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Impact of High-Dose Chemotherapy on Peripheral T-Cell Lymphomas

Groupe d’Etude des Lymphomes de l’Adulte, Hôpital Saint Louis AP-HP, Paris, France

To the Editor:We read with great interest the report of Rodriguez et al¹ published in the September 1, 2001, issue of the Journal of Clinical Oncology concerning the impact of high-dose chemotherapy (HDCT) on peripheral T-cell lymphomas (PTCL). They reported that there was a comparable outcome for PTCL and B-cell lymphoma (BCL) when submitted to HDCT despite the fact that patients with PTCL are known to have a worse prognosis when compared with B-cell non-Hodgkin’s lymphoma. The conclusion was that these T-cell lymphoma patients should be submitted to front-line HDCT and transplantation, autologous or allogeneic, due to the dismal outcome. We are still skeptical on this issue in light of our study.² Among 1,873 patients with reviewed histologic data included in the LNH87 study, 278 were PTCL, and we first reported that nonanaplastic PTCL lymphoma was an adverse independent prognostic factor when compared with B-cell lymphoma or anaplastic T-cell lymphoma despite the intensive chemotherapy regimens used.³ In fact, HDCT with autologous transplantation was performed in 237 patients, including 34 with PTCL. Histologic subtypes included anaplastic T-cell lymphoma in eight patients, angioimmunoblastic lymphadenopathy in three patients, and not otherwise specified in 23 patients. As part of the program, only 16 PTCL and 124 BCL patients were submitted after complete remission (CR) to front-line HDCT; 19 BCL and four PTCL patients received transplants after partial remission (PR) as well as 80 chemosensitive relapses including 65 BCL and four PTCL patients. Five-year survival for treated patients in CR, PR, and relapse were 68%, 75%, and 26%, respectively, for PTCL and 78%, 57%, and 50%, respectively, for BCL. There was no difference between BCL and PTCL, and the results seem to be in agreement with those of the study by Rodriguez et al.¹ However, the sample size is small and considerable bias was encountered. First, in the LNH87-2 study, a randomization between chemotherapy consolidation and HDCT was scheduled after induction chemotherapy for CR patients only.³ Among the 611 patients who were available for histologic review, 91 had PTCL. Fifty-two were in CR, 22 were randomized to HDCT, and 27 were randomized to sequential chemotherapy; however, only 16 received HDCT because of early progression. In an intent-to-treat analysis, there was no difference between HDCT and sequential chemotherapy in terms of 5-year survival rate (63.6% and 66.7%, respectively) and disease-free survival (54.5% and 55.6%, respectively). Among the patients who experienced relapse, there was a trend of a lower 5-year overall survival rate for the PTCL patients, with 26% versus 50%. From this subgroup analysis, it is difficult to demonstrate an argument for a significant improvement with the use of HDCT in this particular poor-prognosis group of patients. The selection is primarily made on the ability to reach CR or to be sensitive to chemotherapy. This goal is only achieved in one half or less of the patients, even with an intensive regimen. Moreover, some of the apparent good results obtained in limited phase II studies or retrospective studies might be related to the mixture of different PTCLs with different prognoses, such as anaplastic T-cell lymphoma (seven patients in the study by Rodriguez et al¹), which has a better prognosis.^2,4 Innovative new phase II studies with new drugs on well-characterized nonanaplastic T-cell lymphomas with the goal of improving response rates are necessary even if HDCT can still be proposed as an effective consolidation therapy up front or after relapse in poor-prognosis chemosensitive patients.

REFERENCES

1. Rodriguez J, Munsell M, Yazji S, et al: Impact of high-dose chemotherapy on peripheral t-cell lymphomas. J Clin Oncol 19: 3766-3770, 2001[Abstract/Free Full Text]

2. Gisselbrecht C, Gaulard Ph, Lepage E, et al: Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas: Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood 92: 76-82, 1998[Abstract/Free Full Text]

3. Haioun C, Lepage E, Gisselbrecht C, et al: Survival benefit of high-dose therapy in poor risk aggressive non-Hodgkin’s lymphoma: Final analysis of the prospective LNH87-2 protocol—A Groupe d’Etude des Lymphomes de l’Adulte study. J Clin Oncol 18: 3025-3030, 2000[Abstract/Free Full Text]

4. Tilly H, Gaulard Ph, Lepage E, et al: Primary anaplastic large-cell lymphoma in adults: Clinical presentation, immunophenotype, and outcome. Blood 90: 3727-3734, 1997[Abstract/Free Full Text]

Response

M.D. Anderson Cancer Center, Houston, TX

In Reply:A prospective randomized study of conventional chemotherapy (CT) versus CT followed by autologous stem-cell transplantation was started at M.D. Anderson Cancer Center in 1985 for patients with poor-risk, aggressive lymphoma having a tumor score of 3.¹ Patients were randomized before starting any treatment. Those randomized to the nontransplantation arm received nine courses of alternating IdSHAP (idarubicin, cytarabine, and cisplatin), MBIDCOS (idarubicin, cyclophosphamide, vincristine, bleomycin, and solumedrol) and MINE (mesna, ifosfamide, mitoxantrone, and etoposide). Patients randomized to the transplantation arm received two courses of chemotherapy (IdSHAP and MBIDCOS) and then, if they responded, they received a course of ifosfamide/etoposide for stem-cell mobilization followed by autologous stem-cell transplantation with BEAM (carmustine, etoposide, cytarabine, and melphalan). Seventeen patients with PTCL were included. An interim intent-to-treat analysis has shown that seven (70%) of 10 patients who received high-dose chemotherapy are alive versus two (28.5%) of seven patients who were randomized to the nontransplantation arm (P = .08). This is another proof of principle that high-dose chemotherapy can potentially overcome the poor prognosis associated with T-cell immunophenotype (R.E. Champlin, personal communication, October 2001).

REFERENCES

1. Rodriguez J, Cabanillas F, McLaughlin P, et al: A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the tumor score. Ann Oncol 3: 711-717, 1992[Abstract/Free Full Text]

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