Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d'Etude de la Greffe de Moelle Osseuse.

Thirty-two children ranging in age from 1.5 to 16 years with poor-prognosis acute lymphoblastic leukemia (ALL) were treated with myeloablative immunosuppressive therapy consisting of cyclophosphamide (CPM) and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) while in first complete remission (CR). The main reasons for assignment to BMT were WBC count greater than 100,000/microL, structural chromosomal abnormalities, and resistance to initial induction therapy. All children were transplanted with marrow from histocompatible siblings. Twenty-seven patients are alive in first CR for 7 to 82 months post-transplantation (median, 30 months). The actuarial disease-free survival rate is 84.4% (confidence interval, 7.2% to 29%) and the actuarial relapse rate is 3.5% (confidence interval, 0.9% to 13%). Four patients died of transplant-related complications, 16 developed low-grade acute graft-v-host disease (GVHD), and six developed chronic GVHD. The very low incidence of relapse (one of 28 long-term survivors) precluded the determination of the prognostic significance of the different poor-outcome features. Moreover, two infants treated with busulfan, CPM, and cytarabine (Ara-C) relapsed promptly in the marrow. In summary, as a means of providing long-term disease-free survival and possible cure, BMT should be considered for children with ALL presenting poor-prognostic features, particularly certain chromosomal translocations [t(4;11), t(9;22)], very high WBC counts, notably if associated with a non-T immunophenotype, and, perhaps, a poor response to initial therapy with corticosteroids (CS), or infants less than 6 months of age.

Improved survival rate in children with stage III and IV B cell non-Hodgkin's lymphoma and leukemia using multi-agent chemotherapy: results of a study of 114 children from the French Pediatric Oncology Society.

Children with B cell non-Hodgkin's lymphoma who have not relapsed 1 year after diagnosis and treatment are generally cured. We report here the results of treatment in 114 children who all had a minimum follow-up of 20 months. The protocol LMB 0281 from the French Pediatric Oncology Society was used. This nine-drug intensive-pulsed chemotherapy was based on high-dose cyclophosphamide, high-dose methotrexate (HD MTX), and cytosine arabinoside (ara-C) in continuous infusion. CNS prophylaxis was with chemotherapy only. No local irradiation was performed. No debulking surgery was recommended. There were 72 patients with stage III lymphoma and 42 patients with stage IV lymphoma or B cell acute lymphocytic leukemia (B-ALL). Among those 42 patients, seven had CNS involvement alone, 21 had bone marrow alone, and 14 had both; 26 had greater than 25% blast cells in bone marrow, 14 of whom had blast cells in blood. The primary site of involvement was the abdomen in 90 patients, the Waldeyer Ring in nine, and various sites in eight; seven patients presented without tumor. Seventy-seven patients are alive with a median follow-up of 2 years and 8 months. Seven patients died due to initial treatment failure, 11 died from toxicity, and 19 died after relapse. Among the 93 patients without initial CNS involvement, only one isolated relapse in CNS occurred. Survival and disease-free survival rates reached 67% and 64%, respectively, for all patients, 75% and 73% for stage III patients and 54% and 48% for stage IV and B-ALL patients. Bone marrow involvement was not an adverse prognostic factor. Contrary initial CNS involvement indicated a bad prognosis with a disease-free survival rate of 19% compared with 76% without CNS disease. This study showed that CNS prophylaxis and local control of the primary tumor can be achieved by intensive chemotherapy alone, without radiotherapy or debulking surgery.

Two additional cases of t dic(9:12) in acute lymphocytic leukemia (ALL): prognosis in ALL with dic(9:12).

We report two occurrences of dic(9;12) in acute lymphoblastic leukemia and review previous cases. Cases of dic(9;12) share common features with cases of 9p and 12p rearrangements, but prognosis seems particularly good in cases of dic(9;12). The persistence of a specific dicentric in stable clones is remarkable and points to unusual centromeric behavior and/or marked selective advantage of the anomaly.

The 8p11 anomaly in "monoblastic" leukaemia.

We report on three cases of monoblastic leukaemia with a chromosomal breakpoint at 8p11. One of our cases exhibited a translocation t(8;16) as has been described in 12 previous cases reported in 1987. The two other cases showed respectively t(6;8) and t(8;19) and they seem to be the first two reports of variant translocation in this disease. The available cases serve to define the main characteristics of this new subtype of non lymphocytic acute leukaemia: phagocytosis in most of the cases, the possible involvement of a granulomonocytic precursor, and a common breakpoint in 8p11.

Nosocomial legionnaires' disease in a bone marrow transplant unit.

We report the outcome of nosocomial legionnaires' disease in three patients who were isolated in the same sterile unit after allogeneic bone marrow transplantation. In all three cases the disease presented with dramatic pulmonary symptoms, and diagnosis was ascertained by direct immunofluorescence on bronchoalveolar fluids. None of the patients underwent seroconversion. This report draws attention to: (1) the fact that bacteriological filters do not ensure absolute security; (2) the need for frequent monitoring of the two factors governing legionella growth, water temperature and chlorination; and (3) the effectiveness of quinolones as a curative and prophylactic treatment of legionnaires' disease in transplanted patients avoiding pharmacological cyclosporin interaction.

The TAM regimen prior to allogeneic and autologous bone marrow transplantation for high-risk acute lymphoblastic leukemias: a cooperative study of 62 patients.

A total of 62 patients with high-risk acute lymphoblastic leukemia (ALL) were treated with fractionated total body irradiation, high-dose cytosine arabinoside and melphalan followed by bone marrow transplantation (BMT). Thirty-six patients received allogeneic and 26 autologous BMT. Eight patients were treated in CR1, 36 in CR2 (first relapse occurring on therapy for 32), seven in further CR, 10 in relapse (five early first relapse, four second relapse and one fourth relapse) and one with refractory ALL. Severe toxicity occurred in 26 of the 62 patients (42%) and 14 died (22.5%) from non-leukemic causes. The actuarial event-free survival at 3.6 years was 28% after autologous BMT and 52% after allogeneic BMT with actuarial relapse rates of 62% and 35%, respectively. The results of this pilot study seem promising for this group of poor risk ALL, but the relapse rate remains high after autologous BMT and needs to be improved.

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.

Translocation t(12;13)(p13.3;q12.2) is Not Restricted to Lymphoid Malignancies; Report of a Further Case with Hypereosinophilia.

We report two cases of t(12;13)(p13;q12). One was found in a lymphoid disorder, as previously described, while the second was observed in a myeloproliferative syndrome with hypereosinophilia. As t(12;13) has already been described in association with hypereosinophilia in a case of acute lymphoblastic leukaemia, we suggest that the association of t(12;13) with hypereosinophilia is not random.

[Evaluation of the actual traceability of labile blood products using medical records]. / Evaluation de la traçabilité effective des produits sanguins labiles à partir des dossiers médicaux.

The traceability of blood products is an essential part of haemovigilance and transfusion safety. A pilot survey assessed the actual traceability by analysing transfusion information collected from medical records of a representative sample of 390 labile blood products transfused in a French university hospital. Transfusion and distribution forms were missing in 2.3% and 6.9% respectively. Availability and validity of transfusion information varied according to the nature of the expected information, elements of patients' records and types of wards. The location where the transfusion was performed was false or ambiguous in 38% of cases in surgery. Crude traceability, evaluated by the feedback of validated distribution forms, was estimated at 85.2% whereas actual traceability was estimated at 81.9% (SD 1.7%). High availability (98.7%) of at least one of the two sheets of the distribution form in medical records, or in the blood bank, revealed that a significant improvement of traceability should come from a better compliance to the rules of information transmission. The actual traceability differed significantly according to clinical services (worse in surgery) and was lower in case of autologous or absence of previous transfusion. An analysis of markers of good traceability should suggest efficient evolution of organization and information systems. This pilot study shows the relevance and feasibility of this kind of survey which could interestingly be performed on a large national representative random sample.

[Prospective study of the causes for destruction of labile blood products during 1999 at a University Hospital Center]. / Etude prospective des causes de destruction des produits sanguins labiles, au cours de l'année 1999 dans un CHU.

The destruction of the blood cell product (BCP) is a situation which is hard to accept in the present context of transfusional safety which aims at covering the transfusional needs in the most appropriate way. In our University Hospital, 500 BCP out of 20,000 are destroyed per year, which represent a cost of 100,000 $. A prospective research was carried out from January 1st to December 31st 1999 in order to analyse the causes of the destruction of the BCP and to differentiate the inevitable destructions for the patient's security from the avoidable destructions which might have benefited from corrective measures. For each group of simultaneously destroyed BCP, an information note specified the patient's pathology, the reasons for the prescription, the number and the type of transfused and destroyed BCP in the same day, the time spent between distribution and return, and the causes of destruction. In 1999, a total of 483 LBP out of 19,802 which were distributed, have been returned and destroyed, that is to say 2.4% for a 99.3% traceability which involved 242 patients. Among these destroyed BCP, 28.3% came from inevitable causes--death or acute intensive care which needed a lot of transfusions--69.7% were categorised as being related to avoidable causes depending on the organisation of transport and care, unadapted safety measures. The corrective measures to be taken, concern the improvement of transport procedures, the set-up of a nominative BCP reservation system in the Blood Center, the scheduling of the BCP deliveries from the blood bank, and a better adaptation of the safety measures to the transfusional needs.

Large outbreak of Salmonella enterica serotype paratyphi B infection caused by a goats' milk cheese, France, 1993: a case finding and epidemiological study.

OBJECTIVE: To assess the magnitude of a nationwide outbreak of infection with Salmonella enterica serotype paratyphi B and identify the vehicle and source of infection. DESIGN: A case finding study of S paratyphi B infection between 15 August and 30 November 1993; a pair matched case-control study; an environmental investigation at a processing plant that produced a raw goats' milk cheese incriminated in the outbreak; phage typing and genotyping of food and human S paratyphi B isolates. SETTING: France, 15 August to 30 November 1993. SUBJECTS: 273 patients with S paratyphi B infection; 59 pairs of cases and controls matched for age, sex, and city of residence. MAIN OUTCOME MEASURES: Numbers of cases and incidence rates by region of residence and age; matched odds ratios for dairy food preferences. RESULTS: Among the 273 cases there was one death; 203 (78%) strains belonged to phage type 1 var 3. The incidence of infection was greatest in the region where goats' milk cheese is commonly produced. Comparison of cases and controls showed a 12-fold greater risk of illness (95% confidence interval 1.6 to 92.3) from eating brand A unpasteurised goats' milk cheese. S paratyphi B isolates of phage type 1 var 3 were recovered from cheese A, goats' milk at the plant processing cheese A, and goats' milk supplied to the plant by a single farm. Genotypic IS 200 typing of food and human 1 var 3 phage type isolates showed a common IS 200 pattern. CONCLUSION: This outbreak emphasises the potential health hazards of widely distributed unpasteurised milk products in France and the need for their close bacterial monitoring.

[Neuroblastoma of the tail of the pancreas. Apropos of a case]. / Le neuroblastome de la queue du pancréas. A propos d'une observation.

We describe the case of a four-year-old child who presented a neuroblastoma of the tail of the pancreas. Diagnosis was evoked on computer tomography and confirmed thanks to the pathological examination of the resected tumour. Malignant tumours of the pancreas are rare in children and most of the cases are carcinoma. Three cases of pancreatic neuroblastoma have been described. Evolution and prognosis depend on the staging once the diagnosis is established.

[Prognostic factors in histiocytosis X]. / Facteurs de pronostic dans l'histiocytose X.

Evaluation of prognostic factors and therapeutic strategies in histiocytosis X is difficult because of this disease's low incidence, heterogeneity related to the multiplicity of possible localizations, unpredictable course, and incompletely elucidated pathogenesis. At the time of diagnosis, parameters with a bearing on prognosis include age, number of involved organs, presence or absence of organ dysfunction, and initial response to treatment. Chemotherapy regimens, of which the most effective are vinblastine-corticosteroids and etoposide-corticosteroids, should be used only in patients with organ dysfunction or involvement of two or more organs before two years of age or three or more organs after two years of age. Duration of treatment ranges from three to twelve months according to the quality of the response. Other treatments, including low dose cytosine, alpha-interferon, or even autologous or allogeneic bone marrow transplantation have yielded promising results that need to be confirmed in a larger number of patients.