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Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphoblastic leukaemia (ALL) achieving complete remission. We questioned the value of such maintenance therapy in adult patients treated with intensive induction/consolidation. In a phase II study (SAKK 33/86) 63 patients between 17 and 72 years of age (median 27 years) with newly diagnosed ALL were treated with three intensive cycles of marrow-ablative chemotherapy. All subtypes were included. No maintenance phase was added. 53 patients (84%) entered a complete remission (CR) and 21 (33%) continue to be in unmaintained remission for 11-69 months (median 21 months). The disease-free survival of patients achieving CR and completing all three cycles is 40% at 3 years, with a 95% confidence interval of +/- 19%. These findings are comparable to the results of conventional studies. We conclude that maintenance therapy might not be needed in all adult ALL patients. Its value should be tested in a randomized trial. For patients failing, novel approaches are needed to improve outcome in adult ALL.

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To examine the biochemical structure of the antigen recognized by the monoclonal pan-B cell antibody, Y29/55, the Daudi- and Jurkat-cell lines were labeled by two different methods and immunoprecipitation experiments were carried out. After surface labeling with iodine, two bands with molecular weights of about 38 and 42 kD were observed. The same two proteins were precipitated after biosynthetic labeling with (35S)-methionine from B cells and, to a lesser extent, from T cells. Therefore, it seems that the same proteins, or proteins with similar molecular weight, exist intracellularly in T cells as exist on the surface of, and possibly intracellularly, in B cells. It was confirmed that 80-90% of normal blood-derived B cells were stained with Y29/55 by indirect immunofluorescence. Double-labeling experiments with the pan-B cell antibodies Leu 16 (CD 20) and Leu 12 (CD 19) showed a B-cell population which could be stained with both antibodies (Y29/55 and Leu 16 or Y29/55 and Leu 12). A minor cell population was stained with the antibody Y29/55 alone. Our findings indicate that the antibody Y29/55 recognizes a B-cell antigen, which has not been described previously.

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Acute lymphoblastic leukemia (ALL) is conventionally treated in three phases: remission induction, consolidation and maintenance. In adults initial remission rates of nearly 80% can be achieved. The 3 to 5 year leukemia free survival is 20 to 40%. Most relapses occur during maintenance, despite continuous therapy for 2 to 3 years. The value of maintenance therapy following intensive induction in adults is not documented. In this pilot study we treated 34 patients with ALL in five Swiss centers between 1986 and 1989 with intensive induction/consolidation therapy alone. Three induction/consolidation courses were applied: course I, 43 days, consisting of daunomycin, vincristine, prednisone, methotrexate, L-asparaginase and intrathecal CNS prophylaxis; course II, 6 days, consisting of high dose cytosine arabinoside and VP-16; course III, three non randomized arms, either allogeneic or autologous bone marrow transplantation (BMT) or high dose cyclophosphamide and repeated intrathecal therapy alone. 32 patients (94%) reached complete remission (CR): 24 after course I (71%), 7 after course II (cumulative 91%) and one after course III only (cumulative 94%). 3 patients had early, relapses before course III, 3 died of infection, and 2 of graft-versus-host disease. One patient had refractory leukemia in all three courses. 26 patients (76%) were in CR after completion of therapy. 16 relapsed within 1 to 17 months (median 5). 10 patients are free of disease after 10 to 44 months (median 24): 5 had had allogeneic BMT, 3 autologous BMT and 2 cyclophosphamide in course III.(ABSTRACT TRUNCATED AT 250 WORDS)

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In the early 1980s a new, although still empirical therapy was proposed for women undergoing recurrent spontaneous abortions of unknown origin, where an immunologic cause is suspected. The treatment consists in immunization of the women with human lymphocytes. We report here on our own first experience with this modality and discuss the results in light of the different immunologic tests which were performed before and after immunization with paternal lymphocytes. 11/13 treated women belong to the group with abortions of alloimmune origin, 6/11 patients were delivered of a normal baby in the 40th week of gestation (median), one patient is pregnant in the 36th week of gestation, 2 had abortions again and two women are not yet pregnant. Further investigations suggest that 2/13 women had abortions of autoimmune origin; one of these women had a normal baby in the 33rd week of gestation and the other is pregnant in the 18th week.

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21 patients with hematological neoplasias (8 ALL, 4 AML, 4 NHL, 5 HD) were treated with high dose therapy and autologous bone marrow rescue (ABMT). At the time of ABMT 12 patients were in CR, 6 in PR and 3 in relapse. 66% of the patients were at high risk at the time of diagnosis. Before ABMT patients received an ablative regimen such as cyclophosphamide or ARA-C, VP-16, DNR and 12 Gy TBI in 6 fractions. In 9 patients the bone marrow was treated in vitro with monoclonal antibodies and complement. The hospital stay was a median 33 (24-57) days and isolation 19 (9-49) days. Complications were septicemia (7), herpes stomatitis (7), infections (6), fungal sepsis (1) and hemorrhagic cystitis (2). Late complications (up to 6 months after ABMT) were pneumococcal sepsis (1), cerebral toxoplasmosis (1) and herpes zoster (3). 10 of 19 evaluable patients are alive and relapse-free 1-33 months (median 10) after ABTM, and 3 of 10 more than 2 years later: 4 of 5 were transplanted in 1. CR, 4 of 6 in greater than or equal to 2. CR and 2 of 8 in PR. 4 patients are living in therapy sensitive relapse 2, 11, 11 and 39 months after ABMT in 2. CR or PR. 5 patients died 1-13 (median 3.5) months on relapse, 2 of 21 from septicemia. The morbidity of ABMT is comparable with conventional high dose chemotherapy. Relapse-free survival was significantly influenced by the remission status at ABMT. Long-term survivors can be expected even in patients with high risk hematological malignancies. However, only wider trials will serve to establish the efficacy of ABMT.

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We report the results of a pilot study of dose intensification with autologous bone marrow support in patients with malignant lymphoma. Since January 1988 11 patients with malignant lymphoma have been treated by intensive chemoradiotherapy or combination chemotherapy followed by autologous bone marrow support. 6 of the patients had non-Hodgkin's lymphoma in first remission with unfavorable histology and/or unfavorable clinical prognostic factors, and 5 patients were in second or subsequent remission (2 non-Hodgkin's lymphoma, 3 Hodgkin's disease). Bone marrow harvest and cryopreservation of marrow cells were uneventful. 10 patients showed full hematologic recovery, while one patient with Hodgkin's disease died early of pneumocystis pneumonia. With the exception of one interstitial pneumonitis of unknown etiology, the clinical course during hospitalization was otherwise uncomplicated. The mean duration of hospital stay was 33 days. 2 patients relapsed after dose intensification, while the others are in continued remission (median 7 months, range 2-14 months).

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Elimination of neoplastic B cell populations from autologous bone marrow grafts also removes normal B lymphocytes. This is potentially hazardous for the reconstitution of the immune system in patients undergoing high-dose chemotherapy and total body irradiation followed by autologous marrow rescue. Five pediatric patients with B cell non-Hodgkin's lymphoma in first remission undergoing such a regimen were studied. They received bone marrow pretreated with anti-Y 29/55 monoclonal antibody and complement. B and T lymphocyte subpopulations reached normal levels within 6 months after autologous bone marrow transplantation (ABMT), and serum immunoglobulin levels became normal within 4 to 9 months. Vaccination with diphtheria and tetanus toxoid, trivalent poliomyelitis vaccine of the Salk type, and pneumococcal capsular antigens (38 to 54 months after transplantation) gave rise to specific antibody production. ABO isoagglutinins could be demonstrated in all patients. The response pattern was similar to that of patients who received unmanipulated autologous bone marrow. It is concluded that ex vivo anti-Y 29/55 depletion of the marrow graft does not induce relevant disturbances of humoral immune functions.

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1,25-dihydroxycholecalciferol (1,25[OH]2D3) is the most important active metabolite of vitamin D3 and has a remarkable antiproliferative effect on megakaryocytes in vitro. It may have a favorable influence on collagen formation and degradation by a megakaryocyte/monocyte dependent modulation. We evaluated the clinical effect of 1,25(OH)2D3 in four patients suffering from idiopathic myelofibrosis. The daily dose ranged from 0.006 to 0.016 microgram/kg. One patient died from asthenia 2.5 months after starting treatment and three were observed for more than a year. Despite treatment with 1,25(OH)2D3, they all needed regular transfusions. During follow-up bone marrow biopsies did not reveal a decrease in fibrosis.

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Autologous bone marrow transplantation was performed in 28 pediatric and adult patients with various neoplasias. Long-term remissions were obtained in one patient with yolk sac tumor and in 9 patients with B-cell non-Hodgkin's lymphoma. The relapse rate was decreased in patients receiving in-vitro decontaminated marrow (anti-Y 29/55 and complement).

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A 50-year-old severely immunodeficient woman with malignant non-Hodgkin lymphoma died from graft-versus-host disease due to transfusion of a single unit of packed red cells. Three days after this transfusion a maculo-papular rash appeared, followed by generalized erythroderma refractory to therapy and eventually progressing into generalized ulcero-squamous dermatitis. This case, and a review of other similar cases published elsewhere, prompt the authors to recommend prophylactic irradiation of blood products prior to their administration to patients with cellular immunodeficiency, particularly in cases of acute leukaemia or malignant lymphoma where patients receive intensive radio- and/or chemotherapy regimens. To appreciate the degree of cellular immunodeficiency in such risk patients, simple criteria should be developed to assess the efficiency of the cellular immune system.

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Reinfusion of undetected tumour cells is a possible cause of relapse after autologous bone-marrow transplantation. In this paper, a system for in-vitro purging of bone marrow is presented which involves the B-cell neoplasia-associated monoclonal antibody anti-Y 29/55 and complement. Five patients with Burkitt's lymphoma were transplanted with purged marrow, demonstrating the clinical feasibility of the method. The pretransplant regimen included vincristine 2 mg/m2, adriamycin 60 mg/m2, four doses of cyclophosphamide 45 mg/kg and total body irradiation with 6 Gy. Tumour control appears to be better in patients with purged bone marrow as compared to an earlier patient group with unpurged marrow.

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The authors present evidence that elimination of tumor cells in the bone marrow is essentially possible by in vitro purging with the monoclonal anti-T-cell antibody LAU-A1 and complement; this procedure does not interfere with regeneration capacity of stem cells. These findings have an important bearing with regard to candidates for autologous bone marrow transplantation.

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Nineteen patients with advanced malignant tumors, less than 20 years old were treated with intensive chemotherapy (vincristine 2 mg/m2 i.v. and adriamycin 60 mg/m2 i.v. on day - 7; cyclophosphamide 45 mg/kg i.v. on days -6 to -3), total body irradiation (TBI, 600 rads on day -1) and autologous bone marrow transplantation (ABMT, day 0). Prior to this procedure induction of complete or partial remission by conventional therapy was attempted. Ten patients had intra-abdominal non-Hodgkin's lymphoma (NHL); three, yolk sac tumor; three, Ewing's sarcoma; and three, neuroblastoma. The supportive care included reverse isolation, immunoglobulin 400 mg/kg i.v. q 2 weeks, cotrimoxazole per os, and cell support as needed. No correlation between the bone marrow dose and the time of hematological reconstitution could be established. Five of seven patients with intra-abdominal NHL stage III (transplanted in first remission) are surviving disease-free for 5+, 5+, 20+, 23+, and 35+ months after ABMT. None of three patients with intra-abdominal NHL stage IV is surviving (two of them were transplanted in second remission). One of three patients with yolk sac tumor is surviving disease-free for 27+ months. There are no survivors among the patients with Ewing's sarcoma and neuroblastoma. Only one of 19 patients was lost due to therapeutic complications, while 12 died due to tumor. Regarding treatment results for advanced intra-abdominal NHL, the procedure described here is comparable to the best conventional regimens. In vitro methods for tumor cell eradication in the collected bone marrow might further improve the results of ABMT.

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The effect of lipid-lowering therapy with high-dose beta-pyridylcarbinol was studied in 16 patients with primary hyperlipoproteinemia of type IIa and type IIb. After a controlled dietary pretreatment period of at least 3 months, the patients received 900 mg beta-pyridylcarbinol (Ronicol 300) per day for 12 weeks. The patients were then given only dietary treatment for a further 6 weeks. Clinical and laboratory controls were carried out every month and included measurement of cholesterol and triglycerides in whole serum and in the isolated lipoprotein fractions after ultracentrifugation. In 2 patients the treatment had to be discontinued due to side effects (flush). The numerous "safety parameters" were not affected by the treatment. Total and LDL cholesterol were lowered by about 15% and total triglycerides by about 25%. The HDL cholesterol levels remained unchanged.

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A case of mediastinal germinoma in a 21-yr-old male is reported. The neoplasm exhibited a morphology similar to that of a testicular seminoma and was heavily infiltrated by lymphocytes and plasma cells. Germinal centres were also present in lymph follicles. Humoral antibodies (IgG), specific for spermatopoietic tissue, were present in the patient's serum. Antibody titres declined after surgical removal of the germinoma over a period of 2 yr, and antibody is no longer detectable at the present time. The implications of this observation are discussed with regard to defence mechanisms of the tumour host, and to the histogenesis of these rare neoplasms.

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