Favorable prognosis associated with hyperdiploidy in children with acute lymphocytic leukemia correlates with extra chromosome 6. A Pediatric Oncology Group study

Pretreatment bone marrow cytogenetic studies were included for 1664 patients with acute lymphoblastic leukemia (ALL) accrued to Pediatric Oncology Group (POG) 8035 laboratory classification study from May 1981 through January 1986. There was a significant difference (P = 0.0001) in distribution of stem-line karyotype (normal, hypodiploid, pseudodiploid, or hyperdiploid) among children with early pre-B, pre-B, or T-cell ALL, with early pre-B patients demonstrating a higher proportion of hyperdiploid karyotypes with modal chromosome numbers greater than 51. Cytogenetic classification of 1216 patients with early pre-B or pre-B ALL evaluable for duration of event-free survival (EFS), with median follow-up of 42 months, showed a significant prolongation of five-year EFS associated with hyperdiploidy greater than 51 (75%; standard error [SE] = 5%) compared with hyperdiploidy 47 to 51 (46%; SE = 7%), hypodiploidy (55%; SE = 11%), and pseudodiploidy (45%; SE = 7%) (P = 0.0001). Five-year EFS was intermediate for patients with normal (58%), constitutionally abnormal (66%), or unsuccessful analyses (66%). The breakpoint defining hyperdiploidy associated with better prognosis was best defined as greater than 51 (P = 0.0002). Of 239 children with hyperdiploid karyotypes, analysis of the contribution of each chromosome to EFS duration showed a significant association between improved EFS and additional chromosome(s) six (P = 0.02). Chromosome translocation was associated with shorter EFS (P = 0.0001).     

Outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia

Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) represents the most common cytogenetic abnormality in adult ALL. It is found in 15% to 30% of patients, and its incidence increases with age. As in children, prognosis in Ph-positive adult ALL is poor. No therapeutic approach has had substantial impact on its unfavorable course. We analyzed the characteristics and outcome of newly diagnosed adults with Ph-positive ALL treated at the M. D. Anderson Cancer Center between 1980 and 1997. The diagnosis of patients was based on typical morphological and immunophenotypic criteria of marrow aspirate and biopsy specimens. Cytogenetic and molecular studies were also performed. A total of 67 patients were included in this study. From 1980 until 1991, 38 patients with Ph-positive ALL were treated with vincristine, Adriamycin, and dexamethasone (VAD), or with acute myeloid leukemia (AML)-like induction protocols. Since 1992 a total of 29 patients received induction therapy with an intensified treatment protocol, called "hyper-CVAD". The outcome of patients treated with standard and intensified treatment regimens was compared and results of our institution contrasted with data obtained from other centers. Ph-positive ALL was present in 67 of 498 patients with newly diagnosed ALL (13%). Patients with Ph-positive ALL had a higher median age (44 versus 34, P=0.007), higher median white blood cell (WBC) counts at presentation (25 versus 8, P=0.0002), and higher peripheral median percentage of blast counts (63 versus 40, P=0.023). FAB subtype L2 (70% versus 49%, P=0.001) and CALLA-positive pre-B immunophenotype (75% versus 37%, P<0.001) predominated among Ph-positive ALL. Myeloid marker coexpression was more frequent in Ph-positive ALL when compared with Ph-negative ALL (52% vs. 27% for CD13, P<0.001, and 44% vs. 27% for CD33, P=0.005). Among patients treated with hyper-CVAD, the complete remission (CR) rate was 90% versus 55% (P=0.002) with pre-hyper-CVAD regimens (VAD and AML-like induction protocols), the median CR duration was 43 weeks versus 32 weeks (P>0.5), median disease-free survival (DFS) was 42 weeks versus 29 weeks (P=0.008), and median survival was 66 weeks versus 45 weeks (P>0.5). Patients with hyperdiploid Ph-positive ALL on hyper-CVAD therapy achieved significantly longer CR duration and DFS than hypo- and pseudodiploid cases (59 weeks versus 42 and 31 weeks, P=0.02 and 0.04, respectively). In contrast, patients treated with regimens prior to hyper-CVAD had significantly shorter CR duration (21 weeks versus 33 and 29 weeks, P=0.03) and DFS with hyperdiploid karyotypes when compared to pseudodiploid and hypodiploid cases (16 weeks versus 30 and 13 weeks, P=0.008). In conclusion, our results demonstrate improved response rate and DFS with current intensive regimens (hyper-CVAD) in patients with Ph-positive ALL, but no advantage in overall survival.     

Prognostic significance of karyotype analysis in children with acute lymphoblastic leukemia.

Chromosome studies, using bone marrow samples of 26 pretreated children (below 15 years of age) with Acute Lymphoblastic Leukemia were carried out to explore the potentialities of applying chromosomal findings as a prognostic indicator in these patients. Abnormal karyotype was identified in 15 patients (57.6 per cent). The chromosomes frequently involved in non-random numerical abnormalities were Nos. 8, 18 and 21. Structural chromosome changes observed consisted of deletion 6q- and translocation t (4;11). After karyotype analysis, patients were grouped into subsets on the basis of the karyotype pattern observed. They were followed up to evaluate their prognosis and survival period. Patients showing hyperdiploid clone with greater than 51 chromosomes had the best prognosis. Patients with normal karyotype and patients with deletion of the long arm of chromosome 6 showed intermediate prognosis whereas patients showing t (4;11), trisomy 8, trisomy 18, trisomy 21, and hypodiploid karyotype were associated with worst prognosis. Thus, karyotype analysis before treatment helps to classify ALL patients as poor, intermediate and good prognosis groups and on this basis therapy can be designed accordingly.     

DNA Image Analysis in Childhood Acute Lymphoblastic Leukemia

DNA index (DI) and percentages of cells in S and G2/M phase were determined in Feulgen stained nuclei of blasts from 31 cases of childhood ALL at diagnosis. In 6 cases the results of DNA analysis and cytogenetics were concordant showing hyperdiploidy. Two other cases with normal karyotype were revealed as DNA aneuploid with image analysis. Cases with cytogenetic abnormalities like translocation, deletion or presence of single or double supernumerary chromosomes had DI within normal ranges. Nine ALL cases (29%) were found to be DNA aneuploid-8 hyperdiploid and 1 hypodiploid.

The percentages of cells in S and G2/M phase for blasts from bone marrow (mean 17.6%) were significantly higher than those estimated in the peripheral blood (mean 1.57%). We conclude that analysis by image cytometry can detect aneuploid DNA content even in cases, which showed a normal karyotype and provides new information concerning the biological aspects of leukemic blasts.     

Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia.

The t(12;21)(p13;q22) is a cryptic abnormality observed in 25% of children with B-lineage acute lymphoblastic leukemia (ALL), associated with a favorable prognosis. To determine whether specific cytogenetic abnormalities accompany the t(12;21), we analyzed the cytogenetic profiles of blast cells from 169 ALL cases positive for the t(12;21), previously identified by molecular methods. Only 13.6% of samples had normal karyotypes. Structural changes were detected in 89.7% of abnormal karyotypes, and numerical abnormalities in 47%. Rearrangements of 12p were the most frequent structural aberration (57 out of 146 patients with chromosomal abnormalities). Nonspecific deletions of chromosomes 6 and 9 were also found. The most frequent numerical abnormalities was trisomy for chromosomes 21. Blast cells were pseudodiploid (45.6%), hyperdiploid with 47 to 51 chromosomes (24.3%), hypodiploid with 44 to 45 chromosomes (10%), near-triploid (0.6%), or near-tetraploid (5.9%). Our results show that the t(12;21) is not associated with hyperdiploidy of 52 to 68 chromosomes or with the prognostic t(1;19), t(4;11) or t(9;22). Only children with B-lineage ALL who lack these abnormalities detected by conventional cytogenetics will probably benefit from additional testing by molecular methods to detect the t(12;21).     

The prognostic value of cytogenetic analyses in patients with acute nonlymphocytic leukemia treated with the same intensive chemotherapy.

BACKGROUND. Some specific chromosome abnormalities for the leukemias have been proven to be associated with the prognosis of acute nonlymphocytic leukemia (ANLL). However, most of these reports included patients treated with different protocols. Therefore, some bias has been involved in the evaluation of the prognostic factors in such reports. METHODS. The authors studied the morphologic, cytogenetic, and clinical features of 136 patients (86 males and 50 females) with de novo ANLL treated with the same protocol of intensive induction chemotherapy using multivariate analyses. RESULTS. Chromosome abnormalities were detected in 62.5% of the patients. The overall complete remission (CR) rate of disease was 85.5% in these patients. More than 90% of the patients with t(8;21) and pseudodiploid abnormalities achieved experienced CR. However, CR rates in the patients with abnormalities of chromosome 5 or 7 were 50%. With multivariate analyses by the type of karyotypic abnormality, CR duration and survival time of the patients with t(8;21) were longer than those of patients with normal karyotype and abnormalities of chromosome 5 or 7. Abnormalities of chromosome 5 or 7 and hyperdiploid were associated with poor prognosis. Older age and lower platelet counts also were factors contributing to shorter survival times. With the analysis with French-American-British (FAB) classification, only hypoplastic leukemia was a poor prognostic factor. CONCLUSIONS. These data suggest that cytogenetic analyses plays an important role in estimating the prognosis of patients treated with intensive induction chemotherapy.     

Improved treatment outcome in adult acute lymphoblastic leukemia using the intensive German protocol,a preliminary report

Thirty-nine consecutive patients with acute lymphoblastic leukemia were treated with an intensive chemotherapy protocol. There were 23 males and 16 females with a median age of 37 years (range: 15–65). Eighteen patients had common ALL, seven had pre-B ALL, three earlyprecursor B ALL, seven T-ALL and four had aberrant expression of myeloid antigens (c-ALL in three and pre-B ALL in one). The median initial leukocyte count was 11.8×10⁹/l (range: 0.65–295). Cytogenetic result of the marrow was available in 16 of 39 patients (41 per cent) and showed Philadelphia positivity in six, a normal result in six and one each of t(4,11), t(1,19), hyperdiploidy and del 12p. Hepatosplenomegaly was present in about 20 per cent of the patients. l-Asparaginase-related hepatic toxicity was the commonest toxicity (48.7 per cent) during phase I of induction. Prolonged pancytopenia and hypoplastic death were common during phase II. With the use of growth factors during the neutropenic period of phase II induction, the rate of hypoplastic death was reduced from 40 per cent to 3 per cent. Common causes of treatment failure included early hypoplastic death (27.8 per cent) and leukemia relapses (50 per cent) while primary refractory leukemia, hepatic failure and perforated peptic ulcer contributed to 11.1, 5.5 and 5.5 per cent of the other deaths. A high complete remission (CR) rate (87·4 per cent) was achieved after phase I induction. The median event-free survival (EFS) was 8 months and the 3-year event-free survival was 43 per cent. This result compared favourably to the other regimens previously employed in our institution. In conclusion, satisfactory survival can be achieved with this intensive regimen. Good supportive care was however, essential to minimize toxicities. © 1997 John Wiley & Sons, Ltd.     

A comprehensive cytogenetic classification of 1466 Chinese patients with de novo acute lymphoblastic leukemia

Cytogenetics and molecular cytogenetics of 1466 Chinese patients with de novo acute lymphoblastic leukemia (ALL) were studied. Cytogenetic results were available in 1175 patients. Cross-correlations of 23 subclasses of cytogenetic abnormalities were described. Childhood cases had higher incidences of normal karyotype, t(1;19), +8, 12q-, +21, +22 and high hyperdiploidy with 51-65 chromosomes, and lower incidences of t(9;22) and -5/5q- than adult ones (all p<0.05). Relationships of cytogenetic subclasses with immunophenotyping subgroups of ALL were studied. Our study presents the cytogenetic characteristics of a large series of Chinese ALL patients.     

Frequency of Chromosomal Abnormalities in Pakistani Adults with Acute Lymphoblastic Leukemia

Background: The difference in prognosis of adult and childhood acute lymphoblastic leukemia (ALL) can beattributed largely to variation in cytogenetic abnormalities with age groups. Cytogenetic analysis in acute leukemiais now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring,prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in orderto take critical decisions in management of the patients. Aim and Objectives: To determine the frequency ofcytogenetic abnormalities in Pakistani adult patients with ALL in order to have insights regarding behavior ofthe disease. Materials and Methods: A retrospective analysis of all the cases of ALL (≥15years old) diagnosed atAga Khan University from January 2006 to June 2014 was performed. Phenotype (B/T lineage) was confirmedin all cases by flow cytometry. Cytogenetic analysis was made for all cases using the trypsin-Giemsa bandingtechnique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature(ISCN) criteria. Results: A total of 166 patients were diagnosed as ALL during the study period, of which 151samples successfully yielded metaphase chromosomes. The male to female ratio was 3.4:1. The majority (n=120,72.3%) had a B-cell phenotype. A normal karyotype was present in 51% (n=77) of the cases whereas 49% (n=74)had an abnormal karyotype. Of the abnormal cases, 10% showed Philadelphia chromosome; t(9;22)(q34;q11.2).Other poor prognostic cytogenetic subgroups were t(4;11)(q21;q23), hypodiploidy (35-45 chromosomes) andcomplex karyotype. Hyperdiploidy (47-57 chromosomes) occurred in 6.6%; all of whom were younger than 30years. Conclusions: This study showed a relatively low prevalence of Philadelphia chromosome in Pakistaniadults with ALL with an increase in frequency with age (p=0.003). The cumulative prevalence of Philadelphianegativepoor cytogenetic aberrations in different age groups was not significant (p=0.6).     

Chromosomal Abnormalities in Pakistani Children with Acute Lymphoblastic Leukemia

Background: Cytogenetic abnormalities have important implications in diagnosis and prognosis of acuteleukemia and are now considered an important part of the diagnostic workup at presentation. Karyotype, ifknown at the time of diagnosis, guides physicians to plan appropriate management strategies for their patients.Aim and Objectives: To determine the cytogenetic profile of acute lymphoblastic leukemia (ALL) in Pakistanichildren in order to have insights regarding behavior of the disease. Materials and Methods: A retrospectiveanalysis of all the cases of ALL (<15years old) diagnosed at Aga Khan University from January 2006 to June2011 was performed. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique.Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN)criteria. Results: A total of 153 patients were diagnosed as ALL during the study period, of which 127 samplessuccessfully yielded metaphase chromosomes. The male to female ratio was 1.8:1. A normal karyotype waspresent in 51.2% (n=65) of the cases whereas 48.8% (n=62) had an abnormal karyotype. Most of the abnormalcases showed hyperdiploidy(13.4%) followed by t(9;22)(q34;q11.2) (7.08%). Conclusions: This study revealeda relative lack of good prognostic cytogenetic aberrations in Pakistani children with ALL.     

Abnormalities of chromosome bands 15q13-15 in childhood acute lymphoblastic leukemia

BACKGROUND: Recurring breakpoints in chromosome bands 15q13-15 occur infrequently in leukemia. To the authors' knowledge, the clinical significance of these breakpoints in childhood acute lymphoblastic leukemia (ALL) has not been previously investigated. METHODS: Centrally reviewed karyotypes of children with newly diagnosed ALL enrolled on Children's Cancer Group protocols from 1988 to 1995 formed the basis of the current report. Statistical analyses used chi-square tests for homogeneity of proportions, and outcome was analyzed using life table methods and associated statistics. RESULTS: Of 1946 cases with centrally reviewed and accepted cytogenetic analyses, 23 cases (1%) had breakpoints in chromosome bands 15q13-15. Most patients with 15q13-15 breakpoints had standard risk ALL, although breakpoints in 15q13-15 occurred more frequently in infants than in older children. The majority of these patients (16 patients; 70%) had balanced 15q13-15 rearrangements. Additional chromosomal abnormalities not involving 15q included abnormal 12p, abnormal 9p, Philadelphia chromosome, deletion 6q, and an 11q23 breakpoint. Thirteen (57%) 15q13-15 breakpoints occurred in pseudodiploid karyotypes; five (22%) were in hyperdiploid karyotypes with 47-50 chromosomes; two (9%) were in hyperdiploid karyotypes with > 50 chromosomes; and three (13%) were in hypodiploid karyotypes. Of the 23 patients with 15q13-15 breakpoints, 21 were survivors, 18 survived event-free for 2.2-9.3 years, and 3 were alive 1 to 3 years after a relapse at time of writing. CONCLUSIONS: The current study suggests that genes at 15q13-15 may be involved in the leukemogenesis of some cases of childhood ALL, but that with current intensive therapy such aberrations do not confer increased risk of treatment failure.     

Chromosome analysis of 31 Wilms' tumors

Cytogenetic analysis was done on 31 Wilms' tumors, including 2 renal tumors of clear cell sarcoma type, using short term cultures of primary tumors and/or nude mouse passages. Nonrandom secondary chromosome abnormalities, in particular, were noted as evidence of clonal evolution. Apparently normal karyotypes were found in 5 Wilms' tumors, all in patients less than or equal to 22 months old, and in one clear cell sarcoma. Abnormal karyotypes were seen in 25 tumors (80%); 6 were pseudodiploid, 3 were hypodiploid, and 16 (52%) were hyperdiploid, of which 8 had a modal number of 47-49 and 8 had a modal number of 50-55. Nonrandom structural abnormalities involved 1p/1q, 11p, 7p/7q, 16p/16q, 12q, and 17p/17q. Nonrandom numerical abnormalities included +6, +8, and +18. Trisomy 12 was the most common abnormality, structural or numerical, seen in 52% of tumors (81% of the hyperdiploid). In 2 tumors the +12 was the only apparent abnormality; in 1 other tumor an i(12q) was seen, suggesting that +12 may have special significance in the clonal progression of Wilms' tumor. Informative karyotypes of 68 Wilms' tumors from other reports were reviewed and compared to results in this series.     

Chromosomal abnormalities in adult non-endemic Burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature

Tumour cell karyotypes from patients with Burkitt lymphoma (BL) or Burkitt's type leukemia (ALL3) were studied for correlation with survival, bone marrow and cerebral spinal fluid involvement (CSF), human immunodeficiency virus (HIV) serology, and for recurrent cytogenetic abnormalities. The records of 22 patients with BL from our institution and of 148 cases of BL and ALL3 reported in the literature with karyotypes were evaluated for clinical and cytological features. Overall survival was only 28 per cent and 88 per cent of deaths occurred within the first nine months after diagnosis. Those who survived at least 18 months were unlikely to relapse. Age and gender did not significantly affect survival. Patients presenting with advanced Ann Arbor stage, bone marrow or CSF involvement had lower survival rates. The association of translocations involving chromosome band 8q24 with this disease is confirmed. Sixty-two per cent of karyotypes had t(8;14)(q24;q32) translocations; the recognized variant translocations t(8;22)(q24;q11) and t(2;8)(p12;q24) affected 12 per cent and 9 per cent respectively. Seventeen per cent had abnormal karyotypes but no classic translocation. Patients with variant translocations had the poorest survival rates, and those with the classic t(8;14)(q24;q32) did the best. Despite a small sample size, the variant translocation t(8;22)(q24;q11) appeared to occur at an increased frequency in the patients with AIDS. In the entire group, recurrent involvement of chromosome regions 1q2, 6q11-14 and 17p1 suggests that alteration of genes at these loci, B Cell Growth Factor (BCGF) at 1q2 and p53 on 17p, may contribute to the development and progression of this tumour. Similarly, the frequent trisomies of chromosomes 7, 8, 12 and 18 may indicate an effect on tumour cell growth due to increased gene dosage. Trisomy 12 was found in eight tumours, five from patients with AIDS, suggesting that chromosome 12 has a site or gene whose allelic dosage is selected for in AIDS related lymphoma cells. Cytogenetic studies of adult Burkitt lymphoma and leukemia suggest several likely loci for gene alterations that in conjunction with myc translocations can lead to tumorigenesis.     

Karyotype complexity and prognosis in acute myeloid leukemia

A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.     

Abnormalities of chromosome bands 13q12 to 13q14 in childhood acute lymphoblastic leukemia.

PURPOSE: Little is known about nonrandom deletions of chromosome bands 13q12 to 13q14 (13q12-14) in acute lymphoblastic leukemia (ALL). We determined the prognostic significance of cytogenetically identified breakpoints in 13q12-14 in children with newly diagnosed ALL treated on Children's Cancer Group protocols from 1988 to 1995. PATIENTS AND METHODS: Breakpoints in 13q12-14 were identified in 36 (2%) of the 1,946 cases with accepted cytogenetic data. Outcome analysis used standard life-table methods. RESULTS: Seventeen patients (47%) with an abnormal 13q12-14 were classified, according to the National Cancer Institute (NCI), as poor risk, and 15 patients (42%) were standard risk; four (11%) were infants less than 12 months of age. Eight cases had balanced rearrangements of 13q12-14, 27 patients had a partial loss of 13q, and one had both a partial gain and a partial loss. The most frequent additional abnormalities among these patients were an abnormal 12p, a del(6q), a del(9p), a 14q11 breakpoint, and an 11q23 breakpoint. Nineteen patients were pseudodiploid, 10 were hyperdiploid, and seven were hypodiploid. Patients with an abnormal 13q12-14 had significantly worse event-free survival than patients lacking such an abnormality, with estimates at 6 years of 61% (SD = 14%) and 74% (SD = 1%), respectively (P =.04; relative risk = 1.74). Overall survival, however, was similar for the two groups (P =.25). The prognostic effect of an abnormal 13q was attenuated in a multivariate analysis adjusted for NCI risk status and ploidy (P =.72). CONCLUSION: Aberrations of 13q12-14 may contribute to leukemogenesis of childhood ALL and confer increased risk of treatment failure but are associated with other poor-risk features.     

Intensive retreatment of adults and children with acute lymphoblastic leukemia.

Twenty-three patients (16 adults) failing their first or subsequent (n = 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four-drug induction phase is followed by early consolidation with teniposide-cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide-cytarabine with vincristine-cyclophosphamide, and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3-11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p less than 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation.     

Ductal Breast Carcinomas with Whole Chromosome Gains as a Particular Subset of Near-Diploid Tumors with Different Metastasis Free Survival

Summary We recently proposed the existence of a subtype of slightly hyperdiploid ductal breast cancers with cytogenetic alterations differing from those usually observed in the majority of these tumors. We aimed to establish whether these tumors, which represent about 50% of those with a DNA index (DI) comprised between 1.1 and 1.3, correspond to a particular clinicopathological entity. A retrospective study of 1771 patients operated for ductal carcinomas was performed. Three classes of tumors constituted according to DI were compared for the usual clinicopathological factors and clinical outcome. About 690 tumors (39%) were diploid/hypodiploid (DI < 1.1), 134 (7.6%) were hyperdiploid (1.1 ≤ DI < 1.3) and 947 (53.4%) were polyploid (DI ≥ 1.3). Median follow-up time was 106 months (range 1–177). Polyploid tumors were significantly associated with large tumor size, advanced clinical stage, high histological grade and S-phase fraction (SPF), positive lymph nodes and loss of steroid receptors. Hyperdiploid and diploid/hypodiploid tumors were similar for all the variables except SPF which was significantly higher in hyperdiploid tumors (p < 0.001). Overall survival was similar in hyperdiploid and diploid/hypodiploid tumors in univariate and multivariate analysis, while hyperdiploid tumors were significantly related to a poorer metastasis free survival, both in univariate (p = 0.023) and multivariate analysis (p = 0.031). Despite very close initial clinicopathological and biological characteristics, hyperdiploid tumors differed from diploid/hypodiploid tumors by a higher risk of metastasis, possibly related to their increased SPF.     

Prognostic relevance of achieving cytogenetic remission in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome following induction chemotherapy

Cytogenetic findings at diagnosis have influence on prognosis in patients with acute myelogenous leukaemia (AML) or MDS who undergo induction chemotherapy. Assessment of remission and treatment decisions are based on cytological findings. We analyzed the prognostic impact of cytogenetic remission status in 118 patients with abnormal karyotype who received induction chemotherapy. Initial cytogenetics were: 28 good-risk (14× t(15;17), 9× t(8;21), 5× inv(16)), 44 intermediate-risk, and 46 high-risk karyotypes. Eighty-three patients achieved complete remission (CR) and 20 achieved partial remission. Twenty-six of the patients who reached cytological CR retained an abnormal karyotype after induction, 13 of whom had been classified as standard-risk and therefore did not receive intensified consolidation. Sixty-one patients achieved cytogenetic CR (CCR), including 24 out of 28 (86%) patients with low-risk cytogenetics. The CCR rate was lower in patients with intermediate-risk (48%) or poor-risk cytogenetics (28%). Median survival (excluding patients with AML M3) of the CCR group was 37 months, as compared to 11 months in patients with persistence of abnormal karyotype (p < 0.0001). This difference remained statistically significant when calculated only for patients with intermediate-risk karyotypes (p = 0.03).Cytogenetic analysis after induction chemotherapy provides meaningful information especially in patients with intermediate-risk karyotypes. Patients with a persisting abnormal karyotype must be regarded as high-risk patients who should receive intensified treatment.     

Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses

Cytogenetic analysis of short-term cultures from 6 tumors of the nasal cavity and paranasal sinuses—one esthesioneuroblas-toma, 2 adenocarcinomas and 3 squamous-cell carcinomas (SCC)—revealed clonal chromosome aberrations in all cases. The esthesioneuroblastoma had a complex hyperdiploid karyotype. None of the aberrations was similar to those previously described in short-term cultures or established cell lines from esthesioneuroblastomas. The 2 adenocarcinomas had complex karyotypic changes, which in both cases included rearrangements of bands 9p22 and 14q11. One SCC had 5 unrelated pseudodiploid clones, I displayed a highly complex karyotype, including rearrangement of band 11 q 13, and I had simple karyotypic changes with loss of 6q material and gain of 3q. These findings are similar to those described in head-and-neck SCC at other sites.