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H Rubie

Publications and source records attributed to H Rubie.

At least 73 records · Page 4Linked to original sources
PubMed1994

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↗
PubMed1994

Recurrent renal salt wasting in a child treated with carboplatin and etoposide.

BACKGROUND: Nephrotoxicity of carboplatin is rare, especially in children with normal renal function. A 3-year-old boy had localized esthesioneuroblastoma and received 2 courses of carboplatin (200 mg/m2/day during a 1-hour infusion for 3 consecutive days) associated with etoposide (150 mg/m2/day after carboplatin). Because of a good tumor response, a second course was given 21 days later. Complete surgical excision and local irradiation were performed. However, the tumor recurred a few months later, and the patient subsequently died of the disease. METHODS: Renal function initially was assessed by standard baseline chemistry and technetium-panetetic acid (Tc-DTPA) clearance. Follow-up included ionic controls and tubular exploration during the episodes of hyponatremia. RESULTS: Hyponatremia occurred 4 days after completion of the first course and resolved after intravenous supplementation. It recurred 20 days after the second course despite salt and magnesium prehydration and posthydration and resolved 17 days later. No glomerular dysfunction was noticed. The association of urinary bicarbonate loss with elevated N-acetyl-beta-glucosaminidase suggested a proximal tubular damage. CONCLUSIONS: Standard doses of carboplatin may lead to recurrent renal salt wasting in children with initially normal renal function.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Childhood anaplastic large cell lymphoma Ki-1/CD30: clinicopathologic features of 19 cases.

The authors report their cumulative experience of 19 children with what was previously called malignant histiocytosis (MH) but is now considered a true lymphoma and termed anaplastic large cell lymphoma (ALCL). The median age at diagnosis was 10 years and 6 months (range 2 y, 11 m, to 15 y). There were 13 males and 6 females. Most cases presented with fever, wasting and enlarged, often tender, lymph nodes. Other features were: fleeting cutaneous rashes in 7 cases; spontaneous regression of lymph nodes and skin lesions were seen in 5 patients. Bone marrow involvement was present in 3 cases, pulmonary infiltrate in 5, kidneys in 2, and central nervous system in none. The morphology of lymph node involvement was consistent with so-called MH, a description originally applied to sinusoïdal infiltration by large "histiocytic" cells. The coexpression of lymphoid activation antigens Ki-1/CD 30 (18/19), epithelial membrane antigen EMA (18/19) and interleukin-2 receptor/CD 25 (10/10) was the unifying immunopathologic feature of the neoplasm. Lineage antigens were not identifiable in 8/19 instances (null phenotype), while 10/19 expressed a T-cell phenotype. None of the tumors expressed histiocytic markers. After variable, but intensive, combination chemotherapy, 15 children out of 18 evaluable achieved complete remission (CR). Among all patients, thirteen are still alive in CR (ten in first CR) with a median follow-up of 5 years. This evaluation in the pediatric age group reinforces that so-called MH is a lymphoid neoplasm, a conceptual change that could lead to improved understanding and therapy.

Adolescent↗
PubMed1994

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↗
PubMed1994

Antenatal detection of subdiaphragmatic pulmonary sequestration: a case report.

Extralobar pulmonary sequestration is part of the spectrum of bronchopulmonary foregut malformations. Usually found in the thorax, it may be located in the retroperitoneum. We report one case of subdiaphragmatic pulmonary sequestration detected by prenatal ultrasound, and diagnosed at surgery after birth. This case illustrates the diagnostic and therapeutic problems occurring during pregnancy and the neonatal period.

Adult↗
PubMed1994

Cerebrospinal fluid drug levels of leukemic children receiving intravenous 5 g/m2 methotrexate.

A multicenter prospective study was conducted in 114 children with acute lymphoblastic leukemia receiving 4 intravenous methotrexate (MTX) courses (5 g/m2 as a 24 hour-infusion) to determine the diffusion of MTX in cerebrospinal fluid (CSF) and to correlate the drug levels to central nervous system (CNS) relapse occurrence. Serum and CSF levels were measured at the end of 446 MTX courses. A significant correlation was found between CSF and serum MTX concentration. CSF MTX level was greater than 1 mumol/l in 66% of the courses. Twelve patients (11%) failed to achieve this potentially cytotoxic drug level at the end of the 4 consecutive MTX courses: only one CNS relapse was observed and the mean age of these children was lower than that of the others. To date 9 (7.8%) children had CNS relapse and no difference was observed in terms of CSF MTX levels when compared to data of children free of CNS relapse. With a median follow up of 32 months, pharmacokinetic data during high-dose MTX therapy do not seem to be an exclusive predictive factor of CNS relapse.

Adolescent↗
PubMed1994

Intensified conditioning regimen with busulfan followed by allogeneic BMT in children with myelodysplastic syndromes.

Four consecutive children with myelodysplastic syndromes (MDS) underwent matched allogeneic bone marrow transplantation (BMT). Ages ranged from 3.2 to 6.3 years. Diagnosis was assessed according to FAB classification: refractory anemia-RA (n = 1), RA with excess of blasts (RAEB) (n = 1), and juvenile chronic myelogenous leukemia (JCML) (n = 2). Initial treatment included transfusions for all of them, splenectomy (n = 2) and chemotherapy (n = 1). Patients were all prepared with busulfan 21 mg/kg (480 mg/m2), cytosine arabinoside 24,000 mg/m2, melphalan 140 mg/m2. Graft-versus-host disease (GVHD) prophylaxis associated cyclosporine-methotrexate. Engraftment was prompt and complete in all children. Toxicity included severe mucositis (n = 3), moderate veno-occlusive disease (n = 2), acute GVHD (n = 3), chronic GVHD (n = 1). Sequelae have not yet been seen. All patients are alive and disease-free with a follow-up ranging from 7 to 35 months, with a Karnofsky score of 90-100%. Combined busulphan conditioning can offer an alternative to total body irradiation-based regimens in order to avoid late side-effects in children.

Anemia, Refractory↗
PubMed1994

[Acute hepatopathy compatible with Reye's syndrome in 3 children treated by chemotherapy].

BACKGROUND: Chemotherapy for malignant diseases sometimes leads to hepatic toxicity. Reye's syndrome has not been described in such a situation. CASE REPORTS: Three children, 4, 5 and 6 years-old, were treated for lymphoma or acute lymphoblastic leukemia. They were given polychemotherapy including drugs that were not potentially hepatotoxic. During remission, they suddenly developed manifestations such as neurologic disturbances, hepatomegaly, increased activity of liver enzymes, and microvesicular steatosis. These disturbances were consistent with the diagnostic criteria for Reye's syndrome recommended by the Centers for Disease Control. Factors such as viral infection, salicylate administration, primary metabolic disorder were not present. One child died and the other two recovered completely. CONCLUSION: Patients given chemotherapy, even though the relationship between them remains to be determined, may develop manifestations compatible with a diagnosis of Reye's syndrome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Malignant neonatal tumors].

Malignant neonatal tumors are rare (2% of childhood cancers, 1-2 cases/30,000 births). However, specificities in diagnosis and therapy must be underlined at this period of life; furthermore, the possibilities of antenatal sonographic diagnosis are improving and it may contribute to increase their incidence. Topographic analysis allows etiologic investigations since these tumors have the same diagnostic features as compared with older children, except Pepper's syndrome and leukemias. Therapeutic management depends on a rather good prognosis and fragility of such newborn. Indeed, surgical excision is the main step of treatment. Radiotherapy must be avoided whenever possible. Chemotherapy may be indicated (metastatic or unresectable tumors, omission or delay of irradiation in brain tumors) and has to be elaborated cautiously, according to the peculiar physiology of the neonate. Whatever the therapeutic strategy is, neonatal homeostasis must be well balanced, which implies a multidisciplinary specialized team. Respecting these conditions will help to cure more than the present 50% and better for future well being of such children.

Abdominal Neoplasms↗
PubMed1993

Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial.

Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.

Adult↗
PubMed1993

High incidence of Epstein-Barr virus detection in Hodgkin's disease and absence of detection in anaplastic large-cell lymphoma in children.

By in situ hybridization with EBER oligonucleotides and immunohistochemistry with anti-latent membrane protein 1 (LMP1) antibody, we compared the detection rate of Epstein-Barr virus (EBV) in Hodgkin's disease and anaplastic large-cell lymphomas in children. Among the 13 cases of Hodgkin's disease tested, 7 (54%) were found to be EBV associated (EBER transcripts +, LMP1 +). None of the 11 cases of ALC lymphomas was found to contain EBV genomes or gene products. This may indicate that EBV is not a pathogenic agent in anaplastic large-cell lymphomas in children in comparison to Hodgkin's disease.

Adolescent↗
PubMed1993

Combined continuous infusion etoposide with high-dose cyclophosphamide for refractory neuroblastoma: a phase II study from the Société Française d'Oncologie Pédiatrique.

PURPOSE: Patients older than 1 year with stage IV neuroblastoma who fail to achieve complete remission (CRem) have a particularly poor long-term prognosis. In an attempt to improve the outcome of these refractory patients, we tested a new drug combination. PATIENTS AND METHODS: Twenty-nine children with advanced neuroblastoma (27 stage IV and two stage III) were entered onto this phase II study. All were refractory to conventional chemotherapy and had measurable disease at the time of the trial. The regimen was a combination of high-dose cyclophosphamide (2 g/m2/d) on days 2, 3, and 4, and etoposide (VP16; 50 mg/m2/d) by continuous intravenous (IV) infusion on days 1 to 5. A pharmacokinetic study of VP16 was conducted in eight patients to determine whether the goal of persistent plasma levels between 1 and 5 micrograms/mL was achieved. RESULTS: Patients received a median of two courses, for a total of 58 courses. The median interval between each course was 32 days. In the 28 assessable patients, the overall response rate was 43%, with one CRem and 11 partial remissions (PRems). No life-threatening complication was observed in these heavily pretreated patients. The median duration of neutropenia (< 5 x 10(9)/L) was 14 days, and that of thrombocytopenia (< 50 x 10(9)/L) was 11 days. The overall incidence of sepsis was 27%. Gastrointestinal toxicity was frequent, but mild. Electrolyte disturbance with antidiuretic hormone (ADH)-like syndrome occurred in eight courses, but resolved rapidly. Grade > or = 2 hemorrhagic cystitis was observed in three courses. No cardiac toxicity was observed. There were no treatment-related deaths. Pharmacokinetic analysis showed that mean steady-state plasma levels (Css) of VP16 were greater than 1 microgram/mL during all the courses. CONCLUSION: This new drug combination appears to be effective in advanced neuroblastoma. Its toxicity remains manageable, with no life-threatening complications. Further evaluation in patients with less-advanced disease is warranted.

Adolescent↗
PubMed1993

Etoposide in relapsed or refractory Wilms' tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group.

PURPOSE: Despite a high cure rate of approximately 85% in Wilms' tumor by multimodality therapy, to date only four drugs are known to be active against such tumors. There is a clear need for new active drugs. PATIENTS AND METHODS: Thirty-one patients with relapsed or refractory Wilms' tumor from three British and 14 French centers were treated with intravenous (IV) etoposide 200 mg/m2 daily for 5 days. Original stage was I (n = 3), II (n = 7), III (n = 9), IV (n = 10), and V (n = 2). Prior chemotherapy, administered initially or at relapse, included vincristine and dactinomycin in all cases, doxorubicin or epirubicin in 30, and ifosfamide in 20. Sites of relapse or resistant disease were lung in 13, abdomen or pelvis in six, liver in one, and multiple in 11. When entered onto the study, 12 patients were in first relapse, 10 in second relapse, and four in third or more relapse. Five had never obtained a complete remission. All but two (progressing) patients received two courses of etoposide, the second course being administered at day 21. RESULTS: A complete response (CR) was documented in two patients, partial response (PR) in 11, stable disease in 10, and progressive disease (PD) in eight. The duration of response could not be evaluated, because all responding patients were subsequently treated with multimodality therapy. The major toxicities observed were neutropenia and thrombocytopenia, but most patients had been heavily pretreated. No toxic death clearly associated with etoposide was noted. CONCLUSION: It is concluded that etoposide in this schedule is an active agent in Wilms' tumor and should be considered for inclusion in regimens for high-risk patients, such as those with metastatic disease at diagnosis and those who relapse after multiagent chemotherapy.

Adolescent↗
PubMed1993

[l-folinic acid versus racemic folinic acid in the treatment of leukemia in children with high dose of methotrexate].

Until now, folinic acid (FA) has been available the racemic mixture d1 FA, whose biological activity is supported by natural 1 FA. The purpose of this trial was to compare, on a pharmacokinetic, biological, and clinical basis, the racemic mixture dl FA with the pure 1 FA in the rescue of high-dose methotrexate (MTX) therapy. Eighteen children with acute lymphocytic leukemia (ALL) were entered in this trial planned with a cross-over design. Four cycles of MTX (5 g/m2, 24h CVI) were administered to each patient, with a 2-week interval between cycles. The rescue was achieved orally every 6h, starting 12h after the end of the MTX infusion, at a dose of 12 mg/m2 for dl FA and 6 mg/m2 for pure 1 FA. dl FA and 1 FA rescues were alternated from one cycle to the next. d FA, 1 FA, and the active metabolite 5-methyltetrahydrofolate (5-MTHF) were measured in plasma using a stereospecific HPLC assay. After administration of dl FA, the accumulation of d FA in plasma was confirmed: mean residual concentrations were 420 and 652 nM after 2 and 6 intakes respectively. Total active folate concentrations (1 FA + 5-MTHF) were similar between the two types of rescue: 92 and 100 nM respectively for dl FA rescue and 1 FA rescue after two intakes, 186 and 184 nM respectively for dl FA rescue and 1 FA rescue after six intakes. Intra-individual statistical analysis of total active folates (1 FA + 5-MTHF) performed on 17 patients did not show any significant difference between dl FA rescue and 1 FA rescue. For both types of rescue, MTX terminal half-lives were identical (average value 13.9 h). Considering each type of toxicity (hematologic, hepatic, renal and digestive) there was no significant difference in the proportion of toxic cycles following l FA rescue or dl FA rescue. In conclusion, the administration of the pure l FA, as compared with the administration of the racemic mixture, results in comparable blood profiles of active folates and MTX, and leads to equivalent treatment tolerance.

Adolescent↗
PubMed1993

Risk factors for cytomegalovirus infection in BMT recipients transfused exclusively with seronegative blood products.

Risk factors for developing cytomegalovirus (CMV) infection and pneumonitis were analysed in 100 unselected consecutive patients undergoing allogenic BMT. This series is homogeneous because of the same diagnostic procedures, BMT technique and supportive care (exclusive seronegative blood products, no CMV immunoglobulin, no prophylactic antiviral). The incidence of CMV infection and CMV interstitial pneumonitis (CMV-IP) were 44% and 13% respectively, of whom five patients died. Variables such as age, sex, underlying disease, conditioning regimen and occurrence of GVHD were not found as significant risk factors. We confirm that the only major factor was recipient's serology as CMV infection and IP occurred in 4% and 0% respectively among negative recipients (R-) compared with 79% and 25% among positive R. In contrast to some studies among R+, neither donor's immunity nor recipient's CMV humoral response improved the clinical outcome. This study validates the good predictive value of viremia and urinary virus excretion for the occurrence of CMV-IP (respectively positive in 11 and 13 patients out of 13 with IP), always preceding IP by a median of 37 and 27 days. The highest risk patients for lethal CMV-IP were older recipients (> 30 years). Thus, prospective prophylactic trials with antiviral agents are suggested in such viremic or viruric patients. Furthermore, the use of seronegative blood products is highly effective and sufficient to prevent CMV infection in R-patients.

Adolescent↗
PubMed1992

l-folinic acid versus d,l-folinic acid in rescue of high-dose methotrexate therapy in children.

BACKGROUND: At this time, folinic acid (FA) is commercially available as the racemic mixture d,l-FA, whose biological activity is supported by natural l-FA. The administration of d,l-FA results in the accumulation of d-FA in plasma relative to the active l-FA form; in vitro studies have shown that d-FA can compete with the polyglutamation of methotrexate (MTX). PURPOSE: Our purpose was to compare, on a pharmacokinetic, biological, and clinical basis, the racemic mixture d,l-FA with the pure l-FA in rescue of high-dose MTX therapy (5 g/m2) in children with acute lymphocytic leukemia (ALL). METHODS: Eighteen children with ALL were entered in this trial, which was planned with a crossover design. Four cycles of MTX were administered to each patient, and rescue was achieved orally every 6 hours at a dose of 12 mg/m2 for d,l-FA and 6 mg/m2 for pure l-FA. The d,l-FA and l-FA rescues were alternated from one cycle to the next. d-FA, l-FA, and the active metabolite 5-methyltetrahydrofolate (5-MTHF) were measured in plasma using a stereospecific high-performance liquid chromatography assay. RESULTS: Considering total active folate levels (l-FA + 5-MTHF), mean residual concentrations were similar for rescue by d,l-FA and l-FA, after two and six intakes, respectively: 92 and 186 nM for d,l-FA rescue versus 100 and 184 nM for l-FA rescue. Intra-individual comparison of total active folates (l-FA + 5-MTHF) did not show any significant difference between d,l-FA rescue and l-FA rescue. After administration of d,l-FA, the accumulation of d-FA in plasma was confirmed. For both types of FA rescue, MTX terminal half-lives were identical (average value, 13.9 hours). Considering each type of toxic effect (hematologic, hepatic, renal, and digestive), there was no significant difference in the proportion of toxic cycles following l-FA rescue or d,l-FA rescue. CONCLUSION: The administration of the pure l-FA, compared with the administration of the racemic mixture, results in comparable blood profiles of active folates and MTX, leads to equivalent treatment tolerance, and avoids the plasma accumulation of d-FA.

Adolescent↗
PubMed1992

Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial.

Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.

Adult↗