OWN - NLM
DA - 20170807
LR - 20170807
IS - 1096-8652 (Electronic)
IS - 0361-8609 (Linking)
VI - 92
IP - 9
DP - 2017 Sep
TI - Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and
PG - 946-965
LID - 10.1002/ajh.24826 [doi]
AB - DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in
western countries. The disease typically occurs in elderly patients and has a
highly variable clinical course. Leukemic transformation is initiated by specific
genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The
diagnosis is established by blood counts, blood smears, and immunophenotyping of
circulating B lymphocytes, which identify a clonal B-cell population carrying the
CD5 antigen and B-cell markers. PROGNOSIS: Two prognostic staging systems exist,
the Rai and Binet staging systems, which are established by physical examination
and blood counts. Various biological and genetic markers also have prognostic
value. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of
the TP53 gene predict resistance to available chemotherapies. A comprehensive
prognostic score (CLL-IPI) using genetic, biological, and clinical variables has
recently been developed allowing to classify CLL into very distinct risk groups.
THERAPY: Patients with active or symptomatic disease or with advanced Binet or
Rai stages require therapy. For physically fit patients, chemoimmunotherapy with
fludarabine, cyclophosphamide, and rituximab remains the current standard
therapy. For unfit patients, currently available evidence supports two options
for a first-line therapy: chlorambucil combined with an anti-CD20 antibody
(obinutuzumab or rituximab or ofatumumab) or a continuous therapy with ibrutinib.
At relapse, the initial treatment may be repeated, if the treatment-free interval
exceeds 3 years. If the disease relapses earlier, therapy should be changed using
alternative agents such as bendamustine (plus rituximab), alemtuzumab,
lenalidomide, ofatumumab, ibrutinib, idelalisib, or venetoclax. Patients with a
del(17p) or TP53 mutation can be treated with ibrutinib, venetoclax, or a
combination of idelalisib and rituximab. An allogeneic SCT may be considered in
relapsing patients with TP53 mutations or del(17p) or patients that are
refractory to chemoimmunotherapy and the novel inhibitors. FUTURE CHALLENGES: The
new agents (ibrutinib, idelalisib, venetoclax, and obinutuzumab) hold the
potential to significantly improve the outcome of CLL patients. However, their
optimal use (in terms of combination, sequence, and duration) remains unknown.
Therefore, CLL patients should be treated in clinical trials whenever possible.
CI - (c) 2017 Wiley Periodicals, Inc.
FAU - Hallek, Michael
AU - Hallek M
AD - Department I of Internal Medicine, Center for Integrated Oncology Koln Bonn,
Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases,"
University of Cologne, Kerpener Strasse 62, Koln, 50937, Germany.
LA - eng
PT - Journal Article
PL - United States
TA - Am J Hematol
JT - American journal of hematology
JID - 7610369
EDAT- 2017/08/08 06:00
MHDA- 2017/08/08 06:00
CRDT- 2017/08/08 06:00
PHST- 2017/06/14 [received]
PHST- 2017/06/15 [accepted]
AID - 10.1002/ajh.24826 [doi]
PST - ppublish
SO - Am J Hematol. 2017 Sep;92(9):946-965. doi: 10.1002/ajh.24826.