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Twenty-five consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12 h, days 1-6) and AMSA (120 mg/m2 i.v., days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h, days 1-4 and AMSA 120 mg/m2 i.v., day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), ten after 1 cycle of induction and two after 2 cycles; 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. Nine patients remained refractory (36%) and four died during hypoplasia (16%). Median DFS of the 12 responders was 2.9 months, median survival from time of CR 8.9 months. Median overall survival of responders and nonresponders was 6 months from time of resistance. Survival advantage of responding patients (n = 12) as compared with nonresponders (n = 13) was 10.7 vs. 3.2 months (p = 0.002). Toxicity of chemotherapy was acceptable: one patient experienced pulmonary edema due to ara C; two patients developed life-threatening systemic fungal infections, one of whom died while in CR.

25 consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB-subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12h days 1-6) and AMSA (120 mg/m2 i.v. days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h days 1-4 and AMSA 120 mgm2 day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), in 10 after 1 cycle of induction and in 2 after 2 cycles. 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. 9 patients remained refractory (36%) and 4 died during hypoplasia (16%) Median DFS of the 12 responders was 2.9 months and median survival from time of CR 8.9 mo. Median overall survival of responders and non-responders was 6 mo from time of resistance. The survival advantage of responding patients (n = 12) as compared to non-responders (n = 13) was 10.7 vs. 3.2 mo (p = 0.002). Toxicity of chemotherapy was acceptable. 1 patient experienced pulmonary edema due to ara C, 2 patients developed life threatening systemic fungal infections, one of whom died while in CR.

AML in elderly patients is a heterogeneous disease which is characterized by a number of unfavorable features such as development, cytogenetics, blast cell differentiation, and poor treatment response. Specifically, the association between a higher incidence of unfavorable cytogenetic abnormalities in elderly patients and poor prognosis has been well documented. Low treatment response may be due to the specific biology of AML in this patient group, but also to host-specific factors such as higher treatment-related morbidity and mortality. Treatment tolerance cannot be judged on grounds of chronological age alone; risk factor analysis with regard to performance status, organ function, and underlying systemic disease need to be considered as well. For effective induction treatment in elderly patients, instant and intensive chemotherapy appears to be necessary, while delayed treatment or administration of supportive care alone provide unsatisfactory results. Standard-dose ara-C/anthracycline-containing regimens are the treatment of choice in patients with good performance status. However, patients with a WHO grading of greater than 3 might rather benefit from reduced regimens such as low-dose ara-C. At present, greatest improvement of AML treatment in elderly patients can be expected from an improvement of supportive care.

Several new cytostatic drugs have entered clinical phase I-II studies for the treatment of leukemia: the most promising are pyrimidine analogs such as 5-aza-cytidine, 5-aza-2'-deoxycytidine, 5-aza-cytosine arabinoside, and 2',2'-difluorodeoxycytidine. Fludarabine, a fluorinated purine analog, appears to be active in CLL and multiple myeloma. Deoxycoformycin, an adenosine analog, showed good activity in the treatment of hairy cell leukemia and T-cell neoplasias. 2-chloro-deoxyadenosine has recently been introduced into the treatment of CLL and hairy-cell leukemia refractory to deoxycoformicin. Tiazofurin, an antimetabolite which interferes with nicotine-adenine-dinucleotide (NAD) metabolism, has been applied in CML blast crisis. Other agents include 13-cis retinoic acid and 1, 25-dihydroxy vitamin D3 as differentiation inducers, and homoharringtonine, an alkylating agent which is widely used for ANLL treatment in China. Among new anthracyclines, aclarubicin, idarubicin, THP-adriamycin and fluoro-adriamycin should be mentioned. Mitoxantrone, a substituted anthraquinone, has successfully been applied in the treatment of relapsed and refractory ANLL. Amsacrine (m-AMSA), finally, is a synthetic aminoacridine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in ANLL treatment. Studies using m-AMSA alone or in combination revealed comparable results to anthracycline--containing regimens. Cardiotoxicity of the anthracycline congestive type has not been observed with m-AMSA. The EORTC Leukemia Cooperative Group has successfully used m-AMSA in several trials prepositioning this drug stepwise: from relapsed and refractory ANLL, into intensive maintenance treatment during first remission in ANLL, and, still on-going, into intensive consolidation.

Mechanisms of tumor growth are concerned with the possibility that neoplasms are disturbed in their response to growth factors. Interleukin 2 (IL 2) is secreted by activated T-cells and is required for autocrine T-cell growth. Controversy exists as to the functional capacity of T-lymphocytes in patients with B-cell chronic lymphocytic leukemia (CLL). We studied 14 patients with previously untreated, early CLL. Data were compared to 16 healthy individuals. Immunophenotyping showed that T-cells in B-CLL are highly activated as evidenced by HLA-DR and IL 2 receptor expression. Membrane receptors for IL 2 on the patients' T-cells were overexpressed. The T4:T8 ratio was 1.5. T-cells for in vitro studies were isolated by their ability to form E-rosettes with AET and repeated Ficoll density gradient centrifugation. Purified T-cells were grown on semisolid agar and their capability to form colonies investigated using a variety of exogenous stimulants. It was found that patients with CLL showed a pronounced impairment in forming T-cell colonies. However, colony formation was restored to normal by adding exogenous recombinant IL 2, indicating that endogenous IL 2 production of T-cells is deficient. This finding might have implications for the therapeutical use of IL 2 in CLL patients.

Out of 515 evaluable patients (median age, 47 years) who entered the study from 1983 to 1986, 67.4% achieved complete remission (CR) after one cycle (256) or two cycles (91) of daunorubicin (DNR) (45 mg/m2 days 1-3), cytosine arabinoside (Ara-C) (200 mg/m2 i.v. days 1-7), and vincristine (VCR) (1 mg/m2 day 2). A partial remission was achieved by 3.7% of patients, 15% were resistant, 11.3% died during hypoplasia, and 2.7% died during induction. Patients achieving CR received one consolidation course in which administration of DNR was limited to 1 day. Two hundred and forty-eight patients were randomized for six courses of maintenance every 6 weeks: either DNR + VRC day 1 + Ara-C s.c. days 1-5, or AMSA 150 mg/m2 day 1 alternating with high-dose (HD)-Ara-C 3 g/m2 q12 h day 1 + 2 or 5-azacytidine 150 mg/m2 days 1-3. Two hundred and thirty-three patients were randomized when bone marrow transplantation (BMT) had not been planned or performed and 15 patients were randomized before the BMT. Sixty patients received BMT, 17 autografts, and 43 allografts. Median time from CR to BMT was 15 weeks. Forty-two patients were not randomized mainly because of toxicity or treatment refusal. Median DFS for both chemotherapy groups was 12 months and 23% were alive at 4 years. Median survival from CR was 22 months, and 34% were alive at 4 years. There was no difference in disease-free interval (DFI) and disease-free survival (DFS) between the two chemotherapy arms. Of 60 transplanted patients, 42% were alive at 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-four consecutive patients with either relapsed (n = 28) or primary refractory AML (n = 6) were treated with one or two cycles of intermediate-dose (ID) cytosine arabinoside (Ara-C) (1 g/m2 i.v. q 12 h days 1-6) and amsacrine (m-AMSA) (120 mg/m2 i.v. days 5-7). Patients reaching complete remission (CR) were consolidated with one cycle of Ara-C 3 g/m2 i.v. q 12 h days 1-4 and m-AMSA 120 mg/m2 i.v. day 5. The median duration of the preceding remission was 8 months and median time from last chemotherapy until relapse 3.1 months. Of the relapsed patients, 22/28 (79%) achieved CR regardless of the type of prior intensive maintenance (HD Ara-C/m-AMSA/5-azacytidine) (AZA) or daunorubicin (DNR/CD-Ara-C). Three of the 28 (11%) patients died during hypoplasia; 3/28 (11%) were refractory to 2x ID-Ara-C/m-AMSA. Three of the 28 patients died in CR during hypoplasia after intensive consolidation with HD-Ara-C. Predictive factors for remission were duration of preceding remission and the time from last chemotherapy to relapse. Three patients were transplanted in second CR. One of the six refractory patients reached CR, two remained refractory, and three died during hypoplasia. The median duration of disease-free survival (DFS) of relapsed patients was 3.3 months without further treatment; median survival of responding patients (20 relapsed patients, 1 refractory patient) was 4.5 months, overall survival (n = 29) was 4.8 months. Patients receiving BMT were censored at the time of BMT. Seven patients experienced lung toxicity due to Ara-C, four of whom died.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of low-dose Ara C (LD-Ara C) (10 mg/m2 q 12 hr s.c.) for a minimum of 10 days was evaluated in 21 patients with acute myeloid leukemia (AML) and 15 patients with dysmyelopoietic syndromes (DMPS). Median age (range) for AML-patients was 47 yrs (19-89), and for DMPS-patients 60 (22-78). From the AML-group, 9 patients were either primary refractory or resistant to intensive re-induction treatment of relapse, 6 others had heavy pretreatment, 1 suffered from myelosclerosis. Five AML-patients had no pretreatment at first presentation and were started on LD-Ara C because of old age (3) or poor condition (2) including 1 patient with a secondary leukemia. DMPS included those with RAEB (8) and RAEB in transformation (7). 12 patients with AML and 4 with DMPS displayed a leukocytosis of greater than 10 X 10(9)/l. Three out of 21 AML-patients reached complete remission (CR), one of them twice, with partial remission (PR) at the third attempt with this type of treatment. Two other AML-patients reached a P.R. of 5 and 1 months duration respectively. Three patients experienced a transient response characterized by improved peripheral blood counts and cessation of transfusion requirements, one of them for 12 months. In 5 AML-patients no effect was seen and 8 pts. died. In the DMPS-group, 5/15 patients reached C.R., one patient twice with the same treatment, 1 patient reached a P.R., 1 improved, 6 showed no effect, and 2 died. In 13 patients final examination of the bone marrow was not performed after treatment because of either early death or obvious progression. Treatment was associated with significant, transient hematologic toxicity. Patients suffering from DMPS had prolonged aplasia and required more blood and platelet support than pts with AML. Responding leukemia patients had a rapid hematologic regeneration. Considering the poor prognosis of both of our treatment groups, this therapeutic approach proved to be of considerable benefit.

Pretreatment characteristics of 295 adults with acute myeloid leukemia who were treated in a large cooperative group of the E.O.R.T.C. between 1976 and 1982 (AML-5) have been evaluated to assess their value as prognostic indicators. Logistic regression methods were applied to derive a model for prediction of achievement of CR. The model was tested prospectively in an independent group of 274 subsequent patients treated with a different but similar induction regimen (AML-6), who were matched in all eligibility criteria. The concordance between the observed percentage of response in the AML-6 trial population and the expected response given by the model built on the AML-5 study was very close for the good response subgroups (WBC less than 50,000/mm3 and age less than 60 yrs), while the discrepancies in the poor prognostic groups were considerable. Furthermore, our study shows that the prognostic value of factors may shift as treatment strategies change and that caution is necessary in applying conclusions from a preceding trial to a current patient population.

Twenty-five institutions are participating in the AML-6-trial designed to improve remission incidence and to delay the time of relapse. Therefore, an intensive cyclic therapy is employed early after achievement of remission using either the same drugs of the induction regimen or rotating combinations of alternative drugs, e.g. AMSA, 5-AZA and HD-araC. So far, 266 patients entered the trial. The overall C.R. rate is 71%. 58 patients are randomized to 'maintenance' arm I, 54 to arm II, 79/112 patients are still being studied. Toxicity was in 7% and 3% respectively a reason to interrupt the study during induction or 'maintenance'. Since the intensity of modern protocols for remission induction of AML presents a major problem in elderly patients due to toxicity, and since most studies indicate low remission rates with an increasing death rate in this age group, the AML-7-study was initiated to prospectively compare survival and quality of life of two different therapeutic strategies: immediate intensive remission induction versus supportive care, 'wait and see' policy, and palliative cytoreduction with hydroxyurea and ara C when necessary. During the first 8 months after activating this study, 27 patients entered, 13 were randomized to branch I, and 14 to branch II.

Twenty nine consecutive patients (pts) with either relapsed (n = 23) or primary refractory AML (n = 6) were treated with 1 or 2 cycles of intermediate-dose (ID) ara-C (1g/m2 IV q 12 h days 1-6) and m-AMSA (120 mg/m2 IV days 5-7). Pts reaching complete remission (CR) were consolidated with 1 cycle of ara-C 3 g/m2 IV q 12 h days 1-4 and m-AMSA 120 mg/m2 IV day 5. The median duration of the preceding remission was 9.5 months, median time from last chemotherapy until relapse 3 months. 18/23 (78%) of relapsed pts achieved CR regardless of the type of prior intensive maintenance (HD-ara-C/m-AMSA/5-AZA or DNR/CD-ara-C). 3/23 (13%) pts died during hypoplasia, 2/23 (9%) pts were refractory to 2x ID-ara-C/m-AMSA. 3/23 pts died in CR during hypoplasia after intensive consolidation with HD-ara-C. Predictive factors for remission were the duration of preceding remission and the time from last chemotherapy to relapse. Three pts were transplanted in 2nd CR. 1/6 refractory pts reached CR, 2 pts remained refractory, and 3 died during hypoplasia. The median duration of disease-free survival (DFS) of relapsed pts was 3.3 months without further treatment, median survival of responding pts (18 replased pts, 1 refractory pt) was 4.6 months, the overall survival (n = 29) was 4.8 months. Pts receiving BMT were censured at the time of BMT. Seven pts experienced lung toxicity due to ara-C, four of whom died. The incidence of lung toxicity was clearly related to the extent of ara-C pretreatment during intensive maintenance. In conclusion, ID-ara-C/m-AMSA is a very effective reinduction treatment in these pts with acceptable toxicity; the impact of HD-ara-C during consolidation for DFS and survival is questionable.

16 patients with CML-BC were treated with vindesine/prednisone. Complete remissions were achieved in 3 cases which lasted 1 month (myeloid), 3 months (mixed) and 5 months (lymphoid). Minor responses, including less than 50% reduction of absolute blast counts and marked regression of organomegaly with a median duration of 3 weeks, occurred in 11 patients. Two patients did not respond to VDS. Leukopenia and thrombocytopenia were severe and prolonged, independent of their phenotype.

Bone marrow from 52 healthy donors has been fractionated on two discontinuous albumin gradients with different osmolarities in an effort to eliminate immunocompetent cells and to isolate hemopoietic stem cells. The nutrient agar system of Robinson was utilised as an assay procedure for the detection of colony-forming cells (CFU-c) in the resulting fractions. CFU-c, early granulocytic progenitors, are consistently present in the lighter fractions. On cytochemical staining, they showed a positive reaction for enzymes bound to lysosomes. The concentration of CFU-c was in an average 7 times that of the original marrow. At best, 1 X 10(5) CFU-c could be isolated from 10 ml marrow corresponding to 2 X 10(8) buffy-coat cells. The presence of immunocompetent cells was monitored by Phytohemagglutinin (PHA)-stimulation and T-cell rosette formation. In a human marrow transplant situation it appears that a better yield of CFU-c is necessary than is afforded by albumin gradient technique.

Sixteen patients in chronic myeloid leukemia blast crisis entered a phase II trial with vindesine and prednisone. Median duration of the chronic phase was 29 months in 13 patients, one previously had polycythemia vera, and two presented with a primary blast crisis. Eleven patients had myeloblastic features, as evidenced by morphology, cytochemistry, and cell surface antigens; three had a mixture of myeloid and lymphoid blast cells with lymphoblastic predominance; one had blast cells which displayed lymphoid characteristics; and one was classified as undifferentiated. Three patients had complete remissions lasting 1 month (myeloid), 3 months (mixed), and 5 months (lymphoid). Eleven patients had minor responses, with a median duration of 3 weeks (eight with myeloid, two with mixed, and one with undifferentiated). Two patients did not respond to vindesine. Leukopenia and thrombocytopenia were severe and prolonged independent of their morphologic or immunologic phenotype.

The Burkitt-like lymphoma is extremely rare. It shows a predominance of presentation in abdominal and pelvic sites and an older median age as compared to the endemic Burkitt's lymphoma. Both are independent prognostic determinants and reflect a poor prognosis. This might be the reason for the low response rate to cytotoxic treatment. Cyclophosphamide is a substantial part of any chemotherapeutic regimen used. Serum lactic dehydrogenase (LDH) levels are closely correlated with the extent of tumor mass and the response to therapy. Chemotherapy might be associated with serious metabolic complications including hyperkalemia, lactic acidosis, anuria, and sudden death from lethal embolization of the lung. In contrast to Burkitt's lymphoma, the Burkitt-like tumor has no association with the Epstein-Barr-virus. In both lymphomas a translocation from the 8q onto 14q chromosome occurs being a characteristic marker for these malignancies.

A comparative study of infectious morbidity and mortality in neutropenic patients with acute leukemia receiving chemotherapy was undertaken to test the effects of a suppression of endogenous and ambient microorganisms. Patients were allocated to receive [1] oral antibiotics (neomycin, colistin, and nystatin) in conventional ward isolation; [2] no antimicrobial suppression but conventional ward isolation; [3] strict isolation, filtered air, sterilized food and oral antibiotics. Significantly fewer infections with Gram-negative bacilli were seen in patients with strict isolation plus endogenous microbial suppression versus patients receiving selective gut decontamination versus patients without nonabsorbable antibiotics in simple reverse isolation. The death rate from infection was significantly reduced in patients who received antibiotics for gut flora suppression in conventional ward isolation compared with the corresponding control group. In addition, a significant improvement of leukemic remission rate was seen in this group. The protocol for decontamination was well tolerated.

58 adult patients with acute leukemia were analyzed in respect to the rate of first remission induction, remission duration, survival, and treatment of relapse. A selection of subgroups has been avoided to reflect clinical reality. Although our results of remission induction were slightly under those reported from other groups, the duration of remission and survival was favorably comparable. The prognostic value of LDH and systemic infection on admission for the outcome of the disease has been evaluated. Selective decontamination of the G.I.-tract reduced the rate of life-threatening infections and increased the rate of complete remissions significantly. LDH was of no importance in predicting the likelihood of achieving complete remission or duration of complete remission.

A renewal of interest in endocrine therapy of breast cancer is resulting from the demonstration of steroid hormone receptors in tumor cells sensitive to antiestrogens and the possibility for predicting endocrine responsiveness. Therefore new therapeutical concepts have been developed and some of the established endocrine regimens have been reduced to historical interest. It is more than doubtful that the present schematization in selecting the proper kind of endocrine treatment has any future as methodical difficulties in demonstrating hormone receptors will be overcome and the understanding of their biological function will increase.

There is no well defined group of patients with primary breast cancer which benefits from combination chemotherapy as an adjuvant treatment, since, at present, the effect of this therapy in respect to the duration of disease-free interval, survival, and possible long-term side effects remain unknown. Therefore, controlled studies need to be initiated. Similarly, there seems to be no beneficial effect from unspecific immunotherapy. As far as combination chemotherapy in advanced breast cancer is concerned, we review on four different protocols which proved to be quite successful in our hands: adriamycine/cyclophosphamide (AC), cyclophosphamide/methotrexate/5-fluorouracil (CMF), CMF/vincristine/prednisone (CMFVP), and adriamycine/vincristine plus CMF plus Tamoxifen.

Cyanelles isolated from the alga Cyanophora paradoxa Korschikoff synthesized cyanelle proteins in vitro. This synthesis was stimulated by light and totally inhibited by chloramphenicol. Cycloheximide had only a small inhibitory effect. Electrophoretic separation of the labelled soluble cyanelle proteins yielded at least 20 discrete polypeptides. The RNA isolated from the cyanelles and the whole cells was successfully translated in a rabbit reticulocyte-lysate system.

The clinical course of two patients with prolymphocytic leukemia of the suppressor T-cell phenotype is presented. Diagnosis was established by specific monoclonal antibody tests, cytochemical, ultrastructural and cytogenetic studies. The bone marrow showed a diffuse infiltration with medium sized lymphocytes displaying a prominent nucleolus. Both patients presented with pronounced splenomegaly, diffuse lymphnode involvement, leukocytosis, thrombocytopenia and anemia. One of them was refractory to chemotherapy using CHOP, Asparaginase, IMVP16, and irradiation to the spleen. He benefited from prednimustin and repeated leukaphereses, without reaching complete remission (C.R.). The second patient achieved a C.R. of 4 months duration with CHOP-Bleomycin. Survival was 16 and 11 months respectively.

Eleven adults have been transplanted for various reasons between July 1979 and July 1982: 2 with aplastic anemia (AA), 1 with paroxysmal nocturnal hemoglobinuria (PNH), 8 with acute leukemia (AL). Four patients suffered from acute lymphocytic leukemia (ALL) and four from acute non-lymphocytic leukemia (ANLL). Two of them were transplanted in relapse, 1 in a partial remission, and 5 in complete remission. All patients were in their late stage of disease. The PNH-patient had an identical twin, 8 patients had an HLA- and MLC compatible sib, 1 an unrelated donor, and 1 was transplanted from his father. Four patients are alive, 2 more than 3 years: 1 with AA and 1 with ALL who was transplanted in relapse. Six patients died of infectious complications (4 of interstitial pneumonia, 1 of a candida sepsis, 1 of acute toxoplasmosis). Patients living more than 3 weeks had a take. Acute graft-versus-host (GvH) disease did not present a major problem. All patients received methotrexate for GvH-prophylaxis, in three instances the marrow was additionally pre-incubated with anti-T-cell globulin.

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.

We report our results on 9 patients with disseminated malignant melanoma, treated with combination of DDP and IF, 3 in addition with VD. In none of them a complete remission was obtained, the median survival was 4.2 months. These disappointing results, in addition to the rather toxic side effects from the chemotherapy, do not present any benefit over less toxic regimens.

In a patient with acute lymphocytic leukaemia (pre-T ALL) and another patient with leukaemic generalization of B-cell lymphoma Auer bodies were found in a few immature cells. The diagnosis in both cases was based on clinical grounds, morphology, cytochemistry, and immunological marker analysis of the blasts. Auer bodies are known to be a marker of high significance for acute non-lymphocytic leukaemias. Therefore the findings described suggest mixed leukaemias with either T-cell or B-cell predominance. It provides further evidence for the existence of a common progenitor of myeloid and lymphoid cells.

The clinical course of a 66 year old male with CML who experienced several " relapse " BC of changing morphology, immunologic phenotype and cytogenetics is reported. The first BC was of lymphoblastic phenotype, the second of myeloid, the third again of lymphoblastic, and the fourth, terminal BC was not further characterized or treated. Whereas a phenotypic switch from lymphoblastic to myeloid has been documented twice, the sequence of myeloid followed by a lymphoblastic BC has, to our knowledge, not been reported so far. Lymphoblastic BC responded to a combination of vindesine/prednisone and 6-mercaptopurin. Myeloid BC was controlled by an AML-type induction regimen consisting of daunorubicin and cytosine arabinoside. This unusual case demonstrates that relapse BC is not necessarily of the same morphologic and phenotypic lineage as the preceding BC. Moreover, treatment should be adjusted to the predominant cell type in order to prolong survival.

Granulocyte/macrophage colony-forming unit (CFU-gm) formation was studied simultaneously in bone marrow and peripheral blood of 52 previously untreated adult patients with acute non-lymphocytic (ANLL) and 36 with acute lymphoblastic leukemia (ALL). They were followed during induction therapy at monthly intervals while in remission and in 19 ANLL and 22 ALL cases, until relapse. Patients showing a decreased colony number in the marrow but normal or increased colony numbers in the peripheral blood had a high probability of entering remission. Non-responding patients displayed an opposite pattern. The higher the degree of marrow repopulation with granulocytic progenitor cells after induction treatment, the longer remission duration and survival for ANLL patients and the longer survival for ALL patients. CFU-gm formation returned to normal in the early stages of complete remission, but then declined progressively. At ANLL and ALL relapse, colony growth was reduced markedly while cluster formation remained normal. The number of marrow colonies and clusters in ANLL were significantly higher at first and second relapse compared to the growth pattern at first presentation. A similar trend had been observed in ALL, suggesting a selection advantage.

The intensity of modern protocols for remission induction of acute nonlymphocytic leukemia presents a major problem in elderly patients because of toxicity. Most studies concerning this question indicate that in higher age groups (greater than 60 yrs.) remission incidence worsens and the death rate increases. Therefore, the purpose of this multicenter study is to prospectively compare survival and quality of life of two different therapeutic strategies: immediate intensive remission induction using Daunomycin and Cytosine Arabinoside (branch I) versus supportive care, "wait and see" policy, and palliative cytoreduction (branch II) with Hydroxyurea and Ara C when necessary. During the first 8 months after activating this study, 27 patients entered, 13 were randomized to branch I and 14 to branch II. It is too early to report meaningful results.

Cancer patients are often extremely cachectic. Therefore, they become poor risks for adequate chemotherapy. Consequently, they are either excluded from antitumor therapy or receive only reduced dosage regimens. Since the patient's response to cancer chemotherapy depends on immunocompetence which, in turn, is related to the nutritional state, adequate nutrition is the key to effective treatment. Parenteral nutrition, which in the literature is often referred to as hyperalimentation, can overcome and prevent cachexia. We treated 19 patients with advanced malignancies of various kinds using aggressive chemotherapeutic regimens and parenteral nutrition. The tolerance for chemotherapy in our patients was improved and the patients gained weight.

The effects of 2-lysophosphatidylcholine (2-LPC), the alkyl lysophospholipid derivatives (ALP) 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) and 1-O-hexadecyl-sn-glycero-3-phospho-trimethyl-ammonio-hexanol, the 2-acetamide analog of platelet-activating factor (PAF) 1-O-octadecyl-2-acetamide-sn-glycero-3-phosphocholine, the thioether lysophospholipid derivative (TLP) BM 41.440 and the ether-linked lipoidal amine CP-46,665 on tritiated thymidine uptake and trypan blue dye exclusion were tested in vitro in various freshly explanted cell samples from human nonneoplastic bone marrow and human leukemias. In both assay systems, a dose range of 1-20 micrograms/ml of the compounds was tested after 24, 48 and 72 hr of coincubation with the cells. The trypan blue dye exclusion revealed statistically significant preferential cytotoxicity in leukemic cells for three compounds with the order of quantitative selectiveness: ET-18-OCH3 greater than BM41.440 greater than 2-acetamide analog of PAF. CP-46,665 was the most toxic compound, but did not reveal significant differences between nonneoplastic bone marrow and leukemic cells when added in concentrations greater than 1 microgram/ml. The trimethyl-ammonio-hexanol compound showed only minor activity in the majority of tests, when added at concentrations less than 20 micrograms/ml. 2-LPC was rather ineffective. The tritiated thymidine uptake showed only preferential antiproliferative effects towards leukemic cells of ET-18-OCH3 and, sometimes, within the dose time frame tested of BM 41.440. All compounds tested except 2-LPC and the trimethyl-ammonio-hexanol compound were active also in this assay (inhibition of uptake greater than 50% of the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Several new cytostatic drugs have entered clinical Phase I-II studies for treatment of leukemia: most promising are pyrimidine analogues such as 5-Azacytosine arabinoside, 5-Aza-2-deoxycytidine, 5-Azacytidine, cyclocytidine, and 2'-2'-difluorodeoxycytidine. They act on different biochemical levels towards DNA-synthesis. Fludarabine is a purin analogue and seems very active in treating CLL. Tiazofurin is an antimetabolite counter-acting nicotinic acid with most promising activity in CML blast crisis. Other substances include deoxycoformycin, an adenosine analogue for treatment of T-cell neoplasias, 1, 25-dihydroxy vitamin D 3 as differentiation inducer, and homoharringtonine, an alkylating agent widely used for treating de novo AML in China. New anthracyclines are THP-adriamycin, fluoroadriamycin, and 4-demethoxydaunorubicin. Amsacrine (mAMSA) finally, is a synthetic aminoacridine with DNA-intercalating properties. The intact acridine ring appears essential for antitumor activity. The plasma clearance of both total amsacrine and unchanged parent species is biphasic. There is a considerable influence of hepatic and renal impairment on plasma clearance. Clinical toxicities include marked myelosuppression, gastrointestinal symptomes, phlebitis, mucocutaneous lesions, occasionally alopecia and neurotoxities. It is a very active drug, particularly in treating AML. Studies using mAMSA alone or in combination revealed comparable results to the anthracyclines. The E.O.R.T.C. Leukemia Cooperative Group has used successfully mAMSA in several trials: relapsed and refractory AML, intensive maintenance treatment during first remission in AML, and, still on-going, during intensive consolidation randomized against BMT in AML-patients under the age of 45 years, and randomized against standard consolidation between the age of 45 and 60 years.(ABSTRACT TRUNCATED AT 250 WORDS)