Biomedical subjects
Publications and source records attributed to S Suciu.
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A continuous series of 649 patients, treated by modified radical mastectomy for primary breast carcinoma, is analyzed after a median follow-up of 92 months. 'True isolated' locoregional recurrences (LR), defined as LR not preceded or followed by distant metastases within 6 weeks, appeared with a cumulative actuarial incidence rate of 6%, 14% and 19% after 1, 5 and 7 years respectively, whereas the respective figures for distant metastases (M1) were 10%, 37% and 48%. The main initial parameters, predicting both the LR-free and the M1-free interval, are presented by statistical analyses in the following order of importance: number of invaded lymph nodes in the axilla, tumor size (T) and histological grading of differentiation. The same factors also predicted the imminence of M1 once LR had occurred, as well as survival after LR. A higher incidence of M1 after LR was also correlated with estrogen-receptor negative tumors and with those LR occurring within one year after mastectomy. LR occurred at the chest wall (65%), in the sub-clavicular fossa (16%) and the axilla (6%); the remaining 13% occurred in two of the sites. There was a trend towards longer survival after chest wall recurrence than after LR recurrence at another site. Axillothoracic irradiations postmastectomy gave a lower rate of LR in 227 patients than did a regimen of 12 months adjuvant chemotherapy with irradiation restricted to the internal mammary lymph nodes in 120 subsequent patients: 17 vs 25% at 5 years (P = 0.03 when adjusted by initial nodal involvement and T-size). Total excision of LR (repeated if new LR occurred) gave better rates of local ultimate control and survival than other kinds of treatments, with or without adjuvant local or systemic therapy. LR is not always a sign of imminent generalized disease. Actuarial 5-year survival after LR is 26.2% overall whereas, if only 'true isolated' LR are considered, the survival is 37%.
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The Dutch Childhood Leukemia Study Group (DCLSG) performed a phase III study-Study (ALL) V-to evaluate the effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for children (0-15 years) with standard risk acute lymphoblastic leukemia (ALL) (white blood cell [WBC] counts less than 50.10(9)/L, absence of mediastinal mass, and/or cerebromeningeal leukemia). Furthermore, the influence of initial patient and disease characteristics on the outcome was analyzed. Between May 1979 and December 1982, 240 patients entered the study and were randomized into two groups: group A (n = 122) received induction treatment with vincristine (VCR), prednisone (Pred), and L-asparaginase (L-Asp); for group B (n = 118), induction therapy consisted of VCR, Pred, L-Asp, and rubidomycin (Rub). All patients subsequently underwent cranial irradiation (doses adjusted to age) in combination with intrathecal methotrexate; maintenance therapy of 6-mercaptopurine and methotrexate for 5 weeks followed by vincristine and prednisone for 2 weeks was given for 24 months. The complete remission (CR) rate was similar in both groups (94.5%). Event-free survival (EFS) 5 years after diagnosis was higher in group B (62.5 +/- 4.5%) than in group A (54.7 +/- 4.5%), although the difference is not significant (p = 0.20). A high initial WBC (greater than or equal to 10.10(9)/L), age (greater than or equal to 10 years), a low platelet count (less than 100.10(9)/L), and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.05). Sex, French-American-British (FAB) classification group, immunophenotype, and treatment in specialized centers did not have a significant impact on event-free survival.
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Four cases with trisomy 11 as the sole chromosomal anomaly are reported, three with de novo acute nonlymphocytic leukemia (ANLL) and one with a myelodysplastic syndrome (MDS) after treatment for multiple myeloma. In reviewing the literature, we found 19 additional cases with trisomy 11 as the sole cytogenetic defect. All patients except one were reported to have ANLL or MDS. Thus, it seems that trisomy 11 is another rare but nonrandom chromosomal anomaly in ANLL and MDS. So far, no apparently characteristic clinical or cytologic signs have been found in these cases.
A Phase II study combining cisplatin, vindesine, and dacarbazine was performed on patients with disseminated malignant melanoma by the European Organization for Research and Treatment of Cancer (EORTC) Malignant Melanoma Cooperative Group (MMCG). The treatment consisted of intravenous administrations of dacarbazine 450 mg/m2, vindesine 3 mg/m2, and cisplatin 50 mg/m2 on day 1 and 8 of each course. Courses were repeated every 4 weeks. Treatment was discontinued in case of progression after two courses, otherwise continued until progression or for a minimum of six courses. One hundred five patients entered the trial with 92 patients being evaluable. The response rate calculated after clearance by the Extramural Review Committee shows four complete and 18 partial responses, i.e., 24%, with a median remission duration of 23 weeks. Toxicity and subjective tolerance to this regimen were moderate, requiring 140 modifications of 642 administrations (22%). Main toxicities were nausea and vomiting (95%), leucopenia (70%), alopecia (56%), peripheral neuropathy (32%), and nephrotoxicity (17%). The discussion emphasizes some particular points of interest in the management of advanced malignant melanoma.
Two cases of acute myelocytic leukemia (AML) type M4 with trisomy 4 are presented. In one case trisomy 4 was associated with del(3). Both patients had no history of exposure to mutagenic events. In our material the frequency of trisomy 4-AML is not higher than 1%.
The factor-dependent myeloid precursor cell line D35 mutates spontaneously at a frequency greater than 2.4 x 10(-7) to growth factor autonomy. This frequency could be increased at least 20-fold by retrovirus insertional mutagenesis. The isolation and characterization of factor-independent mutants allowed the identification of genes involved in growth autonomy. Mutants could be subdivided into two sets: those that secreted a stimulating factor (10/11) and those that did not (1/11). In one case, the factor released was distinct from previously characterized growth factors. In most mutants (6/9), the activation of a growth factor gene was associated with rearrangement that could be attributed to the insertion of a transposable-like element either 5' or 3' of the factor coding region in all cases examined, excluding oncogene involvement. All factor-independent mutants were tumorigenic, consistent with the hypothesis that growth-factor independence initiated by aberrant growth factor gene activation is an important and early step in tumorigenesis.
Between 1981 and 1986 cytogenetic studies of bone marrow and/or blood cells in 139 patients with de novo acute myeloid leukemia (AML) were performed. The overall incidence of chromosomal aberrations was 53%, and this was not significantly influenced by sex, age nor the FAB classification. The aberrations most often found were: complex anomalies (n = 13), t(8; 21) (n = 10), trisomy 8 (n = 9), monosomy 7 (n = 6), monosomy 5, 5q-, trisomy 11, 12p- (n = 4) and trisomy 6, 11q-, inv (n = 3). The prognostic significance of chromosomal findings was evaluated in 112 patients treated by combination chemotherapy. The chromosomal status NN, AN, AA did neither significantly influence complete remission rate (NN: 68%, AN: 71%, AA: 60%) nor mean survival (NN: 24, AN: 26.6, AA: 35.6 months). On the other hand, certain types of chromosomal anomalies were of prognostic value. CR was obtained in all 10 patients with t(8; 21) but only in 2 out of 9 patients with complex aberrations. Median duration of CR in patients with t(8; 21) was significantly longer than in patients with a normal karyotype (30 vs 7 months).
A case of T-cell acute lymphoblastic leukemia with a translocation between chromosomes #1 and #18 is described. The breakpoints were at bands 1q23 and 18q21. A single cell contained the translocation t(1;19)(q23;p13). The breakpoint on chromosome #1 was the same in both translocations, and the breakpoint on chromosome #18 was the same as that in t(14;18)(q32;q21) associated with follicular lymphoma. The possible relationship between chromosome bands 1q23 and 18q21 and the morphologic features of the leukemia cells is discussed.
Seventy-nine patients (aged 17-76 years) with acute myelogenous leukemia in first (56) or second (3) relapse, primary refractory leukemia (15) or leukemia occurring as secondary malignancy that developed after a preleukemic phase (3) or after another tumor (2) were given remission induction therapy consisting of cytosine arabinoside (Ara-C, 1 g/m2 as a 2-h infusion every 12 h for 6 days) and m-AMSA (120 mg/m2, i.v. on days 5, 6, 7). In total 45 patients (57%) achieved complete remission. Younger patients and those with a relatively low initial white blood cell count, a good performance status or in first relapse had a higher response rate. Thirty-five patients were given one or two courses of consolidation chemotherapy consisting of Ara-C (3 g/m2 as a 2-h infusion every 12 h for 4 days) and m-AMSA (120 mg/m2 i.v. on day 5). Three patients received an allogeneic bone marrow graft after the induction courses and four patients received an autologous bone marrow transplantation after consolidation therapy. The median of the disease-free survival curve was 21 weeks. The median duration of survival was 25 weeks. The response rate for this intermediate dose Ara-C regimen is satisfactory and does not differ from that reported for high dose Ara-C. The impact of consolidation chemotherapy in bad risk acute myelogenous leukemia is questionable.
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The Dutch Childhood Leukemia Study Group performed a phase III study (Study ALL V) to evaluate the effectiveness of addition of rubidomycin to induction treatment with vincristine, prednisone and L-asparaginase in children (0-15 years) with standard risk acute lymphoblastic leukemia: WBC less than 50.10(9)/l, absence of mediastinal mass and/or cerebromeningeal leukemia. Furthermore, the influence of some initial patient- en disease-characteristics on the outcome was analysed. Between May 1979 and December 1982 240 patients entered into the study and were randomized into 2 groups: group A (n = 122) received induction treatment with vincristine, prednisone and L-asparaginase; group B (n = 118) received induction treatment with vincristine, prednisone, L-asparaginase and rubidomycin. All patients received cranial irradiation (doses adjusted to age) and intrathecal methotrexate, followed by maintenance treatment with 6-mercaptopurine and methotrexate for 5 weeks, alternated with vincristine and prednisone for 2 weeks, up to 24 months. Complete remission rate was 94% in both groups. Event-free survival at 5 years after diagnosis was higher in group B (62% +/- 4.6%) than in group A (54.2% +/- 4.6%) but the difference was not significant. A higher initial WBC, age greater than or equal to 10 years and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.01). Sex, FAB-morphology, immunophenotype and place of treatment (center or general hospital) were not significant factors.
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During A-ALL induction treatment, HD-ara-C (2.5 g/m2 IV, day 1), does not produce any beneficial effect, whereas the hematologic toxicity is increased. A 3-month consolidation phase comprising intermittent MTX, ara-C and 6-TG is not significantly affecting either DFI or survival in A-ALL. The association of HD-ara-C and m-AMSA appears to be a promising salvage therapy for the 20% A-ALL refractory to first induction therapy. The quality of autologous bone marrow graft, harvested after HD-ara-C, seems to be impaired as suggested by a delayed recovery of PMN and platelets. HD-ara-C (3 g/m2 X N) given the days before cyclophosphamide and TBI as conditioning treatment for BMT does not seem to induce prohibitory additional toxicity. Whether HD-ara-C was given four to six times or eight to 12 times gave no significant difference in early toxicity.