Contributions
Abstract: PB1368
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Clinical
Background
Translocation t(12;21)(p13;q22) and presence of the chimeric gene ETV6-RUNX1 occurs more frequently (25-30%) in children with acute lymphoblastic leukemia (ALL), however only in 1-4% of adults. This translocation t(12;21)(p13;q22) cannot be detected through conventional cytogenetics, thus can only be diagnosed through FISH and RT-PCR methods and confers a favorable prognosis. However, 20% of the patients may relapse after years.
Aims
To study the frequency, type and long-term clinical impact of additional cytogenetic aberrations detected along with t(12;21)(p13;q22) in ALL patients.
Methods
We studied 41 B-ALL patients, 21 males and 20 females. Median age at diagnosis was 4 (range 2-24) years old. Flow cytometry revealed common ALL in 25 and pre-B ALL in 16 patients. Median WBC count at diagnosis was 6,7 K/μl (0,84-120). ETV6-RUNX1 transcripts were detected in all patients. Further transcript study was performed in 31 patients. Type I (298 bp zone) and type II (259 bp) transcripts were found in 24 and 7 patients respectively. All patients underwent bone marrow cytogenetic analysis.
Results
Complete cytogenetic analysis was performed in 39/41 patient samples. Karyotype was normal in 12 and abnormal in 27 (69%) patients. Thirteen patients had diploidy, 7 had hyperdiploidy, 3 had hypodiploidy, 2 had hypotriploidy and 2 had hypotetraploidy. Structural chromosomal abnormalities were detected in 10/27 samples, numerical in 2/27 while both type of abnormalities in 15/27. Aberrations of chromosomes 12p or 21 or both (12p/21) were detected in ten, nine and one patient respectively. Deletion of 11q, and aberrations of 6q and 9p were detected in four, six and two patients respectively. Complex karyotype (three or more aberrations) was found in eighteen patients with median number of aberrations 5 (range 3-15). Ten patients had more than 4 aberrations. Clinical data was available for 40/41 patients. They all achieved hematologic remission. In a median follow up of 57.47 months (27-161), 10-year possibility of overall survival (OS) was 94% and 10-year disease free survival DFS was 92%. 10 year DFS was 86% for patients bearing abnormal karyotype and 100% for the normal karyotype group. Thirty-seven patients still remain in first remission, while two have relapsed. One of the relapsed patients died, while the other one is in second remission. One patient died in first remission. At the time of relapse the karyotype was abnormal in two relapsed patients. Clonal evolution with abnormalities as –Y, +21 and add(22)(q11) was detected in the one, whose diagnostic cytogenetic sample was available .
Conclusion
ALL with t(12;21)(p13;q22) is a disease with favorable prognosis and of wide heterogeneity. Additional aberrations involving chromosome 12, 21, 6, 9 and 11 as well as complex karyotype are frequently detected. Abnormal karyotype and clonal evolution is observed in relapse. Further study is needed in larger cohorts as well as with longer monitoring in order to investigate the biological and prognostic significance of additional chromosomal abnormalities.
Keyword(s): Acute lymphoblastic leukemia, Cytogenetic abnormalities, ETV6, RUNX1
Abstract: PB1368
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Clinical
Background
Translocation t(12;21)(p13;q22) and presence of the chimeric gene ETV6-RUNX1 occurs more frequently (25-30%) in children with acute lymphoblastic leukemia (ALL), however only in 1-4% of adults. This translocation t(12;21)(p13;q22) cannot be detected through conventional cytogenetics, thus can only be diagnosed through FISH and RT-PCR methods and confers a favorable prognosis. However, 20% of the patients may relapse after years.
Aims
To study the frequency, type and long-term clinical impact of additional cytogenetic aberrations detected along with t(12;21)(p13;q22) in ALL patients.
Methods
We studied 41 B-ALL patients, 21 males and 20 females. Median age at diagnosis was 4 (range 2-24) years old. Flow cytometry revealed common ALL in 25 and pre-B ALL in 16 patients. Median WBC count at diagnosis was 6,7 K/μl (0,84-120). ETV6-RUNX1 transcripts were detected in all patients. Further transcript study was performed in 31 patients. Type I (298 bp zone) and type II (259 bp) transcripts were found in 24 and 7 patients respectively. All patients underwent bone marrow cytogenetic analysis.
Results
Complete cytogenetic analysis was performed in 39/41 patient samples. Karyotype was normal in 12 and abnormal in 27 (69%) patients. Thirteen patients had diploidy, 7 had hyperdiploidy, 3 had hypodiploidy, 2 had hypotriploidy and 2 had hypotetraploidy. Structural chromosomal abnormalities were detected in 10/27 samples, numerical in 2/27 while both type of abnormalities in 15/27. Aberrations of chromosomes 12p or 21 or both (12p/21) were detected in ten, nine and one patient respectively. Deletion of 11q, and aberrations of 6q and 9p were detected in four, six and two patients respectively. Complex karyotype (three or more aberrations) was found in eighteen patients with median number of aberrations 5 (range 3-15). Ten patients had more than 4 aberrations. Clinical data was available for 40/41 patients. They all achieved hematologic remission. In a median follow up of 57.47 months (27-161), 10-year possibility of overall survival (OS) was 94% and 10-year disease free survival DFS was 92%. 10 year DFS was 86% for patients bearing abnormal karyotype and 100% for the normal karyotype group. Thirty-seven patients still remain in first remission, while two have relapsed. One of the relapsed patients died, while the other one is in second remission. One patient died in first remission. At the time of relapse the karyotype was abnormal in two relapsed patients. Clonal evolution with abnormalities as –Y, +21 and add(22)(q11) was detected in the one, whose diagnostic cytogenetic sample was available .
Conclusion
ALL with t(12;21)(p13;q22) is a disease with favorable prognosis and of wide heterogeneity. Additional aberrations involving chromosome 12, 21, 6, 9 and 11 as well as complex karyotype are frequently detected. Abnormal karyotype and clonal evolution is observed in relapse. Further study is needed in larger cohorts as well as with longer monitoring in order to investigate the biological and prognostic significance of additional chromosomal abnormalities.
Keyword(s): Acute lymphoblastic leukemia, Cytogenetic abnormalities, ETV6, RUNX1