Bone Marrow Transplant Registry Data on Treatment of Follicular Lymphoma

Abstract & Commentary

Synopsis: Follicular lymphoma is considered incurable by standard chemotherapeutic approaches, but speculation has arisen that more intensive therapy followed by allogeneic or autologous transplants may produce more durable remissions and possibly cures. In this analysis of bone marrow transplant registries, an attempt was made to determine which of the transplant strategies (allogeneic, purged autologous, or unpurged autologous) results in the most favorable outcomes. From this large data set of patients transplanted in the 1990s, it was apparent that transplant-related mortality was higher for those receiving allogeneic transplant, but relapses were fewer. Overall, the 5-year survival was comparable, approximating 50% in each group. Thus, bone marrow transplant remains an excellent option for patients with follicular lymphoma. However, when and which type of transplant are variables that need to be determined by future clinical trial.

Source: van Besien K, et al. Blood. 2003;102: 3521-3529.

Follicular lymphoma is oftentimes clinically indolent but considered incurable by standard chemotherapy regimens. However, autologous stem cell transplantation has been shown in several phase II studies to induce remissions in patients with recurrent or newly diagnosed disease, and the speculation is that some of these may have been cured.1 Furthermore, after allogeneic transplant, disease recurrence rates have been low, but treatment-related mortality has been high.2-4 In the current report from the Lymphoma Working Committee of the International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry, the data from 904 patients undergoing transplantation for follicular lymphoma were presented. A total of 176 (19%) received allogeneic, 131 (14%) received purged autologous, and 597 (67%) received unpurged autologous transplants. Five-year treatment-related mortality rates were 30%, 14%, and 8%, and 5-year recurrence rates were 21%, 43%, and 58% after allotransplantation, purged autotransplantation, and unpurged autotransplantation, respectively.

In multivariate analyses, allotransplantaion had higher treatment-related mortality and lower disease recurrence. Purged autotransplantation had a 26% lower recurrence risk than unpurged autotransplantation. Five-year probabilities of survival were 51%, 62%, and 55% after allogeneic, purged autotransplantation, and unpurged autotransplantation, respectively. Advanced age, prolonged interval from diagnosis to transplantation, high lactic dehydrogenase (LDH), refractory disease, bone marrow involvement, and low performance scores were associated with adverse outcomes.

There was no association of acute or chronic graft-vs-host disease and recurrence after allotransplantation. van Besien and colleagues concluded that both allogeneic and autologous transplantation can induce durable remissions and suggest that there may be a benefit to graft purging in autologous transplantation. The decreased recurrence after allotransplantation is offset by increased treatment-related mortality.

Comment by William B. Ershler, MD

There has not been consensus on how best to achieve long remissions for patients with recurrent, follicular lymphoma; transplantation currently remains a commonly chosen approach, particularly for those with recurrent or refractory disease. There remains, however, a question about which transplantation strategy is likely to provide superior outcomes. Short of a randomized, prospective study, the analysis of the transplantation registry data may be the best approach to this question.

The International Bone Marrow Transplantation Registry is a voluntary working group of more than 350 transplantation centers worldwide, whereas the Autologous Blood and Bone Marrow Registry, maintained at the same data-coordinating center in Milwaukee, captures data from more than 250 transplantation centers in North and South America. It is estimated that approximately 35% of allogeneic transplantations worldwide and 50% of autotransplantations in North and South America are therein registered. From this data set, it is reasonable to make comparisons about treatment success. These comparisons, of course, need to be considered as retrospective assessments between groups that may not be comparable, due to selection bias. For example, patients may be referred for allogeneic transplantation because of characteristics that would suggest more aggressive disease. Similarly, patients may be referred for autotransplant at an earlier stage because of perceived lower transplant-associated mortality. The biostatistical expertise at the transplant registries is well aware of these potential confounders, and the data are presented in a fair manner, and the conclusions are not overstated.

The findings are as what might be expected: 1) Allogeneneic transplantation is associated with lower recurrence rates but higher transplant-related mortality; 2) Unpurged autotransplants are associated with higher recurrence rates and lower transplant-related mortality; and, 3) Purged autotransplants are intermediate in both categories. Overall, the 5-year probabilities of survival were not significantly different for the 3 approaches (a little better than 50%).

To this reviewer, the unexpected finding from this review was the improved (lower) recurrence rate for those who received purged compared to those who received unpurged autografts. With all the technical problems associated with such procedures, the findings would imply that continued research in the fine-tuning of marrow purging regimens is a worthwhile focus for continued intensive research.

Dr. Ershler is INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.

References

1. Hunault-Berger M, et al. Blood. 2002;100:1141-1152.

2. van Besien KW, et al. Blood. 1998;92:1832-1836.

3. Toze CL, et al. Bone Marrow Transplant. 2000;25: 605-612.

4. Stein RS, et al. Bone Marrow Transplant. 1999;23: 227-233.