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Journal of Clinical Oncology, Vol 23, No 9 (March 20), 2005: pp. 2110-2111 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.306
In Reply:Department of Hematology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy In our study,1 histologic diagnosis was performed by the local pathologist at each center. Those cases that presented with difficult diagnostic features were reviewed centrally. In all cases, a large panel of monoclonal antibodies was used to support the diagnosis. In particular, B lineage antigens (such as CD19, CD20, CD23, and CD79a) were always used to rule out a B-cell origin. In addition, some patients of our study were tested for immunoglobulin gene rearrangement, and the results were always negative. According to the Revised European-American Lymphoma (REAL) classification,2 angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is considered to be synonymous with angioimmunoblastic T-cell lymphomas. Although the majority of patients in our series had chemosensitive disease, because of the study design no patient was enrolled onto the trial and subsequently excluded because of chemorefractory disease. Therefore, we suggest that reduced-intensity conditioning (RIC) followed by allogeneic transplantation is an effective strategy for chemosensitive patients; but we do not have enough data to support its role in chemorefractory disease. Different studies of RIC followed by allografting in high-grade lymphomas have shown that chemotherapy sensitivity is an important factor that influences the patient's outcome,3,4 and our data confirmed the previous observations. Three of five patients with a long disease history (more than 60 months from diagnosis to allograft) had failed a previous autologous transplantation, which is considered to be a poor prognostic factor. The effect of conditioning chemotherapy can indeed explain the response at first disease reassessment post-transplant, but it cannot explain the durable response observed in patients with longer follow-up (eg, six patients have more than 30 months of follow-up). Therefore disease control in these patients can be attributed to the postulated immune mediated effect. Five patients experienced progressive disease (n = 3) or relapse (n = 2). In all cases, progressive disease occurred at the same sites where lymphoma masses were detected before transplant. Thus, we argued that histologic reassessment was not required. In one patient with relapsed disease, the histology was confirmed postmortem. Usually, convincing evidence supporting the existence of a graft-versus-lymphoma effect derives from the observation of a lymphoma regression after immunomodulatory treatments, or by the correlation between graft-versus-host disease and disease-free survival. In this letter, we can update the duration of response to donor lymphocyte infusions (DLI) for the patients in our study: patient 5, who achieved complete remission (CR) after the first DLI, is alive in CR at 31 months after allograft with extensive chronic graft-versus-host disease (cGVHD; the patient is currently being treated with low-dose cyclosporine); patient 15 has minimal residual disease after four DLIs with occurrence of limited cGVHD at 21 months after allograft; and patient 11 responded to cyclosporine withdrawal and, at present, is in CR with limited cGVHD at 16 months after transplantation. In addition, it has to be noted that all the patients who had cGVHD are free from disease recurrence. In conclusion, our data suggest the existence of a graft versus T-cell–lymphoma effect, but, as is the case with any pilot study, a longer follow-up and a large multicenter trial are needed to confirm the long-term efficacy of this approach. Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES
1. Corradini P, Dodero A, Zallio F, et al: Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol 22:2172-2176, 2004
2. Harris NL, Jaffe ES, Stein H, et al: A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 84:1361-1392, 1994
3. Robinson SP, Goldstone AH, Mackinnon S, et al: Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: An anlysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 100:4310-4316, 2002
4. Morris E, Thomson K, Craddock C, et al: Outcome following Alemtuzumab (CAMPATH-1H) –containing reduced-intensity allogeneic transplant regimen for relapsed and refractory Non-Hodgkin's Lymphoma (NHL). Blood 104:3865-3871, 2004
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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