Page 1529 - Hematology_ Basic Principles and Practice ( PDFDrive )

1356 Part VII Hematologic Malignancies

focused on the results obtained with PTCL-NOS and ALCL patients, therapy (n = 40) or as a component of a subsequent course of therapy
emphasizing that the histologic subtype can influence the outcome (n = 75), with survival outcomes in favor of the front-line group:
after autologous SCT. The Toronto group compared relapsed and 3-year PFS of 58% versus 50% and 3-year OS of 70% versus 53%.
refractory PTCL patients with those achieved with DLBCL patients, Patients affected by ALCL were an exception. In this group, autolo-
who were transplanted for the same indication over the same period gous SCT after first CR was still associated with good survival out-
of time. The 3-year OS and EFS were 48% and 37%, respectively, comes (3-year PFS 50% and OS 74%). Of note, ALK status was not
for PTCL patients, compared with 53% and 42%, respectively, for available for these analyses.
DLBCL patients. Nevertheless, a significantly different outcome has In conclusion, the role of autologous SCT for the therapy of
been reported when the subtypes of PTCL were analyzed individu- patients with PTCL may be summarized as follows: (1) young
ally. Patients with PTCL NOS had an inferior EFS (3-year EFS, patients affected by PTCL appear to have an advantage when receiv-
23%) when compared with patients with DLBCL. By contrast, ing an autologous SCT while in first CR; (2) ALK-positive ALCL
patients with ALCL exhibited similar outcomes to patients with patients have a more favorable outcome after autologous SCT, but
DLBCL. These results are consistent with data from a retrospective they also do well with conventional chemotherapy, allowing this
study performed at the Memorial Sloan-Kettering Cancer Center that strategy to be possibly delayed to the salvage setting; (3) clinical
reported a 5-year PFS of 24% for relapsed or refractory ALK-negative protocols should be designed with more innovative pretransplant
ALCL. The more favorable prognosis of ALCL after autologous SCT therapies in order to achieve optimal disease control prior to trans-
was confirmed by Northern Europe Investigators. plantation and thereby increasing the number of patients who are
AITL patients have a median survival of 18 months after conven- eligible to receive an autologous SCT.
tional chemotherapy, with less than 50% of the patients achieving a
CR. A retrospective analysis of the European Group for Blood and
Marrow Transplantation (EBMT) of autologous SCT in 146 AITL Allogeneic Stem Cell Transplantation
patients demonstrated an OS and PFS of 59% and 42%, respectively,
at 4 years. PFS was longer in patients who received an autologous aSCT has been most frequently used in PTCL patients with progres-
SCT in CR, 56% at 4 years, compared with 23% in the case of sive or refractory disease after several courses of chemotherapy or in
patients with chemotherapy-refractory disease. the case of relapse after an autologous SCT. This strategy is associated
EATL is another very poor prognosis PTCL subgroup, commonly with the infusion of a lymphoma-free graft and the generation of a
associated with celiac disease. Because of its rarity, very few data on potentially active graft-versus-lymphoma (GvL) effect. Survival after
EATL treatment are available. In a prospective observational study myeloablative aSCT has been hampered by the high nonrelapse
using ASCT as front-line treatment, 5-year OS was 60% versus 22% mortality (NRM) caused by graft-versus-host disease, infections, and
for patients treated with standard chemotherapy. A retrospective acute organ toxicities.
study from EBMT confirmed these results on a cohort of 44 patients Retrospective comparative analyses of autologous SCT versus
affected by EATL and treated with autologous SCT with a 4-year aSCT in PTCL suffer the limitation of significant selection bias.
PFS and OS of 54% and 59%, respectively. Being in first CR or PR In fact, patients receiving aSCT usually had more advanced disease,
at the time of autologous SCT was associated with a trend for better more prior lines of therapy, and/or bone marrow involvement.
survival compared with patients with a less favorable disease status However, these studies have demonstrated that aSCT is associated
(4-year OS 66% vs. 36%, p = .062). with a lower relapse risk compared with autologous SCT, but also
Besides the differences in outcomes based on histologic subtypes with a higher NRM, which offsets the survival benefit. The results of
and induction therapies, a common feature of PTCLs is that only aSCT as a therapeutic strategy are listed in Table 85.2. A small ret-
two thirds of young patients are able to undergo the final autografting rospective comparative study conducted by the Spanish Lymphoma/
phase with a satisfactory disease response. Autologous Bone Marrow Transplant Study Group (GELTAMO)
To increase the number of patients undergoing autologous SCT compared the outcome of patients receiving autologous SCT (n = 29)
in CR or at least PR, some trials were designed with a more intense versus aSCT (n = 7) for PTCL. The 3-year OS was 39% and 29%
pretransplant phase. The Nordic Lymphoma Group included a dose- for autologous SCT and aSCT, respectively. However, the majority of
dense induction phase for 160 PTCL patients. After six cycles of patients in the group receiving allogeneic grafts in CR died because of
CHOEP every 2 weeks, 85% of patients achieved CR and 70% transplant-related complications. In 2006 a Japanese group published
proceeded with autologous SCT at last follow-up. Five-year OS and the first large analysis on the outcome of PTCL after myeloablative
PFS were 50% and 43%, respectively. A Spanish group used alternat- aSCT from matched related and unrelated donors. Kim and col-
ing CHOP and ESHAP (etoposide, methylprednisolone, cytarabine, leagues recently compared outcomes of patients affected by PTCL
cisplatin) during the induction phase of 41 ALK-negative patients: treated with autologous SCT (n = 135) versus myeloablative or
58% of the patients were in CR or PR after the induction phase, but reduced-intensity conditioning (RIC) aSCT (n = 96). No differences
only 41% underwent autologous SCT. More recently, the Italian in survival was noted between the two groups (5-year OS 46% vs.
Lymphoma Foundation performed an intensive front-line induction 48%, p = .34), even though the aSCT group had more unfavorable
chemotherapy before transplant in young PTCL patients (excluding features than the autologous SCT group in terms of prior courses
ALK-positive ALCL cases). Two cycles of CHOP plus alemtuzumab of therapy and disease status at the time of transplant. Of note,
were followed by two cycles of HyperCHidam (methotrexate fol- despite a higher NRM, aSCT was able to induce a prolonged OS
lowed by hyperfractionated cyclophosphamide and cytarabin). in 40% of patients who had chemorefractory disease, showing the
Patients achieving a CR or PR received consolidation therapy with efficacy of this salvage strategy for that group of PTCL patients that
an autologous SCT or aSCT (in case of a compatible donor). With cannot achieve a response with standard chemotherapy. Similarly,
an intent-to-treat analysis, the 4-year PFS and OS were 44% and Smith and colleagues compared 241 PTCL patients who received an
49%, respectively. In fact, a clinical response was obtained in 62% autologous SCT (n = 115) or aSCT (n = 126). Also in this study,
of the study cohort, highlighting the need for more effective induc- the two groups were different in terms of prior courses of therapy,
tion therapy for PTCLs. chemosensitive disease, and histologic subtypes. In fact, the aSCT
Finally, the prognosis of PTCL patients seems poor when autolo- group had more unfavorable features including a lower number of
gous SCT is used in patients with relapsed disease, where long-term ALCL patients. Two interesting results emerged from this study: the
remissions have been observed in less than one third of patients. first was to confirm that performing a transplant (either autologous
Those who benefit the most are patients with ALK-positive ALCL in or allogeneic) later during the course of disease (after two or more
CR at time of transplant or those with a low IPI. A registry analysis prior courses of therapy) was associated with a threefold increased
from the Center for International Blood and Marrow Transplant risk of relapse, fivefold increased risk of overall mortality, and a
Research (CIBMTR) confirmed these results. One hundred and sevenfold risk of NRM; the second one was that autologous SCT
fifteen patients received autologous SCT as front-line consolidation at relapse was beneficial for those patients affected by ALCL (ALK