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Purpose: To determine whether, after very intensive induction and consolidation therapy in childhood AML, further maintenance therapy (MT) confers any advantage., Patients and Methods: Three hundred-nine children with previously untreated AML were registered in the LAME 89/91 protocol. This three-cycle intensive regimen included an induction phase (mitoxantrone plus cytarabine) and, for non-allografted patients, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine. In the LAME 89 study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to be given or not MT after consolidation therapy., Results: Out of 309 patients, 276 (90%) achieved a complete remission. The overall survival (OS) and event-free survival at 6 years for all patients were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no further treatment than in patients randomized for MT (81% +/- 13% vs 58% +/- 15%; p = 0.04) whilst the 5-year disease-free survival was not significantly different (60% +/- 19% vs 50% +/- 15%; p = 0.25). The improvement of OS in MT-patients appeared to be related to a higher salvage rate after relapse., Conclusion: Over 50% of patients can be cured of AML in childhood. In the context of a very short and drug-intensive regimen, low-dose MT, owing to the lack of improvement in disease control and the worsening of survival, should not be recommended. Over the past 20 years, the outcome of acute myeloid leukemia (AML) in children has improved substantially. In the eighties, complete remission (CR) was achieved in nearly 90% of patients but event-free survival (EFS) was poor. Myeloablative therapy followed by allogenic bone-marrow transplantation (allo BMT) from an HLA-identical sibling was demonstrated, in our experience, to be the treatment of choice for improving DFS in children with AML in first remission. The major issue was how best to maintain complete remission for patients without an HLA sibling donor. Whereas several groups continued to include low-dose MT and others decided to omit it, in 1991, our group undertook a prospective randomized trial (LAME 91 protocol), the main aim of which was to assess the efficacy of MT in addition to an intensive induction and consolidation chemotherapy. The main results have been published previously and are now updated and described in a higher number of patients.

Purpose: In a previous randomized study, the authors reported that granulocyte colony-stimulating factor (G-CSF) increased the chemotherapy dose-intensity delivered during the consolidation therapy of high-risk childhood acute lymphoblastic leukemia (ALL). The aim of the current study was to perform an economic evaluation in the same cohort., Methods: In this open-label multicenter randomized trial, prophylactic G-CSF was administered after consolidation therapy courses. Economic data were retrospectively quantified for each patient: hospital stays, drugs, and blood products., Results: Sixty-seven children were enrolled in the very high-risk branch of the FRALLE 93 protocol. Chemotherapy dose-intensity was significantly increased (105 +/- 5% in the G-CSF group vs. 91 +/- 4% in the non-G-CSF group, P < 0.001). The mean total costs per child were not statistically different: 32,309 dollars in the G-CSF group versus 31,569 dollars in the non-G-CSF group. Further analysis per child and per course (R3 or COPADM) demonstrated that the mean cost of hospitalization and the mean cost of intravenous antibiotics were significantly decreased in the G-CSF group after R3 courses (3,857 dollars vs. 4,993.80 dollars, P < 0.001; 171.40 dollars vs. 306.20 dollars, P = 0.029, respectively), but the cost of platelet transfusion was significantly increased (P = 0.03). Conversely, post-COPADM costs were similar. Finally, mean costs per course in the two randomized groups were not significantly different: 5,848.80 dollars versus 6,181 dollars and 7,388.10 dollars versus 6,475.70 dollars for R3 and COPADM, respectively. The 3-year probability of event-free survival between the two groups was not different., Conclusions: G-CSF can increase chemotherapy dose-intensity in very high-risk ALL without raising costs, but event-free survival was not improved. The cost benefit of prophylactic treatment by G-CSF relies on the chemotherapeutic regimen given prior to G-CSF administration.

Purpose: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML)., Patients and Methods: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT., Results: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% +/- 19% v 50% +/- 15%; P =.25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% +/- 13% v 58% +/- 15%; P =.04) due to a higher salvage rate after relapse., Conclusion: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.

Background: Serum CA125 (sCA125) was recently reported to be of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma (NHL). This report aims to investigate the prognostic value of a new serologic index combining sCA125 and LDH serum levels., Patients and Methods: One hundred thirty-seven patients were studied, sixty-three with histologically proven low-grade NHL, and seventy-four with a high-grade subtype., Results: sCA125 and LDH levels were elevated in more than one third of patients. sCA125 was more frequently increased than LDH in low-grade NHL. In this group, complete remission (CR) was achieved in 87, 45, and 0% (P = <2 x 10(-6)) of patients with normal sCA125 and LDH serum levels (Low-risk group), one parameter increased (Intermediate-risk group), and increased sCA125 and LDH serum levels (high-risk group), respectively. The estimated five-year overall survival was 97%, 67% and 22% for low, intermediate, and high-risk groups, respectively. This combination was the only parameter predictive of RFS and OS in multivariate analysis (P < 0.0001)., Conclusions: In this study the combination of s-LDH and sCA125 levels (normal vs. abnormal) was found to be an important prognostic factor in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

Purpose: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL)., Patients and Methods: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval)., Results: CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups., Conclusion: G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.

The value of high-dose therapy with autologous stem cell transplantation as first-line therapy in poor prognosis Hodgkin's disease is controversial and we report the results of evaluation of twenty-six patients who were selected for this procedure from February 1989 to July 1994. They were all patients with stage IV at diagnosis with at least two other unfavourable characteristics, i.e. B symptoms, mediastinal mass greater than 0.45 of the thoracic diameter, two or more extranodal sites, bone marrow involvement, inguinal node involvement, serum lactic dehydrogenase greater than 400 IU/L, or low hematocrit. At the time of transplantation, 19 patients were in complete remission and 10 were in partial remission > or = 50%. Procedure-related mortality in the first 90 days post-graft was 7% overall. Of the 24 evaluable patients, 22 (92%) were assessed as complete responders, and 2 (8%) had progression of disease at 6 months. The actuarial overall survival (OS), disease-free survival (DFS) and event-free survival (EFS) at 5 years were 69%, 79% and 58%, respectively. The Cox proportional hazards model was used to assess prognostic factors. In univariate analysis only one prognostic factor was found to be significantly associated with improved DFS, i.e. low serum lactic dehydrogenase (LDH) (DFS at 5 years: 92% if LDH < 400 IU/L vs 44% if LDH 400 IU/L, P = 0.007). DFS rates between first complete remission and first partial remission groups were not significantly different (DFS at 5 years: 87% vs 66%, p = 0.15). These first results are encouraging but randomized studies are needed.

Chronic lymphocytic leukemia cell (CLL) usually (95%) express B-phenotype and the CD5 antigen which is usually present on the surface of normal T cells. However, among B CLL, 7 to 20% do not express CD5. The significance of the lack of CD5 expression remains unclear. We reviewed 42 consecutive CD5- B CLL seen in three French medical centers from 1985 to 1991 and compared them with 79 CD5+ B CLL. Immunophenotype studies were performed using indirect immunofluorescence under light microscopy as well as flow cytometry after 1988. B CLL was considered to be CD5 negative when less than 5% of mononuclear cells expressed CD5 after subtraction of the number of T-cells. Cases with CD5- B CLL had isolated splenomegaly more frequently (p = 2.10(-7)). They frequently expressed a higher level of surface immunoglobulin (S-Ig) or the switch mu/delta phenotype (p = 4.7 10(-2)). The median survival time was not reached but no significant difference between CD5 negative and positive B CLL was observed at the time of our data analysis (p = 0.97). Clinical presentation of CD5- B CLL seems to be different from other forms of B CLL. Although, no conclusion can be reached in terms of prognosis, CLL with low expression of CD5 should be regarded as a subtype of CLL with a different clinical presentation than CD5+ CLL.

Mediastinal large-cell lymphoma with sclerosis (MLCLS) is a distinctive subtype of non-Hodgkin's lymphoma (NHL) with unique clinicopathology aspects and aggressive behavior. Prompt diagnosis and aggressive chemotherapy followed by consolidation radiotherapy may result in long-term survival in the majority of cases. However, a subset of patients do not respond to first-line or salvage treatment and have a poor prognosis. We report here a 27-year-old man with MLCLS resistant to several conventional chemotherapies and to radiotherapy who achieved a very good partial remission after one year's treatment with daily oral cyclophosphamide (100 mg/day). This is the first report of refractory MLCLS with good response to daily oral cyclophosphamide. This case suggests that daily oral monochemotherapy might be beneficial for some patients with mediastinal large-cell lymphoma with sclerosis refractory to conventional intravenous chemotherapies and radiotherapy.

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as an adjunct to autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell (PBPC) transplantation was evaluated in 59 lymphoma patients. Patients were divided into three groups. In group I (n = 21) patients received rhGM-CSF (5 micrograms/kg daily) at the time of PBPC collection and during the recovery phase post-infusion. In group II (n = 12) patients received rhGM-CSF as an adjunct to ABMT. In group III (n = 26) they were grafted with bone marrow without rhGM-CSF. Administration of rhGM-CSF (groups I and II) significantly reduced the time to myeloid engraftment, the number of febrile days and the median duration of antibiotics administration and of hospital stay when compared with the group in which patients did not receive rhGM-CSF. The only difference between ABMT and PBPC, given with rhGM-CSF support, was observed in the duration of hospitalization (group I > group II, P < 0.05). These data show that rhGM-CSF is highly effective in reducing the duration of aplasia following BMT and PBPC transfusion, and there appears to be little difference in efficacy between these techniques, provided that patients also receive rhGM-CSF.

We report the experience of three French centres which evaluated high-dose therapy (HDT) as consolidation therapy for poor prognosis Hodgkin's disease (HD). From March 1986 to April 1990, 23 consecutive patients with poor prognosis stage IV HD underwent HDT followed by autologous bone marrow transplantation (ABMT) after achieving either complete remission (CR1) or good partial response (GPR1) (reduction mass> 75%). The median age was 31 years (range 18 to 55 years), 14 were male. All patients except one initially had at least 2 poor prognosis factors such as: systemic symptoms (n = 19), bulky tumor (n = 16), more than one extranodal site (n = 9), bone marrow involvement (n = 5), lymphocyte count < or = 1.10(9)/1 (n = 8) and biological stage B (n = 21). All patients had previously been treated with alternating MOPP/ABVD. Ten patients were in GPR1 and 13 in CR1 before transplant. The conditioning regimens were: CBV (n = 17), BEAM (n = 5), BEAC (n = 1) followed by bone marrow rescue. Radiotherapy was introduced just before the conditioning regimen for 6 patients or after ABMT for 5 patients. Nine of 10 patients in GPR1 achieved CR after ABMT but one died early of treatment-related toxicity. Five of 22 patients who were in CR posttransplant, relapsed (3, 4, 4, 18, 36 months). Seventeen patients remain alive in continuous CR with a median follow-up of 60 months (range: 30-100 months). The overall survival (OS) and disease-free survival (DFS) projected at 5 years are 92% and 77% respectively. Consolidation by HDT and ABMT proved to be well tolerated. An international trial is currently underway to attempt to demonstrate a clear benefit on survival for this subset of poor prognosis HD patients.

To evaluate the modification of pharmacodynamic parameters induced by the administration of L-asparaginase loaded into red blood cells, 13 patients received a single dose of L-asparaginase internalised into the carrier. The enzyme was loaded using a reversible lysis-resealing process. The dose per patient ranged from 30 to 200 i.u. kg-1. Considerable heterogeneity occurred between patients. the level of L-asparaginase circulating after 24 h represented 47% of the total injected dose as compared to 74.8% for red blood cells (RBCs). However, the half-life of the enzyme remaining in the circulation was very similar to that of the RBC carrier, i.e. 29 days and 27 days, respectively, compared with 8-24 h for the free enzyme. Sustained elimination of plasma L-asparagine occurred, the duration of which was dependent on the injected dose. A single injection of 30.i.u.kg-1 was sufficient to eliminate plasma L-asparagine over 10 days. With 150-200 IU.kg-1 the elimination period was extended to 50 days. These data show that the use of RBCs as carriers of L-asparaginase greatly improves the pharmacodynamic parameters of the drug.

Objective: A pilot clinical study was conducted to evaluate the toxicity of a single dose of L-asparaginase loaded in red blood cells (RBCs)., Methods: Thirteen patients received a single dose of L-asparaginase in the range 30-200 i.u.kg-1. The enzyme was loaded in one autologous blood unit using a lysis-resealing process. A control population of 33 patients receiving L-asparaginase intravenously were tested in parallel. IgG, IgM and IgE class anti-L-asparaginase antibodies were detected using specific radioimmunoassays., Results: L-Asparaginase pharmacodynamic parameters may be greatly improved by administration of the drug after internalisation in RBCs as compared to intravenous injection of free drug. The drug elimination was prolonged and similar to that of circulating carrier. After one injection of 30 i.u.kg-1, plasma L-asparagine was eliminated in 10 days and this was extended to 50 days for 150-200 i.u.kg-1. The drug was well tolerated and only transient variations were observed for some of the biological parameters measured. We did not reach the maximum tolerable dose (MTD) of L-asparaginase loaded in RBCs. No significant clinical toxicity was detected. In particular, no immune adverse effects were observed., Conclusion: This study opens new perspectives for the clinical utilisation of L-asparaginase. This mode of administration of the drug is able to improve pharmacodynamic parameters and enzymic efficacy and to increase the general tolerance of the treatment.

In this study we used a long-term culture system to evaluate engraftment potential of human peripheral blood (PB) cells mobilized by chemotherapy (CT) associated or not with granulocyte-macrophage colony-stimulating factor (GM-CSF). In six patients who underwent blood cell transplantation, PB CD34+ cells were cultured after mobilization and were compared to CD34+ cells in steady state from PB and bone marrow (BM). Qualitative differences were shown between PBC samples obtained after CT with and without GM-CSF. Despite similar CFU-GM counts at culture initiation, GM-CSF-mobilized CD34+ cells might contain a lower proportion of primitive stem cells, as suggested by the significant decrease in CFU-GM numbers produced beyond week 5 compared to CT-mobilized CD34+ cells (p = 0.033). Likewise, the percentage of CFU-GM produced beyond week 5 in relation to initial input was significantly lower than steady-state PB (p = 0.039) and than CT-mobilized CD34+ cells (p = 0.033). However, this CFU-GM production with GM-CSF-mobilized PB CD34+ cells was not different from cultures with BMC CD34+ cells. These results suggest that GM-CSF can mobilize CFU-GM in the blood mainly by differentiation at the expense of the primitive stem cell compartment. It appears valuable to define clearly for each mobilizing procedure a particular threshold of CFU-GM which reflects sufficient numbers of primitive stem cells to ensure long-term engraftment.

We assessed the effect of antitumoural therapy at intensive doses on the haemopoietic system using long-term marrow cultures (LTMC) established from 33 patients (25 with haematological diseases and eight with solid tumours) after autologous bone marrow transplantation (ABMT). When compared to 42 pre-graft patients, a decreased CFU-GM production and a defect in stromal layer (SL) confluence were found after ABMT on day 90 but also on day 365. However, these abnormalities were observed only in patients with haematological diseases and no differences between pre-graft and post-graft results were found in patients with solid tumours. Among the patients with haematological diseases, on day 90 those with acute lymphoid leukaemias showed lower CFU-GM production whereas patients with non-Hodgkin's lymphomas developed more frequently subconfluent or confluent SL. Other factors studied such as sex, patient age, disease status, marrow purging and post-graft administration of growth factors did not appear to influence post-graft LTMC results. Multivariate analysis including all the patients has shown (a) that solid tumours were associated with higher CFU-GM production, and (b) that conditioning regimens with total body irradiation (TBI) or busulfan led more frequently to non-confluent SL. In conclusion, high-dose therapy followed by ABMT can induce a persistent impairment of the stem cell and stromal cell compartments, particularly in patients with haematological diseases conditioned with TBI, despite the absence of any alloimmune reaction and post-graft immunosuppressive therapy.

Background: The vital outcome for treated medulloblastoma in children is generally positive provided there is no evidence of recurrence 18 months after initial surgery and radiotherapy. Late recurrences have, however, been reported., Case Report: A medulloblastoma in the posterior fossa of a 10 year-old-boy was treated by almost complete surgical excision, radiotherapy and chemotherapy. One year later, the CT scan was normal but, 4 years after surgery, it showed supra-and infratentorial tumors. Progressive hydrocephaly required a ventriculoperitoneal shunt. 9 years after the initial surgery, progressive neurological degradation and the presence of cells in the CSF were treated by several courses of chemotherapy, with subsequent improvement of the neurological condition. This boy is in a stabilized condition 11 years after the discovery of the tumor., Conclusion: The first symptomatic recurrence of medulloblastoma was late, more than seven years after surgery. This recurrence was supra-and infratentorial and responded to non intensive chemotherapy.

Simultaneous tumors are rarely encountered during the course of acute leukemias. We report on a case of seminoma of the testis that occurred during the evolution of acute myelogenous leukemia. To our knowledge, this simultaneous association has not previously been described, but a causal relationship was not apparent in the present case. The likelihood of a common carcinogenesis existed, but direct exposure to carcinogens could not be established. Although the results of a physical examination and echography were normal at the time of diagnosis, we cannot exclude the presence of microscopic cancer of the testis. Since the dissemination pattern of seminoma is usually slower than that observed in this case and the disease remains limited to the lymph nodes for long periods following dissemination, the rapid development of the present case might have been attributable to the immunosuppression and the scrotal sepsis that occurred during the induction therapy. Immunosuppression might have stimulated the progression of a primary microscopic seminoma and the development of metastasis, whereas the scrotal sepsis and inflammation might have favored the occurrence of metastasis through bypass of the lymphatic barrier.

Twenty six adult patients with low grade nodular non Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation. Conditioning regimen was BEAM-BEAC in 15 patients and TBI + Cyclophosphamide in 11 patients. Twenty one patients were grafted with haematopoietic stem cells, 12 after bone marrow purging and five with peripheral blood stem cells (PBSC). Two patients were treated in CR1 of leukemic phase, six in PR1 and eighteen in sensitive relapse. With a median follow-up of 30 months, the actuarial survival is 91% and actuarial event free survival 67%. These data confirm some interest of ABMT in the treatment of low grade follicular NHL.

Background: Much progress has been made in the last ten years in the treatment of non Hodgkin's lymphomas by increasing drug schedules and by using non cross-resistant regimens., Methods: So we decided in 1984 to test a new multiple drug protocol (Tours-Poitiers-Limoges = TPL protocol) which used a sequence of three courses of classical high-dose induction therapy, three courses of consolidation therapy using Teniposide, Cytosine Arabinoside, L Asparaginase and high-dose Methotrexate, and three courses of late intensification using the same drugs as induction therapy. Results. Thirty-eight patients younger than 60 years were included. Complete remission was obtained in 27 patients (71%). The median follow-up was 3 years and 9 months with one third of CR patients having been followed beyond 5 years. Seven patients relapsed (26% of CR patients) and one died of toxicity in complete remission. At present 22 patients (58%) are in complete remission, 19 in first CR, 1 in first CR after allogenic bone marrow transplantation, and 2 in second prolonged CR after autologous bone marrow transplantation. The median survival time is 48 months and the actuarial disease-free survival curve seems to have a plateau at 48.5%, with no relapse after 24 months., Conclusions: These results confirm the efficacy of alternating high-dose conventional chemotherapy in the treatment of intermediate and high-grade NHL, with about half of the patients being cured. However, more intensive chemotherapy regimens are needed to improve cure rates.

Forty-six patients with non-Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation (ABMT) in two different institutions. All patients were pretreated with conventional chemotherapy. Three different conditioning regimens were used, and 20 patients underwent bone marrow purging. Twelve patients were treated in first complete remission (CR); eight are in unmaintained CR 8 to 104 months after ABMT. Five patients were grafted in first partial remission (PR) after conventional therapy; all achieved CR, and all remain in prolonged CR (first CR for four patients, second CR for one patient). Of 21 patients with chemosensitive relapses, 13 patients are in prolonged unmaintained CR 8 to 94 months after ABMT. Eight patients with resistant disease remained uncured by ABMT; all eight died, six from progressive illness and two from toxicity. The current 3-year disease-free probability is 60% for all patients, 0% for refractory disease; 82% for first PR or CR, and 60% for sensitive relapses (SRs). These results confirm the efficacy of ABMT in the treatment of chemosensitive NHL with bad prognosis.

High doses of carboplatin or cisplatin combined with cyclophosphamide and etoposide followed by autologous bone marrow transplantation (ABMT) rescue have been used in the treatment of testicular tumors that have had a bad prognosis. Unusual cutaneous complications, evoking radiation-induced dermatitis, have been seen in two of eight patients with the same regimen. This new type of toxicity seems to be related to high-dose combination chemotherapies. Good results in the treatment of patients with testicular tumors on relapse who continue to respond to chemotherapy lead to the extension of this type of schedule and cutaneous toxicity will probably develop.

We report a prospective study concerning the association of surgery-chemotherapy and radiotherapy in the treatment of primary high grade digestive non-Hodgkin's lymphomas in 19 patients. The analysis of 11 stages IE, 5 stages II1E and 3 stages II2E allowed us to evaluate the efficacy and the tolerance of this triple therapeutic association. Fifteen patients are alive and well with a median follow-up of 54 months. One of these patients relapsed, but after autologous bone marrow transplantation is in second unmaintained complete remission. Four patients died of intercurrent aetiology although one death was related to treatment morbidity. Our results and the analysis of literature data lead us to recommend the triple association in the treatment of stage II2E high grade primary digestive lymphomas (PDL) and for PDL without complete resection. However, surgery and chemotherapy appear to be sufficient in the treatment of stages IE and II1E with complete resection.

Immunocompetence was evaluated in 36 untreated and noninfected patients affected with myelodysplastic syndromes (MDS). T-cell number and activity were evaluated by counts of total T-cells and T-lymphocyte subsets, and by measure of DNA synthesis in response to phytohemagglutinin and Concanavalin A. B-cells were evaluated as surface immunoglobulin- (SIg+) bearing cells and by serum immunoglobulin levels. Granulocyte activities were evaluated by responses to chemotaxis and to nitroblue tetrazolium test. Complement activity was measured by classic hemolytic complement assay. In addition, circulating immune complexes were detected in serum. MDS were associated with a significant decrease in the absolute numbers of total T (E-rosetting and T3+) cells, T4+, and T8+ cells and a dramatic decrease of the responses to Concanavalin A. An impairment of either chemotaxis or of nitroblue tetrazolium (NBT) test was frequently encountered. An increase in the levels of IgG or IgA was also a frequent feature. The findings reveal that all patients with a high degree of T-cell impairment have refractory anemia associated with an excess of medullary blast cells. All in all, the data suggest that the counts of the absolute number of cells bearing the T3 and T8 phenotypes could be of prognostic value: the higher the number, the better the patient's survival.

405 children with acute lymphoblastic leukemia were stratified according to age, initial leucocytes count, lymph nodes, liver and spleen size, into three prognostic classes I, II, III. Protocol 08 LA 74 which they were applied included: 1)initial randomization between Prednisone, Vincristine, Daunorubicin or the same plus Cyclophosphamide for induction and reinductions; 2)doses adjustments to prognostic factors, increased doses being given to increased risk patients; 3)comparison between intrathecal Methotrexate and intrathecal Methotrexate plus Ara-C in addition to skull irradiation for CNS prophylaxis; 4)L-Asparaginase consolidation for all patients; 5)maintenance by 6-Mercaptopurine and Methotrexate in all patients and reinductions. The most striking conclusions to date are the improvement for increased risk patients, the frequency of primary testicular relapses contrasting with the low rate of meningitis, the prognostic implication of sex, the influence on remission duration of the number of courses necessary to achieve complete remission, the importance of using Cox Method to improve the identification of prognostic groups.

The authors report a case of Fanconi's disease equilibrated for a period of 8 years by androgen therapy. The patient died after interruption of treatment; the clinical picture comprised hepatomegaly, jaundice, pancytopenia. The autopsy showed hepato-splenic peliosis and acute tuberculosis. The subject of peliosis is brought up to date by a thorough review of current literature and the relationships between steroid treatment and hepatic complications are discussed.

Non seminomatous germ cell testicular tumors (NSGCTT) is a very chemosensitive cancer; vepeside, cyclophosphamide or ifosfamide and cisplatin are the most effective drugs. Carboplatin is also active with a lack of nephrotoxicity, but there is probably a cross-resistance to cisplatin. High dose chemotherapy with autologous bone marrow transplantation is able to cure poor prognosis testicular cancers in first partial remission or in sensitive relapse. We report one case of non seminomatous testicular cancer which was progressive after chemotherapy with cisplatin and vepeside or teniposide, and which is in prolonged complete remission after conventional chemotherapy (vepeside, ifosfamide, carboplatin) and high dose chemotherapy (carboplatin, vepeside, cyclophosphamide) with autologous bone marrow transplantation.

Haemostasis in the new-born is a product of various factors which are both qualitative and quantitative. The only factors that compare in levels and quality with those in the adult are factors V, VIII and XIII. They are alterations in the semi-analytical tests for coagulation except in the Stypven time. In contrast with this deficit shown up in haemostasis by global tests coagulation is normal and in truth there is hypercoagulability. Using Laurell's method of immunoelectrophoresis for levels of alpha 2 M high levels of this are shown contrasting with progressively lowered antithrombitic action. These paradoxes no doubt arise from the fact that neonatal haemostasis is analysed using standardised techniques and reactions which were developed for adult haemostasis, from which it is certainly as different as from those of other animals. Neonatal haemostasis is perfectly balanced in normal conditions. Important changes occur however in respiratory distress where there is a drop in factor V and soluble complexes appear, bringing about rough shapes suggestive of the subclinical syndrome of defibrination. This situation will be further developed in a forthcoming article.