Intracranial haemorrhage (ICH) is known to be a severe although uncommon complication of haemophilia. A national survey has been conducted in France in order to collect information about ICHs which ...occurred in haemophiliacs between 1991 and 2001 and to propose recommendations for the diagnostic and treatment of ICH. Within this period, 123 episodes of ICH were recorded from 106 patients. Two‐thirds of ICH concerned patients with severe haemophilia. Half of the cases occurred in patients under 15 years of age, 67.2% of which were post‐traumatic. Ten cases occurred in neonates with three fatal outcomes. Overall mortality was high (21.9%) suggesting that availability of clotting factor concentrates has not improved the prognosis of this event. Morbidity was also high with 60% of long‐term sequelae. The following parameters have been identified as prognostic factors for death: thrombocytopenia, HCV infection, intraventricular or intraparenchymatous haemorrhage. A delay in diagnosis was mentioned in 43.3% of cases, often related to the lack of recognition of the initial symptoms, which may be very common (apathy, tearfulness in young children and headache in elder patients). Delayed replacement therapy was recorded in 37.2% of cases. Emergency units initially dealt with half of these patients. Information concerning recognition and management of these episodes, not only in severe haemophilia, but also in moderate and mild forms, should be regularly supplied to paediatricians in maternity and physicians from emergency units, as well as to patients and their relatives.
The purpose of this study is to evaluate the antitumor activity of combination carboplatin and etoposide in measurable medulloblastoma. From January '89 to January '92, 26 patients with ...medulloblastoma were included in a multicentric phase II study of 2 courses of carboplatin 160 mg/m2/d day 1 to day 5 and VP16 100 mg/m2/d day 1 to day 5. Median age was 10 years (19 months-14.5 years). First treatment was surgery alone in 1 patient, surgery + radiotherapy in 4 patients, surgery + chemotherapy in 2 patients less than 3 years old, surgery + radiotherapy + chemotherapy in 19 patients ("8 drugs in 1 day" based:17, SIOP I:1, SIOP II:1). Previous treatment included cisplatin (20 cases), carboplatin (1 case), and VP16 (7 cases). Measurable disease was evaluated by CT scan, MRI or myelogram and CSF. Response rate (RR) was 72 +/- 10%:8 complete responses (CR), 10 partial responses (PR), 1 objective effect (OE), 6 progressive disease (PD), 1 non-evaluable. Thirty-six courses were evaluated for toxicity. Median duration of WHO grade 4 neutropenia was 8 days (0-23). One patient died at day 18 after the first course because of diffuse haemorrhage during septic aplasia. Five other non-life-threatening septicemias were recorded. Median number of platelet transfusions was 1 (0-4). One child who had achieved a PR after two courses died from CNS bleeding after the third course. This drug combination achieves a high response rate in childhood medulloblastoma. Severe toxicity has been mainly encountered in previously heavily treated patients. Tolerance may be acceptable in newly diagnosed children, but careful hematological follow-up and platelet transfusional support are definitely mandatory.
Forty-two evaluable pediatric patients with a variety of recurrent primary brain tumors participated in a phase II ifosfamide trial. Their mean age was 10 years. All patients were treated with ...ifosfamide, 3 g/m2/day for 2 days every 2 weeks. Response was assessed on clinical and radiological criteria after at least 2 courses of therapy. The overall response rate was 12% (5/42). One complete and 2 partial responses were documented in 21 patients with medulloblastoma. A partial response was demonstrated in 1 patient with primitive neurectodermal tumor (PNET) and in 1 patient with ependymoma. No activity was observed in astrocytic tumors. Toxicity was primarily neurologic (16 out of 54 patients, 30%). Hematological toxicity, without severe morbidity, was encountered in 9% of courses (16/179). Ifosfamide, administered at this dose regimen has modest efficacy in the treatment of recurrent childhood medulloblastoma and ependymoma and appears inactive for gliomas. Further trials with other dose schedules are necessary to assess the activity of this drug. However, according to the neurotoxicity observed in our trial, we would not recommend building a protocol using ifosfamide for highly progressive brain tumors.
Two cases of pancreatoblastoma in children are reported here. Only biopsies were made at laparotomy as surgical resection by duodeno-pancreatectomy was not possible. In both children a dramatic ...response was observed with chemotherapy: doxorubicin plus cisplatin for one, cyclophosphamide, actinomycin D, bleomycin, vinblastine sulfate, and cisplatin for the other. After completion of the chemotherapy the first patient had a local resection; then he had radiotherapy. He is alive in first remission 40 months after the end of the treatment. In the second patient, regional recurrence occurred 8 months after chemotherapy was ended. A transient second remission was obtained with ifosfamide plus etoposide alternating with epirubicin plus vincristine. The patient died 36 months after the diagnosis. Therefore, these two cases suggest that chemotherapy may be proposed before any attempt at surgical excision. Nevertheless, early consolidation by radical resection or irradiation must be considered.
Karyotypic analysis of a clear cell sarcoma revealed a translocation t(12;22) (q13-14;q12) as a primary chromosomal change. This case is the third clear cell sarcoma cytogenetically analyzed; the two ...previously reported cases had t(12;22)(p11;p11), and a complex karyotype with trisomy 22, respectively.
A total of 252 chromosomes from 126 patients with phenylalanine hydroxylase (PAH) deficiencies were analyzed for both mutant genotypes and restriction fragment length polymorphism (RFLP) haplotypes ...at the PAH locus. The mutant genes studied originated either from Western Europe (116 alleles) or from Mediterranean countries (136 alleles). Only 27% of all mutant alleles were found to carry identified mutations, particularly mutations at codon 252 (2.3%), 261 (7.5%), 280 (6.3%), 408 (3.5%) and at the splice donor site of intron 12 (6.3%). The mutant genotypes were associated with RFLP haplotypes 7, 1, 38, 2 and 3 at the PAH locus respectively. Except for the splice mutation of intron 12, these associations were preferential, but not exclusive, since the other four mutations were found on the background of at least two RFLP haplotypes. These results, together with the observation that 85% of PAH deficient patients are heterozygotes for their mutant genotypes, emphasize the great heterogeneity of PAH deficiencies in Mediterranean countries and hamper systematic DNA testing for carrier status in this population.
Platelet aggregation of an afibrinogenaemic patient's platelet rich plasma (PRP) was greatly decreased when ADP was used for stimulation. In the presence of collagen or arachidonic acid the changes ...in light transmission recorded during platelet aggregation of patient's PRP were similar to those observed with normal PRP but the size of aggregates appeared to be smaller in comparison with those observed with normal platelets. In addition, thrombin-induced aggregation of washed platelets was similar to normal platelets. The interpretation was made possible because the fibrinogen level in plasma and in platelets was found to be almost nil as demonstrated by both an Elisa procedure described here and the determination of fibrinopeptide A (fpA). Furthermore, fibrinogen fragments, which could result from abnormal synthesis and therefore replace fibrinogen in platelet aggregation, were undetectable by immunological analysis using specific antibodies against A alpha, B beta and gamma chains and 10 different monoclonal antibodies against fibrin degradation products.
In a child with acute megakaryoblastic leukemia--severe thrombocytopenia and myelofibrosis, EM studies on bone marrow showed a strict topographic relationship between the presence of clusters of ...abnormal megakaryocytes and the increased number of fibroblasts and extracellular fibers. Megakaryocytes and platelets lacked alpha-granules while the plasma thromboglobulin level was three times the normal level. This suggested that the alpha-granular proteins were synthesized but not retained in alpha-granules. If this occurs, the increased marrow levels of platelet-derived growth factor and factor 4 would favor the proliferation of fibroblasts and the synthesis of collagen, and thereby promote myelofibrosis. After therapy-induced remission, the number of marrow megakaryocytes decreased, the alpha-granules were normally produced, the plasma beta-thromboglobulin level was normal and the myelofibrosis disappeared. These observations suggest that during acute megakaryoblastic leukemia, an acquired gray-platelet syndrome occurs and that the local excretion of alpha-granule proteins triggers the myelofibrosis.
The simultaneous occurrence of malignant T-cell lymphoma and chronic myelogenous leukemia is reported. The lymph nodes contained E rosette forming cells. Blood and bone marrow cell morphology were ...consistent with the diagnosis of chronic myelogenous leukemia. Lymph nodes, bone marrow and blood mitosis showed a t(6;8) (6pter---6q27 ::8p12---8pter;6qter---6q27 ::8p12---8qter) translocation. So far a number of recent reports have shown simultaneous B lymphoid and myeloid proliferations in some malignancies, this is apparently the first reported case of simultaneous T lymphoid and myeloid proliferations.
