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Journal of Clinical Oncology, Vol 23, No 9 (March 20), 2005: pp. 2109-2110 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.213
Graft Versus T-Cell–Non-Hodgkin's Lymphoma EffectDepartments of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria, Australia To the Editor: Corradini et al,1 in reporting a favorable outcome in 17 patients with relapsed peripheral T-cell–non-Hodgkin's lymphoma after a reduced-intensity conditioning allograft, argue for a graft-versus-lymphoma effect. There are a number of issues, however, that should be clarified to help interpret the significance of these results. First, the histology was based on the Revised European-American Lymphoma (REAL) classification.2 Four cases were listed as angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) in the body of Table 1, but described in the legend as angioimmunoblastic T-cell lymphomas. The distinction is important because not all AILDs have T-cell–receptor gene rearrangements; some may be B-cell lymphomas.3 Four cases were CD30+ anaplastic lymphoma kinase (ALK)–negative anaplastic large-cell lymphomas (ALCL). ALK negativity, which occurs in 15% to 40% of ALCL, is not mentioned in the REAL classification, but is recognized in the WHO Classification of Tumors.4 The authors of this latter classification make the point that genetic studies of ALK-negative ALCL have not been performed. Moreover, ALCL of B-cell phenotype are ALK negative.5 The authors should provide evidence of T-cell clonality in the AILD- and ALK- negative ALCL cases that were included.
Second, many of the patients included in the study had favorable pretransplantation characteristics, including chemosensitivity; 14 of 16 patients had responded to salvage chemotherapy. Of note, five patients had biologically indolent disease with Third, five patients have relapsed; the histology at relapse is not provided. Assuming that all five patients had biopsy-proven relapse with unaltered histology, and that T-cell clonality had been demonstrated, this is the cohort in which graft versus T-cell–lymphoma effects can be unequivocally evaluated. It seems that three patients received donor lymphocyte infusions (DLI) with progressive disease, CR, and a partial remission responses, but the duration of the response to DLI is not specified. Another patient who did not receive DLI had stable disease (durability not specified) in response to cessation of cyclosporine. Whether a clinically relevant graft versus peripheral T-cell lymphoma–effect is a frequent or rare phenomenon will require a much larger study evaluating the durability of responses to immunologic manipulations in patients with biopsy-proven relapse postallograft and unequivocal molecular evidence of T-cell clonality. 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. Feller A, Griesser H, Schilling H, et al: Clonal gene rearrangement patterns correlate with immunophenotype and clinical parameters in patients with angioimmunoblastic lymphadenopathy. Am J Pathol 133:549-556, 1988[Abstract] 4. Delsol G, Ralfkiaer E, Stein H, et al: Anaplastic large cell lymphoma, in World Health Organization Classification of Tumours: Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France, IARC Press, 2001, pp 230-235 5. Haralambieva E, Pulford KF, Lamant L, et al: Anaplastic large-cell lymphomas of B-cell phenotype are anaplastic lymphoma kinase (ALK) negative and belong to the spectrum of diffuse large B-cell lymphomas. Br J Haematol 109:584-591, 2000[CrossRef][Medline]
6. Corradini P, Tarella C, Olivieri A, et al: Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 99:75-82, 2002 Related Article
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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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5 years from diagnosis to transplantation. Moreover, while reduced intensity compared with conventional myeloablative regimens, the conditioning regimen was at least moderately intensive with the addition of thiotepa and fludarabine to cyclophosphamide 60 mg/kg. These are each active agents in lymphoma and sufficiently immunosuppressive to produce early full-donor chimerism in the majority of patients.
