Therapy-related acute myelogenous leukemia and myelodysplastic syndrome in patients with acute lymphoblastic leukemia treated with the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimens

Dushyant Verma, Susan O'Brien, Deborah Thomas, Stefan Faderl, Charles Koller, Sherry Pierce, Partow Kebriaei, Guillermo Garcia-Manero, Jorge Cortes, Hagop Kantarjian, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children. METHODS: A total of 641 patients with de novo ALL who were treated with the hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its variants were analyzed. RESULTS: Sixteen patients (2.49%) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients). At the time of ALL diagnosis, the median age was 53 years; cytogenetics were normal in 11 patients, pseudo-diploidy with del(2) in 1 patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy included hyper-CVAD in 7 patients, hyper-CVAD with rituximab in 8 patients, and hyper-CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was -5, -7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients. Secondary AML/MDS developed at a median of 32 months after ALL diagnosis. Cytarabine plus anthracycline-based treatment was given to 12 patients with AML and high-risk MDS. One patient with MDS received arsenic trioxide, 1 received clofarabine, and 2 received decitabine. Response to treatment was complete remission in 3 patients, partial remission in 6 patients, and no response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5-11 months) after transplantation. The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months). CONCLUSIONS: Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper-CVAD regimens, and response to therapy is poor.

Original languageEnglish (US)
Pages (from-to)101-106
Number of pages6
JournalCancer
Volume115
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Myelodysplastic Syndromes
Vincristine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Doxorubicin
Cyclophosphamide
Dexamethasone
Therapeutics
decitabine

Keywords

  • Acute lymphoblastic leukemia
  • Hyper-CVAD
  • Secondary acute myelogenous leukemia
  • Secondary myelodysplastic syndrome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Therapy-related acute myelogenous leukemia and myelodysplastic syndrome in patients with acute lymphoblastic leukemia treated with the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimens. / Verma, Dushyant; O'Brien, Susan; Thomas, Deborah; Faderl, Stefan; Koller, Charles; Pierce, Sherry; Kebriaei, Partow; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop; Ravandi, Farhad.

In: Cancer, Vol. 115, No. 1, 01.01.2009, p. 101-106.

Research output: Contribution to journalArticle

Verma, Dushyant ; O'Brien, Susan ; Thomas, Deborah ; Faderl, Stefan ; Koller, Charles ; Pierce, Sherry ; Kebriaei, Partow ; Garcia-Manero, Guillermo ; Cortes, Jorge ; Kantarjian, Hagop ; Ravandi, Farhad. / Therapy-related acute myelogenous leukemia and myelodysplastic syndrome in patients with acute lymphoblastic leukemia treated with the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimens. In: Cancer. 2009 ; Vol. 115, No. 1. pp. 101-106.
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abstract = "BACKGROUND: Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children. METHODS: A total of 641 patients with de novo ALL who were treated with the hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its variants were analyzed. RESULTS: Sixteen patients (2.49{\%}) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients). At the time of ALL diagnosis, the median age was 53 years; cytogenetics were normal in 11 patients, pseudo-diploidy with del(2) in 1 patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy included hyper-CVAD in 7 patients, hyper-CVAD with rituximab in 8 patients, and hyper-CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was -5, -7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients. Secondary AML/MDS developed at a median of 32 months after ALL diagnosis. Cytarabine plus anthracycline-based treatment was given to 12 patients with AML and high-risk MDS. One patient with MDS received arsenic trioxide, 1 received clofarabine, and 2 received decitabine. Response to treatment was complete remission in 3 patients, partial remission in 6 patients, and no response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5-11 months) after transplantation. The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months). CONCLUSIONS: Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper-CVAD regimens, and response to therapy is poor.",
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AU - O'Brien, Susan

AU - Thomas, Deborah

AU - Faderl, Stefan

AU - Koller, Charles

AU - Pierce, Sherry

AU - Kebriaei, Partow

AU - Garcia-Manero, Guillermo

AU - Cortes, Jorge

AU - Kantarjian, Hagop

AU - Ravandi, Farhad

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N2 - BACKGROUND: Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children. METHODS: A total of 641 patients with de novo ALL who were treated with the hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its variants were analyzed. RESULTS: Sixteen patients (2.49%) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients). At the time of ALL diagnosis, the median age was 53 years; cytogenetics were normal in 11 patients, pseudo-diploidy with del(2) in 1 patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy included hyper-CVAD in 7 patients, hyper-CVAD with rituximab in 8 patients, and hyper-CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was -5, -7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients. Secondary AML/MDS developed at a median of 32 months after ALL diagnosis. Cytarabine plus anthracycline-based treatment was given to 12 patients with AML and high-risk MDS. One patient with MDS received arsenic trioxide, 1 received clofarabine, and 2 received decitabine. Response to treatment was complete remission in 3 patients, partial remission in 6 patients, and no response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5-11 months) after transplantation. The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months). CONCLUSIONS: Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper-CVAD regimens, and response to therapy is poor.

AB - BACKGROUND: Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children. METHODS: A total of 641 patients with de novo ALL who were treated with the hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its variants were analyzed. RESULTS: Sixteen patients (2.49%) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients). At the time of ALL diagnosis, the median age was 53 years; cytogenetics were normal in 11 patients, pseudo-diploidy with del(2) in 1 patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy included hyper-CVAD in 7 patients, hyper-CVAD with rituximab in 8 patients, and hyper-CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was -5, -7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients. Secondary AML/MDS developed at a median of 32 months after ALL diagnosis. Cytarabine plus anthracycline-based treatment was given to 12 patients with AML and high-risk MDS. One patient with MDS received arsenic trioxide, 1 received clofarabine, and 2 received decitabine. Response to treatment was complete remission in 3 patients, partial remission in 6 patients, and no response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5-11 months) after transplantation. The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months). CONCLUSIONS: Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper-CVAD regimens, and response to therapy is poor.

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