Page 1722 - Williams Hematology ( PDFDrive )

1696 Part XI: Malignant Lymphoid Diseases Chapter 104: Mature T-Cell and Natural Killer Cell Lymphomas 1697

53
94 percent, although the translocation was only detected in 39 percent. 20 to 30 percent seen in the larger retrospective series. Efforts to improve
2–4
These findings suggest a potential role for SYK inhibitors in these the efficacy of first-line therapy by adding new agents to CHOP, such
54
cases. Mutations involving the TET2 gene appear to be common in as alemtuzumab, bortezomib, or denileukin diftitox, have not clearly
AITL as well as PTCL-NOS expressing T-follicular helper (T ) cell resulted in significant benefit. 20,12,19 The addition of etoposide to CHOP
FH
markers; they are less frequent among the other PTCL-NOS cases appears to provide some benefit over CHOP in more favorable young
55
(24 percent) and absent in ALCL. TET2 is involved in epigenetic con- patients, according to a retrospective analysis of seven prospective stud-
trol of transcription through DNA methylation and inactivating mutations ies conducted by the DSHNHL. Moreover, in a prospective study of
21
of this gene were first identified in myeloid malignancies. These mutations CHOEP followed by ASCT, the ORR to CHOEP was 82 percent, with 51
signify a biologic connection between AITL and PTCL-NOS with AITL fea- percent achieving a CR. Newer agents approved in the relapsed setting,
22
tures (T -like PTCL-NOS) and suggest a role for hypomethylating agents. such as romidepsin and brentuximab vedotin, are currently being com-
FH
bined with CHOP-based regimens and compared to standard CHOP in
PERIPHERAL T-CELL LYMPHOMA, ongoing phase III clinical trials.
Another strategy for improving frontline therapy for PTCL-NOS
NOT OTHERWISE SPECIFIED has been through consolidation with ASCT in first remission, as dis-
cussed in “Approach to Initial Therapy” above. Even though there are no
DEFINITION randomized trials of ASCT in first remission, three prospective phase II
PTCLs that do not fit into any of the currently recognized histopatho- trials support this approach. 15,22,23 The largest of these studies demon-
logic categories are designated PTCL, not otherwise specified (PTCL- strated 5-year OS and PFS of 47 percent and 38 percent, respectively in
NOS; Chap. 96.) patients with PTCL-NOS. 22
Allogeneic transplantation provides long-term disease con-
EPIDEMIOLOGY trol for a select group of patients with relapsed PTCL-NOS. Although
transplant-related mortality is significant, retrospective studies have
PTCL-NOS is the most common of the mature T-cell neoplasms, repre- demonstrated up to 61 percent OS at 2 years in some trials. Conse-
senting approximately 25 to 30 percent of the total cases of T-cell lymphoma quently, allogeneic transplantation is often considered for fit patients
in Western countries. 56–58 In the United States, there are approximately who fail frontline therapy. 23,39,66
62
0.4 cases per 100,000 adults. In Asia, PTCL-NOS accounts for 20 to Several promising new agents, including belinostat, bendamustine,
3,57
25 percent of cases mature T-cell neoplasms (see Table 104–2). The gemcitabine, and alemtuzumab, have become available for the treatment
median age of diagnosis is 60 years with a male predominance (2:1). 3,7 of PTCL-NOS in the relapsed setting. 28,40–42 Pralatrexate, romidepsin,
and belinostat are approved broadly for PTCL, with an approximately
CLINICAL FINDINGS 20 to 30 percent ORR in large phase II studies (see Table 104–4). 27,71,72
In general, patients with PTCL-NOS have aggressive, rapidly growing Overall, the 5-year FFS for PTCL-NOS is 20 percent with a 5-year
60
disease. Diffuse lymphadenopathy, constitutional symptoms, extran- OS of 32 percent in patients treated with CHOP-based therapy. The
odal involvement, an elevated LDH level, and advanced stage disease IPI and PIT have been used to risk stratify patients with PTCL-NOS
are common. 56,57 Hepatomegaly and splenomegaly occur in 17 percent and estimate prognosis. For patients with PIT scores of 0, 1, 2, or 3
and 24 percent of patients, respectively. Stages I, II, III, and IV disease or greater, the 5-year FFSs are 34 percent, 22 percent, 13 percent, and
are observed in approximately 14 percent, 17 percent, 26 percent, and 43 8 percent, respectively. For patients with IPI scores of 1 or less, 2, 3, or
percent of cases, respectively. The marrow is involved in approximately 4 or greater, 5-year FFSs are 36 percent, 18 percent, 15 percent, and
7
20 percent of cases. Pruritus, peripheral eosinophilia, hypercalcemia, 9 percent, respectively. PIT scores have not been used to direct treat-
2,4
and hemophagocytic syndrome may accompany PTCL. 60,61 ment decisions, however (see Table 104–3). 13,12
LABORATORY FINDINGS ANGIOIMMUNOBLASTIC T-CELL
Histopathology LYMPHOMA
The majority of cases arise in lymph nodes, which exhibit mixtures
of small and large atypical lymphoid cells, typically admixed with an DEFINITION
inflammatory background (Chap. 96). The immunophenotype is typ- AITL was initially described as angioimmunoblastic lymphadenopathy
62
ically that of a mature T-cell expressing either a CD4 or CD8 pheno- with dysproteinemia in 1974. It is now known that these entities are
type, most commonly CD4, although CD4/CD8 double-positive and identical. 1,68
6,63
double-negative cases have been reported. Malignant cells are often
characterized by antigen aberrancy that may vary from one patient to EPIDEMIOLOGY
another or even vary during the course of the disease within a single AITL represents approximately 1 percent of all cases of lymphoma
patient. Deletion of one or more pan–T-cell antigens is frequently and approximately 20 percent of all T-cell lymphomas. International
6,7
57
observed, along with rearrangements of the TCR.
64
series show that AITL represents a higher portion of T-cell lymphomas
in Europe than North America or Asia. The male-to-female ratio is
3
TREATMENT AND PROGNOSIS approximately 1:1 and the median age at diagnosis is approximately
As discussed previously, patients with PTCL-NOS are most commonly 65 to 70 years. 3,4,7
treated with CHOP-based regimens, although there is no uniform stan-
dard of care for first-line treatment. Little prospective data exists for CLINICAL FINDINGS
CHOP alone in PTCL, but based on clinical trials employing CHOP Common features at presentation include B symptoms (fever, drench-
as a component of therapy, it appears that CHOP produces an ORR as ing sweats, and weight loss), generalized lymphadenopathy, rash, poly-
high as 79 percent and a CR rate as high as 39 percent. However, with clonal hypergammaglobulinemia, blood eosinophilia, and autoimmune
15
CHOP alone long-term remissions are uncommon, with PFS rates of hemolytic anemia (direct Coombs positive). Some patients experience

Kaushansky_chapter 104_p1693-1706.indd 1697 9/21/15 12:47 PM