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Biomedical subjects

D Komp

Publications and source records attributed to D Komp.

At least 19 recordsLinked to original sources

A randomized trial of treatment for multisystem Langerhans' cell histiocytosis.

OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. STUDY DESIGN: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. RESULTS: Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children > or = 2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy.

Adolescent↗

LCH-I: a randomized trial of etoposide vs. vinblastine in disseminated Langerhans cell histiocytosis. The Histiocyte Society.

An international randomized trial in Langerhans cell histiocytosis (LCH) has been initiated by the Histiocyte Society. This report reviews the rationale, design, and progress of LCH-I, which compares etoposide (VP-16) and vinblastine in the treatment of disseminated LCH. Data on the risk of etoposide-associated (therapy-induced) malignancy, in the setting of histiocytosis, are reviewed. The available evidence leads to the recommendation that the study of etoposide in LCH should be continued.

Drug Administration Schedule↗

Brain MR in patients with Langerhans cell histiocytosis: findings and enhancement with Gd-DTPA.

The brains of eight patient with Langerhans Cell Histiocytosis (LCH) were studied with magnetic Resonance Imaging (MRI). One scan was normal and a spectrum of abnormalities was seen in the others. Five patients had absence of the posterior pituitary bright spot, and four with evidence of pituitary dysfunction had a lesion in the region of the hypothalamus. An orbital extraconal mass was noted in one child with exopthalmus. This decreased in a follow-up study after Vinblastine therapy. The cerebellum was abnormal in two patients; the area of the dentate nuclei exhibited abnormal signal in one asymptomatic child and the MRI of another boy with a ten year history of progressive cerebellar dysfunction showed cerebral and cerebellar atrophy. Three of the five patients with deficiency of antidiuretic hormone (ADH) were studied both before and after the administration of intravenous Gadolinium-DTPA. In all three, after administration of the contrast agent, there was enhancement of involved areas.

Adolescent↗

Low-dose adriamycin remission maintenance for advanced acute lymphoblastic leukemia: a Southwest Oncology, Group study.

A low-dose maintenance schedule of adriamycin was evaluated in children with advanced acute lymphoblastic leukemia. Thirty-six evaluable patients who achieved two or more remissions were given adriamycin, 10 mg/m2/week, as a single maintenance agent. The median duration of second remission was 17 weeks, but only 5 weeks for third and fourth remission. Although the therapy was not found effective in more advanced disease, the median duration of second remission approached that obtained from various multi-agent treatment schedules. We conclude that the therapeutic efficacy of this treatment schedule makes it appealing for incorporation into multi-drug combination regimens.

Adolescent↗

Phase I evaluation of vindesine in children: a Southwest Oncology Group pilot study.

Twenty-one children (19 with leukemia) were given 34 courses of vindesine on a weekly or twice-weekly schedule in escalating doses. Thirty-three courses were fully or partially evaluable for response and/or toxicity. Granulocytopenia was the dose-limiting toxicity. Transient jaw, neck, or bone pain was common after each dose. Motor weakness, paresthesias, and constipation were neither frequent nor severe. In this Phase I study, vindesine had some antileukemia activity in children previously treated with vincristine and other drugs. Phase II studies are warranted and a starting does of 1.85% mg/m2 twice weekly appears tolerable.

Adolescent↗

Repeated use of L-asparaginase in multi-drug therapy of childhood leukemia.

The capacity of 1-asparaginase in two separate schedules (consecutive and intermittent), along with vincristine and prednisone to produce multiple responses, was evaluated in previously treated children with acute leukemia in relapse. The response rates varied inversely with previous 1-asparaginase exposure. A history of prior resistance to prednisone and vincristine appeared to reduce the response rate. Hypersensitivity reactions occurred in 14%.

Acute Disease↗

Possible effects of growth hormone on development of acute lymphoblastic leukaemia.

Growth hormone (G.H.) or a G.H.-dependent somatomedin may be involved in the process of acute lymphoblastic leukaemia (A.L.L.). Growth hormone has a trophic effect on lymphoid tissue and also specific receptors on lymphocytes, most probably T cells. Hypophycess. Resting concentrations of G.H. and somatomedin activity are raised in some children with A.L.L. and may be reduced after remission is achieved. It is suggested that control of G.H. and/or somatomedin concentrations may be necessary for adequate treatment of some cases of A.L.L. in children.

Adolescent↗

Effects of continuous or discontinuous maintenance therapy on subsequent remission maintenance in childhood leukemia.

This study was designed to determine if resistance to a standard drug during the second remission of children with acute leukemia was reduced by discontinuation of therapy during the initial remission. The initial maintenance therapy was either 6-mercaptopurine (6-MP), methotrexate (MTX), or cyclophosphamide (CYC) given continuously to relapse or discontinued (at random) at 2 or 6 months. Following the initial relapse and after induction of a second complete remission, 72 evaluable patients received (continuously to relapse) either 6-MP (53 patients) or CYC (19 patients) for the second remission maintenance. Resistance of 6-MP occurred during the second maintenance, regardless of the drug used during the initial maintenance, in that the length of second remissions was significantly shorter than the length of first remissions. However, this resistance was most pronounced in patients who initially relapsed while on continuous 6-MP maintenance (medium duration of remission [MDR] of 9 weeks). Patients whose initial relapse occurred after the discontinuation of 6-MP had a MDR of 23 weeks and patients whose second remission was maintained with CYC (after relapse from initial continuous remission on 6-MP) had a MDR of 25 weeks.

Acute Disease↗

Combination intrathecal therapy for meningeal leukemia: two versus three drugs.

The comparative effectiveness of intrathecal (IT) combination chemotherapy using two agents, methotrexate (MTX) and hydrocortisone (HDC), and three agents, MTX, HDC, and cytosine arabinoside (CA), in treating meningeal leukemia was determined in a randomized Southwest Oncology Group study. Following central nervous system (CNS) remission induction the same regimen was used for periodic maintenance until CNS relapse supervened. Complete CNS remission was achieved in 100% of 43 children given two-agent therapy and in 96% of 48 children given three-agent therapy. Length of CNS remission for two-agent therapy was 1-150+ wk, median 47.2 wk; for three-agent therapy, remissions were 1-190+ wk, median 64.6 wk. Differences in length of remission curves were not of statistical significance (p=0.71). Toxicity of combination IT chemotherapy in the two- and three-agent regimens was reduced compared to that of IT MTX alone for CNS remission induction and maintenance. The additive effects of the IT drug combinations have been less than expected. The cytocidal activity of these agents when administered simultaneously of sequentially is not fully understood. Further studies are clearly indicated to determine optimum doses, schedules, and sequences for the chemotherapeutic agents which can be given intrathecally in combination.

Brain Neoplasms↗

Clinical trials with 1-acetyl-2-picolinoylhydrazine (NSC-68626) in children.

Thirty-seven children with various malignant neoplasms were treated with 1-acetyl-2-picolinoylhydrazine. Complete regressions were documented in one child with embryonal rhabdomyosarcoma, in one child with generalized histiocytosis-X, and in one child with Hodgkin's disease. One patient had renal failure while receiving the drug but no conclusive cause and effect relationship could be established. Toxic effects otherwise were mild and consisted primarily of nausea and vomiting.

Adolescent↗

Evaluation of daunorubicin (NSC-82151) and methotrexate (NSC-740) in combination as a remission maintenance regimen in the treatment of acute leukemia.

The addition of a single monthy dose of daunorubicin (25 mg/m given intravenously) to the maximum tolerated dose of methotrexate (25 mg/m/dose given orally twice weekly) was evaluated as a maintenance regimen in 0 children with acute lymphoblastic leukemia. Seven patients who were nonevaluable were excluded from the study; 31 patients received methotrexate alone and 32 patients received a combination of methotrezate and daunorubicin. There was no significant difference between the distribution of remission times for the two maintenance regimens (medians of 147 and 162 days, respectively). For patients with only one previous remission, the median length of remission in this study was significantly shorter than that of the original remission time. Despite the known myelosuppressive effects of both agents, daunorubicin did not cause additional toxicity nor did it interfere with the scheduled methotrexate therapy. Although the addition of daunorubicin to methotrexate does not appear to be beneficial in the treatment of acute leukemia, this combination could be evaluated in other cancers in which both agents are known to be effective.

Child↗