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Biomedical subjects

J L Pico

Publications and source records attributed to J L Pico.

At least 109 records · Page 6Linked to original sources
PubMed1986

High-dose busulfan and cyclophosphamide with autologous bone marrow transplantation support in advanced malignancies in children: a phase II study.

Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.

Adolescent↗
PubMed1986

Short-term culture of acute myeloid leukemia blasts: analysis of acquired susceptibility to activated natural killer cells.

Following a cryopreservation step, short-term cultures of circulating leukemic blasts from a patient with acute myeloid leukemia (AML) were performed. Because cultured tumor cells became susceptible to natural killer (NK) activity, in vitro alteration of the blasts was studied. Immediately after thawing, cell suspensions consisted of a relatively homogeneous population of undifferentiated blasts. In culture, tritiated thymidine uptake by the leukemic cells was low during the first 24 hours and then increased (X20) to a peak on day 7. The cell concentration started to increase on day 4. On day 8, less than 10% of the cultured cells still appeared as undifferentiated blasts, whereas up to 60% were granular and 30% to 40% had a monocytoid morphology. Prior to being cultured, the blasts were resistant to resting and IL2-activated natural killing. When the kinetics of in vitro acquired susceptibility were studied, it was found that maximum cytotoxicity against these leukemic cells was reached within 24 hours. Thus, the blasts had become NK-sensitive prior to increase in DNA synthesis, proliferation, and differentiation based on morphological and cytochemical criteria. In contrast, there was a positive correlation between acquired susceptibility and surface expression of an activation antigen, termed TNKtar. To dissect further the mechanisms of acquired susceptibility, a series of six NK clones representing four distinct phenotypes of NK active lymphocytes were tested against the leukemic cells. Immediately after thawing, blasts were essentially resistant to all clones, whereas they were strongly killed by 5 of 6 clones when cultured for 24 hours. Cold target inhibition assays indicated that resistance of fresh blasts was likely to be due to a binding defect. These results suggested that tumor cells became susceptible because they surface-expressed NK target structure(s) in the early phase of an activation process leading to their proliferation and/or differentiation. This hypothesis was substantiated for one clone, termed JT9, because the anti-TNKtar antibody blocked cytotoxicity of JT9 cells against the cultured blasts.

Adult↗
PubMed1986

High-dose melphalan with or without marrow transplantation: a study of dose-effect in patients with refractory and/or relapsed acute leukemias.

Dose-effect relationships of high-dose melphalan were evaluated in 37 patients with measurable relapsed or refractory acute leukemias. Thirteen patients (Group 1) received 70-100 mg/m2 of melphalan without marrow rescue and 24 patients (Group 2) received 140-180 mg/m2 of melphalan followed by marrow transplantation. Patients in both groups were comparable with respect to age, sex, diagnosis, and status of the leukemia. The complete remission rate was 23% in Group 1 versus 75% in Group 2 (P less than 0.01). Hematological recovery of remission patients was not statistically different in either group. Nonhematological toxicity was comparable in the two dose ranges examined. These results demonstrate the existence of a dose-response effect of high-dose melphalan regimens in relapsed acute leukemias, without marked increases in nonhematological toxicity with these doses.

Acute Disease↗
PubMed1986

Modified chemotherapy with carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) and autologous bone marrow transplantation in 24 poor-risk patients with acute lymphoblastic leukemia.

Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.

Adolescent↗
PubMed1985

[Alternating chemotherapy and radiotherapy in the induction treatment of small cell bronchial carcinoma (forms limited to the thorax)].

Sixty three patients with limited small cell lung carcinoma were entered into a pilot study alternating monthly cycles of combination chemotherapy (doxorubicin, VP16213, cyclophosphamide and methotrexate (group A) or cis platinum (group B) with 3 courses of mediastinal radiotherapy. The total mediastinal dose was 45 Gy for the first 28 patients (group A) and 55 Gy for the remaining 35 (group B). The complete response rate was 86% in group A (median survival 14 months) and 91% in group B (median survival 20 months). Local control at two years was 61% in group A and 82% in group B, while relapse-free 2 year survival rates were 32% and 37% respectively. The acceptable toxicity and high response rate of this combined modality therapy lead us to further research in maintenance therapy.

Antineoplastic Agents↗
PubMed1985

Hematopoietic recovery following autologous bone marrow transplantation: role of cryopreservation, number of cells infused and nature of high-dose chemotherapy.

Twenty-nine patients were treated with single or combined high-dose melphalan therapy followed by autologous bone marrow transplantation. Hematopoietic recovery from these treatments was studied. No correlation was found between the number of GM-CFC infused and the time required for hematopoietic recovery. It is suggested that this correlation is only demonstrable for low 'doses' of infused bone marrow cell and/or GM-CFCs. The role of bone marrow cell preservation techniques was examined and results were similar for fresh and cryopreserved bone marrow. The erythrocyte, lymphocyte and granulocyte levels of the patients reported here reached a normal or subnormal hematological steady state 3 months after autograft. Our results confirm the value of cryopreservation techniques. Hematopoietic recovery was short and of the same duration whether the patients were given single or combined high-dose melphalan before autologous bone marrow transplantation. These results also demonstrate the value of such transplantation in shortening the myelosuppression caused by high-dose chemotherapy.

Adolescent↗
PubMed1985

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease.

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85% (with fiberoptic bronchoscopy and histological verification). Local control at 2 years was 61% in the first study and 82% in the second. Relapse-free survival at 2 years was 32 and 37%, respectively. Toxicity was acceptable. We conclude that our results justify further clinical research in alternating radiotherapy and chemotherapy schedules.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Erythropoietic recovery in human after extended field radiotherapy. Ferrokinetic studies of patients treated by radiotherapy followed by autologous bone marrow transplantation and of patients treated by moderate doses (20 Gy) of radiotherapy.

The ability of human irradiated bone marrow to provide suitable environment for migrating stem cells has been studied in four patients. These had received chemotherapy plus doses of 40 Gy to thoracic vertebrae and sternum, followed by autologous bone marrow transplantation. The erythropoietic activity in the non-irradiated areas was increased but it was low in irradiated areas at 3.5 weeks and undetectable at 6 months after autotransplantation. This shows that no nidation of migrating stem cells actively contributed to bone marrow regeneration after 40 Gy and suggests the existence of environmental lesions. No extramedullary erythropoiesis and no bone marrow extension were found in these patients. Four patients who had received doses of 20 Gy to extended bone marrow volume were submitted to ferrokinetic studies from one to 18 years after radiotherapy. In non-irradiated areas the erythropoietic activity was within the normal range. In irradiated areas, it was significantly lower than in the non-irradiated areas and was intermediate between the erythropoietic activity in the sacrum of six healthy control subjects and in the irradiated areas of the four autografted patients. Bone marrow extension was found in these patients. This study suggests that bone marrow recovery after irradiation might not be an all-or-none phenomenon. It would be of interest to better document the dose-effect relationship.

Adult↗
PubMed1982

[Sequential chemotherapy and radiotherapy modalities in small cell lung carcinoma. Preliminary results].

Two non randomized therapeutic trials have been conducted in oat cell carcinoma of the lung with limited disease. The first protocol combined chemotherapy (adriamycin, cyclophosphamide, VM 26, procarbazine) with mediastinal and supra-clavicular radiotherapy in classical fractionation (40 grays in 4 weeks). The second combined a more intensive chemotherapy (adriamycin, VP 16, methotrexate, cyclophosphamide) with an alternating radiotherapy (3 series of 15 grays). All patients received prophylactic brain irradiation. Preliminary results show a 9 month survival rate of 34 per cent and 62.5 per cent respectively. In addition, all patients in the second protocol presented a complete response at the end of the induction treatment. These preliminary data encourage proceeding with this kind of combined treatment.

Antineoplastic Agents↗
PubMed1980

Specific immunotherapy of acute lymphoid leukemia patients by REH cell line.

Of 25 patients with acute lymphoid leukemia (ALL) in remission who were submitted to immunotherapy with BCG plus irradiated REH cells, 17 had positive sera in microcytotoxicity against REH cells after immunization. The follow-up of 28 months indicates that the microcytotoxicity varies in the same patient and may become negative and positive again. The results obtained after convenient absorption of one positive serum strongly suggest that REH cells in leukemic patients can raise antibodies directed against an antigenic structure closely related to the cALL antigen. Moreover, REH cells demonstrate in vitro suppressive activity, which could be a common property of some subcategories of human ALL.

Cell Line↗
PubMed1979

Phase-II trial with vindesine for regression induction in patients with leukemias and hematosarcomas.

Vindesine (VDS) has been submitted to a phase-II trial, the results of which were assessed in terms of regression induction. VDS was given weekly IV in doses of 2 mg/m2 on two consecutive days to 59 patients, 55 of whom were evaluable. A high proportion of complete (36%) and over 50% partial regressions were obtained in acute lymphoid leukemias (ALL) (overall response 63%) whatever the perceptible phase, in blastic crisis of chronic myeloid luekemia (55%), and some responses were recorded in lymphosarcoma (40%). No effect has so far been seen in acute myeloid keukemia or in Hodgkin's disease. Malignant neoplasms of the immunoblastic type seem to be particularly sensitive to VDS. Continuous 48 h IV infusion can induce a remission where an IV push administration of the same dose has failed. One remarkable characteristic of VDS is the apparent absence of cross-resistance with VCR: in acute leukemic forms, 55% of patients who failed to obtain remission induction after three weekly injections of VCR (used in combination chemotherapy) achieved a complete or partial remission with VDS. The toxicity was mainly neurologic (paralytic ileus, constipation, paresthesias, loss of reflexes) and hematologic (leukopenia and thrombopenia), and was not more significant than with the other agents: four patients died of infection or hemorrhage.

Acute Disease↗
PubMed1978

[Leukaemias and lymphomas treatment by vindesine. Result of a phase II trial in terms of remission induction (author's transl)].

Vindesine is a derivative of vinblastine and of vincristine. A high proportion of remissions were obtained in acute lymphoid leukaemia (6 complete and 1 incomplete remissions in 15 patients), in blastic crisis of chronic myeloid leukaemia, and a few responses have been registered in lymphosarcoma and Hodgkin's disease. Permanent 48 h i.v. infusion may include a remission where i.v. pusch of the same dose has failed. The most remarkable characteristic of vindesine is the absence of cross-resistance with vincristine as documented in acute lymphoid leukaemia.

Adolescent↗
PubMed1978

Phase II clinical trial with vindesine for remission induction in acute leukemia, blastic crisis of chronic myeloid leukemia, lymphosarcoma, and hodgkin's disease: absence of cross-resistance with vincristine.

Vindesine, an analog of vinblastine and vincristine, has been submitted to a phase II trial, the results of which are judged in terms of remission induction. A high proportion of remissions were obtained in acute lymphoid leukemia and blastic crisis of chronic myeloid leukemia, and a few responses have been registered in lymphosarcoma and Hodgkin's disease. A continuous 48-hour iv infusion may induce a remission where an iv push of the same dose has failed. The most remarkable characteristic of vindesine is the absence of cross-resistance with vincristine as documented in acute lymphoid leukemia.

Acute Disease↗
PubMed1978

Modifications of lectin binding on human leukemic cells after neuraminidase treatment.

Cell surface modifications after vibrio cholerae neuraminidase treatment were investigated using three different tritiated lectins: Concanavalin A, Ricinus sanguineus agglutinin (R.S.A.) and Robinia pseudoacacia lectin. Lectin binding measurements were performed on untreated and enzyme treated cells. The cells used were from chronic and acute leukemic donors. After neuraminidase treatment, a significant increase in the number of receptor sites, from 1 to 3 times, was found in all cases tested and for all three lectins utilized with only one exception. The affinity constant was generally decreased after neuraminidase treatment. The increase in number lectin binding sites, indicating extensive modification of the cell surface, is completely consistant with the known importance of sialic acid in determining immunogenicity.

Binding Sites↗