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J L Pico

Publications and source records attributed to J L Pico.

At least 55 records · Page 3Linked to original sources

[Piperacilline/tazobactam combination+amikacin versus ceftazidime+amikacin in patients with neutropenia and fever. An open multicenter study. Groupe d'étude des Aplasies Fébriles].

OBJECTIVES: To evaluate the toxicity and effectiveness of piperacillin+tazobactam and amikacin compared with a reference treatment with ceftazidime and amikacin given as first line therapy in neutropenic patients with fever. METHODS: A multicentric randomized trial was conducted in 222 adults who had fever (38 degrees C for > 3 h) during a period of aplasia (white cell count < 0.5.10(9)/l for 22.9 +/- 10.4 days) induced by chemotherapy for acute leukaemia (68.1%) or by bone marrow autograft for lymphoma, myeloma or solid tumour (30.3%). 109 patients were assigned to the piperacillin (12 g/d)/tazobactam (1.5 g/d)+amikacin group and 113 to the ceftazidime (3 g/d)+amikacin group. Evaluation criteria were the frequency of apyrexia after a 72-hour antibiotic regimen and major infectious events defined as death due to infection and severe infections causing a delay in the chemotherapy protocol. RESULTS: Data obtained in 188 patients who fulfilled all the protocol criteria were evaluated. The episode of fever was controlled better with the piperacillin/tazobactam+amikacin combination (apyrexia achieved in 60.6% of the patients vs 44.7% in the ceftazidime+amikacin group, p = 0.028) and there were fewer superinfections (23% vs 41% respectively, p < 0.008). Tolerance was similar in the two groups. In vitro, 56% of the strains resistant to piperacillin and isolated prior to treatment were sensitive to the piperacillin/tazobactam combination. Among the strains isolated (41 Gram-, 61 Gram+), 72% were sensitive to ceftazidime and 84% were sensitive to the piperacillin/tazobactam combination. There were 16 deaths due to infection (8.5%) with no difference according to antibiotic regimen. There was no difference in toxicity. CONCLUSION: Tolerance was similar in the two groups. A combined regimen of piperacillin/tazobactam can be proposed as first line treatment for neutropenic patients with fever.

Adult↗

Safety of tracheotomy in neutropenic patients: a retrospective study of 26 consecutive cases.

OBJECTIVE: To evaluate the safety of tracheotomy in neutropenic ventilated cancer patients, in terms of infectious and haemorrhagic complications. DESIGN: Retrospective study. SETTING: A medical-surgical intensive care unit in a Cancer-hospital. PATIENTS AND PARTICIPANTS: 26 consecutive patients undergoing a tracheotomy in neutropenic period, from 1987 to 1990. INTERVENTIONS: Tracheotomy, performed at the bedside or in operating room. MEASUREMENTS AND RESULTS: In all neutropenic patients undergoing a tracheotomy, the characteristics and duration of both neutropenia and mechanical ventilation have been recorded. Stomal bleeding and infection, and infectious pneumonias and alveolar haemorrhage have been carefully reviewed. Platelets were transfused in 23 of the 26 patients at the time of the procedure; no local haemorrhage was observed. Neither stomal nor pulmonary infections secondary to tracheotomy were noted. No respiratory worsening was attributable to the tracheotomy. Nineteen patients (73%) died in ICU, without direct link between tracheotomy and death. CONCLUSIONS: These findings suggest that a tracheotomy can be safely performed in neutropenic patients requiring mechanical ventilation.

Decision Making↗

Successful chemotherapy including epirubicin in a pregnant non-Hodgkin's lymphoma patient.

We report a case of non-Hodgkin's lymphoma (NHL) successfully treated with combination chemotherapy during pregnancy. The histological diagnosis was large-cell B-type NHL. Four courses of chemotherapy with epirubicin, vincristine and prednisolone were given before delivery. The patient is in complete remission and her baby, now four years old, has developed normally. To our knowledge, this is the first reported case of epirubicin administration during pregnancy and in which chemotherapy was given safely to NHL patients during the second and third trimester of pregnancy.

Adult↗

High-dose chemotherapy followed by hematological support: experience in the treatment of germ cell tumors.

Etoposide, bleomycin, and cisplatin based combination chemotherapy (BEP) and the surgical removal of residual disease is the standard treatment of metastatic germ cell tumors (GCT). Standard treatment including three cycles of BEP for good risk patients and four cycles of BEP for poor risk patients allows 95 and 65% cure rates in these groups respectively. However, about 10% of patients achieving CR after first line therapy eventually relapse. Conventional second line treatment (VeIP) includes a combination of vinblastin, ifosfamide and cisplatin or (VIP) with etoposide replacing vinblastin for patients pretreated by noncontaining etoposide chemotherapy regimens. These protocols induce a 60% CR rate and a 20-30% long term nonevolutive disease (NED) rate. Trials with high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (AHSCT) have been undertaken during the past decade. The main experiences were obtained with combinations of etoposide, platin derivatives, and either cyclophosphamide or ifosfamide. The majority of studies concerned heavily pretreated patients. Few studies have included HDCT and AHSCT as part of consolidation first line treatment for poor risk patients. A randomized multicenter French trial showed no significant benefit of this procedure (Droz, ASCO 1992). In refractory patients, HDCT and AHSCT induces a potential of 10% NED rate and this appears to be the maximum effect that can be obtained. An analysis of prognostic factors at first salvage chemotherapy revealed four adverse factors: high serum levels of HCG (> 10,000 mIU/ml) or AFP (> 1,000 g/ml); extragonadal origin; presence of lung metastases at salvage; and an incomplete response to first line treatment. Three prognostic groups have been defined according to a combination of these variables (Droz, Kramar, ASCO 1993). The use of HDCT followed by AHSCT as consolidation salvage treatment seems more promising since 25-45% of patients have long-term NED. It can be assumed that this procedure may increase the long term NED rate by 20% and produce a success rate up to 40%, but further studies are warranted in this setting. In order to evaluate HDCT with AHSCT rescue, an international randomized study has been undertaken in relapsed or first partial remission GCT patients. Randomization is stratified according to the three prognostic groups previously defined. Salvage regimens for eligible patients include two cycles of PEI or VeIP and in case of response, two more cycles of the same protocol (arm A) or one more cycle of PEI or VeIP followed by HDCT (CarboPEC: carboplatin, etoposide, and cyclophosphamide) (arm B).(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Salvage therapy of relapsing or refractory malignant lymphoma with non-myelotoxic combined chemotherapy. Results of combination of cisplatin, bleomycin, methyl-GAG and prednisolone (Cis-BMP)].

Fifty-one patients with primary refractory or relapsed malignant lymphoma (47 non-Hodgkin's lymphoma and four Hodgkin's disease) were treated with a new chemotherapeutic regimen (cisplatinum, methyl GAG, bleomocyin, methyl prednisolon). Among these 51 patients, 41 had measurable disease. Three of these 41 patients achieved complete remissions (7.3%) and 17 showed partial response (41.5%). The low hematological toxicity of this chemotherapeutic combination allowed us to give the full dose at the planned cycle date in 90% of the cycles. No major toxicity were observed (two minor neurological toxicities, one ototoxicity associated with oral mucositis toxicity, 6 febrile episodes) during 164 courses. With a median follow-up of 12 months, 18% of patients were alive without disease. We conclude that in this particular population of malignant lymphomas, Cis-BMP is an effective therapy with minimal toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

In vivo T-cell clonal amplification at time of acute graft-versus-host disease.

In a series of patients transplanted with HLA-matched allogeneic bone marrow grafts (alloBMT), we previously showed that a few T-cell receptor (TCR) V alpha and V beta gene segment transcripts were overexpressed in skin compared with blood at the time of acute graft-versus-host disease (aGVHD). Here, in one selected patient with overexpressed V beta 16 and V alpha 11 transcripts in skin, we analyzed the junctional variability of these transcripts in donor blood, patient blood, and skin collected at aGVHD onset. A unique junctional region sequence accounted for 81% of in frame V beta 16 transcripts (13 of 16) in skin and 59% (13 of 22) in patient blood. Similarly, two recurrent junctional region sequences were found in skin V alpha 11 transcripts, one accounting for 66% (21 of 32) and the other for 16% (5 of 32). These recurrences were also found in patient blood (36% and 15% of V alpha 11 transcripts, respectively). To extend our analysis, a polymerase chain reaction (PCR)-based method was used to precisely determine TCR beta transcript length in run-off reactions using uncloned bulk cDNA samples. All V beta-C beta PCR products analyzed in donor blood, as well as the majority of those analyzed in patient blood, included transcripts with highly diverse junctional region sizes. As expected from the sequence data, most V beta 16-C beta PCR products in skin and patient blood were of the same size (ie, same junctional region). In addition, V beta 3, V beta 5, and V beta 17 transcripts in skin were shown to display highly restricted size variability. The clonality of the V beta 16-C beta and V beta 17-C beta transcripts was further supported by the results of run-off reactions using 13 J beta specific primers. We have identified several recurrent TCR transcripts in skin, some of them also present in patient blood. These data support the view that several T-cell subpopulations are clonally expanded in vivo at the time of aGVHD onset in this case of related HLA-matched alloBMT.

Adult↗

Interleukin-2 treatment in lymphoma: a phase II multicenter study.

A phase II study was undertaken to assess whether continuous infusion of high-dose recombinant interleukin-2 (rIL-2) alone was active against different histologic subtypes of heavily pretreated lymphoma. Sixty one lymphomas were included in the study. rIL-2 (Roussel UCLAF, Romainville, France) was administered by continuous infusion at 20 x 10(6) IU/m2 for three cycles of 5 days, 4 days, and 3 days, during the first week, third week, and fifth week, respectively. Twenty-four low-grade non-Hodgkin's lymphomas (NHL) were resistant to an anthracycline-containing regimen. Twenty-three intermediate and high-grade NHL were refractory to initial treatment or to salvage therapy. Seven Hodgkin's diseases were refractory to at least three regimens or relapsed after autologous bone marrow transplantation. Seven mycosis fungoides were refractory to chemotherapy. In low-grade NHL, one complete response (CR) was observed. In aggressive NHL, there were three CRs and two partial responses (PRs). No response was noted in Hodgkin's disease. One CR and four PRs were observed in mycosis fungoïdes. Complete response durations were 23, 20, 17, 12, and 4 months. Grade 4 toxicity was observed in 29 patients leading to arrest of therapy in 12 patients. The response to rIL-2 therapy in lymphoma differs according to histologic subtypes. Five responses were observed in 23 aggressive lymphomas. Five of seven mycosis fungoïdes responded; these preliminary results warrant testing of a larger number of patients.

Adult↗

Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation.

Haemopoietic growth factors are accepted as accelerating haemopoietic recovery after bone-marrow grafting, yet no large randomised trials have been published that convincingly show benefit. Lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) was given to 315 patients after bone-marrow transplantation in a prospective randomised placebo-controlled multicentre trial. 1 day after bone-marrow infusion, 163 patients received lenograstim 5 micrograms/kg per day by 30-min infusion, and 152 patients received placebo daily for 28 days or until neutrophil recovery. 137 patients had lymphoma, 35 myeloma, 85 acute lymphoblastic leukaemia, and 58 a solid tumour. Patients were stratified by age and by type of bone-marrow transplantation (BMT). Neutrophil recovery to above 10(9)/L for 3 consecutive days was seen earlier in lenograstim-treated patients (16 vs 27 days, p < 0.001). Time to neutrophil recovery above 0.5 x 10(9)/L was reduced (14 vs 20 days, p < 0.001). The difference was significant both in autograft (20 vs 14 days, p < 0.001) and allograft (20 vs 14 days, p < 0.01) patients, in children (20 vs 13 days, p < 0.001), and adults. Lenograstim-treated patients had fewer days of infection, and of antibiotic administration, and also spent less time in hospital. However, clinical and microbiological sepsis was similar in both groups. There was no significant toxicity ascribed to lenograstim. Survival was the same at days 100 and 365. In patients undergoing autologous or allogeneic BMT for neoplastic disease, lenograstim significantly reduced duration of neutropenia and led to earlier hospital discharge.

Adjuvants, Immunologic↗

Prevention of oral mucositis in patients treated with high-dose chemotherapy and bone marrow transplantation: a randomised controlled trial comparing two protocols of dental care.

Between February 1986 and November 1989, 166 patients who were candidates for a bone marrow transplantation entered a randomised controlled clinical trial to compare limited oral hygiene care (LIM) and intensive oral hygiene care (INT) in the prevention of mucositis. Randomisation was stratified on the initial oral status (good vs. bad IOS). Intensive oral hygiene care included an initial treatment of dental lesions and tooth and gum brushing during aplasia. Limited oral hygiene care excluded preventive dental treatment and gingival and tooth brushing. Mucositis was classified as absent, mild, moderate or severe, according to the clinical aspects of the different sites in the mouth and to two scales of pain evaluation. Of the 150 evaluable patients (75 in each group), 134 developed moderate/severe mucositis (64 in the INT group and 70 in the LIM group) (log-rank test P < 0.02). The superiority of intensive oral care was observed both in patients with and without total body irradiation (TBI) and in patients with a good or bad IOS; the observed risk of mucositis was reduced by 70% in each of these four subgroups. Duration of moderate/severe mucositis was, although not significantly, lower in the INT group (17 days, S.D. = 12) than in the LIM group (19 days, S.D. = 13). The median time of mucositis occurrence was 11 days in the INT group and 9 days in the LIM group. Contrary to a widespread belief, the percentage of documented septicaemia was not higher in patients who underwent intensive oral care. We conclude that, although statistically significant, the superiority of intensive oral hygiene care is not clinically impressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Therapy of Burkitt and other B-cell acute lymphoblastic leukaemia and lymphoma: experience with the LMB protocols of the SFOP (French Paediatric Oncology Society) in children and adults.

Burkitt's lymphoma and L3-ALL are different forms of the same disease: B-cell disease. Therapeutic improvement has been considerable over the past 10 years. In France, four consecutive multicentre LMB studies of the SFOP greatly contributed to this improvement. An overall cure rate of 90% can now be achieved in children with a short intensive risk adapted polychemotherapy regimen based on high-dose fractionated CPM, HD MTX (3 g/m2), Ara-C in continuous infusion. For patients with ALL or with CNS involvement, the addition of CNS-directed therapy with a higher dose of MTX (8 g/m2), HD Ara-C (3 g/m2 x 4), VP 16, triple intrathecal injections and cranial irradiation greatly improved survival: 87% for ALL and 73% for patients with CNS involvement. In adults, the application of the paediatric protocol is possible with acceptable toxicity and a retrospective study of 41 cases treated according to a LMB protocol showed a cure rate of 71%. Such a regimen should now be proposed to adults and studied prospectively.

Abdominal Neoplasms↗

Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.

PURPOSE: To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS: The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS: The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION: Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.

Antineoplastic Combined Chemotherapy Protocols↗

[Exudative gastropathy associated with cytomegalovirus infection after allogenic bone marrow transplantation].

The authors report a case of protein losing gastropathy associated with cytomegalovirus. This form which is extremely rare in adults occurred alone after allogenic bone marrow transplantation and become apparent by a hypoalbuminaemia causing oedema of the lower limbs. Gastrocopy showed large red folds of approximately a centimetre covered in a whitish hypersecretion coating. Biopsy demonstrated active gastritis which appeared on a hypertrophic and hypersecretive gastritis. Outcome was favourable within 3 months without treatment.

Adult↗

Prediction of long-term response after high-dose chemotherapy with autologous bone marrow transplantation in the salvage treatment of non-seminomatous germ cell tumours.

High-dose chemotherapy (HDCT) and autologous bone-marrow transplantation (ABMT) are widely used in the salvage treatment of non-seminomatous germ cell tumours (NSGCT). We compiled 10 published series with NSGCT patients treated by HDCT and ABMT. Several prognostic factors for long-term non-evolutive disease (NED) were studied: dose of etoposide (ETO), oxazaphosphorine derivative (OXA) (expressed in cyclophosphamide equivalents using a cyclophosphamide/ifosfamide ratio of 1:3), platin-derivate (PLAT) (expressed in cisplatin equivalents using a cisplatin/carboplatin ratio of 1:4), disease status (refractory or responder), OXA and PLAT compounds. Strong interactions were shown between disease status and PLAT and ETO. In refractory patients, logistic regression analysis showed that the doses of OXA and PLAT increase the probability of NED. Conversely, in responder patients only ETO and OXA dosages increase the probability of NED. It is concluded that the status of the disease is the most important prognostic factor for long-term NED after HDCT + ABMT in NSGCT.

Antineoplastic Combined Chemotherapy Protocols↗

Prospective study of the clinical symptoms of therapeutic whole body irradiation.

Thirty-one selected patients with various haematological malignancies who received a 10 Gy-4 h total body irradiation (TBI) at the Institut Gustave Roussy 24 h before high dose cyclophosphamide for bone marrow transplantation, were prospectively evaluated for gastrointestinal symptoms, body temperature, consciousness, headache, xerostomia, parotiditis, ocular symptoms, blood pressure, and respiratory and cutaneous signs for 24 h. In spite of prophylactic administration of various anti-emetic agents, 90% of the patients experienced nausea and 80% experienced vomiting. An almost constant body temperature peak--up to 40.8 degrees C--was registered 6 h after the start of irradiation. No drowsiness was reported since the introduction of the new anti-emetic agent Ondansetron. Nearly half the patients (42%) complained of headache. The proportion of patients experiencing early (during TBI) xerostomia was 61%. 74% of patients complained of parotiditis in the first 24 h. Although this low dose rate whole body irradiation is not likely to be exactly replicated in many accidental human exposures, the incidence rate and the time-course of the observed prodromal phase symptoms may prove helpful for early triage in the case of accidental irradiation.

Adolescent↗

Escalating high-dose carboplatin and autologous bone marrow transplantation in solid tumors.

Twenty-seven patients with poor-prognosis malignancies were treated with a combination (CARBOPEC) of fixed-dose etoposide (1,750 mg/m2), cyclophosphamide (6,400 mg/m2), and escalating doses of carboplatin (from 800 to 1,600 mg/m2) followed by autologous bone marrow transplantation (ABMT). All patients had previously received platinum derivatives. The diagnoses were as follows: germ cell tumors (GCTs; n = 15); ovarian carcinomas (n = 8); rhabdomyosarcomas (n = 3), and Hodgkin's disease (n = 1). All 27 patients were fully evaluated for toxicity. The median duration of granulocytopenia (leukocytes < 0.5 x 10(9)/l) and thrombocytopenia (platelets < 20 x 10(9)/l) was 23 and 20 days, respectively. Hematologic growth factors were used in 3 cases. The main nonhematologic toxicity was gastrointestinal, with moderate to severe diarrhea in 18 patients. No significant renal toxicity was observed. The overall response rate to this high-dose chemotherapy was 55%, with a complete response (CR) rate of 45% (9 patients). The median duration of CR was 9 months. Five of the 27 patients are alive with no evidence of disease (NED) at 5, 22, 27, 40, and 43 months after ABMT. Four of the 11 patients with refractory GCTs have NED at 5, 22, 27, and 40 months, together with 1 of the 3 responders (43 months). Our study shows the encouraging antitumor activity of this regimen. Similar chemotherapy schedules have also been used with high response rates in GCT, ovarian cancer, breast cancer, and soft tissue sarcoma in children. The CARBOPEC protocol seems to be a good candidate for therapy intensification in patients with various malignancies. A European trial for salvage therapy in GCT will be activated in the near future. Moreover, results should improve with the widespread use of hematopoietic growth factors and optimization of carboplatin administration that takes pharmacokinetic parameters into account.

Adolescent↗

Early intensified chemotherapy with autologous bone marrow transplantation in first line treatment of poor risk non-seminomatous germ cell tumours. Preliminary results of a French randomized trial.

UNLABELLED: For 30 months we have treated 115 non-pretreated non-seminomatous germ cell tumour (NSGCT) patients with poor risk characteristics. Patients were allocated randomly to either arm A: NCI regimen with vinblastine, etoposide (E), bleomycin and double dose cisplatin (P2) (PVeBV) 3 or 4 cycles Q3W, or arm B: modified PVeBV protocol (bleomycin in continuous infusion) Q4W than a cycle of high-dose E + cyclophosphamide + P2 (PEC) and autologous bone marrow transplantation (ABMT). 114 patients are evaluable: 81 testicular, 18 mediastinal and 15 retroperitoneal primaries. RESULTS: Arm A 57 patients: 7 patients did not complete the treatment. There were 15 failures, 9 PR, 33 CR. Seven patients relapsed. The 2-year survival is 82%. Arm B 57 patients: 16 patients did not complete the treatment. There were 26 failures, 7 PR and 24 CR. Nine patients relapsed. The 2-year survival is 60%. Both CR rates and survival are not statistically different. This trial fails to show any benefit of early intensified chemotherapy + ABMT to increase the CR and survival rates in poor risk NSGCT.

Adult↗