Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study

J. L. Slack; D. C. Arthur; D. Lawrence; K. Mrózek; R. J. Mayer; F. R. Davey; R. Tantravahi; M. J. Pettenati; S. Bigner; A. J. Carroll; K. W. Rao; C. A. Schiffer; C. D. Bloomfield

doi:10.1200/JCO.1997.15.5.1786

Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study

J. L. Slack, D. C. Arthur, D. Lawrence, K. Mrózek, R. J. Mayer, F. R. Davey, R. Tantravahi, M. J. Pettenati, S. Bigner, A. J. Carroll, K. W. Rao, C. A. Schiffer, C. D. Bloomfield

Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

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Abstract

Purpose: To examine, in newly diagnosed patients with acute promyelocytic leukemia (APL), the prognostic significance of secondary cytogenetic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) mRNA types. Patients and Methods: One hundred sixty-one patients with t(15; 17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in acute myeloid leukemia (AML), were studied. Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and survival. PML- RARα, mRNA type was determined using reverse transcriptase polymerase chain reaction (RT-PCR) in 56 patients. Results: The incidence of secondary cytogenetic abnormalities was 32%. Among 80 patients treated with chemotherapy, the presence of a secondary chromosome abnormality was associated with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P = .03) and longer event-free survival (EFS) duration (median, 17.0 v 12.2 months; P = .03). There was no difference in overall survival (P = .28). In a separate group of 56 patients with both cytogenetic and molecular data, 32 had the type L PML-RARα transcript (intron 6 PML breakpoint). Of these 32 patients, four (12.5%) had chromosome changes in addition to t(15; 17), whereas 12 of 20 patients (60%) with the type S PML-RARα transcript (intron 3 PML breakpoint) had secondary cytogenetic changes (P < .001). Conclusion: (1) Secondary cytogenetic changes do not confer a poor prognosis in APL patients treated with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant relationship exists between the PML-RARα S isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL.

Original language	English (US)
Pages (from-to)	1786-1795
Number of pages	10
Journal	Journal of Clinical Oncology
Volume	15
Issue number	5
DOIs	https://doi.org/10.1200/JCO.1997.15.5.1786
State	Published - May 1997

ASJC Scopus subject areas

Oncology
Cancer Research

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Slack, J. L., Arthur, D. C., Lawrence, D., Mrózek, K., Mayer, R. J., Davey, F. R., Tantravahi, R., Pettenati, M. J., Bigner, S., Carroll, A. J., Rao, K. W., Schiffer, C. A., & Bloomfield, C. D. (1997). Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study. Journal of Clinical Oncology, 15(5), 1786-1795. https://doi.org/10.1200/JCO.1997.15.5.1786

Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study. / Slack, J. L.; Arthur, D. C.; Lawrence, D. et al.
In: Journal of Clinical Oncology, Vol. 15, No. 5, 05.1997, p. 1786-1795.

Research output: Contribution to journal › Article › peer-review

Slack, JL, Arthur, DC, Lawrence, D, Mrózek, K, Mayer, RJ, Davey, FR, Tantravahi, R, Pettenati, MJ, Bigner, S, Carroll, AJ, Rao, KW, Schiffer, CA & Bloomfield, CD 1997, 'Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study', Journal of Clinical Oncology, vol. 15, no. 5, pp. 1786-1795. https://doi.org/10.1200/JCO.1997.15.5.1786

Slack JL, Arthur DC, Lawrence D, Mrózek K, Mayer RJ, Davey FR et al. Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study. Journal of Clinical Oncology. 1997 May;15(5):1786-1795. doi: 10.1200/JCO.1997.15.5.1786

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title = "Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study",

abstract = "Purpose: To examine, in newly diagnosed patients with acute promyelocytic leukemia (APL), the prognostic significance of secondary cytogenetic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) mRNA types. Patients and Methods: One hundred sixty-one patients with t(15; 17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in acute myeloid leukemia (AML), were studied. Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and survival. PML- RARα, mRNA type was determined using reverse transcriptase polymerase chain reaction (RT-PCR) in 56 patients. Results: The incidence of secondary cytogenetic abnormalities was 32%. Among 80 patients treated with chemotherapy, the presence of a secondary chromosome abnormality was associated with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P = .03) and longer event-free survival (EFS) duration (median, 17.0 v 12.2 months; P = .03). There was no difference in overall survival (P = .28). In a separate group of 56 patients with both cytogenetic and molecular data, 32 had the type L PML-RARα transcript (intron 6 PML breakpoint). Of these 32 patients, four (12.5%) had chromosome changes in addition to t(15; 17), whereas 12 of 20 patients (60%) with the type S PML-RARα transcript (intron 3 PML breakpoint) had secondary cytogenetic changes (P < .001). Conclusion: (1) Secondary cytogenetic changes do not confer a poor prognosis in APL patients treated with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant relationship exists between the PML-RARα S isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL.",

author = "Slack, {J. L.} and Arthur, {D. C.} and D. Lawrence and K. Mr{\'o}zek and Mayer, {R. J.} and Davey, {F. R.} and R. Tantravahi and Pettenati, {M. J.} and S. Bigner and Carroll, {A. J.} and Rao, {K. W.} and Schiffer, {C. A.} and Bloomfield, {C. D.}",

year = "1997",

month = may,

doi = "10.1200/JCO.1997.15.5.1786",

language = "English (US)",

volume = "15",

pages = "1786--1795",

journal = "Journal of Clinical Oncology",

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publisher = "American Society of Clinical Oncology",

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T1 - Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene

T2 - A Cancer and Leukemia Group B study

AU - Slack, J. L.

AU - Arthur, D. C.

AU - Lawrence, D.

AU - Mrózek, K.

AU - Mayer, R. J.

AU - Davey, F. R.

AU - Tantravahi, R.

AU - Pettenati, M. J.

AU - Bigner, S.

AU - Carroll, A. J.

AU - Rao, K. W.

AU - Schiffer, C. A.

AU - Bloomfield, C. D.

PY - 1997/5

Y1 - 1997/5

N2 - Purpose: To examine, in newly diagnosed patients with acute promyelocytic leukemia (APL), the prognostic significance of secondary cytogenetic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) mRNA types. Patients and Methods: One hundred sixty-one patients with t(15; 17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in acute myeloid leukemia (AML), were studied. Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and survival. PML- RARα, mRNA type was determined using reverse transcriptase polymerase chain reaction (RT-PCR) in 56 patients. Results: The incidence of secondary cytogenetic abnormalities was 32%. Among 80 patients treated with chemotherapy, the presence of a secondary chromosome abnormality was associated with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P = .03) and longer event-free survival (EFS) duration (median, 17.0 v 12.2 months; P = .03). There was no difference in overall survival (P = .28). In a separate group of 56 patients with both cytogenetic and molecular data, 32 had the type L PML-RARα transcript (intron 6 PML breakpoint). Of these 32 patients, four (12.5%) had chromosome changes in addition to t(15; 17), whereas 12 of 20 patients (60%) with the type S PML-RARα transcript (intron 3 PML breakpoint) had secondary cytogenetic changes (P < .001). Conclusion: (1) Secondary cytogenetic changes do not confer a poor prognosis in APL patients treated with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant relationship exists between the PML-RARα S isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL.

AB - Purpose: To examine, in newly diagnosed patients with acute promyelocytic leukemia (APL), the prognostic significance of secondary cytogenetic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) mRNA types. Patients and Methods: One hundred sixty-one patients with t(15; 17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in acute myeloid leukemia (AML), were studied. Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and survival. PML- RARα, mRNA type was determined using reverse transcriptase polymerase chain reaction (RT-PCR) in 56 patients. Results: The incidence of secondary cytogenetic abnormalities was 32%. Among 80 patients treated with chemotherapy, the presence of a secondary chromosome abnormality was associated with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P = .03) and longer event-free survival (EFS) duration (median, 17.0 v 12.2 months; P = .03). There was no difference in overall survival (P = .28). In a separate group of 56 patients with both cytogenetic and molecular data, 32 had the type L PML-RARα transcript (intron 6 PML breakpoint). Of these 32 patients, four (12.5%) had chromosome changes in addition to t(15; 17), whereas 12 of 20 patients (60%) with the type S PML-RARα transcript (intron 3 PML breakpoint) had secondary cytogenetic changes (P < .001). Conclusion: (1) Secondary cytogenetic changes do not confer a poor prognosis in APL patients treated with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant relationship exists between the PML-RARα S isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL.

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Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A Cancer and Leukemia Group B study

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