scholarly journals Flow Cytometric DNA Index and Karyotype in Childhood Lymphoblastic Leukemia

1998 ◽  
Vol 17 (3) ◽  
pp. 145-156 ◽  
Author(s):  
Erik Forestier ◽  
Gösta Holmgren ◽  
Göran Roos
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chromosome Number ◽  
Chromosome Numbers ◽  
Lymphoblastic Leukemia ◽  
Prognostic Information ◽  
Dna Index ◽  
Treatment Protocols ◽  
Flow Cytometric ◽  
Modal Chromosome Number ◽  
Flow Cytometric Measurement

Flow cytometric DNA-index (DIFCM) and karyotype were analysed in 82 consecutive children with acute lymphoblastic leukemia (ALL) during a 10 year period. A statistically significant correlation existed between modal chromosome number and DIFCM(p= 0.009). DIFCMcould reliably identify leukemias with >51 chromosomes, whereas only three out of 12 cases with modal chromosome numbers between 47–51 were classified as aneuploid by DIFCM. In the pseudodiploid group only one out of 20 leukemias had a DIFCM>1.0. Five leukemias with a diploid karyotype showed an aneuploid DIFCMand in three patients the flow cytometric measurement revealed biclonality undetected by karyotyping. During treatment aneuploid clones could be detected by DIFCMin a substantial number of cases where the cytogenetic analysis was normal, and the opposite was also demonstrated in one case. DIFCMgave prognostic information, showing that cases with a DI >1.12 (corresponding to 51 chromosomes) had a superior outcome with treatment protocols today in use.

scholarly journals Prognostic importance of chromosome number in 136 untreated children with acute lymphoblastic leukemia

Blood ◽  
1982 ◽  
Vol 60 (4) ◽  
pp. 864-871 ◽  
Author(s):  
DL Williams ◽  
A Tsiatis ◽  
GM Brodeur ◽  
AT Look ◽  
SL Melvin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Chromosome Number ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Time To Failure ◽  
Prognostic Information ◽  
Prognostic Group ◽  
Induction Failure

Abstract Leukemia cell karyotypes were determined at diagnosis for 136 of 159 consecutive patients with acute lymphoblastic leukemia (ALL) who were followed for up to 35 mo. Ninety patients (67%) had abnormal karyotypes. Five chromosome categories were designated, based on the distribution of modal numbers: hyperdiploid greater than 50 (n = 41), hyperdiploid 47–50 (n = 18), pseudodiploid (n = 28), normal (n = 46), and hypodiploid (n = 3). Treatment response was assessed for the categories in terms of time to failure (induction failure, first relapse, or death). Children in the hyperdiploid greater than 50 category had the best responses to treatment, with only 2 failures, and those in the pseudodiploid category had the poorest (p less than 0.001). The remaining 3 chromosome categories had intermediate responses and formed a third prognostic group. This same influence of chromosome number on time to failure was evident within the 2 clinical prognostic groups: high risk, signified by a leukocyte count greater than 100 X 10(9)/liter, meningeal leukemia, mediastinal mass, or the presence of blasts that formed rosettes with sheep erythrocytes at 37 degrees C, and standard risk, indicated by the absence of these features. The influence of chromosome number on time to failure was also the same within the historically favorable prognostic group that had common ALL. Results of a multivariate analysis indicated that chromosome number was the strongest single predictor of outcome (p less than 0.001) and was the only variable that added significant prognostic information to leukocyte count (p less than 0.001). The combination of chromosome number and leukocyte count should more clearly distinguish patients with ALL at low or high risk of relapse.

Prognostic Impact of Trisomies of Chromosomes 10, 17, and 5 Among Children With Acute Lymphoblastic Leukemia and High Hyperdiploidy (> 50 Chromosomes)

2000 ◽  
Vol 18 (9) ◽  
pp. 1876-1887 ◽  
Author(s):  
Nyla A. Heerema ◽  
Harland N. Sather ◽  
Martha G. Sensel ◽  
Tracy Zhang ◽  
Raymond J. Hutchinson ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chromosome Number ◽  
Lymphoblastic Leukemia ◽  
Chromosome 17 ◽  
Significant Prognostic Factor ◽  
Prognostic Impact ◽  
Chromosome 5 ◽  
Chromosome 10 ◽  
Modal Chromosome Number ◽  
Improved Outcome

PURPOSE: Children with acute lymphoblastic leukemia (ALL) and high hyperdiploidy (> 50 chromosomes) have improved outcome compared with other ALL patients. We sought to identify cytogenetic features that would predict differences in outcome within this low-risk subset of ALL patients. MATERIALS AND METHODS: High-hyperdiploid ALL patients (N = 480) were enrolled between 1988 and 1995 on Children’s Cancer Group (CCG) trials. Karyotypes were determined by conventional banding. Treatment outcome was analyzed by life-table methods. RESULTS: Patients with 54 to 58 chromosomes had better outcome than patients with 51 to 53 or 59 to 68 chromosomes (P = .0002). Patients with a trisomy of chromosome 10 (P < .0001), chromosome 17 (P = .0002), or chromosome 18 (P = .004) had significantly improved outcome compared with their counterparts who lacked the given trisomy. Patients with a trisomy of chromosome 5 had worse outcome than patients lacking this trisomy (P = .02). Patients with trisomies of both chromosomes 10 and 17 had better outcome than those with a trisomy of chromosome 10 (P = .09), a trisomy of chromosome 17 (P = .01), or neither trisomy (P < .0001). Multivariate analysis indicated that trisomy of chromosome 10 (P = .001) was the most significant prognostic factor for high-hyperdiploid patients, yet trisomy of chromosome 17 (P = .02) or chromosome 5 (P = .01) and modal chromosome number (P = .02) also had significant multivariate effects. CONCLUSION: Trisomy of chromosomes 10 and 17 as well as modal chromosome number 54 to 58 identify subgroups of patients with high-hyperdiploid ALL who have a better outcome than high-hyperdiploid patients who lack these cytogenetic features. Trisomy of chromosome 5 confers poorer outcome among high-hyperdiploid patients.

scholarly journals Prognostic importance of chromosome number in 136 untreated children with acute lymphoblastic leukemia

Blood ◽  
1982 ◽  
Vol 60 (4) ◽  
pp. 864-871 ◽  
Author(s):  
DL Williams ◽  
A Tsiatis ◽  
GM Brodeur ◽  
AT Look ◽  
SL Melvin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Chromosome Number ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Time To Failure ◽  
Prognostic Information ◽  
Prognostic Group ◽  
Induction Failure

Leukemia cell karyotypes were determined at diagnosis for 136 of 159 consecutive patients with acute lymphoblastic leukemia (ALL) who were followed for up to 35 mo. Ninety patients (67%) had abnormal karyotypes. Five chromosome categories were designated, based on the distribution of modal numbers: hyperdiploid greater than 50 (n = 41), hyperdiploid 47–50 (n = 18), pseudodiploid (n = 28), normal (n = 46), and hypodiploid (n = 3). Treatment response was assessed for the categories in terms of time to failure (induction failure, first relapse, or death). Children in the hyperdiploid greater than 50 category had the best responses to treatment, with only 2 failures, and those in the pseudodiploid category had the poorest (p less than 0.001). The remaining 3 chromosome categories had intermediate responses and formed a third prognostic group. This same influence of chromosome number on time to failure was evident within the 2 clinical prognostic groups: high risk, signified by a leukocyte count greater than 100 X 10(9)/liter, meningeal leukemia, mediastinal mass, or the presence of blasts that formed rosettes with sheep erythrocytes at 37 degrees C, and standard risk, indicated by the absence of these features. The influence of chromosome number on time to failure was also the same within the historically favorable prognostic group that had common ALL. Results of a multivariate analysis indicated that chromosome number was the strongest single predictor of outcome (p less than 0.001) and was the only variable that added significant prognostic information to leukocyte count (p less than 0.001). The combination of chromosome number and leukocyte count should more clearly distinguish patients with ALL at low or high risk of relapse.

scholarly journals Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1079-1086 ◽  
Author(s):  
AT Look ◽  
PK Roberson ◽  
DL Williams ◽  
G Rivera ◽  
WP Bowman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Dna Content ◽  
Proportional Hazards Model ◽  
Lymphoblastic Leukemia ◽  
Sheep Erythrocyte ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Current Therapy ◽  
Prognostic Impact ◽  
Dna Index

Using flow cytometric techniques, we determined the pretreatment distribution of DNA content in propidium iodide-stained leukemic blasts from 205 children with “standard-risk” acute lymphoblastic leukemia (ALL). Risk assignment was based on an initial WBC count less than 100 X 10(9)/L, no thymic mass, no meningeal leukemia, and lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. A single aneuploid leukemic line was detected in 74 cases (36.1%): 70 hyperdiploid and four hypodiploid. For hyperdiploid cases, the DNA index (DI, or ratio of the DNA content of leukemic v normal G0/G1 cells) ranged from 1.06 to 2.0 (median, 1.20). A secondary leukemic line with hyperdiploid cellular DNA content was identified in 21 cases with diploid primary lines. Children whose primary leukemic line showed a DI greater than or equal to 1.16 (n = 57) had significantly better responses to treatment than did those with either a diploid DI (n = 130; P = .002) or values in the range of 1.01 to 1.15 (n = 14; P = .001). The relative risk of failure for hyperdiploid cases with DI greater than or equal to 1.16, corresponding to greater than or equal to 53 chromosomes, was one-third that of the other two groups. Treatment responses of patients with both diploid and hyperdiploid lines were identical to those associated with single diploid lines, but significantly worse than those associated with single hyperdiploid lines with DI greater than or equal to 1.16 (P = .016). The most favorable prognostic variables selected by a Cox proportional hazards model were: DI greater than or equal to 1.16 (P = .001), white race (P = .022), WBC less than or equal to 25 X 10(9)/L (P = .032), age between 2 and 9 years (P = .075), and hemoglobin less than 7.0 g/dL (P = .094). DNA index greater than or equal to 1.16 retained its significant prognostic impact even after adjustment for other variables (P = .001). With the combination of DI greater than or equal to 1.16 and WBC less than or equal to 25 X 10(9)/L, one can identify a group of children with ALL who have a low probability of relapse when treated with current therapy. If they remain disease-free after longer follow-up, it may be advisable to treat them with less intensive, hence less toxic, chemotherapy than patients with higher WBC counts or lower DI values.

scholarly journals RUSSIAN-BELARUSIAN MULTICENTER GROUP STANDARD GUIDELINES FOR CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA FLOW CYTOMETRIC DIAGNOSTICS

2018 ◽  
Vol 13 (1) ◽  
pp. 73-82 ◽  
Author(s):  
I. A. Novikova ◽  
T. Yu. Verzhbitskaya ◽  
L. V. Movchan ◽  
G. A. Tsaur ◽  
М. V. Belevtsev ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Group Standard ◽  
Flow Cytometric
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