TY - JOUR
T1 - What are the endpoints of therapy for acute leukemias? Old definitions and new challenges.
AU - Smith, B. Douglas
AU - Karp, Judith E.
N1 - Funding Information:
Dr. Judith E. Karp has received grant or research funding from Genzyme Corp; Sunesis Pharmaceuticals, Inc; Aegera; and Kyowa; has received honoraria from Genzyme Corp; and has served on an advisory committee or review panel for Xanthus Pharmaceuticals, Inc.; Actinium; and Cerus.
Funding Information:
Grant support was provided from the following National Cancer Institute grants: U01 CA70095, 2P30 CA06973-44.
Funding Information:
Dr. B. Douglas Smith has received grant or research funding from Novartis Pharmaceuticals Corp; Syndax; and Eisai, Inc.; has served on a Speaker’s Bureau for Celgene Corp; has served on an advisory committee or review panel for Bristol-Myers Squibb Company.
PY - 2009
Y1 - 2009
N2 - Acute leukemias are complex diseases on multiple levels, and laboratory efforts over the past 3 decades have focused on better understanding of the molecular underpinnings and their stem cell biology. We now have a panoply of technologic advances that allow us to characterize individual leukemias by molecular profiles that relate directly to clinical behavior, to detect minimal residual disease, and to begin to develop "targeted" therapeutic strategies based on molecular considerations. There are a number of challenges surrounding this task: first, how to combine these agents with traditional chemotherapeutics and/or with each other to maximize leukemic cell kill and increase the cure rate; second, how to use these targeted agents in the minimal residual disease with potential curative intent; third, for patients unable to tolerate or unlikely to benefit from aggressive approaches, how to use one or more of these agents to reduce tumor bulk and either permit some restoration of normal marrow function or induce morphologic and functional differentiation of the leukemic clone to overcome the leukemia-associated bone marrow failure; and lastly, how to measure the effects of these agents on the molecular and cellular biologic levels in ways that correlate with and might even predict overall clinical outcome. These challenges are further complicated by the inherent heterogeneity in host biology; disease etiology and biology; and interactions among host, disease, and treatment that ultimately determine individual clinical outcomes. Toward this end, we will discuss selected issues surrounding new clinical trial designs and the development of clinically relevant molecular endpoints that might facilitate the development of new treatment approaches that will improve the outlook for adults with acute leukemias.
AB - Acute leukemias are complex diseases on multiple levels, and laboratory efforts over the past 3 decades have focused on better understanding of the molecular underpinnings and their stem cell biology. We now have a panoply of technologic advances that allow us to characterize individual leukemias by molecular profiles that relate directly to clinical behavior, to detect minimal residual disease, and to begin to develop "targeted" therapeutic strategies based on molecular considerations. There are a number of challenges surrounding this task: first, how to combine these agents with traditional chemotherapeutics and/or with each other to maximize leukemic cell kill and increase the cure rate; second, how to use these targeted agents in the minimal residual disease with potential curative intent; third, for patients unable to tolerate or unlikely to benefit from aggressive approaches, how to use one or more of these agents to reduce tumor bulk and either permit some restoration of normal marrow function or induce morphologic and functional differentiation of the leukemic clone to overcome the leukemia-associated bone marrow failure; and lastly, how to measure the effects of these agents on the molecular and cellular biologic levels in ways that correlate with and might even predict overall clinical outcome. These challenges are further complicated by the inherent heterogeneity in host biology; disease etiology and biology; and interactions among host, disease, and treatment that ultimately determine individual clinical outcomes. Toward this end, we will discuss selected issues surrounding new clinical trial designs and the development of clinically relevant molecular endpoints that might facilitate the development of new treatment approaches that will improve the outlook for adults with acute leukemias.
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U2 - 10.3816/clm.2009.s.027
DO - 10.3816/clm.2009.s.027
M3 - Review article
C2 - 19778856
AN - SCOPUS:74049092362
SN - 2152-2669
VL - 9 Suppl 3
SP - S296-301
JO - Clinical lymphoma & myeloma
JF - Clinical lymphoma & myeloma
ER -