Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.

Urate-oxidase in the prevention and treatment of metabolic complications in patients with B-cell lymphoma and leukemia, treated in the Société Française d'Oncologie Pédiatrique LMB89 protocol.

PURPOSE: To evaluate the frequency of metabolic complications and dialysis due to tumor lysis syndrome in patients with B-cell advanced-stage non-Hodgkin's lymphoma (NHL) and L3 leukemia at initiation of chemotherapy including the use of urate-oxidase. PATIENTS AND METHODS: Retrospective review of the clinical records of 410 patients with stage III and IV B-cell NHL and L3 leukemia treated in France and prospectively registered in the LMB89 protocol. RESULTS: During the first week of chemotherapy, only 34 of 410 patients recorded metabolic problems that included hypocalcemia (< 70 mg/dl) in 24 patients, hyperphosphatemia (> 6.5 mg/dl) in 28 and elevation of creatinine > or = 2 SD in 16. Six patients underwent dialysis for life-threatening problems and a seventh as a preventive measure. In the other 27 cases, metabolic problems were successfully resolved using urate-oxidase in combination with alkaline hyperhydration. Among the 410 patients, one case of hemolysis was reported and there was no severe allergic reaction to urate-oxidase. CONCLUSIONS: Only 1.7% of patients in our study receiving urate-oxidase during their induction chemotherapy needed renal dialysis. Urate-oxidase was well tolerated, and used as prophylaxis and/or treatment of hyperuricemia and tumor lysis syndrome consistently gave a lower rate of renal and metabolic complications than in other series of similar patients.

The Children Leukemia Group: 30 years of research and achievements.

The EORTC Children Leukemia Group (CLG) is part of the offspring of the EORTC Hemopathies Working Party which in 1978 split into a paediatric and to an 'adult' branch. At that time, the Berlin-Frankfurt-Munster (BFM) designed by H. Riehm for acute lymphoblastic leukaemia (ALL) appeared much more efficacious than all others and the CLG decided to adapt that treatment strategy for its own clinical trials. The main results of these may be summarised as follows:for standard risk patients, the deletion of cyclophosphamide from consolidation and reconsolidation courses does not jeopardise the patient's outcomefor medium- and high-risk patients receiving high-dose methotrexate (MTX), cranial radiotherapy is superfluouswith the dose scheduling of the BFM regimen, E-Coli L-Asparaginase is more efficacious than Erwinia L-Asparaginasethe addition of monthly intravenous (i.v.) 6-mercaptopurine to conventional maintenance chemotherapy is detrimentalthe assessment by quantitative polymerase chain reaction (PCR) of minimal residual disease at completion of induction is feasible in a cooperative setting and can be used as a powerful and independent prognostic factor. The CLG also conducted clinical studies of acute myeloblastic leukaemia. Since 1989, lymphoblastic non-Hodgkin's lymphomas have been treated within the ALL trials. The CLG collaborates with other Groups within the I-BFM Study Group and participants in the meta-analytic studies conducted by the Oxford team by the Oxford Children ALL Collaborative Group.

Outcome of radiation-related osteosarcoma after treatment of childhood and adolescent cancer: a study of 23 cases.

PURPOSE: We analyzed the clinical features and outcome of patients with radiation-associated osteosarcoma treated during the era of contemporary chemotherapy. PATIENTS AND METHODS: The characteristics and outcome of 23 patients (17 males and six females) treated during childhood or adolescence for a solid tumor who later developed osteosarcomas within the radiation field between 1981 and 1996 were reviewed. RESULTS: The median dose of radiation delivered to the first cancer was 47 Gy. Nineteen patients also received chemotherapy. The median time between radiotherapy and the diagnosis of secondary osteosarcoma was 8 years. Histologic slide review showed conventional central osteosarcoma with various differentiation patterns in 21 cases, together with one case of high-grade surface osteosarcoma and one of periosteal osteosarcoma. The sites of involvement were the craniofacial bones in six cases, the first cervical vertebra in one, the girdle bones in seven, and the extremities of long bones in nine. Three patients had metastatic disease at the diagnosis of osteosarcoma. Palliative therapy was administered to seven patients. The aim of treatment was curative for 16 patients, two of whom underwent amputation without further therapy. Intensive chemotherapy regimens were administered to 14 patients before and/or after surgery. Fifteen patients achieved complete surgical remission. Twelve patients were alive and disease-free at a median follow-up duration of 7.5 years. Overall and event-free survivals at 8 years were 50% and 41%, respectively. CONCLUSION: Patients with radiation-related osteosarcoma and resectable lesions can be cured with surgery and intensive preoperative and postoperative chemotherapy.

Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.

[High grade osteosarcoma of the lower limb. Complications and results of the treatment of 20 patients]. / Ostéosarcome de haut grade de malignité du membre inférieur. Complications et résultats du traitement de 20 patients.

UNLABELLED: Over 11 years we treated 30 osteosarcomas: 20 of them were high grade non metastatic osteosarcomas of the lower limb, which were treated by neoadjuvant chemotherapy (Rosen T10, or OS 87 protocol of the French Society for Pediatric Oncology). MATERIAL AND METHODS: There were 12 males and 8 females; the mean age was 19 years (range 12-51). The site of the tumor was the femoral neck (1 case), femoral diaphysis (2 cases), distal femur (12 cases), proximal tibia (4 cases), distal tibia (1 case), 3 were IIA and 17 IIB according to Enneking system. Conservative treatment was performed in 17 cases: there were 12 knee prostheses, 4 allografts and 1 knee arthrodesis with allograft. RESULTS: a) Surgical complications: Mechanical complications occurred in 10 patients. The function was preserved 8 times. In 2 patients the knee became stiff. An infection occurred in 3 patients: a conservative treatment was possible in 2 of them with a fair result. In the third case, an above-the-knee amputation had to be done. b) Functional results were studied according to Enneking rating. 14 arthroplasties (12 done as first surgical treatment and 2 after mechanical complication) had a 68, 19 score. c) Oncologic results: 8 patients were good respondents and 12 patients were bad respondents to chemotherapy according to Huvos grading. One local relapse was observed which could be treated by mean of a second chemotherapy and a prosthetic reconstruction. The patient is still alive and disease-free at 7 years (9 years after the diagnosis of the osteosarcoma). 5 patients had distant metastasis (lung, bones, and brain). One out of 5 was good respondent and 4 out of 5 are presently dead. Using Kaplan Meier statistical analysis, the overall survival wzs 76.8 per cent and the event-free survival was 67.4 per cent at 80 months. CONCLUSION: We preferred a simple prosthetic reconstruction without osseous sleeve or an intercalary allograft if possible: these procedures allow the patient very rapid autonomy to have despite a prolonged chemotherapy.

Can amputation be avoided in local recurrence after limb salvage for high grade osteosarcoma? A case report and a review of the literature.

We report a case of local recurrence after a limb salvage procedure for high grade osteosarcoma. We carried out a second salvage operation because the lesion was small, there were no distant metastases, the patient had initially responded to chemotherapy and was able to receive more drugs. She is still alive, well and free of disease more than 6 years after the second operation, and 9 years after the diagnosis was made. Amputation is not always needed for every case of recurrence.

A phase II study of recombinant human granulocyte-colony stimulating factor (rHuG-CSF, lenograstim) in the treatment of agranulocytosis in children.

The present study evaluated the clinical efficacity and tolerability of the subcutaneous (SC) administration of lenograstim, a glycosylated form of rHuG-CSF identical to human G-CSF, in the treatment of congenital agranulocytosis. Assessment criteria included neutrophil response and response stability, incidence and severity of infection and gingivostomatitis and quality of life. Lenograstim, at induction dosages of 5 (n = 9), 10 (n = 2) or 20 (n = 1) microgram/kg/day SC, produced neutrophil recovery in all of 12 children with congenital agranulocytosis. There was a median delay of 7 days to recovery after establishment of the effective induction dose. Whereas this dosage maintained a stable neutrophil response in 7 patients, the remaining 5 required dosage increases and dose reduction during maintenance therapy was not possible in these 5 cases. Among 4 patients stabilised at a dosage of 5 micrograms/kg/day, in 2 cases a lower minimum effective dose of 2 micrograms/kg/day was attained over the maintenance phase. Administration of twice the daily dose of lenograstim on alternate days was feasible in 3 of 8 patients. Lenograstim therapy reduced the incidence of infection and hospitalisation for infection relative to the prestudy period, while in 6 of 9 cases there was complete recovery from gingivostomatitis. Only one patient discontinued treatment on account of adverse events. Finally, perceived health and disease related symptoms showed a significant (p < 0.001) amelioration in the course of the study. Thus, lenogastrim produced sustained neurotrophil recovery in patients with congenital agranulocytosis, decreased the incidence and severity of infection and improved the quality of life.

[Intrafamilial bone marrow donation: the role of the parents]. / Don de moelle osseuse intrafamilial: la place des parents.

Bone marrow transplantation (BMT) is the last chance of recovery for some children suffering from malignant hemopathy or congenital blood disease. BMT with related donor radically alters previous family relationships: each member of the nuclear family becomes actively involved. Parents and siblings all undergo HLA typing. Only 30% of those who would benefit from bone marrow transplantation are lucky enough to have an HLA matched related donor, brother or sister. Our retrospective study concerned related donors and their parents. This paper reports the parents study. It was carried out at Strasbourg University Hospital. Parents were invited to speak about the child's illness, the graft reasons and their own position to regarding the choice of donor. Semi-structured interviews were used and their content analysed. The results highlight the expression by the parents of the need to maintain some control over the action which will save their child and establish an other gift system to keep their parental status.

Improved survival for acute lymphoblastic leukaemia in infancy: the experience of EORTC-Childhood Leukaemia Cooperative Group.

Out of 744 newly diagnosed ALL children under the age of 18 years treated according to the EORTC-CLCG protocols 58831 and 58832, 28 (4%) were infants less than 1 year of age. An elevated risk factor, which takes into account the sizes of the liver and spleen and the number of circulating blasts, was present in 25 cases. Most patients had non-common ALL. Among 15 patients studied by cytogenetics, nine present chromosomal abnormalities, six of them having a t(4;11) translocation. Complete remission was achieved in 86% of cases. One patient died in complete remission of therapy-related infection. The overall EFS is 43%. It is not statistically different in very young infants as compared to infants older than 6 months. Except for patients with AUL or with t(4;11) translocation, a continuous complete remission rate above 50% can be achieved with a median follow-up of 4 years. The results obtained in infant ALL with EORTC-CLCG protocols are currently better than those obtained with some other protocols, but remains inferior when compared to the ones obtained in older children. Thus, further improvements are needed and should be evaluated in large cooperative trials.

[Clinical experience with totally implantable venous access systems in pediatric hematology and oncology]. / Expérience clinique des systèmes veineux totalement implantables en hématologie et oncologie pédiatriques.

Forty-three children with malignant diseases who received 48 totally implanted venous accesses (TIVA) were retrospectively analyzed. More than half the patients had acute leukemia. Mean age was 6 years 10 months. Mean duration of use of the TIVA was 473 +/- 50 days (range 28 to 1,285 da; median 424 days). Removal of the TIVA was required because of an adverse event in 33% of cases. Main reasons for removal included infection (22.9%), thrombosis (6.25%), and catheter dysfunction (4.16%). Catheter-related infections were most often due to staphylococci (90%), especially S. epidermidis (63%). Infection rate was 0.48 per 1,000 patient-days. Flushing with a vancomycin-heparin solution can be expected to decrease this rate. Selection of the implantation site is discussed. In children under 6 years of age, the cephalic vein and external jugular vein are often frail or absent and are therefore less appropriate than the internal jugular vein or subclavian vein.

Primitive malignant nonepithelial hepatic tumors in children.

Primary intrahepatic malignant nonepithelial tumors are very rare in children and account for 2% of all malignant mesenchymatous tumors under the age of 15 years. Clinical presentation, radiologic features, and histologic types are not unequivocal. The predominant role of surgery takes place either initially in small localized tumors or later, after initial reductive chemotherapy. In all cases, complete resection is the necessary but not sufficient condition for cure. Additional radiotherapy seems ineffective. High-dose chemotherapy and/or liver transplantation can be proposed for resistant cases. The disease-free survival rate is 37% at 2 years for the whole series.

[Rhabdomyosarcoma of the prostate. Diagnostic course and current therapy. Report of a case of a 17-year-old boy]. / Le rhabdomyosarcome de la prostate. Evolution diagnostique et thérapeutique actuelle. A propos d'un cas chez un garçon de 17 ans.

The authors report a case of rhabdomyosarcoma in a 17 year old boy which recurred after combination chemotherapy and radical prostatectomy, followed by death of the patient due to haematological complications of second-line chemotherapy. The diagnosis of these rhabdomyosarcomas is facilitated by the various immunohistochemical stains now available. Chemotherapy is undeniably effective and, combined with surgery and radiotherapy, ensures a 5-year survival of 47% to 93% depending on the stage. The first-line chemotherapy avoids the need for radiotherapy in the early stages and allows less mutilating surgical procedures, while maintaining the survival rate.

Results of initial doxorubicin, 5-fluorouracil, and cyclophosphamide combination chemotherapy for inflammatory carcinoma of the breast.

Forty-three patients with nonmetastatic inflammatory breast carcinoma have been treated by initial doxorubicin, 5-fluorouracil, and cyclophosphamide (FAC) combination chemotherapy. After three chemotherapy cycles, responding patients underwent surgery. Chemotherapy was then completed for nine cycles of FAC followed by locoregional radiation therapy. All patients received tamoxifen 40 mg/day for 1 year from the time of diagnosis. Thirty-eight patients (88%) had a clinical response to chemotherapy and underwent surgery. On histologic examination 17 patients had a residual tumor mass less than 1 cm diameter or a complete tumor disappearance; lymph nodes dissection was negative in 15 patients. With a median follow-up of 48 months, the predicted 5-year disease-free survival (DFS) is 48% (median DFS, 46 months). Analysis of prognosis factors shows that age, menopausal status, and histologic grade have no predictive value. The DFS and overall survival were significantly improved by the presence of hormonal receptors and a low number of positive lymph nodes (less than 4) at surgery. The most significant prognosis factor was the residual tumor mass after initial chemotherapy with an 80% predicted 5-year DFS for the responding patients versus 30% for the no responding patients (P less than 0.001).

[The value of perforating cryopreserved massive bone allograft. Histologic data of an allograft removed after 27 months]. / De l'intérêt de perforer les allogreffes osseuses massives cryoconservées? Données histologiques à propos d'une allogreffe déposée à 27 mois.

The authors reported one documented observation of a deep-frozen, non irradiated, intercalary allograft; it was perforated by drilling and then fixed by a blade plate. This allograft was removed 27 months after its implantation. Histological examination of the removed bone graft showed newly formed mature bone which developed near preexisting devitalized bone. The external cortex was also revitalized and reossified close to the periosteum, as it was previously reported. But osteogenesis filled all the paths of the perforations and extended to the haversian canals located in the vicinity of the perforations. The authors conclude that cortical perforations induce both cortical and medullary osteogenesis of the graft. If osteogenesis is observed in the whole medullary canal, it is more focal and located in the vicinity of the holes in the cortex.

Initial chemotherapy including ifosfamide in the management of Ewing's sarcoma: preliminary results. A protocol of the French Pediatric Oncology Society (SFOP).

Phase II studies using ifosfamide both alone and combined with vindesine and cisplatin have shown the effectiveness of this drug in patients with Ewing's sarcoma (ES) who had relapsed during VAC (vincristine, actinomycin, cyclosphosphamide)/VAd (vincristine, Adriamycin) therapy. In November 1984, these results led the SFOP to adopt a protocol consisting of (1) initial chemotherapy with three cycles of IVA (ifosfamide, 3 g/m2 on days 1 and 2; actinomycin D, 750 mg/m2 on days 1-3; vincristine, 1.5 mg/m2 on day 1) alternating every 3 weeks with IVAd (vincristine on day 22; ifosfamide on days 21-23; Adriamycin, 60 mg/m2 on day 22); (2) radical surgery if possible; (3) local radiotherapy (RT); and (4) maintenance chemotherapy with alternating IVA and VAd (vincristine, Adriamycin) for up to 9 months. In May 1987, 87 patients with previously untreated ES entered the study; 61 had localized ES. To date, 54 patients with localized disease and 22 with metastatic disease have finished initial chemotherapy; 40 patients with localized disease have been evaluated. In all, 28 patients (70%) were in complete remission (17 patients) or had a tumor regression of greater than 50% 11 patients) and were considered to be good responders; 12 patients were considered to be poor responders. After local radiotherapy in all but 7 patients and surgical resection in 29, 52 of 54 were considered to be in clinical remission. A total of 13 patients with metastatic disease were good responders at the completion of the initial chemotherapy. These results confirm the efficacy of primary chemotherapy using ifosfamide for the treatment of ES.

[Results of cisplatin-based polychemotherapy and analysis of prognostic factors in ovarian cancer. Apropos of 106 cases]. / Résultats d'une polychimiothérapie à base de cisplatine et analyse des facteurs pronostiques dans les cancers de l'ovaire. A propos de 106 cas.

One hundred and six patients with stage Ic to IV ovarian carcinoma were treated by a protocol consisting of optimal debulking surgery followed by 9 cycles of CHAP chemotherapy. Clinical response was confirmed by a second-look procedure. Sixty-nine patients (65%) responded with 54 histological complete remissions (50.8%). Nineteen patients did not receive any complementary treatment due to a negative reaction, or prolonged neutropenia. Seven patients received maintenance chemotherapy, 10 an abdominal radiotherapy, 22 intraperitoneal chemotherapy and 11 autologous bone marrow transplantation. The 5-year survival rate was 32.5% and disease-free survival rate was 39.7%. Prognostic-factor analysis showed that age, initial staging, residual disease and cytological grading were significant. The authors propose a classification based on the risk of relapse, and different therapeutic indications for improving response rate and patient survival.

[Hepatic undifferentiated (or embryonal) sarcoma. Diagnostic and therapeutic problems apropos of botryoid rhabdomyosarcoma]. / Sarcomes indifférenciés (ou embryonnaires) hépatiques. Problèmes diagnostiques et thérapeutiques à propos d'un rhabdomyosarcome botryoïde.

Primary undifferentiated sarcomas (also called embryonal sarcomas or malignant mesenchymomas) are an exceptional form of cancer of the liver, occurring preferentially in children or adolescents. They can exhibit poor differentiation, embryonal rhabdomyosarcoma being the most frequent. To date, therapeutic success has been reported only rarely. The authors describe the case of a 16 year old boy with primary hepatic sarcoma showing a rhabdomyoblastic differentiation, who is in complete remission two years after total surgical resection and polychemotherapy.