Autologous or Allogeneic Stem Cell Transplantation in Advanced Low-Grade Lymphomas?

To the Editor:

In the November 15, 1997 issue of Blood, Verdonck et al1 reported their results with autologous and allogeneic bone marrow transplantation (BMT) in patients with refractory or recurrent low-grade non-Hodgkin's lymphoma. Their experience deserves several comments, because, in our opinion, the investigators describe an unrealistically good outcome after allotransplantation and nonrepresentative poor results in autologous recipients.

Ten patients received an allogeneic BMT in their series. Despite the fact that 7 of them had chemotherapy-resistant disease, all allografted patients achieved a complete remission after the procedure. In addition, there were no relapses at a median follow-up of 41 months. Transplant-related mortality occurred in 3 patients, which is a relatively low rate for a series with a median age of 43 years. To our knowledge, only one other series has reproduced such impressive results after allogeneic transplantation for follicular lymphoma.2 In that study, the MD Anderson team reported 8 survivors in a series of 10 patients with advanced chemoresistant disease.2 In contrast, most BMT groups have less encouraging experience in this setting. A recent report from the IBMTR3 has summarized the results obtained in 81 patients who received an allograft for poor-risk low-grade lymphoma. It is noteworthy that the 3-year relapse rate was 24% and the transplant-related mortality was 44%. These findings translated into a 43% disease-free survival and a 46% overall survival. These data probably appear more realistic to many physicians involved in this field, ie, advanced low-grade lymphomas do relapse after allogeneic transplant and treatment-related mortality is considerable, at least as high as seen in other situations in groups of patients of comparable age. However, the report of Verdonck et al1 provides further support for the continuing clinical research in the application of allogeneic stem cell transplantation for the management of low-grade lymphoproliferative disorders.

On the other hand, the results of the study of Verdonck et al1 with autologous BMT are unreasonably poor. In their group of 18 patients, all with advanced but chemosensitive disease, the 2-year progression-free survival was only 22% and the probability of relapse was as high as 83%. Fifteen of the 18 patients relapsed, despite the fact that, in all instances, the procedure was performed as treatment for chemosensitive disease. More specifically, 11 of 12 patients autografted in partial remission relapsed, in addition to 4 of 6 patients in complete remission before transplantation. This relapse rate is much higher than that reported by other studies1,4-8 and compares unfavorably with our own results.5 At our institution, we have autografted 27 patients (median age, 46 years) suffering from relapsed or primary refractory low-grade lymphoma. After a median follow-up of 16 months, 6 patients have progressed between 6 and 19 months posttransplantation. The estimated 2-year progression-free survival is 67%.5Our results are similar to those of previous reports showing disease-free survival rates of 53% to 76% at 2 years and 43% to 59% at 4 years.4-8 Treatment-related mortality after autotransplantation is usually low, usually less than 10% (4% in our series). To justify the discrepancies observed, a shorter follow-up of our patients compared with those of the series of Verdonck et al1 could be argued. However, in their report, 14 of the 15 relapses were observed in the first 16 months after autograft, the median follow-up time of our series.

We recognize that autologous transplantation is associated with a continuous rate of relapse and with the development of secondary myelodysplasia.4 However, we feel that this procedure offers a better perspective than that reflected in the report by Verdonck et al.1Allogeneic transplantation merits further research. The short-term risks of this procedure have to be seriously taken into account, and despite a likely graft-versus-lymphoma effect, disease recurrence remains a problem in a significant proportion of patients.