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CHAPTER 104 aimed at improving upon CHOP by adding novel agents or using alternate reg-

MATURE T-CELL AND imens. Although controversial, patients are often considered for consolidation
with autologous stem cell transplant in first remission to improve remission
NATURAL KILLER CELL durations. Recently, targeted agents specific for particular T-cell and NK-cell
lymphomas, such as brentuximab vedotin for ALCL and crizotinib for anaplastic
LYMPHOMAS lymphoma kinase (ALK)-positive ALCL, are now allowing the investigation
of more individualized therapy for these entities. Furthermore, for a consid-
erable number of the T-cell and NK-cell lymphoma entities, including ENKTL
and ATL, CHOP-based therapy is ineffective, and treatment strategies are
Neha Mehta, Alison Moskowitz, and Steven Horwitz disease-specific. There is still much to learn about the biology and potential
drug targets for these diseases and ongoing studies using gene expression
profiling and genomics may help answer some of these questions. In addition,
SUMMARY ongoing clinical trials evaluating disease-specific treatment approaches and
employing novel and often targeted agents will hopefully lead to improved
The mature T-cell and natural killer (NK)-cell lymphomas represent 10 to 15 outcomes for patients with these diseases.
percent of the non-Hodgkin lymphomas by incidence and comprise 23 clini-
copathologic entities in the most recent classification. They include cutaneous
T-cell lymphomas, discussed in Chap. 103, and systemic T-cells lymphomas, OVERVIEW OF MATURE T-CELL
which are discussed here. The systemic T-cell lymphomas have highly variable LYMPHOMAS
courses and are typically aggressive and frequently less responsive to con-
ventional chemotherapy than their B-cell counterparts. The most common The peripheral T-cell lymphomas (PTCLs) represent approximately 10 to
systemic T-cell and NK-cell lymphomas worldwide include peripheral T-cell 15 percent of non-Hodgkin lymphomas and are made up of 23 hetero-
1
lymphoma, not otherwise specified (PTCL-NOS) and angioimmunoblastic geneous diseases (Table 104–1). The most common entities, peripheral
T-cell lymphoma (AITL), representing 26 percent and 19 percent of systemic T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmu-
T-cell and NK-cell lymphomas, respectively. There is considerable geographic noblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase
variation in the incidence of certain entities, such as adult T-cell leukemia/ (ALK)-positive anaplastic large cell lymphoma (ALCL), and ALK-negative
ALCL, account for approximately 60 percent of cases. This overview
lymphoma (ATL) and extranodal NK/T-cell lymphoma (ENKTL). In view of the primarily pertains to these most common subtypes of PTCL and more
rarity of systemic T-cell and NK-cell disorders, large randomized trials are lack- detailed discussion of other subsets of PTCL follows this discussion.
ing to guide therapies. Treatment strategies are generally based upon the best As a result of the rarity of these disorders, there are no random-
data available, which includes prospective phase II studies and retrospective ized controlled clinical trials to drive treatment decisions in PTCL. Our
analyses. The most frequently used regimens for the more common entities, most comprehensive knowledge of the expected outcomes for patients
PTCL-NOS, AITL, and anaplastic large cell lymphoma (ALCL) are cyclophos- with PTCL is mainly based upon three large retrospective series: the
phamide, doxorubicin, vincristine, prednisone (CHOP)-based, although long- International Peripheral T-Cell Lymphoma Project (IPTCLP), the
term outcomes are often unsatisfactory. Therefore, ongoing clinical trials are British Columbia Cancer Agency (BCCA) series, and a Swedish series
which reported outcomes on 1314 cases, 199 cases, and 755 cases,
2–4
respectively. The prospective Comprehensive Oncology Measures
for Peripheral T-Cell Lymphoma Treatment (COMPLETE) study is an
ongoing registry of patients from the United States that has reported
Acronyms and Abbreviations: AITL, angioimmunoblastic T-cell lymphoma; data on 253 subjects to date. These registries underscore the geographi-
5
ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; ASCT, cal variations in the incidence of these disorders (Table 104–2).
autologous stem cell transplantation; ATL, adult T-cell leukemia/lymphoma; BCCA,
British Columbia Cancer Agency; CHOEP, cyclophosphamide, doxorubicin, vincris- DIAGNOSIS OF PERIPHERAL T-CELL
tine, etoposide, prednisone; CHOP, cyclophosphamide, hydroxydaunorubicin (dox-
orubicin), vincristine (Oncovin), prednisone; CR, complete response; CT, computed LYMPHOMA
tomography; DHAP, dexamethasone, cytarabine, cisplatinum; DSHNHL, German High- The diagnosis of PTCL is based on histologic features, immunopheno-
Grade Non-Hodgkin Lymphoma Study Group; EBV, Epstein-Barr virus; EFS, event-free type, molecular studies, and clinical presentation. While B-cell lympho-
survival; ENKTL, extranodal NK/T-cell lymphoma; FFS, failure-free survival; HTLV, mas are often characterized by a specific immunophenotypic profile,
human T-lymphotrophic virus; hyper-CVAD, cyclophosphamide, vincristine, dox- T-cell lymphomas are often characterized by antigen aberrancy that
orubicin, methotrexate, cytarabine; ICE, ifosfamide, carboplatin, etoposide; IVAC, may vary within a subtype or even during the course of the disease.
6,7
ifosfamide, etoposide, cytarabine; IPI, International Prognostic Index; IPTCLP, Inter- In the IPTCLP, a consensus diagnosis (three of four expert pathologists
national Peripheral T-Cell Lymphoma Project; LDH, lactate dehydrogenase; MACOP-B, arriving at the same diagnosis) was reached only 74 to 81 percent of the
high-dose methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, time for ALK-negative ALCL, PTCL-NOS, and AITL. Diagnoses were
bleomycin; NK, natural killer; ORR, overall response rate; OS, overall survival; PCR, significantly refined in 154 out of 1314 cases when clinical information
3
polymerase chain reaction; PET, positron emission tomography; PFS, progression- was available. In establishing the diagnosis of T-cell non-Hodgkin lym-
free survival; PIT, prognostic Index for T-cell lymphoma; PR, partial response; PTCL, phoma, it is important to exclude a reactive process, particularly when
peripheral T-cell lymphoma; PTCL-NOS, peripheral T-cell lymphoma, not otherwise the clinical picture is not congruent with the pathologic features, when
specified; SMILE, dexamethasone, methotrexate, ifosfamide, l-asparaginase, and the diagnostic biopsy is small, or when a clonal T-cell receptor (TCR)
etoposide; TCR, T-cell receptor. rearrangement is the primary or only reason for the diagnosis because
reactive nonmalignant conditions often mimic PTCL. 8–10

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