Lay Summary: Transplants for transformed follicular lymphoma are supported by follicular lymphoma (transformed) guidelines of the NCCN. There is trial evidence supporting this approach.
Takvorian and colleagues (1987) studied 49 patients with either high-grade (n = 29), intermediate-grade (n =14) or low-grade (n = 6) lymphoma. All patients were considered to have a poor prognosis either due to relapse (n = 41) or poor prognostic factors (n = 8). These latter 8 patients were in at least partial remission but were considered to be at high-risk for relapse due to a bulky tumor mass, or multiple sites of extranodal involvement. All patients had a good performance status. The common feature of all these patients was that they were responsive to conventional induction therapy such that at the time of HDC, all patients had a minimal disease burden. In fact, 23 patients were considered to be in complete remission. A total of 34 of the 49 patients remained in complete remission for 2 to 52 months post-HDC, which translated into a 65 % probability that patients would remain disease free for greater than 11 months. Two patients died from treatment-related toxicity and relapse occurred in 13 others. All relapses occurred before 11 months. Other earlier studies of HDC had included all patients relapsing from disease, regardless of their performance status or whether the lymphoma was chemo-resistant. In these studies the mortality rate ranged from 20 to 40 % and long-term disease survival was seen in only 20 % of patients. Considering their improved results, the authors suggested that HDC should be a treatment option for patients with relapsing disease but with a minimal tumor burden that is still responsive to chemotherapy.
Schouten et al (1994) reported their findings of 92 patients with low-grade NHL treated with HDC and ASCT. At the time of ASCT, the majority of patients had chemosensitive disease in first or subsequent remission (37 %) or disease with a good response to chemotherapy (49 %). At a median follow-up of 19 months, the progression free survival is 52 %. Patients with complete remission or responding relapse at the time of ASCT had a significantly better progression-free survival compared to patients with refractory disease. Patients with transformed low-grade NHL at ASCT had a very poor outcome. Despite the relatively short follow-up of this study, the data suggested that chemosensitive disease responded better to HDC followed by stem cell transplant than refractory disease at the time of ASCT.
Mills and colleagues (1995) reported the main prognostic factors in 107 patients with relapsed or resistant intermediate- or high-grade NHL who underwent HDC with ASCT. All patients had failed to achieve a complete remission to conventional chemotherapy or had subsequently relapsed. Additionally, there was no bone marrow involvement in any of the patients. Forty-two patients (40 %) had chemoresistant disease at the time of HDC, 55 (51 %) had chemosensitive disease, and 10 (9 %) had untested relapse. At 3 months, 44 patients (41 %) were assessed to be in complete remission, 34 (32 %) were in partial remission and 22 (21 %) showed no response or had progressive disease. There were 7 early procedure-related deaths. Overall survival rate at 5 years is 41 % and progression free survival rate is 35 %. None of the patients who were unresponsive to HDC survived beyond 18 months, whereas at a median follow-up of 34 months, 50 % of the partial responders were alive. Patients with chemosensitive disease, small masses, and ASCT after one line of chemotherapy had the best outcome.
In a randomized clinical trial (The European CUP trial), Schouten, et al. (2003) examined if high-dose therapy (HDT) followed by ASCT is more effective than standard treatment with regard to progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular NHL; and evaluated the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS. Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P). A total of 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were 0.0037 and 0.079, respectively. The authors concluded that HDT significantly improves PFS and OS in patients under age of 60 years with recurrent chemosensitive disease. Furthermore, there is no clear evidence of benefit through purging. This is in agreement with the observations of Alvarnas and Forman (2004) who stated that data to justify routine use of hematopoietic stem cell graft purging are insufficient.
In a recent review on stem cell transplantation in follicular lymphoma, Tse, et al. (2004) stated that ASCT or allogeneic stem cell transplantation in first remission remains an investigational procedure.
A 2011 review concludes: “Stem cell transplantation (SCT) including both autologous and allogeneic SCT or experimental agent therapy is considered for recurrent disease.”
Freedman A. Follicular lymphoma: 2011 update on diagnosis and management.Am J Hematol. 2011 Sep;86(9):768-75.
HC Schouten, PJ Bierman, WP Vaughan, A Kessinger, JM Vose, DD Weisenburger, and JO Armitage
Autologous bone marrow transplantation in follicular non-Hodgkin’s lymphoma before and after histologic transformation
Blood 74: 2579-2584.
Arnold S. Freedman Biology and Management of Histologic Transformation of Indolent Lymphoma Hematology 2005 © 2005 The American Society of Hematology