The role of autologous and allogeneic stem-cell transplantation (SCT) in the treatment of cutaneous T-cell lymphoma (CTCL) is reviewed. Patients most likely to benefit are those with advanced-stage disease, multiple relapses, and short remissions; chemosensitive disease is also a prerequisite for these treatments. Autologous SCT produces high response rates in patients with peripheral T-cell lymphoma, but these are generally of short duration. This therapy is relatively safe to administer, with little transplant-related mortality. In contrast, allogeneic SCT may be highly toxic and result in transplant-related mortality, but it has the potential to produce long-lasting responses. Prospective studies of these treatments in patients with CTCL are required. Nevertheless, selected patients could be considered for allogeneic SCT, preferably early in their disease when their performance status is still good.
There are currently limited data, particularly from randomized, controlled trials, on the efficacy of many of the therapies that are used in the treatment of cutaneous T-cell lymphoma (CTCL), and stem-cell transplantation (SCT) is no exception. Indeed, there is little information from randomized, controlled trials on the use of SCT for any indication, even those in which this procedure has a well-established role. Nevertheless, there does appear to be a role for SCT in the management of some patients with CTCL. In this review, the use of both autologous and allogeneic SCT in peripheral T-cell lymphomas (PTCL) will be discussed.
Which Patients With CTCL Should Receive a Transplant?
The patients most likely to benefit from SCT are those who are currently at poor risk: those with advanced-stage disease, a low response to systemic therapies, multiple relapses, and short remissions. In particular, some patients with Sézary syndrome fall into this category—those patients with advanced disease (stages III and IV) who have a median survival of only about 2 years. For both forms of SCT, and particularly autologous SCT, to be effective, it is almost essential that patients have demonstrated some chemosensitivity and have obtained a degree of remission from previous treatments prior to transplantation. Other considerations include the patient's age, performance status, and the presence or absence of other comorbidities. In addition, for allogeneic transplants, donor availability is a factor, although this is becoming less of an issue now—for Caucasian patients, it is possible for more than 75% to find a donor through extensive registries.
Use of SCT
Data from the European Group for Blood and Marrow Transplantation (EBMT) registry show that, overall, the use of SCT has decreased in the past 3 years. This is largely because it is no longer standard practice for SCT to be used in patients with solid tumors, such as breast cancer, resulting in a halving of the number of these procedures in the early 2000s.
On the other hand, the use of SCT in patients with lymphomas showed a steady increase to 2000, followed by a subsequent plateau, which probably reflects the emergence of new therapies that are allowing clinicians to use other treatment options before transplantation. In addition, with the first-line use of more efficacious therapies, fewer patients relapse and therefore fewer patients require a transplant.
Rationale for Use of Autologous SCT
Autologous SCT relies on the principle of a dose-response relationship for chemotherapy and/or radiotherapy. The use of these therapies is limited by their toxicity—particularly their toxicity to the hemopoietic stem cell— causing myelosuppression and failure of recovery of normal blood cells. By collecting and storing normal autologous hemopoietic stem cells, the dose of chemotherapy or radiotherapy can be increased and the consequent myelosuppression supported by replacement of the stored hemopoietic stem cells. It is therefore important that patients undergoing autologous SCT have chemosensitive disease. This procedure is performed in the hope of inducing or improving remissions and prolonging a patient's disease-free survival (DFS) and overall survival (OS). Autologous SCT is now the standard of care for myeloma in first remission and for many lymphomas in second remission.
Autologous Transplantation in PTCL
Little information is available on the use of autologous transplantation in CTCL alone. However, some studies on PTCL have included a few patients with CTCL, as the term PTCL describes a diverse group of blood cancers that orginate from post-thymic T cells. Autologous SCT in 35 young patients with relapsed or refractory PTCL resulted in a 5-year DFS of approximately 25% and an OS of about 33%. Interestingly, a plateau in DFS emerged after 3.5 years—some of the patients were showing prolonged remissions many years after autografting. This is an unusual feature of survival curves following autografts. Another study reported results for autologous SCT in 29 patients with PTCL and allograft in 7 patients. Results for autologous SCT were similar to those in the previous study, with a 3-year progression-free survival (PFS) of 32% and an OS of 39%. Survival was lower for the seven patients who received allografts: PFS was 14% and OS was 29%.
When autologous SCT was used for patients with PTCL in first remission, there was an improvement in outcomes compared with the two previous studies. Among 75 young patients with advanced-stage disease and high International Prognostic Index, and who received a standard carmustine (BiCNU), etoposide, cytarabine, and melphalan (Alkeran) conditioning regimen for autograft, 5-year PFS was 65% and OS was 69%, approximately doubling the percentages reported above. However, the fact that the PFS and OS are similar means that patients who did relapse were not susceptible to subsequent therapies. In another large study of autologous transplantation in patients in first remission, most (91%) showed a good response to the induction chemotherapy. However, because of its early disease progression, only 33% of patients proceeded to consolidation with SCT, and 85% of those remain in complete remission at the relatively short follow-up of 1 year.
Autologous Transplantation in CTCL
Only two small studies have investigated autologous SCT in patients with CTCL. The first was published in the early 1990s and included six patients with advanced-stage mycosis fungoides who were heavily pre-treated. They underwent a variety of conditioning regimens, and four also had total skin electron beam radiotherapy for disease control immediately before transplantation. The initial response rate was high, and four of the six patients experienced complete remission. Nevertheless, their PFS was short (64 days to 1 year), and three patients relapsed within the first 3 months.
The second study, in nine patients with tumor-stage mycosis fungoides, reported similar results. In this study, hemopoietic stem cells were positively selected using the cell-surface antigen CD34 and underwent negative selection for contaminating T cells. After autologous SCT, one patient died at day 15 from sepsis (ie, a transplant-related death), but the eight patients who survived the procedure all reached complete remission. Again, however, there was a short median PFS of only 7 months (range: 2-14 months) and median OS was 11 months, with three patients dying within 1 year. These patients were at a late disease stage; therefore, it appears that autologous SCT had not significantly prolonged remission in most patients beyond that expected for their disease stage.
Dr. Dearden has received speaker fees from Schering AG, Berlex Oncology, and Cephalon Europe.
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