[Prenatal cytogenetic diagnosis. The beginning of a new stage in cytogenetics in Mexico].
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Amniocentesis↗
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[Cytogenetic studies in the gynecological field. 2. Cytogenetic studies on primary sterility].
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Adult↗
[Realization of a program of pesticide cytogenetic study: the initial evaluation of the cytogenetic activity and potential mutagenic hazard of 24 pesticides].
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Animals↗
[A review of the data from cytogenetic and molecular cytogenetic research on human supernumerary minichromosomes].
The literature about the nature of marker chromosomes (mini-chromosomes of unknown origin) in patients with mental retardation, hereditary defects of development as well as in healthy individuals is reviewed. The advantage of the use of modern molecular methods of research for the analysis of nature and origin of additional mini-chromosomes is demonstrated.
Abnormalities, Multiple↗
[Cytogenetic analysis of the chromosome region containing the Drosophila radiosensitivity gene. I. Cytogenetic mapping of the radiosensitivity gene].
Eleven deletions were obtained in the rad(2)201 radiosensitivity gene region and the 41-45B4 fragment duplication in the Y chromosome were made by using chromosome rearrangements that transfer the material of the 44F - 45D site of chromosome 2 in Drosophila melanogaster to heterochromatin. The locus rad(2)201 was mapped in thin band region 45B3 by using these rearrangements and 13 deletions isolated before. Analysis of the complementation of the rad(2)201G1 radiosensitivity mutation by lethals and chromosome rearrangements in the 44F2-3; 45C5-6 region did not reveal any lethal alleles of this gene. The translocation T(Y;2)G6 was isolated; in this translocation, the change of the rad(2)201 gene expression causes high sensitivity of rad(2)201G1/T(Y;2)G6 heterozygotes of the initiation of the radiation-induced morphoses, while the survival rate of individuals remains at the level of wild-type flies.
Animals↗
Lack of cytogenetic abnormalities in Castleman's disease.
BACKGROUND: Castleman's disease (CD) is a distinctive type of atypical lymph node hyperplasia that is often clonal. In a previously reported series of CD, clonal populations of plasma cells were detected by immunohistology in 4 of 39 cases (10%, lambda restricted), and immunoglobulin gene rearrangements were detected by paraffin polymerase chain reaction (PCR) analysis in 10 of 37 cases (27%). Cytogenetic analysis has been used to detect clonal proliferations of plasma cells in myeloma and clonal proliferations of lymphocytes in lymphomas and has identified critical gene loci that are important in the histopathogenesis of these disorders. Cytogenetic studies have not been done on a large series of patients with CD. Thus, we reviewed the archives of our institution for cases of CD and lymphoma that had had cytogenetic analysis. METHODS: The cytogenetic and lymphoma archives of our institution (a tertiary care center) from 1985 to 1998 were reviewed for the diagnoses of CD and lymphoma. There were 21,006 lymphomas, 701 of which had cytogenetic analysis (400 abnormal). There were 162 cases of CD, 7 of which had cytogenetic analysis. The frequency of cytogenetic abnormalities in CD was compared with that in lymphoma. The sensitivity of cytogenetics for defining clonality in CD was compared with immunohistology and paraffin PCR-amplified immunoglobulin heavy-chain gene rearrangement. RESULTS: From 1985 to 1998, 162 cases of CD and 21,006 cases of lymphoma were diagnosed. Cytogenetic analysis yielded adequate numbers of metaphases for analysis of 4 cases of CD and 701 lymphomas. Cytogenetic abnormalities were not identified in CD but were identified in 400 lymphomas (57%). Although 1 of 4 cases of CD was clonal by immunohistology (lambda restricted), no immunoglobulin gene rearrangements were detected by paraffin PCR analysis. CONCLUSIONS: The frequency of cytogenetic abnormalities in lymphomas and the lack of cytogenetic abnormalities in CD suggest that cytogenetic abnormalities, as detected by conventional cytogenetic analysis, are important in the pathogenesis of lymphoma but not CD. The lack of cytogenetic abnormalities in CD supports the hypothesis that CD is an interleukin-6-driven lymphoproliferative disorder.
Castleman Disease↗
Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine.
Decitabine (5-aza-2'-deoxycytidine) acts as a powerful demethylating agent in vitro. Clinically, low-dose decitabine ameliorates cytopenias including induction of trilineage responses in approximately 50% of patients with high-risk myelodysplastic syndrome (MDS). We examined the incidence and kinetics of cytogenetic responses to decitabine in these patients. Of 115 successfully karyotyped patients, 61 (53%) had clonal chromosomal abnormalities prior to treatment. Major cytogenetic responses were observed in 19 patients (31% of those with abnormal cytogenetics, 17% of all patients by intention-to-treat) after a median of three courses (range, 2-6) until best cytogenetic response. Progressive decrease of the abnormal clone over time was also determined using fluorescence in situ hybridization (FISH) analysis in two patients. Median duration of cytogenetic responses was 7.5 months (range, 3-15). Analysis of response by the International Prognostic Scoring System (IPSS) cytogenetic risk groups revealed three out of five cytogenetic responses (60%) in the IPSS 'low-risk' group, 6 out of 30 with 'intermediate risk' (20%) and 10 out of 26 in the 'high-risk' group (38%). Median survival in these cytogenetic subgroups was 30, 8 and 13 months respectively. The relative risk of death in patients achieving a major cytogenetic response was 0.38 (95% confidence interval 0.17-0.88) compared with patients in whom the cytogenetically abnormal clone persisted (P = 0.0213). In conclusion, repeated courses of low-dose decitabine induce cytogenetic remissions in a substantial number of elderly MDS patients with pre-existing chromosomal abnormalties; these are associated with improved survival compared with patients in whom the cytogenetically abnormal clone persists. Patients with 'high-risk' chromosomal abnormalities may particularly benefit from this treatment.
Adult↗
Cytogenetic correlation with disease status and treatment outcome in advanced stage leukemia post bone marrow transplantation: a Southwest Oncology Group study (SWOG-8612).
A retrospective cytogenetic study was performed to determine whether non-random chromosome aberrations were related to the outcome of marrow transplantation for advanced stage acute leukemia (AL) and chronic myelogenous leukemia (CML). The patients were registered on SWOG-8612, a randomized comparison of busulphan and cyclophosphamide (BU/CY) to fractionated total body irradiation and etoposide (FTBI/VP16) as preparatory regimens for allogeneic bone marrow transplant (BMT). Blume K. G., Kopecky K. J., Henslee-Downey J. P., Forman S. J., Stiff P. J., Le Maistre C. F. & Appelbaum F. R. (1987) Blood 81, 2187. Pretreatment cytogenetic studies were available for 90 (78%) of the 115 patients who proceeded to BMT. Patients were categorized by diagnosis (ALL/AML/CML), disease status ['good' risk = second complete remission (CR2) or CML-accelerated phase (AP); 'poor' risk = third complete remission (CR3), induction failure, florid relapse or CML-blast phase (BP)] and cytogenetic status (favorable = normal cytogenetics in AL or Philadelphia chromosome positive (Ph+) standard or variant translocation as the sole findings in CML; unfavorable = all other cytogenetic aberrations). Chromosomal aberrations observed in the unfavorable category included -7, t(9;22) in AL, t(8;21) in association with complex karyotypes, t(6;9), del(9q), t/del(11q), t(1;19), hypotetraploidy, and complex karyotypes (> 3 cytogenetic anomalies). Unfavorable cytogenetic status was significantly more frequent among patients with 'poor' risk clinical disease status (P < 0.0001). In multivariate analysis, disease-free survival (DFS) was significantly poorer for patients with unfavorable cytogenetic status (P = 0.002) but not significantly related to disease status (P = 0.43). These data indicate that certain secondary chromosome aberrations [+8,i(17q), duplication of Ph] should be reclassified as relatively favorable predictors of successful BMT in CML and, therefore, be separated from the unfavorable cytogenetic aberrations characteristic of drug resistant disease [-7, inv(3), complex karyotypes]. The limited number of patients precluded definitive assessment of the prognostic significance of specific cytogenetic aberrations for any single diagnosis. Nevertheless, these findings suggest that cytogenetic status may be an important and independent factor in predicting outcome following allogeneic bone marrow transplantation.
Adolescent↗
GM-CSF can improve the cytogenetic response obtained with interferon-alpha therapy in patients with chronic myelogenous leukemia.
Patients with chronic myelogenous leukemia (CML) who achieve a major cytogenetic remission when treated with interferon-alpha (IFN-A) have a survival advantage when compared to patients with no cytogenetic response. We investigated the effect of combining granulocyte-macrophage colony-stimulating factor (GM-CSF) with IFN-A in the cytogenetic response of patients with minor responses to IFN-A alone. CML patients were eligible if they had shown sensitivity to IFN-A as determined by achievement of a hematologic or cytogenetic response, but failed to achieve or lost a major cytogenetic response after a minimum of 12 months of therapy with IFN-A alone. Patients received GM-CSF 30 microg/m2 daily, subcutaneously and the dose was escalated to 60 microg/m2 if tolerated. IFN-A was continued at the same dose being received by the patient and escalated when possible. Fourteen evaluable patients were included, 13 in chronic phase and one in accelerated phase. The best response prior to GM-CSF was a transient major cytogenetic response in two patients (14%), minor cytogenetic response in nine (64%), and complete hematologic response in three (22%). The median time on IFN-A prior to the start of GM-CSF was 39 months (range 12-72 months). Four patients achieved a significant cytogenetic response, including two complete (14%) and two partial (14%) cytogenetic remissions during therapy. One partial cytogenetic remission converted to complete shortly after therapy was discontinued. Two other patients had a significant reduction in the percentage of Philadelphia chromosome-positive metaphases. The dose of IFN-A could be escalated in half of the patients treated. No toxicity could be attributed to the addition of GM-CSF. We conclude that the addition of GM-CSF to the treatment with IFN-A in CML patients who are sensitive to IFN-A alone but fail to achieve a major cytogenetic response may be beneficial in some patients and should be further investigated.
Adult↗
Correlation of cytogenetics, BCR-ABL PCR studies and fluorescence in situ hybridisation (FISH) in adult acute lymphoblastic leukaemia.
BACKGROUND: Philadelphia positive (Ph+) acute lymphoblastic leukaemia (ALL) accounts for 11-29% of adult ALL. Reverse transcriptase polymerase chain reaction (RT-PCR) for the BCR-ABL fusion mRNA has identified patients with the fusion mRNA without cytogenetic evidence of the 9;22 translocation. The reason for discrepancies between cytogenetic and molecular diagnoses is unclear. AIM: Our aim was to study cases of ALL with discordant cytogenetic and RT-PCR results and identify any reasons for such discrepancies. METHODS: Laboratory records were scanned for cases of ALL tested by both RT-PCR and cytogenetics and positive by either for the 9;22 translocation. Fluorescence in situ hybridisation (FISH) was used to study discordant results where a specimen was available. RESULTS: We identified 15 patients with ALL who had both cytogenetic and RT-PCR studies for BCR-ABL. Seven had discordant results; five patients had positive RT-PCR studies with normal (four/five) or abnormal but Ph negative cytogenetics (one/five), and two were Ph+ but RT-PCR negative. FISH, using Vysis LSI bcr/abl translocation probes, showed fused signals in 12% interphase cells but not in metaphase cells in one specimen with normal cytogenetics, and 6% interphase cells in the Ph negative patient with abnormal cytogenetics. This second patient subsequently relapsed with a minor Ph+ cell line derived from the Ph negative line. CONCLUSIONS: These results confirmed the need for both cytogenetics and RT-PCR to identify Ph+ ALL. FISH did not show sub-microscopic rearrangements of BCR-ABL in normal metaphases. Failure to identify the Philadelphia chromosome cytogenetically appeared due rather to Ph+ cells failing to divide.
Adolescent↗
Cytogenetics in pediatric low-grade astrocytomas.
BACKGROUND: Cytogenetic analysis in certain tumors is a vital part of classification and assignment of prognosis. Few studies have examined the value of cytogenetic analysis in pediatric brain tumors. This is especially true of low-grade astrocytomas (LGA) of childhood. This study examines the correlation between cytogenetic abnormalities and survival in children with low-grade astrocytomas. The literature on adults with LGA suggest better survival for those whose tumors have normal cytogenetics compared to those with abnormal. We hypothesized this would also be true of children with low-grade astrocytomas. PROCEDURE: A retrospective study was performed of children presenting between 1980 and 1998 to The Children's Hospital, Denver, who had LGA and on whose tumors informative cytogenetics had obtained. RESULTS: One hundred and forty-nine children were diagnosed with histologically proven LGA. Twenty-nine had successful cytogenetic analysis. One or more chromosomal abnormalities were observed in eight tumors while normal karyotypes were observed in 21 tumors. Actuarial progression-free survival at 5 years was 87.5% for the eight children with abnormal cytogenetics and 43% for those with normal (P=0.56). Overall survival at 5 years was 83% for those with abnormal cytogenetics and 78% for those with normal (P=0.8). The differences in progression-free survival and overall survival between these two groups were not significant. Those children with WHO Grade I tumors had significantly superior progression-free and overall survival than those with Grade II tumors. CONCLUSIONS: It appears unlikely that, for children with LGA, those with normal cytogenetics have a better prognosis than those with abnormal. Histologic grade is a better predictor of outcome than cytogenetics.
Adolescent↗
Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma.
We compared the prognostic value of conventional cytogenetic analysis and established factors such as beta2-microglobulin and plasma cell labeling index in 70 patients undergoing autologous blood cell transplantation for multiple myeloma. Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Factors studied were age, sex, beta2-microglobulin, response to prior therapy, plasma cell labeling index, cytogenetic analysis, bone marrow plasma cell percentage, lactate dehydrogenase and C-reactive protein. Twenty-eight of 65 patients (43%) had abnormal marrow cytogenetics. Overall survival measured from transplantation was significantly better in patients with normal cytogenetics than in those with abnormal cytogenetics (median survival, 25 vs 12 months, P = 0.003). Progression-free survival was better, with median times of 12 vs7 months, respectively (P = 0.005); overall survival measured from the time myeloma was first diagnosed was also longer, with median survivals of 62 and 39 months, respectively (P = 0.001). Median plasma cell labeling index was 1.5% in patients with abnormal cytogenetics and 0. 2% in those with normal cytogenetics (P < 0.001). Abnormal bone marrow cytogenetics predict poor survival after blood cell transplantation for myeloma. There is a significant correlation between abnormal cytogenetics and high plasma cell labeling index, suggesting that certain cytogenetic abnormalities may offer a proliferative advantage to myeloma cells.
Adult↗
Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study.
PURPOSE: To prospectively compare cytogenetics and reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), aberrations characteristic of core-binding factor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed with primary AML. PATIENTS AND METHODS: Cytogenetic analyses were performed at local laboratories, with results reviewed centrally. RT-PCR for AML1/ETO and CBFbeta/MYH11 was performed centrally. RESULTS: CBF AML was ultimately identified in 48 patients: 21 had t(8;21) or its variant and AML1/ETO, and 27 had inv(16)/t(16;16), CBFbeta/MYH11, or both. Initial cytogenetic and RT-PCR analyses correctly classified 95.7% and 96.1% of patients, respectively (P =.83). Initial cytogenetic results were considered to be false-negative in three AML1/ETO-positive patients with unique variants of t(8;21), and in three CBFbeta/MYH11-positive patients with, respectively, an isolated +22; del(16)(q22),+22; and a normal karyotype. The latter three patients were later confirmed to have inv(16)/t(16;16) cytogenetically. Only one of 124 patients reported initially as cytogenetically normal was ultimately RT-PCR-positive. There was no false-positive cytogenetic result. Initial RT-PCR was falsely negative in two patients with inv(16) and falsely positive for AML1/ETO in two and for CBFbeta/MYH11 in another two patients. Two patients with del(16)(q22) were found to be CBFbeta/MYH11-negative. M4Eo marrow morphology was a good predictor of the presence of inv(16)/t(16;16). CONCLUSION: Patients with t(8;21) or inv(16) can be successfully identified in prospective multi-institutional clinical trials. Both cytogenetics and RT-PCR detect most such patients, although each method has limitations. RT-PCR is required when the cytogenetic study fails; it is also required to determine whether patients with suspected variants of t(8;21), del(16)(q22), or +22 represent CBF AML. RT-PCR should not replace cytogenetics and should not be used as the only diagnostic test for detection of CBF AML because of the possibility of obtaining false-positive or false-negative results.
Adult↗
Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype.
Advances in the treatment of acute myeloid leukemia (AML) have occurred with the introduction of new therapies including high-dose cytarabine and the identification of powerful prognostic factors such as cytogenetics that predict for long-term outcome. To date, the prognostic impact of cytarabine dose escalation within various cytogenetic groups of AML has not been assessed. We describe 285 newly diagnosed patients with primary AML who had adequate karyotypes and were enrolled on a prospective Cancer and Leukemia Group B cytogenetic study. All patients were randomly assigned to postremission treatment with standard-, intermediate-, or high-dose cytarabine intensification. Patients were categorized to one of three cytogenetic groups: (a) core binding factor type [(CBF); ie., t(8;21) inv(16), t(16;16), and del(16)]; (b) normal; and (c) other abnormality karyotype. An evaluation of these patients after a median follow-up time of over 7 years was performed to determine the relationship of intensification to outcome by cytogenetic group. Patients included 57 patients with CBF AML, 140 patients with normal karyotype AML, and 88 patients with other cytogenetic abnormalities. The treatment outcome of CBF AML patients was superior, with an estimated 50% still in complete remission (CR) after 5 years as compared with 32 and 15% for patients with normal karyotype AML and other abnormality AML, respectively (P < 0.001). Univariate analysis showed the following nonkaryotype factors to predict a prolonged CR duration: (a) younger age (P < 0.008); (b) lower leukocyte count (P=0.01); (c) the presence of Auer rods (P=0.004); (d) a lower percentage of bone marrow blasts (P=0.001) at the time of diagnosis, (e) and a higher postremission cytarabine dose (P < 0.001). The impact of cytarabine dose on long-term remission was most marked (P < 0.001) in the CBF AML group (after 5 years, 78% of those with a dose of 3 g/m2 were still in CR, 57% of those with a dose of 400 mg/m2 were still in CR, and 16% of those with a dose of 100 mg/m2 were still in CR) followed by normal karyotype AML (P=0.01; after 5 years, 40% of those with a dose of 3 g/m2 were still in CR, 37% of those with a dose of 400 mg/m2 were still in CR, and 20% of those with a dose of 100 mg/m2 were still in CR). In contrast, cytarabine at all doses produced only a 21% or less chance of long-term continuous CR for patients with other cytogenetic abnormalities. A multivariate analysis of CR duration assessed the independent impact of each of these variables on cure. Significant factors entering this model in descending order of importance were cytogenetic group (CBF > normal > other abnormality; P=0.00001), cytarabine dose (3 g/m2 > 400 mg/m2 > 100 mg/m2; P=0.00001), logarithm of leukocyte count at the time of diagnosis (P=0.0005), and histological subtype of AML (P=0.005). This study demonstrates that the curative impact of cytarabine intensification varies significantly among cytogenetic groups and results in a substantial prolongation of CR among patients with CBF and normal karyotypes, but not in those with other karyotypic abnormalities. These findings support the use of pretreatment cytogenetics in risk stratification of postremission AML therapy.
Acute Disease↗
[Analysis of cytogenetic response in Ph+ chronic myeloid leukemia patients treated with interferon alpha].
Ph chromosome occurs in nearly all patients with CML, and eliminating Ph-positive clone is a major target in the treatment of CML. IFN-alpha is a well-known effective treatment in chronic phase CML. The cytogenetic response and the prognostic factors in 128 CML patients treated with IFN-alpha were retrospectively studied. IFN-alpha administered singly at a dose of 3 million U/day for 2 - 3 times a week or in combination with either hydroxyurea (Hu), busulfan (Bu), low dose Ara-C or harringtonine. Karyotyping was examined by G-banding before and after IFN-alpha-based treatment. The results showed that all patients achieved complete hematological remission. Cytogenetic response occurred in 36 of 118 patients with standard t (9;22) translocation; 3 of these 36 patients had a complete cytogenetic response (Ph = 0), 13 had major cytogenetic responses (Ph < 35%) and 20 had minimal response (Ph > 35%). The total cytogenetic effectiveness was 13.6% (16/118). Four of seven patients with complicated variant translocation also achieved cytogenetic response, 2 of them had a major cytogenetic response and 2 had minimal response. Factors influenced the prognosis associated with cytogenetic response included sex, patient status at diagnosis and IFN-alpha administered singly or in combination with other chemotherapeutic agents. IFN-alpha could not prevent the progression of CML. It is concluded that Ph(+)CML patients with both standard and variant translocation had major cytogenetic response to IFN-alpha treatment at a dose of 6 - 9 million U/week in single or combination with Hu/Bu, however, IFN-alpha treatment could not prevent disease progression. Long term survival was also observed in patients with variant translocation treated with IFN-alpha. Regular cytogenesis examination in CML patients is necessary during IFN-alpha therapy, which is useful to reflect curative effect and progression of the disease.
Adolescent↗
Molecular and cytogenetic analysis of chromosome 7 in uterine leiomyomas.
Uterine leiomyomas are benign tumors that arise clonally from smooth muscle cells of the myometrium. Cytogenetic studies of uterine leiomyomas have shown that about 40% have chromosome abnormalities and that deletion of 7q is a common finding. The observations suggest the possible location of a growth-suppressor gene within the 7q21-q22 region. Molecular genetic analysis of cytogenetically normal tumors has frequently shown somatic loss of specific tumor suppressor genes detected by loss of heterozygosity in the critical region. To test the hypothesis that chromosome region 7q21-q22 contains a growth-suppressor gene involved in the development of leiomyomas, we examined 92 leiomyomas for allelic loss of 7q markers spanning the cytogenetically defined critical region. Forty tumors with cytogenetically defined 7q deletion, 45 tumors without cytogenetically visible 7q deletion, and seven tumors with no cytogenetic information were examined for allelic loss of loci D7S489, D7S440, D7S492, D7S518, D7S471, D7S466, and D7S530. Loss of heterozygosity for one or more of these loci was observed in 23 of 40 (57.5%) of the tumors with deletion of 7q and in 2 of 45 cases without a cytogenetically visible deletion. The tumors with cytogenetic deletion of 7q, but no loss of 7q21-q22 markers, were mosaics, with only a minority of cells containing the cytogenetic deletion. The critical region of loss is defined by the markers D7S518 and D7S471, each showing loss in approximately 50% of informative cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Chromosome Deletion↗
Cytogenetics of lymphomas.
Cytogenetic analysis is now a routine part of the diagnosis and management of a significant number of lymphoid malignancies. Whilst conventional cytogenetics remains the most comprehensive method for assessing chromosome abnormalities, the technical difficulties associated with conventional cytogenetics in most lymphomas has resulted in increased use of fluorescence in situ hybridisation (FISH) to identify specific abnormalities that are useful in either the diagnosis or management of these disorders. The finding of one of the Burkitt's translocations is of major importance in the diagnosis of Burkitt's and Burkitt's-like lymphomas, whereas the t(14;18), although seen in most follicular lymphomas (FL), is not usually required to make a diagnosis. Thus, whilst cytogenetics may be of interest in FL, it is not an essential part of the diagnostic work-up. Conventional cytogenetics may be useful for identifying markers of resistance to Helicobacter pylori therapy in MALT lymphomas. In disorders such as Hodgkin lymphoma, hairy cell leukaemia and lymphoplasmacytoid lymphoma, although many cytogenetic abnormalities have been observed, no consistent or specific abnormalities have been identified and so, at this point in our knowledge of the genetics of these disorders, cytogenetics cannot be considered a useful test for either diagnosis or prognosis. In contrast, the diagnosis of mantle cell lymphoma is now dependent upon the identification of the 11;14 translocation that results in cyclin D1 up-regulation. It is widely acknowledged that FISH is the most consistently useful test to identify the juxtaposition of the CCND1 and IGH genes in mantle cell lymphoma and is regarded as the 'gold standard'. FISH also has a role in identifying genetic abnormalities of prognostic significance in chronic lymphocytic leukaemia. Given the wealth of genetic and cytogenetic abnormalities that are continuing to be found in chronic lymphoid malignancies, it will be some time before the optimal use of both conventional cytogenetics and FISH is established in the diagnosis and management of lymphomas.
Chromosome Aberrations↗
Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy.
Cytogenetic clonal evolution (CE) is a known poor prognostic factor in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph-positive CML). However, its prognostic relevance in the era of imatinib therapy is unknown. We investigated the independent prognostic relevance of CE in 498 patients with Ph-positive CML treated with imatinib for chronic or accelerated phases. One hundred twenty-one patients had CE alone (n = 70) or with other accelerated phase criteria (n = 51). Patients were compared in 4 categories: chronic phase (n = 295), CE only (n = 70), accelerated phase without CE (n = 82), and accelerated phase with CE (n = 51). Statistical methods used established methodologies for univariate and multivariate analyses. In chronic and accelerated phases of CML, CE was not associated with significant differences in major or complete cytogenetic response rates, but it was an independent poor prognostic factor for survival by multivariate analyses in both chronic (P =.005) and accelerated phase (P =.03). Multivariate analyses conducted at the 3-month landmark (including the 3-month cytogenetic response) identified the lack of cytogenetic response at 3 months to be a stronger independent poor prognostic factor for survival than CE for both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response versus other). We conclude that cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, but it is an independent poor prognostic factor for survival in both chronic and accelerated phases of CML. The 3-month cytogenetic response to imatinib mesylate refined the prognostic relevance of such studies in patients on imatinib mesylate therapy.
Age Factors↗