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Biomedical subjects

R Kuse

Publications and source records attributed to R Kuse.

At least 37 records · Page 2Linked to original sources
PubMed1988

Deoxycoformycin in therapy of refractory lymphoid neoplasms.

Knowledge of the vital role of the purine degradative enzyme adenosine deaminase (ADA) in the differentiation of T and B lymphocytes has stimulated interest in the pharmacologic inhibition of ADA as specific cytotoxic therapy for lymphoproliferative diseases. 2'-Deoxycoformycin (DCF) is a tight-binding ADA-inhibitor and has shown activity in T and B cell neoplasms. In this phase-II study, the efficacy and toxicity of DCF in chronic T and B cell neoplasms is investigated. We report the preliminary results of treatment in 27 patients (8 with Sézary syndrome, 11 with B-chronic lymphocytic leukemia (CLL), and 8 with hairy cell leukemia (HCL)), who were refractory to conventional therapy. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Three of the 8 patients with Sézary syndrome and 3 of the 11 patients with B-CLL attained a partial remission. One complete and 7 partial remissions have been achieved thus far in the 8 patients with HCL refractory to interferon alpha treatment. Other than nausea in 10 patients (mainly grade 1 and 2), transient skin rash in 4 patients and Herpes infections in 4 patients (mainly grade 2), no other major toxicities were observed. Thus DCF is highly active in hairy cell leukemia that did not respond to interferon alpha, and shows moderate activity in refractory Sézary syndrome and B-CLL.

Antineoplastic Agents↗
PubMed1988

[Long-term results in highly malignant stage I and II non-Hodgkin's lymphomas during management with polychemo- and radiotherapy].

In 159 patients treated from 1976-1986 with an age median of 62 (16-85) years the survival probability amounted to 66% after ten years, where stage I (n = 82) with 77% was more favourable than stage IIA (n = 54) with 60% and stage IIB (n = 23) with 43%. With 61% the prognosis of the 7th to 9th decade of age (n = 82) was not worse than that of younger age groups (n = 77) with 70%. In prognostic respect immunoblastic (n = 49), centroblastic (n = 65) and unclassifiable (n = 45) subtypes as well as sexes do not differ and, therefore, they could be evaluated in total. With 81% the relapse-free survival time after sequential or simultaneous combination of polychemo- and large-scale radiotherapy the relapse-free survival time was markedly higher in stage IA (n = 45), stage IB (n = 5) and stage IIA (n = 26) than after single radiotherapy (n = 21) with only 30%. Even in elder patients the combined method was so far not accompanied by a higher complication rate so that this procedure may be considered as an essential progress in the treatment of highly malignant lymphomas. Thus, certain uncertainties as to insufficient division of stages which have frequently to be taken into account in elder people due to their limited invasive burdening capacity may be neglected.

Adolescent↗
PubMed1988

Clonal gene rearrangement patterns correlate with immunophenotype and clinical parameters in patients with angioimmunoblastic lymphadenopathy.

T cell receptor beta (TcR beta) chain gene rearrangements have been reported in cases of angioimmunoblastic lymphadenopathy (AILD) and provided evidence for the presence of clonal T cell proliferations in this disorder. Twenty-three cases of AILD and two cases of hyperimmune reaction (HR) were investigated. In the two HR cases, essentially the same histologic pattern was present as in AILD but lymph node follicles were hyperplastic. Both HR cases showed germline configuration for the TcR and immunoglobulin heavy chain (IgH) genes. All other patients diagnosed with AILD had clonal rearrangements for TcR gamma and beta chain genes. In addition, seven out of these cases had clonally rearranged their IgH genes. These two different rearrangement patterns (TcR with or without Ig gene rearrangement) correlated to immunohistochemical and clinical data. Cases with TcR but without Ig gene rearrangements (group I) exclusively showed CD4+ proliferating T cells, whereas those cases with TcR and Ig gene rearrangements had significantly elevated numbers of CD8+ proliferating cells (group II). Group II patients significantly more often presented with hemolytic anemia and went into transient remission spontaneously or under steroid treatment. Group I patients, however, had a higher response to chemotherapy and a longer survival time. These data show that, based on different rearrangement patterns, it is possible to divide AILD into two different groups with distinct immunophenotypic properties and differences in clinical parameters. Immunogenotyping in AILD thus will have prognostic and therapeutic implications.

Adult↗
PubMed1987

2'-Deoxycoformycin (Pentostatin) in hairy cell leukemia: response in patients refractory to interferon alpha.

Three patients with advanced hairy cell leukemia received low-dose deoxycoformycin treatment after failure to respond to therapy with interferon alpha. Patients 1 and 2 had progressive disease after splenectomy and subsequent treatment with recombinant interferon alpha (for 7 and 3 months, respectively). DCF was administered at 4 mg/m2 weekly for 3 weeks, and then once every week for 6 weeks. Patient 1 was in complete remission after 9 weeks of treatment and patient 2 in partial remission with normalization of peripheral blood counts. The third patient, also splenectomized, developed hepatotoxicity after therapy trial with interferon for 24 days and no objective improvement was observed at this stage. She subsequently responded to DCF treatment with improvements in blood counts and bone marrow. This report demonstrates that DCF is highly effective in hairy cell leukemia and non-cross-resistant with interferon alpha.

Adult↗
PubMed1987

[Risk-adapted treatment of immunocytomas].

For 176 patients seen between 1976 and 1984, with a mean age of 65 years, the probability of survival after ten years was 56% for lymphoplasmocytoid (n = 86), lymphoplasmocytic (n = 38) and non-classifiable (n = 10) subtypes, while it was 0% at the end of 6.5 years for the polymorph cell type (n = 42). Patients up to 60 years of age had, at 68%, a generally better prognosis than older ones, at only 30%. Cases with bone-marrow infiltration or leukemic washout (n = 114) were, like chronic lymphoid leukemia cases, classified according to the scheme of Rai and co-workers, while the remaining cases (n = 62) were classified according to the Ann Arbor scheme. There was a three-step prognosis of ten-year probability of 85% for stages I A, Rai 0, Rai I (n = 49), 50% for II A/B, III A, Rai II (n = 43), and 27% for III B/IV B and Rai III/IV (n = 41) of the non-polymorph cell subtypes. For the polymorph cell forms there was also a triple division with 88%, 53% and 14% after only four years. Additional unfavorable factors were rapid lymphoma growth, leukemic course, high paraprotein gradient and autoimmune hemolysis. The flexible employment of polychemotherapy and large-field radiotherapy, adapted to the mentioned unfavorable risk factors and age, contributed to the improved results in this heterogeneous group.

Adult↗
PubMed1987

[Long-term results in 172 highly malignant non-Hodgkin's lymphomas with special reference to older patients].

In 172 patients of the years 1976-1984 with a median age of 61 (16-89 years) the probability of survival was 55% after nine years. The seventh to ninth decade of life (n = 88) did not differ significantly in terms of the survival prognosis (47%) from the younger age groups (n = 84) with 59%. Immunoblastic (n = 72), centroblastic (n = 65) and unclassifiable (n = 35) lymphomas were prognostically similar and could hence be evaluated together. Stages I A (n = 58) with 83% and IV B (n = 15) with 20% differed from all others (n = 99), for which a survival rate of 41% was calculated. With the CHOP scheme (n = 76), a complete remission could be induced in 70% of the stages II A/B, III A/B and IV A (n = 54) and in 95% of stage I A (n = 19). In stage IV B (n = 14), more intensive schemata were not successful, only inducing two remissions. After sequential combination of polychemotherapy and large-field radiotherapy, the relapse-free survival was higher than after radiation or cytostatics alone. This was shown most distinctly in stage I A, in which a value of 82% compared to only 29% after radiotherapy was found for the combined method. Since this was not associated with higher rates of complications so far even with the older patients, we regard this procedure as major advance in the therapy of prognostically unfavorable lymphomas.

Adolescent↗
PubMed1987

Postinduction and preremission chemotherapy alternatives for adult AML: three multicenter studies of the AML Cooperative Group.

Major chemotherapeutic alternatives for AML have been implemented and compared in three multicenter studies, including a total of 877 adult patients of all ages. The results strongly suggest that myelosuppressive postinduction treatment is a prerequisite for the achievement of long-term remissions. In addition, it was possible to establish an important antileukemic effect of monthly maintenance chemotherapy. Initial results from an intensive two-course preremission therapy concept revealed good practicability and acceptable toxicity, as well as promising response and remission durations by this new approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Cytogenetic studies in 69 patients with myelodysplastic syndromes (MDS).

Cytogenetic studies were performed in 69 patients with myelodysplastic syndromes classified according to the FAB proposals. Overall incidence of chromosomal anomalies was 48% with 5q-, +8, 12p-,-7/7q- being the aberrations most often found. The 12p- chromosome showed a close correlation with a prior exposure to mutagenic agents and CMML. Although there were no group-specific cytogenetic anomalies, FAB classification strongly influenced their incidence. They were lower (36%) in RA/RA-S than in RAEB/RAEB-T/CMML (53%). Chromosomal anomalies were significantly more often found in patients with a prior exposure to carcinogenic agents (80%) than in unexposed patients (33%). The presence of chromosomal anomalies did not predict a higher risk of leukemic transformation.

Adult↗
PubMed1987

[Alternatives and further development of therapy of acute myeloid leukemia in adults. Update of West German multicenter studies].

The 1982 randomized, multicenter trial on adult-AML in West Germany revealed a superiority of remission duration (p = 0.004) and survival (p = 0.06) for patients receiving monthly myelosuppressive maintenance chemotherapy after TAD9-induction and consolidation as compared to patients without maintenance. In the 1985 pilot study double induction as a new approach followed by consolidation and monthly maintenance in patients up to 60 years of age was found well practicable, with 77% complete remissions and 12% early deaths in 81 patients. In addition preliminary remission duration and survival at 1 1/2 years appear favorable.

Adolescent↗
PubMed1987

[Chronic hemorrhagic iron deficiency. Sources of hemorrhage, blood loss and systematic iron substitution].

In only 121/436 (28 per cent) patients with chronic haemorrhagic iron deficiency bleeding sources could be removed by appropriate management or healed spontaneously. In 61 per cent of all cases the disease lasted from 1 year to greater than 20 years. The fall of haemoglobin per month correlated closely with blood losses per month as calculated by determinations of 59Fe whole body iron loss. Over prolonged periods estimations of the magnitude of blood loss (range 1- greater than 721 per year) based on changes of the iron status under normal diets and under systematic iron substitution. Oral iron administration with appraisable bioavailability was able to compensate blood losses up to 151 and with increasing doses up to 361 per year with maintenance of normal or borderline haemoglobin values. However, side reactions increased considerably after years and with rising doses. Under such circumstances combinations of i.v. iron, oral iron and blood transfusions were successful over prolonged periods.

Adolescent↗
PubMed1986

[Acute myeloid leukemia (AML) in adults. Further development of therapy based on clinical phase II and phase III studies].

By a review of relevant clinical studies on adult AML no substantial progress can be seen in the eighties so far. After the development of successful chemotherapy regimens during the seventies, further improvement can only be expected in small steps. Clinical studies, therefore, should concentrate on the analysis of the different components and new elements of treatment in order to utilize and combine them more effectively. For this purpose, a standardization of treatment and, for many aspects, a randomized comparison is inevitable. Thus, the role of monthly maintenance as well as of a special type of immunotherapy could be elucidated for the first time by our multicenter trial.

Adult↗
PubMed1985

Blood lymphocyte volumes and diameters in patients with chronic lymphocytic leukemia and normal controls.

The electronic modal lymphocyte volumes of 151 patients with chronic lymphocytic leukemia (CLL) and 305 normal controls were determined by the hydrodynamically focused multi-channel Coulter TF analyser. The mean volumes of the normally distributed groups were 166 +/- 19.3 (range 126-216) fl in patients with CLL and 206 +/- 14.4 (range 126 +/- 246) fl in normal controls. The calculated cell diameters were 6.8 (6.2-7.4) micron and 7.3 (6.8-7.8) micron respectively. Our data do not support previous reports about relations between cell size and clinical stages of the Rai and Binet classifications.

Blood Volume↗
PubMed1985

Aclarubicin (aclacinomycin A) in the treatment of relapsing acute leukaemias.

Forty patients with relapsing acute leukaemias were treated with aclacinomycin A (aclarubicin, ACM), 25 mg/m2 i.v. daily for 7 days. Twenty-nine patients with acute myeloid (AML) and five with acute lymphoblastic (ALL) leukaemia were evaluable. The overall response rate was 29.5%. Eight complete (CR) and one partial (PR) remissions were achieved in AML (31%). A high CR rate was induced in patients treated at first relapse without prior reinduction (6/12 patients). A small proportion of leukaemias resistant to daunorubicin or doxorubicin responded to ACM (3/17 patients). Median remission duration was 5.5 months (range: 2-9 months). The most common toxic effects were nausea, vomiting, stomatitis and diarrhoea. Acute cardiotoxic effects were documented in three patients. Congestive cardiomyopathy was not observed despite prior treatment with anthracyclines. We conclude that the present dose scheduling of ACM is effective in the treatment of relapsing AML and that it should be introduced in combined chemotherapy in phase III trials to compare its activity to that of daunorubicin or doxorubicin.

Aclarubicin↗
PubMed1985

[Non-hematologic toxicity in high-dose cytarabine therapy].

The hence reported non-haematologic toxicity in high-dose cytarabin mainly concerned CNS (cerebellar dysfunction), eyes (keratitis and conjunctivitis), skin (erythema), and gastrointestinal tract (vomiting, diarrhea). It partly depends on dosage and partly on duration of treatment. A dose of 48 g/sq m within one cycle apparently represents a critical upper limit as hence especially the risk of irreversible brain damage increases. Considering the fact that the indication for high-dose cytarabin is given mainly for poor prognostic failures and relapses in acute leukemias toxicity seems to be acceptable.

Acute Disease↗