study suggested that mitoxantrone is not fully cross-resistant with anthracycline antibiotics and that MCOP is an effective regimen in patients with previously treated non-Hodgkin's lymphoma. However, when salvage chemotherapy for CHOP-failure is intended, cyclophosphamide and vincristine in MCOP should be further substituted by other agents such as etoposide and cis-platinum.

Adult↗

[A phase II study of mitoxantrone in refractory and relapsed malignant lymphomas. Cooperative Study Group of Mitoxantrone in Malignant Lymphomas].

A phase II clinical trial of mitoxantrone in refractory or relapsed malignant lymphomas was conducted by a cooperative study involving 17 institutions. Of 46 patients entered, 33 were evaluable for responses and toxicity. Thirty-one of the 33 had been previously exposed to adriamycin at a median dose of 220 mg/m2 (range 21-489 mg/m2), and two additional patients had each been given THP-adriamycin at a dose of 80 mg/m2 or 4'-epi adriamycin at a dose of 69 mg/m2. Mitoxantrone was administered in 3 different schedules: 8-12 mg/m2, every 3-4 weeks in 23 patients; 4-6 mg/m2, weekly, in 3 patients; and 2-4 mg/m2, for 5 days, in 7 patients. Summarizing the responses obtained in the 3 schedules, there were 2 partial responders among 5 with Hodgkin's disease, while there were 8 complete responders and 4 partial responders among 28 with non-Hodgkin's lymphoma. The overall response rate for all the evaluable patients was 42% with a complete response rate of 24%. The median response duration was 7+ weeks (range 4-27+ weeks) for complete responders and 7 weeks (range 4-46+ weeks) for partial responders. The major toxicity was myelosuppression: leukocytopenia less than 3,000/microliter occurred in 79% of patients, and thrombocytopenia less than 75,000/microliter in 35%. Other toxic effects were minimal, mild nausea and/or vomiting occurred in 39%, and diarrhea in 3%. Possible drug-related liver and renal dysfunctions were observed in 19% and 10%, respectively. The favorable response to mitoxantrone in patients with prior anthracycline antibiotic therapy suggests that the drug is not fully cross-resistant with anthracycline antibiotics, and that this drug is of value in combination with other drugs as a salvage therapy for patients with refractory or relapsed malignant lymphomas.

Adolescent↗

[Pharmacokinetic study of mitoxantrone].

The pharmacokinetics of mitoxantrone, an anthraquinone antitumor agent, were cooperatively investigated at 5 institutions including 4 patients with breast cancer and 3 patients with malignant lymphoma. A single dose of 10 mg/m2 was intravenously infused into 5 patients, and a 5-day schedule of repeated 4.2 mg/m2 or 3 mg/m2 was given to each of 2 patients. With single administration, the blood concentrations showed that the half-life for the alpha phase was 0.16 h, for the beta phase 1.58 h, and for the gamma phase 83.4 h. The distribution volume at steady state was 1,112 l/m2. The total body clearance was 326.8 ml/m2, showing rapid clearance from the blood. The cumulative urinary excretion in 96 h was 5.17% of the dose. With repeated administration, in one patient without third space, the pharmacokinetics were similar to those of the patients given single administration, but in the other patient with third space, lowered clearance was noted. The pharmacokinetics of mitoxantrone in the Japanese patients were nearly the same as those of European patients, and the blood concentration fitted the three-compartment model, with rapid distribution to the tissues.

Adult↗

Discrepancy between in-vitro and in-vivo inductions of differentiation by retinoids of human acute promyelocytic leukemia cells in relapse.

In-vitro studies of leukemic cells with retinoic acid and a therapeutic clinical trial with its derivative, etretinate, in a 58 yr-old male patient with 15;17 translocation-positive acute promyelocytic leukemia (APL) in relapse are reported. Actinomycin D was used in combination. Bone marrow promyelocytes from the patient prior to etretinate and actinomycin D matured morphologically in the liquid culture with retinoic acid; 98% were matured myeloid cells after 6 days at a concentration of 10(-6) M of retinoic acid as compared with 2% in the control culture. Positive NBT reactions were seen in none of the cells in the latter but in 95% of the cells in the former. Actinomycin D, when added alone, only induced NBT positivity, but, when used in combination with retinoic acid, increased both NBT positivity and morphologically matured cells. The patient was treated daily with 2 micrograms/kg of actinomycin D (or 20 mg/m2 or 33 mg/m2 cytosine arabinoside after the 6th day) in 24-h infusions and per oral 90 mg/body of etretinate. No effectiveness was observed both morphologically and clinically. The patient expired 15 days after the initiation of etretinate. Thus, a discrepancy existed in the response of leukemic cells from this relapsed patient with APL to the in-vitro and in-vivo attempts to include differentiation by retinoids and actinomycin D.

Cell Differentiation↗

[Phase II trial of peplomycin in non-Hodgkin's lymphoma].

Seventeen patients with malignant lymphoma were entered into a phase II study of peplomycin (PEP) to determine the efficacy of the drug. There were 8 males and 9 females with a median age of 64 yrs (range 3-74 yrs) and a median PS 3 (range 2-4). Three of these were children. At first PEP was given intermittently and intramuscularly (8 cases) at a dose of 10 mg every one (3 cases) or two (5 cases) weeks, and then intravenously by 22-hr continuous infusion (9 cases) at a dose of 5 mg per day for 5 days. Mean cumulative dose was 78 mg. Objective responses were obtained in 6 patient (35%). CR lasting 4 weeks was obtained in one patient with diffuse mixed-type lymphoma. Five patients, one with diffuse medium-sized cell type and 3 with diffuse large cell type, had PR, lasting 6, 7, 7, 9, and 50+ weeks, respectively. Pulmonary fibrosis was found in two patients on autopsy and interstitial pneumonia in two patients clinically. Temporary high fever occurred in 7 patients, stomatitis in 3 patients and anorexia in 3 patients.

Adolescent↗