By James Foran, MD
There is trouble with T-cell lymphoma. While there have been
significant advances in the biology and treatment of B-cell lymphomas,
peripheral T-cell lymphomas (PTCLs), which comprise almost 15 percent
of all non-Hodgkin lymphomas, remain a difficult challenge. There is
significant heterogeneity within PTCLs, and they are known to have a
prognosis inferior to B-cell lymphoma. In the PTCL education session
this morning and afternoon, advances in pathology, molecular profiling,
and treatment and prognosis are reviewed.
Session Chair Dr. Kerry Savage, of the British Columbia Cancer
Agency, will discuss specific PTCL subtypes and their prognosis, with a
particular focus on CD30-positive anaplastic large cell lymphoma
(ALCL). As part of the International PTCL Project, Dr. Savage has
recently published a detailed study of ALCL pathology and prognosis.
Importantly, she has demonstrated that the ALK-negative ALCLs represent
a unique subset, making the distinction from other PTCLs clinically
important. As Dr. Savage notes, the International Prognostic Index
(IPI) is able to distinguish prognostic groups effectively in PTCL in
general, but does not distinguish well in higher-risk patients.
Specific prognostic models have been developed for PTCL, recognizing
unique adverse prognostic factors such as bone marrow involvement.
Pathologic features, such as γδ phenotype, are also associated with
worse prognosis, and it appears that a single prognostic model may not
apply uniformly in this heterogeneous group of diseases.
The cell of origin of PTCLs is uncertain. Dr. Laurence de Leval of
the University of Liège in Belgium notes that this is due to the
complexity of the T-cell system, with “… only few phenotypic and no
genotypic markers of normal T-cell maturation, and numerous functional
subsets.” In a fascinating presentation, she will review the current
understanding of pathobiology and molecular profiling of PTCLs, with a
focus on angioimmunoblastic T-cell lymphoma (AITL) and ALCL, two of the
more common subtypes.
Dr. de Leval will review the interaction between the malignant T
cells in AITL — where accumulating evidence suggests that the cell of
origin is the follicular helper T cell — and the tumor
microenvironment, which may include clonal (but not neoplastic)
EBV-infected B cells, which may predominate in the clinical
presentation of the disease. On the other hand, in ALCL the cell of
origin is uncertain, although some features suggest they are derived
from a T cell with Th2 phenotype. In ALK-positive disease, the major
oncogenic event is the t(2;5), and secondary genetic alterations appear
to be common; less is known about ALK-negative ALCL. Ongoing studies of
PTCL subtypes are beginning to advance our understanding of T-cell
lymphoma development and oncogenesis.
Lastly, Dr. Steven Horwitz of Memorial Sloan-Kettering Cancer Center
in New York will review the state of treatment of PTCLs in his
presentation titled “If not CHOP?” Both he and Dr. Savage make the
point that CHOP is inadequate in most PTCLs, and new regimens are
needed. Dr. Horwitz will discuss the role of stem cell transplantation,
and feels that if there is efficacy it is likely that “… the benefit is
greatest up front.” As he notes, new agents are being developed in
PTCL, and based on promising results both pralatrexate (antifolate) and
depsipeptide (HDAC inhibitor) are being evaluated in multicenter
registration trials. Other agents such as bevacizumab and denileukin
diftitox are being studied in combination with CHOP.
Common themes throughout the session are the need to develop
T-cell-specific treatment regimens and the importance of supporting
clinical trials in PTCL. The session is being held in the Yerba Buena
Ballroom of the San Francisco Marriott, Salons 7-8, today at 9:30 a.m.
and again at 4:00 p.m.
Dr. Foran indicated no relevant conflicts of interest.
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