Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia

Judith E Karp; Amanda Blackford; B Douglas Smith; Katrina Alino; Amy Hatfield Seung; Javier Bolaños-Meade; Jacqueline M Greer; Hetty E Carraway; Steven D Gore; Richard J Jones; Mark J Levis; Michael A McDevitt; L Austin Doyle; John J Wright

doi:10.1016/j.leukres.2009.11.007

Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia

Leuk Res. 2010 Jul;34(7):877-82. doi: 10.1016/j.leukres.2009.11.007. Epub 2009 Dec 4.

Authors

Judith E Karp¹, Amanda Blackford, B Douglas Smith, Katrina Alino, Amy Hatfield Seung, Javier Bolaños-Meade, Jacqueline M Greer, Hetty E Carraway, Steven D Gore, Richard J Jones, Mark J Levis, Michael A McDevitt, L Austin Doyle, John J Wright

Affiliation

¹ Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA. [email protected]

Abstract

Flavopiridol, a cyclin-dependent kinase inhibitor, is cytotoxic to leukemic blasts. In a Phase II study, flavopiridol 50 mg/m(2) was given by 1-h infusion daily x 3 beginning day 1 followed by 2 g/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9 (FLAM) to 45 adults with newly diagnosed acute myelogenous leukemia (AML) with multiple poor-risk features. Thirty patients (67%) achieved complete remission (CR) and 4 (9%) died. Twelve (40%) received myeloablative allogeneic bone marrow transplant (BMT) in first CR. Median OS and DFS are not reached (67% alive 12.5-31 months, 58% in CR 11.4-30 months), with median follow-up 22 months. Sixteen received FLAM in CR, with median OS and DFS 9 and 13.1 months, and 36% alive at 21-31 months. Short OS and DFS correlated with adverse cytogenetics, regardless of age or treatment in CR. The addition of allogeneic BMT in CR translates into long OS and DFS in the majority of eligible patients.

Publication types

Clinical Trial, Phase II
Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged
Allopurinol / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Bone Marrow Transplantation
Combined Modality Therapy
Cytarabine / administration & dosage
Cytarabine / adverse effects
Disease-Free Survival
Female
Flavonoids / administration & dosage
Flavonoids / adverse effects
Follow-Up Studies
Heart Diseases / chemically induced
Humans
Hyperkalemia / chemically induced
Hyperkalemia / prevention & control
Kaplan-Meier Estimate
Leukemia, Myeloid, Acute / drug therapy*
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / surgery
Male
Middle Aged
Mitoxantrone / administration & dosage
Mitoxantrone / adverse effects
Piperidines / administration & dosage
Piperidines / adverse effects
Polyamines / therapeutic use
Premedication
Remission Induction
Risk
Sepsis / etiology
Sepsis / mortality
Sevelamer
Transplantation, Homologous
Treatment Outcome
Tumor Lysis Syndrome / etiology
Tumor Lysis Syndrome / prevention & control
Young Adult

Substances

Flavonoids
Piperidines
Polyamines
Cytarabine
alvocidib
Allopurinol
Sevelamer
Mitoxantrone

Abstract

Publication types

MeSH terms

Substances

Grants and funding