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CD18 antibodies react with the common beta chain of the human leukocyte function antigen (LFA1)* and thus block the functions mediated by the three identified molecules in humans. A murine CD18 monoclonal antibody was infused in 8 leukemic patients receiving allogeneic T-depleted bone marrow transplantation in order to prevent graft rejection. This was part of the conditioning, including total-body irradiation and high-dose chemotherapy, given to all patients. To prevent graft-versus-host disease the donor bone marrow T cells were depleted using complement-mediated cytolysis or a ricin A conjugate immunotoxin, and cyclosporine or methotrexate were given posttransplant. A persistent level of free circulating anti-LFA1 antibody was detected in 5/8 patients. Despite this, 5 graft failures occurred, with 2 patients experiencing late rejection (days 60 and 97) following HLA-identical transplantation and 3 patients having no engraftment following haplo-mismatched transplant. One other patient died of early sepsis. Only 2 patients (who differed at 1 HLA locus from their donor) are alive with long-term complete chimerism (300 and 315 days). Transient inhibition of recipients' leukocyte functions with an anti-LFA1 antibody did not appear to facilitate engraftment of allogeneic T-depleted marrow transplantation for leukemias.

Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.

Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.

Twenty-one patients with refractory germ cell tumors were treated with a chemotherapy regimen containing etoposide (VP-16) (V) 75 mg/m2/day (days 1 to 5), ifosfamide (I) 3 g/m2/day (days 1 and 2) with a 3.6 g/m2 continuous infusion of mesna (days 1 and 2), and high-dose cisplatin (hP) 40 mg/m2/day (days 1 to 5). The regimen is referred to as VIhP. Nineteen patients were evaluable for response. Five patients (26%) achieved a complete remission (CR) with chemotherapy alone, and three patients (16%) were in CR after resection of a residual nonactive tumoral mass (e.g., necrosis and/or fibrosis and/or mature teratoma). Thus, a CR rate of 42% was achieved with the entire treatment. One additional patient achieved a CR after resection of active, bulky disease. Among the responders, five patients (26%) are still alive and disease-free at 6, 7, 9, 10, and 18 months after the initiation of the chemotherapy. However, toxicity was heavy in this protocol. Severe myelosuppression was observed with 10 patients developing aplasia and six patients documented sepsis. Reversible Grade 1-2 renal toxicity occurred in 14 patients, and Grade 2-3 peripheral neurotoxicity occurred in six patients. No hemorrhagic cystitis was encountered. We conclude that a VIhP regimen seems to play an active role in refractory germ cell tumors although the presence of high-dose cisplatin in this regimen does not appear to improve the response rate compared to that of a conventional dose. Toxicity, which seems to be enhanced, is currently under detailed study. However, the contribution of VIhP as a first-line treatment in poor prognosis, advanced germ cell tumors warrants further study.

In a preliminary study of 21 febrile episodes in neutropenic patients ceftazidime used as empirical treatment in doses of 3 grams per day succeeded in controlling fever in 74 per cent of the cases. Laboratory studies performed in patients with Gram-negative septicaemia showed clinically effective plasma concentrations of the antibiotic. A trial of ceftazidime (3 g/day) administered alone or combined with amikacin or vancomycin is currently in progress in two medical centres. No statistically significant conclusions could be reached from an intermediate study.

Angio-lymphoblastic lymphadenopathies are a newly described haematological entity, though not rare, characterised by a histological triad (vascular neogenesis, highly polymorphic or predominantly immunoblastic cellular proliferation and the presence of acidophilic protein deposits), a clinical syndrome consisting essentially of voluminous disseminated lymphadenopathy and hepatosplenomegaly and abnormal laboratory findings dominated by a polyclonal dysproteinaemia. This disorder, the first four French cases of which are described here, does not appear to be malignant in its early stages and is sensitive to corticosteroid therapy at that time. Secondary sarcomatous transformation is possible.

Following a cryopreservation step, short-term cultures of circulating leukemic blasts from a patient with acute myeloid leukemia (AML) were performed. Because cultured tumor cells became susceptible to natural killer (NK) activity, in vitro alteration of the blasts was studied. Immediately after thawing, cell suspensions consisted of a relatively homogeneous population of undifferentiated blasts. In culture, tritiated thymidine uptake by the leukemic cells was low during the first 24 hours and then increased (X20) to a peak on day 7. The cell concentration started to increase on day 4. On day 8, less than 10% of the cultured cells still appeared as undifferentiated blasts, whereas up to 60% were granular and 30% to 40% had a monocytoid morphology. Prior to being cultured, the blasts were resistant to resting and IL2-activated natural killing. When the kinetics of in vitro acquired susceptibility were studied, it was found that maximum cytotoxicity against these leukemic cells was reached within 24 hours. Thus, the blasts had become NK-sensitive prior to increase in DNA synthesis, proliferation, and differentiation based on morphological and cytochemical criteria. In contrast, there was a positive correlation between acquired susceptibility and surface expression of an activation antigen, termed TNKtar. To dissect further the mechanisms of acquired susceptibility, a series of six NK clones representing four distinct phenotypes of NK active lymphocytes were tested against the leukemic cells. Immediately after thawing, blasts were essentially resistant to all clones, whereas they were strongly killed by 5 of 6 clones when cultured for 24 hours. Cold target inhibition assays indicated that resistance of fresh blasts was likely to be due to a binding defect. These results suggested that tumor cells became susceptible because they surface-expressed NK target structure(s) in the early phase of an activation process leading to their proliferation and/or differentiation. This hypothesis was substantiated for one clone, termed JT9, because the anti-TNKtar antibody blocked cytotoxicity of JT9 cells against the cultured blasts.

Vindesine, an analog of vinblastine and vincristine, has been submitted to a phase II trial, the results of which are judged in terms of remission induction. A high proportion of remissions were obtained in acute lymphoid leukemia and blastic crisis of chronic myeloid leukemia, and a few responses have been registered in lymphosarcoma and Hodgkin's disease. A continuous 48-hour iv infusion may induce a remission where an iv push of the same dose has failed. The most remarkable characteristic of vindesine is the absence of cross-resistance with vincristine as documented in acute lymphoid leukemia.

Of 25 patients with acute lymphoid leukemia (ALL) in remission who were submitted to immunotherapy with BCG plus irradiated REH cells, 17 had positive sera in microcytotoxicity against REH cells after immunization. The follow-up of 28 months indicates that the microcytotoxicity varies in the same patient and may become negative and positive again. The results obtained after convenient absorption of one positive serum strongly suggest that REH cells in leukemic patients can raise antibodies directed against an antigenic structure closely related to the cALL antigen. Moreover, REH cells demonstrate in vitro suppressive activity, which could be a common property of some subcategories of human ALL.

Of 25 patients with acute lymphoid leukemia (ALL) in remission who were submitted to immunotherapy with BCG plus irradiated REH cells, 17 had positive sera in microcytotoxicity against REH cells after immunization. The follow-up of 28 months indicates that the microcytotoxicity varies in the same patient and may become negative and positive again. The results obtained after convenient absorption of one positive serum strongly suggest that REH cells in leukemic patients can raise antibodies directed against an antigenic structure closely related to the cALL antigen. Moreover, REH cells demonstrate in vitro suppressive activity, which could be a common property of some subcategories of human ALL.

Nineteen patients were treated with high dose chemotherapy followed by an autologous bone marrow transplantation. The chemotherapy regimen was an association of BCNU, procarbazine, etoposide, melphalan. Six patients had a progressive disease; 4 short-term complete remissions were observed. In 13 responding patients, 6 maintained complete remissions were noted.

The ability of human irradiated bone marrow to provide suitable environment for migrating stem cells has been studied in four patients. These had received chemotherapy plus doses of 40 Gy to thoracic vertebrae and sternum, followed by autologous bone marrow transplantation. The erythropoietic activity in the non-irradiated areas was increased but it was low in irradiated areas at 3.5 weeks and undetectable at 6 months after autotransplantation. This shows that no nidation of migrating stem cells actively contributed to bone marrow regeneration after 40 Gy and suggests the existence of environmental lesions. No extramedullary erythropoiesis and no bone marrow extension were found in these patients. Four patients who had received doses of 20 Gy to extended bone marrow volume were submitted to ferrokinetic studies from one to 18 years after radiotherapy. In non-irradiated areas the erythropoietic activity was within the normal range. In irradiated areas, it was significantly lower than in the non-irradiated areas and was intermediate between the erythropoietic activity in the sacrum of six healthy control subjects and in the irradiated areas of the four autografted patients. Bone marrow extension was found in these patients. This study suggests that bone marrow recovery after irradiation might not be an all-or-none phenomenon. It would be of interest to better document the dose-effect relationship.

With the method used, the concentrations of carcinoembryonic in antigen serum can be said to be abnormal above 10 ng/ml. The concentrations are normal in benign mastopathies. In 131 cases of breast cancer were studied, they are high in 8 p. cent of T1 and T2 breast cancers, and in 53.9 p. cent of T3 and T4 cancers. They are high in 22 p. cent of cases in the first perceptible phase of their disease, and 92 p. cent relapsed cases. They are also high in 23 p. cent of cases without metastasis, in 32 p. cent of cases with only nodal metastasis, in 82 p. cent of cases with extra-nodal metastasis, and in 94 p. cent of cases with nodal and extra-nodal metastasis. Concentrations of carcinoembryonic in antigen serum which are abnormal before treatment and which do not completely return to normal after treatment, of which rise again, enable one to predict the appearance of a metastasis several months before its clinical manifestation. Determination of the concentrations of carcinoembryonic in antigen serum therefore deserves to become part of the battery of routine for all breast cancers. An initial high concentration is an argument for suggesting systematic chemotherapy. The fluctuations in the concentrations of carcinoembryonic in antigen serum under chemotherapy allow one to assess the efficiency of the treatment.