[Pediatric non-Hodgkin's lymphoma: primary surgical management of patients presenting with abdominal symptoms. Recommendations of the Lymphoma Committee of the French Society to Combat Pediatric Cancers (SFCE)]. / Lymphome non-Hodgkinien de l'enfant: prise en charge chirurgicale lors d'un tableau abdominal révélateur.

Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.

[Not Available]. / Lymphome non-Hodgkinien de l'enfant : prise en charge chirurgicale lors d'un tableau abdominal révélateur: Recommandations du « Comité lymphome ¼ de la Société française de lutte contre les cancers de l'enfant et de l'adolescent (SFCE).

A. Delarue, C. Bergeron, F. Mechinaud-Lacroix, C. Coze, M. Raphael, C. Patte, pour le « Comité Lymphome ¼ de la SFCE Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.

Allogeneic bone marrow transplantation following a busulfan-based conditioning regimen in young children with acute lymphoblastic leukemia: a Cooperative Study of the Société Française de Greffe de Moelle.

A subgroup of children with ALL remains at high risk of relapse despite the administration of intensive chemotherapeutic protocols and may benefit from allogeneic BMT. The cytoreductive regimen used most often combines TBI with cyclophosphamide. Nevertheless, miscellaneous long-term sequelae have been consequent upon radiotherapy, especially in young children. This retrospective multicentric study analyzes the outcome of children with ALL under 4 years of age receiving an HLA-genoidentical BMT following a radiation-free preparative regimen. A busulfan-based regimen with cyclophosphamide or melphalan +/- etoposide +/- cytarabine was given to 21 children (median age: 28 months, range 6-48). Sixteen patients with initial poor prognostic factors were transplanted in first complete response (CR) and five patients in relapse or second CR. With a median follow-up of 47 months, the results show an overall 4-year DFS of 61.1%. Leukemic recurrence was observed in eight patients. The preparative regimen was well-tolerated and there were no transplant-related deaths. A busulfan-based BMT preparative regimen may be a therapeutic alternative to TBI-containing regimens in young children. Efforts are currently aimed at reducing the relapse rate in these children by optimizing the tumoricidal potential of chemotherapy and the graft-versus-leukemia effect of allogeneic BMT.

Total body irradiation and high-dose cyclophosphamide, BCNU and VP-16 (CBV) as a new preparatory regimen for allogeneic bone marrow transplantation in patients with advanced hematologic malignancies.

To increase the cure rate of advanced hematologic malignancies following allogeneic bone marrow transplantation we sequentially evaluated two intensified conditioning regimens. Eleven patients with acute myeloblastic leukemia (AML) beyond the first complete remission or chronic myelogenous leukemia (CML) not in first chronic phase received an association of 13.5 Gy of fractionated total body irradiation (TBI) followed by cyclophosphamide (CY) 120 mg/kg. Following this regimen, the probability of relapse was 47% at 3 years and the non-relapse mortality rate was 27%. Given the acceptable tolerance of this regimen, 13.5 Gy fractionated TBI was associated with intensified chemotherapy consisting of a combination of CY 120 mg/kg, carmustine 300 mg/m2 and etoposide 600 mg/m2 (CBV). This regimen was administered to 22 patients with comparable diseases. Of these patients, 7 received a transplant from a matched unrelated donor and 2 other patients received a second transplant from the original genoidentical donor. For 15 patients with a genoidentical donor, including the 2 second transplant, the 3 year probability of survival, disease-free survival and relapse are 40%, 40% and 14%, respectively. No regimen-related toxic deaths were recorded during the first 100 days. Of 7 patients with matched unrelated donors, 3 died before day 100, one death being directly attributable to the regimen. Early non-fatal regimen-related toxicity consisted mainly in grade II mucositis with no grade III or IV toxicity in recipients of genoidentical marrow. The late deaths were mainly due to chronic GVH-related complications. In conclusion, the association of fractionated 13.5 Gy TBI and CBV carries a high antileukemic activity and an acceptable toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary Epstein-Barr virus infection with clonal T-cell lymphoproliferation.

A case of fatal Epstein-Barr virus infection in a previously healthy girl who was first found to have severe infectious mononucleosis with spontaneous recovery is reported. Because an abnormal immune response to the virus persisted, the disease relapsed, manifesting in cutaneous and pulmonary lesions associated with hemophagocytic syndrome responsible for death. Pathologic findings were characterized by polymorphous atypical lymphoid infiltrate, prominent necrosis, and histiocytic hyperplasia. Lymphoid cells displayed CD8 phenotype and clonal T-cell receptor gene rearrangement. Viral genome was detected in lesions by Southern blot and located in nuclei of lymphoid cells by in situ hybridization. Pathologic findings suggested fatal infectious mononucleosis; however, phenotype and genotype favored a malignant diagnosis. Clonality was demonstrated to have arisen during primary infection. Virologic examination indicated that Epstein-Barr virus was a causative agent. Such a process belongs to the recently recognized spectrum of Epstein-Barr virus-related T-cell lymphoproliferative disorders that might overlap fatal infectious mononucleosis in patients who are especially vulnerable to the virus.

Early intensive therapy with autotransplantation for high-risk Hodgkin's disease.

The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy. In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction < 75%) (16 pts) or refractory (4 pts) to 3-4 courses of conventional HD chemotherapy received high-dose therapy followed with autologous bone marrow (14 pts) or peripheral blood stem cell (6 pts) transplantation. They were 13 males, 7 females, median age 26 years (8-45). At the time of initial diagnosis, all but one of the patients had B symptoms, all had high-risk HD defined as Ann Arbor stage IV (7 pts) or large mediastinal involvement (LMI = tumor/thorax > 0.45 at T5-T6) (6 pts) or both stage IV+LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2 x 4, BCNU 300 mg/m2, etoposide 200 mg/m2 x 3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radio-therapy was performed after hematological recovery. Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease).(ABSTRACT TRUNCATED AT 250 WORDS)

[Neonatal acute leukemia: apropos of 7 cases]. / Leucémies aiguës néonatales: à propos de sept observations.

BACKGROUND: Acute leukemia in neonates is rare and is more severe than leukemia in childhood. POPULATION: Seven cases (four girls, three boys) were included in this series. Leukemia was diagnosed at birth in three cases; hepatosplenomegaly was seen in five cases and skin nodules in three. Hyperleukocytosis more than 100,000/mm3 was present in four cases; the WBC and differential counts were normal in two. A meningeal involvement was seen in one case. The leukemia was lymphoblastic (ALL) in three cases and myeloblastic (AML) in four. Intensive chemotherapy induced complete remission in five patients, persisting 5 and 4 years after the diagnosis in two. Classic risk factors such as high white blood counts, central nervous system involvement, myeloblastic lineage, absence of CALLA (common acute lymphoblastic leukemia antigen) expression and abnormal blast cell karyotype interesting the 11q23 area were found again in this series. Risk related to drug toxicities and infectious complications were also noted in this series of very young patients. CONCLUSIONS: The outcome may depend on progress in pharmacology, search for new drugs and use of bone marrow transplantation.

[Abdominal lymphomas in children: place of surgery]. / Les lymphomes abdominaux de l'enfant: place de la chirurgie.

To determine the place of surgery in the management of abdominal Burkitt's lymphoma, we retrospectively reviewed the records of 17 children treated over a period of 10 years (1983-1992). Patients were 14 males. Seven patients presented with acute abdominal pain, 6 with an abdominal mass and 5 with intestinal obstruction. In 3 cases, the diagnosis was made without laparotomy (2 percutaneous tumoral puncture, 1 pleural puncture). In the 14 other cases, the diagnosis was made by laparotomy with 3 biopsies and 11 resection of the tumor (7 complete and 4 incomplete). These laparotomies were complicated by 1 evisceration and 2 intestinal obstruction. At the end of the initial chemotherapy, 1 children was reoperated for a residual mass with no histological viable tumor. Sixteen children were long term survivors (14 > 2 years); 1 died. Surgery was indicated in cases of intestinal intussusception. In cases of abdominal mass, surgery could have been avoided twice (positive ascitic fluid). A complete tumoral resection had no influence on survival which depend of extra-abdominal extension and more over of response to chemotherapy.

Production and role of macrophage colony stimulating factor (CSF-1 or M-CSF) in hematological pathology.

M-CSF, an homodimeric glycoprotein initially identified as a Colony Stimulating Factor, can now be considered as a cytokine-produced by multiple cell types, including T cells and acting on hematological and non hematological tissues. In this short article, we bring evidence that the production of M-CSF is inducible in T cells in vitro and in vivo and that it plays a central role in several hematological disorders. A particular emphasis will be given to EBV induced hemophagocytic syndromes and to related disorders during the oral presentation.

[Cerebral granulocytic sarcoma disclosing acute non-lymphoblastic leukemia]. / Sarcome granulocytaire intracérébral révélateur d'une leucémie aiguë non lymphoblastique.

A case of acute non lymphoblastic leukemia in a 9 year-old girl is reported. This case presented with intracranial hypertension with exophthalmos and parietal subcutaneous tumor; imaging techniques showed their subcutaneous, orbital and intracranial localizations. Complete remission was obtained within 7 months with polychemotherapy. The rare cases of granulocytic sarcoma of central nervous system in children are reviewed.

Probable disseminated cerebral aspergillosis: recovery with medical treatment.

Cerebral aspergillosis has a very poor prognosis. When this complication occurs in the immunocompromised host, evolution is virtually fatal in all cases despite surgical and medical treatment. We describe in this report the case of a child with acute lymphoblastic leukaemia who developed pulmonary aspergillosis, and subsequent cerebral dissemination during therapeutic induction. Due to multifocal cerebral lesions, surgery was impossible. The patient was administered long term treatment including amphotericin B, flucytosine and itraconazole for 9 months, during which time a neutropenic period occurred with reactivation of cerebral mycotic lesions, in spite of modification of antileukaemic therapy. Seven years later, he nevertheless remains in complete remission without any neurological sequelae. Thus cerebral aspergillosis requires early diagnosis and can be treated using a strong combination of antimycotic drugs (amphotericin B, flucytosine and itraconazole) on a long term basis, even when aspergillomas cannot be removed surgically. Antileukaemic therapy must be concomitantly adapted to avoid or limit neutropenia.

An attempt to treat pediatric intracranial alphaFP and betaHCG secreting germ cell tumors with chemotherapy alone. SFOP experience with 18 cases. Société Française d'Oncologie Pédiatrique.

PURPOSE: Intracranial alphaFP and betaHCG secreting germ cell tumors have a very poor prognosis with local treatment alone. Because of efficacy of chemotherapy in extracranial forms, we tried in the SFOP (Société Française d'Oncologie Pédiatrique) to treat them with chemotherapeutic treatment exclusively. PATIENTS AND METHODS: Eighteen patients (10 alphaFP, 2 betaHCG, 6 alphaFP and betaHCG secretion) were enrolled from January 1988 to December 1992. After biological diagnosis patients were to receive 6 cycles of chemotherapy (vinblastine bleomycin - carboplatin or etoposide - carboplatin/ifosfamide - etoposide). After completion of chemotherapy, surgery was to be performed in case of residual tumor. Focal radiation was only to be delivered in case of viable residual tumor. RESULTS: All patients had biological remission and tumor reduction. Fifteen patients were treated according to the protocol by chemotherapy alone (13) or chemotherapy and radiation of residue (2). Twelve of the 13 non irradiated patients relapsed, 8 in local and/or regional area, 3 in cerebrospinal area and 1 in undeterminated area with mild elevation of markers except in one case. Six patients are alive in second complete remission after chemotherapy and/or surgery and then a consolidation treatment with radiation and/or high dose chemotherapy (5) or craniospinal radiation (1). Three patients received radiation after 2 or 3 cycles of chemotherapy as protocol violations and didn't relapse. Thus, 12 patients out of the 18 patients are alive with a median follow up of 68 months. All but 1 had focal radiation as part of treatment. No toxic death was observed. CONCLUSION: Although survival rate is noteworthy (66%), these tumors were not curable with this conventional chemotherapy alone and focal radiotherapy should be part of the treatment.

Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Société Française d'Oncologie Pédiatrique.

Conventional therapy for intracranial germinomas is craniospinal irradiation. In 1990, the Société Française d'Oncologie Pédiatrique initiated a study combining chemotherapy (alternating courses of etoposide-carboplatin and etoposide-ifosfamide for a recommended total of four courses) with 40 Gy local irradiation for patients with localized germinomas. Metastatic patients were allocated to receive low-dose craniospinal radiotherapy. Fifty-seven patients were enrolled between 1990 and 1996. Forty-seven had biopsy-proven germinoma. Biopsy was not performed in ten patients (four had diagnostic tumour markers and in six the neurosurgeon felt biopsy was contraindicated). Fifty-one patients had localized disease, and six leptomeningeal dissemination. Seven patients had bifocal tumour. All but one patient received at least four courses of chemotherapy. Toxicity was mainly haematological. Patients with diabetus insipidus (n = 25) commonly developed electrolyte disturbances during chemotherapy. No patient developed tumour progression during chemotherapy. Fifty patients received local radiotherapy with a median dose of 40 Gy to the initial tumour volume. Six metastatic patients, and one patient with localized disease who stopped chemotherapy due to severe toxicity, received craniospinal radiotherapy. The median follow-up for the group was 42 months. Four patients relapsed 9, 10, 38 and 57 months after diagnosis. Three achieved second complete remission following salvage treatment with chemotherapy alone or chemo-radiotherapy. The estimated 3-year survival probability is 98% (CI: 86.6-99.7%) and the estimated 3-year event-free survival is 96.4% (CI: 86.2-99.1%). This study shows that excellent survival rates can be achieved by combining chemotherapy and local radiotherapy in patients with non-metastatic intracranial germinomas.