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Chapter 85 T-Cell Lymphomas 1355

aggressive B-cell lymphomas, resulting in 40%–50% long-term
Treatment of Peripheral T-Cell Lymphoma
disease-free survival. The role of autologous SCT in PTCL is less
Given that the mature T-cell lymphomas are relatively rare diseases, clear, and whether or not autografting during first or subsequent
there is a lack of large randomized clinical trials comparing the remissions may be of clinical benefit remains uncertain.
“standard” CHOP (cyclophosphamide, hydroxydaunomycin, vincristine Autologous SCT is usually performed as front-line consolidation
[Oncovin], and prednisone) and CHOP-like regimens to other more therapy for young patients with PTCL. In this setting there are several
intensified chemotherapy strategies, or even other novel drug platforms. prospective and retrospective studies evaluating this approach (see
Our approach involves tailoring the treatment to the specific histologic Table 85.1).
subtype and age of the patient. From the outset, we send HLA typing In a retrospective analysis, the Japan registry demonstrated that
for possible allogeneic stem cell transplant, assuming the patient is long-term outcome of PTCL was better in patients transplanted
eligible, and request immunohistochemical staining of the primary during first CR or partial remission (PR) than those not in remission
tissue for CD30. Where possible, we preferentially try to put all patients
on a clinical trial. For the majority of peripheral T-cell lymphomas, our (5-year OS, 72.9% vs. 45.8%; progression-free survival [PFS], 73.1%
standard initial approach is to use an etoposide-based regimen (CHOEP vs. 42.2%). The British Society of Bone Marrow Transplantation
[cyclophosphamide, hydroxydaunomycin, vincristine (Oncovin), etopo- (BSBMT) and Stanford University reported similar data. The 2-year
side, and prednisone] or EPOCH [etoposide, prednisone, vincristine OS and PFS were 62% and 59%, respectively, for patients receiving
3
(Oncovin), cyclophosphamide, and hydroxydaunomycin]), especially autologous SCT as consolidation during first CR . The Spanish
for young patients or older adult patients with an excellent performance group published a retrospective analysis of 74 patients undergoing
status. As alluded to earlier, there are some data to suggest a reduced autologous SCT after the achievement of CR with front-line
failure-free interval and higher complete response rate. For patients anthracycline-based induction chemotherapy. After a median
with a poor performance status or older adult patients, standard CHOP follow-up of 67 months, 5-year OS and PFS were 68% and 63%,
administered on an every-21-day basis for six to eight cycles would be
our preferred recommendation. In select cases, where an older adult respectively, and the main cause of death was disease progression.
patient is not a candidate for combination chemotherapy and requires After a multivariate analysis, only the PIT score was significantly
palliative care, we have successfully used single-agent gemcitabine to associated with OS and PFS. Although data about ALK expression
obtain disease control and improve performance status. Those patients were lacking, patients affected by ALCL had a significantly better
who attain a complete remission are usually referred for an autologous outcome compared with other PTCL subtypes. The same authors
stem cell transplant. Those patients who do not attain a complete published the results of a prospective study in 26 high-risk nodal
remission with standard front-line chemotherapy are typically referred PTCL patients, excluding those with ALK-positive ALCL. The
for treatment with one of the drugs recently approved by the Food and patients who were positron emission tomography positive after three
Drug Administration for patients with relapsed or refractory disease, cycles of dose-escalated CHOP (MegaCHOP) received salvage che-
including pralatrexate, romidepsin, belinostat, or brentuximab vedotin
+
(if CD30 ), or clinical studies exploring the merits of these agents in motherapy followed by autologous SCT. After a median follow-up of
combination. For patients who relapse or are refractory to front-line and 35 months, the 3-year OS and PFS of the entire cohort of patients
beyond therapy, we typically consider allogeneic stem cell transplant, were 73% and 56%, respectively, whereas those patients who were
assuming they are transplant eligible and have an appropriate human rescued by high-dose chemotherapy achieved a 2-year disease-free
leukocyte antigen match. survival of 63%.
An Italian multicenter prospective study employed high-dose
sequential chemotherapy followed by autologous SCT as front-line
therapy in 62 patients with high-risk PTCL (stage III–IV and/or
age-adjusted IPI >1) including 19 ALK-positive ALCL patients. On
+
are common, and variable numbers of CD20 large B-blasts, often an intent-to-treat analysis, only 46 of 62 patients (74%) completed
infected by EBV virus, are found in the neoplastic tissues. It has the whole program. Progressive disease during the induction phase
recently been suggested that the disruption of putative B- and T-cell was the main obstacle for proceeding to autologous SCT and the
interactions and/or depletion of the EBV reservoir by anti-CD20 main reason for treatment failure. The high progression rate led to
monoclonal antibody (rituximab) might improve clinical outcome disappointing 12-year OS and EFS curves (34% and 30%, respec-
observed with conventional chemotherapy. Twenty five newly diag- tively). However, in the cohort of patients who did undergo autolo-
nosed patients were treated in a phase II study with eight cycles of gous SCT, the RR was high: 89% of these patients achieved a CR.
rituximab plus chemotherapy (R-CHOP21). The complete RR was As in the Spanish study, patients with ALCL had the most favorable
44%, the 2-year PFS rate was 42%, and OS was 62%. This trial OS and EFS (62% and 54%, respectively, compared with 21% and
showed no clear benefit of adding rituximab to conventional chemo- 18%, respectively, of non-ALCL). On the other hand, when patients
therapy (see box on Treatment of Peripheral T-Cell Lymphoma). with PTCL-NOS were in CR at the time of transplant, the EFS was
62% versus 10% for those not in CR. The CR status remained a
significant predictor of long-term outcome in multivariate analysis.
Role of Stem Cell Transplantation in Treatment The German group published the results of a prospective multi-
center study employing myeloablative doses of cyclophosphamide
Because of the poor outcomes often seen with conventional chemo- and total-body irradiation as the conditioning regimen for 83 ALK-
therapy in patients with PTCL, many investigators have explored negative ALCL patients who were at least in PR after six cycles of
high-dose chemotherapy followed by autologous or aSCT as front- CHOP. Similar to the Italian data, 34% of patients did not complete
line therapy and in patients who have relapsed. Despite the growing the study because of progressive disease. The estimated 3-year OS was
number of reports, one must keep in mind a number of limitations 71% for patients who received an autologous SCT compared with
associated with these reports: (1) most of the studies are retrospective; 11% for those who did not. A large registry study from the Swedish
(2) randomized trials comparing chemotherapy and SCT have not group confirmed a survival advantage for those patients who received
been published to date; (3) many prospective studies of autologous an autologous SCT as front-line consolidation therapy. In this study,
SCT include both front-line treatment and relapsed patients with ALK-positive ALCL patients were excluded. Also after multivariate
diverse subtypes of PTCL, making the results difficult to interpret. analysis, front-line ASCT was associated with a favorable PFS and
OS compared with the cohort treated without autologous SCT. Of
High-Dose Chemotherapy and Autologous note, the addition of etoposide to CHOP chemotherapy was associ-
ated with a higher PFS in patients younger than 60 years, but this
Stem Cell Transplantation was not true for OS.
Although most of the published data include different histologic
High-dose chemotherapy followed by autologous SCT is currently subtypes of PTCL, efforts have been made to define the role of
accepted as the treatment of choice for patients with relapsed autologous SCT in specific subtypes of PTCL. Some studies have