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SAN DIEGO – High hyperploidy – 50 or more chromosomes – has been recognized since the 1980s as a favorable prognostic feature in children with B-lineage acute lymphoblastic leukemia, but it appears that the best results occur in patients who have 58 or more chromosomes.
Patients with B-lineage acute lymphoblastic leukemia (B-ALL) who had a modal number of chromosomes (MNC) ranging from 58 to 66 had a 6-year event-free survival rate of 99% in a study reported at the annual meeting of the American Society of Hematology.
In comparison, the event-free survival rate was 80% for patients with MNC 51-53 and 89% for patients with MNC 54-57 (P less than .001), said Dr. Nicole Dastugue from the Centre Hospitalier Universitaire – Hôpital Purpan in Toulouse, France, on behalf of colleagues in the EORTC (European Organisation for Research and Treatment of Cancer) CLG 58951 trial.
"In our study, the best indicator of excellent outcome was ploidy assessed with karyotype," she said, adding that patients with a DNA index of 1.24 or greater also had good outcomes, with a 94% event-free survival rate at 6 years (P = .03).
The investigators recommended assessing ploidy with both karyotyping and DNA index methods, a combination that can better detect hyperploidy greater than 50 chromosomes, and exclude near-triploidy or duplication of hypoploidy of 30-40 chromosomes, which indicate poor prognosis.
Previous studies have suggested that factors predicting better outcomes in childhood B-ALL included a DNA greater than 1.16, 56 or more chromosomes, triple trisomies (+4,+10,+17), double trisomies (+4,+10), and trisomy 18, Dr. Dastugue said.
She and her colleagues tested the above factors in 541 patients with hyperploidy greater than 50 who were enrolled in the trial, which studied combination chemotherapy plus steroids in children with ALL and lymphoblastic non-Hodgkin’s lymphoma.
Hyperploidy was identified by cytogenetics (karyotype and fluorescent in situ hybridization [FISH]) and/or DNA index via flow cytometry.
Patients were stratified by risk group (very low risk, average risk 1 or 2, and very high risk) according to DNA index, MNC, white blood count, central nervous system and/or gonadal involvement, or presence of very high risk features. Of the 541 patients, MNC could be evaluated in 446 (82%) and DNA index in 490 (91%).
In all, 87 patients were found to have 51-53 chromosomes, 258 had 54-57 chromosomes, and 101 had 58 or more chromosomes. Significant prognostic factors for event-free survival included MNC, DNA index, triple and double trisomies, and minimal residual disease, Dr. Dastugue said.
Among the patients with 58 or more chromosomes, all had a good response to prophase therapy, only three had minimal residual disease after induction chemotherapy, and only one patient experienced a relapse. The investigators could not identify specific patterns of chromosome gains associated with prognosis because all chromosomes except chromosome 1 were found to contribute to trisomies or tetrasomies.
Higher DNA index also was significantly associated with better outcomes, with patients who had a DNA index of 1.24 or greater having a 95% 6-year event-free survival, compared with 83% for DNA index below 1.16 and 90% for DNA index from 1.16 through 1.23 (P = .01), she reported.
Triple trisomies were associated with a 96% 6-year event-free survival rate vs. 86% for no triple trisomies (P = .005). The 6-year event-free survival rate for double trisomies was 94%, compared with 84% for no double trisomies (P = .003).
When the investigators ranked variables based on the presence of 58 or more chromosomes and trisomies, they found that the 6-year event-free survival rate for 58+ chromosomes was 99%, compared with 93% for triple trisomies with lower chromosome numbers and 84% for double trisomies with lower chromosome numbers (P = .04).
This finding implies that the favorable outcomes seen in patients with triple and double trisomies were at least partly due to their frequent association with high MNC, Dr. Dastugue said.
Noting that the investigators had consistently found triple trisomies of chromosomes 4, 10, and 17, session comoderator Dr. Christine J. Harrison of the Northern Institute for Cancer Research at Newcastle University in Newcastle upon Tyne, England, asked whether they had found any other trisomies associated with a favorable prognosis.
Dr. Dastugue said that no trisomies tested were significant predictors of outcome.
The trial was sponsored by the European Organisation for Research and Treatment of Cancer. The authors reported no relevant conflicts of interest. Dr. Harrison reported no relevant conflicts.
High
hyperdiploidy and trisomy of specific chromosomes have been appreciated for
quite some time as favorable biologic characteristics that predict for a successful
outcome to therapy for children with acute lymphoblastic leukemia. The specific
chromosomes (4, 10, and 17), additional copies of which confer a good
prognosis, have been identified and used in risk-adjusted therapy paradigms. The
question of how high is high enough with respect to hyperdiploidy has not been
quantified.
This report from the
EORTC suggests that the important modal chromosome number is 58. Since all but
chromosome 1 were associated with observed trisomies and tetrasomies, however,
no consistent pattern of single chromosome excess appears related to the
prognostic significance of a modal chromosome number of 58 or greater.
Confirmation in larger series of patients and validation in patients exposed to
different therapy regimens is required before these data can be generalized for
treatment stratification decision-making.
Dr. Gregory H. Reaman, an associate editor of The
Oncology Report, is professor of pediatrics at the George Washington University
School of Medicine and Health Sciences and Children’s National Medical Center
in Washington.
High
hyperdiploidy and trisomy of specific chromosomes have been appreciated for
quite some time as favorable biologic characteristics that predict for a successful
outcome to therapy for children with acute lymphoblastic leukemia. The specific
chromosomes (4, 10, and 17), additional copies of which confer a good
prognosis, have been identified and used in risk-adjusted therapy paradigms. The
question of how high is high enough with respect to hyperdiploidy has not been
quantified.
This report from the
EORTC suggests that the important modal chromosome number is 58. Since all but
chromosome 1 were associated with observed trisomies and tetrasomies, however,
no consistent pattern of single chromosome excess appears related to the
prognostic significance of a modal chromosome number of 58 or greater.
Confirmation in larger series of patients and validation in patients exposed to
different therapy regimens is required before these data can be generalized for
treatment stratification decision-making.
Dr. Gregory H. Reaman, an associate editor of The
Oncology Report, is professor of pediatrics at the George Washington University
School of Medicine and Health Sciences and Children’s National Medical Center
in Washington.
High
hyperdiploidy and trisomy of specific chromosomes have been appreciated for
quite some time as favorable biologic characteristics that predict for a successful
outcome to therapy for children with acute lymphoblastic leukemia. The specific
chromosomes (4, 10, and 17), additional copies of which confer a good
prognosis, have been identified and used in risk-adjusted therapy paradigms. The
question of how high is high enough with respect to hyperdiploidy has not been
quantified.
This report from the
EORTC suggests that the important modal chromosome number is 58. Since all but
chromosome 1 were associated with observed trisomies and tetrasomies, however,
no consistent pattern of single chromosome excess appears related to the
prognostic significance of a modal chromosome number of 58 or greater.
Confirmation in larger series of patients and validation in patients exposed to
different therapy regimens is required before these data can be generalized for
treatment stratification decision-making.
Dr. Gregory H. Reaman, an associate editor of The
Oncology Report, is professor of pediatrics at the George Washington University
School of Medicine and Health Sciences and Children’s National Medical Center
in Washington.
SAN DIEGO – High hyperploidy – 50 or more chromosomes – has been recognized since the 1980s as a favorable prognostic feature in children with B-lineage acute lymphoblastic leukemia, but it appears that the best results occur in patients who have 58 or more chromosomes.
Patients with B-lineage acute lymphoblastic leukemia (B-ALL) who had a modal number of chromosomes (MNC) ranging from 58 to 66 had a 6-year event-free survival rate of 99% in a study reported at the annual meeting of the American Society of Hematology.
In comparison, the event-free survival rate was 80% for patients with MNC 51-53 and 89% for patients with MNC 54-57 (P less than .001), said Dr. Nicole Dastugue from the Centre Hospitalier Universitaire – Hôpital Purpan in Toulouse, France, on behalf of colleagues in the EORTC (European Organisation for Research and Treatment of Cancer) CLG 58951 trial.
"In our study, the best indicator of excellent outcome was ploidy assessed with karyotype," she said, adding that patients with a DNA index of 1.24 or greater also had good outcomes, with a 94% event-free survival rate at 6 years (P = .03).
The investigators recommended assessing ploidy with both karyotyping and DNA index methods, a combination that can better detect hyperploidy greater than 50 chromosomes, and exclude near-triploidy or duplication of hypoploidy of 30-40 chromosomes, which indicate poor prognosis.
Previous studies have suggested that factors predicting better outcomes in childhood B-ALL included a DNA greater than 1.16, 56 or more chromosomes, triple trisomies (+4,+10,+17), double trisomies (+4,+10), and trisomy 18, Dr. Dastugue said.
She and her colleagues tested the above factors in 541 patients with hyperploidy greater than 50 who were enrolled in the trial, which studied combination chemotherapy plus steroids in children with ALL and lymphoblastic non-Hodgkin’s lymphoma.
Hyperploidy was identified by cytogenetics (karyotype and fluorescent in situ hybridization [FISH]) and/or DNA index via flow cytometry.
Patients were stratified by risk group (very low risk, average risk 1 or 2, and very high risk) according to DNA index, MNC, white blood count, central nervous system and/or gonadal involvement, or presence of very high risk features. Of the 541 patients, MNC could be evaluated in 446 (82%) and DNA index in 490 (91%).
In all, 87 patients were found to have 51-53 chromosomes, 258 had 54-57 chromosomes, and 101 had 58 or more chromosomes. Significant prognostic factors for event-free survival included MNC, DNA index, triple and double trisomies, and minimal residual disease, Dr. Dastugue said.
Among the patients with 58 or more chromosomes, all had a good response to prophase therapy, only three had minimal residual disease after induction chemotherapy, and only one patient experienced a relapse. The investigators could not identify specific patterns of chromosome gains associated with prognosis because all chromosomes except chromosome 1 were found to contribute to trisomies or tetrasomies.
Higher DNA index also was significantly associated with better outcomes, with patients who had a DNA index of 1.24 or greater having a 95% 6-year event-free survival, compared with 83% for DNA index below 1.16 and 90% for DNA index from 1.16 through 1.23 (P = .01), she reported.
Triple trisomies were associated with a 96% 6-year event-free survival rate vs. 86% for no triple trisomies (P = .005). The 6-year event-free survival rate for double trisomies was 94%, compared with 84% for no double trisomies (P = .003).
When the investigators ranked variables based on the presence of 58 or more chromosomes and trisomies, they found that the 6-year event-free survival rate for 58+ chromosomes was 99%, compared with 93% for triple trisomies with lower chromosome numbers and 84% for double trisomies with lower chromosome numbers (P = .04).
This finding implies that the favorable outcomes seen in patients with triple and double trisomies were at least partly due to their frequent association with high MNC, Dr. Dastugue said.
Noting that the investigators had consistently found triple trisomies of chromosomes 4, 10, and 17, session comoderator Dr. Christine J. Harrison of the Northern Institute for Cancer Research at Newcastle University in Newcastle upon Tyne, England, asked whether they had found any other trisomies associated with a favorable prognosis.
Dr. Dastugue said that no trisomies tested were significant predictors of outcome.
The trial was sponsored by the European Organisation for Research and Treatment of Cancer. The authors reported no relevant conflicts of interest. Dr. Harrison reported no relevant conflicts.
SAN DIEGO – High hyperploidy – 50 or more chromosomes – has been recognized since the 1980s as a favorable prognostic feature in children with B-lineage acute lymphoblastic leukemia, but it appears that the best results occur in patients who have 58 or more chromosomes.
Patients with B-lineage acute lymphoblastic leukemia (B-ALL) who had a modal number of chromosomes (MNC) ranging from 58 to 66 had a 6-year event-free survival rate of 99% in a study reported at the annual meeting of the American Society of Hematology.
In comparison, the event-free survival rate was 80% for patients with MNC 51-53 and 89% for patients with MNC 54-57 (P less than .001), said Dr. Nicole Dastugue from the Centre Hospitalier Universitaire – Hôpital Purpan in Toulouse, France, on behalf of colleagues in the EORTC (European Organisation for Research and Treatment of Cancer) CLG 58951 trial.
"In our study, the best indicator of excellent outcome was ploidy assessed with karyotype," she said, adding that patients with a DNA index of 1.24 or greater also had good outcomes, with a 94% event-free survival rate at 6 years (P = .03).
The investigators recommended assessing ploidy with both karyotyping and DNA index methods, a combination that can better detect hyperploidy greater than 50 chromosomes, and exclude near-triploidy or duplication of hypoploidy of 30-40 chromosomes, which indicate poor prognosis.
Previous studies have suggested that factors predicting better outcomes in childhood B-ALL included a DNA greater than 1.16, 56 or more chromosomes, triple trisomies (+4,+10,+17), double trisomies (+4,+10), and trisomy 18, Dr. Dastugue said.
She and her colleagues tested the above factors in 541 patients with hyperploidy greater than 50 who were enrolled in the trial, which studied combination chemotherapy plus steroids in children with ALL and lymphoblastic non-Hodgkin’s lymphoma.
Hyperploidy was identified by cytogenetics (karyotype and fluorescent in situ hybridization [FISH]) and/or DNA index via flow cytometry.
Patients were stratified by risk group (very low risk, average risk 1 or 2, and very high risk) according to DNA index, MNC, white blood count, central nervous system and/or gonadal involvement, or presence of very high risk features. Of the 541 patients, MNC could be evaluated in 446 (82%) and DNA index in 490 (91%).
In all, 87 patients were found to have 51-53 chromosomes, 258 had 54-57 chromosomes, and 101 had 58 or more chromosomes. Significant prognostic factors for event-free survival included MNC, DNA index, triple and double trisomies, and minimal residual disease, Dr. Dastugue said.
Among the patients with 58 or more chromosomes, all had a good response to prophase therapy, only three had minimal residual disease after induction chemotherapy, and only one patient experienced a relapse. The investigators could not identify specific patterns of chromosome gains associated with prognosis because all chromosomes except chromosome 1 were found to contribute to trisomies or tetrasomies.
Higher DNA index also was significantly associated with better outcomes, with patients who had a DNA index of 1.24 or greater having a 95% 6-year event-free survival, compared with 83% for DNA index below 1.16 and 90% for DNA index from 1.16 through 1.23 (P = .01), she reported.
Triple trisomies were associated with a 96% 6-year event-free survival rate vs. 86% for no triple trisomies (P = .005). The 6-year event-free survival rate for double trisomies was 94%, compared with 84% for no double trisomies (P = .003).
When the investigators ranked variables based on the presence of 58 or more chromosomes and trisomies, they found that the 6-year event-free survival rate for 58+ chromosomes was 99%, compared with 93% for triple trisomies with lower chromosome numbers and 84% for double trisomies with lower chromosome numbers (P = .04).
This finding implies that the favorable outcomes seen in patients with triple and double trisomies were at least partly due to their frequent association with high MNC, Dr. Dastugue said.
Noting that the investigators had consistently found triple trisomies of chromosomes 4, 10, and 17, session comoderator Dr. Christine J. Harrison of the Northern Institute for Cancer Research at Newcastle University in Newcastle upon Tyne, England, asked whether they had found any other trisomies associated with a favorable prognosis.
Dr. Dastugue said that no trisomies tested were significant predictors of outcome.
The trial was sponsored by the European Organisation for Research and Treatment of Cancer. The authors reported no relevant conflicts of interest. Dr. Harrison reported no relevant conflicts.
FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY
Major Finding: Children with B-lineage acute lymphoblastic leukemia who had a modal number of chromosomes (MNC) ranging from 58-66 had a 6-year event-free survival rate of 99%, compared with 80% for patients with MNC 51-53 and 89% for patients with MNC 54-57 (P less than .001).
Data Source: Analysis of flow cytometry and cytogenetic findings from the EORTC CLG 58951 trial.
Disclosures: The trial was sponsored by the European Organisation for Research and Treatment of Cancer. The authors reported no relevant conflicts of interest. Dr. Harrison reported no relevant conflicts.