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High-Dose Therapy With Autologous Stem-Cell Transplantation in Aggressive Non-Hodgkin's Lymphoma

University Hospital, Utrecht, the Netherlands

To the Editor: The report of the jury evaluating the available data on high-dose therapy with autologous stem-cell transplantation (ASCT) in aggressive non-Hodgkin's lymphomas (NHL) at the international consensus conference held in Lyon, France, in April 1998, and published in the January issue of the Journal of Clinical Oncology¹ made some false statements about the Dutch cooperative group trial.² In that study, patients with aggressive NHL that responded slowly to three courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either early ASCT or continuation of CHOP (a total of eight courses).

First, the response definition of complete remission with residual masses from partial remission with persistent viable tumor does not apply in our study because response was evaluated after three courses of CHOP and not at the completion of chemotherapy. It is very unlikely that patients with aggressive NHL are already disease-free after three courses of CHOP.

Second, the statement that the treatment arms were imbalanced with regard to clinical prognostic factors is incorrect. Both treatment arms were very well balanced.²

Third, not few patients but approximately half of the patients (44%) were in the high/intermediate-risk or high-risk (International Prognostic Index) groups.

Of course, the number of patients who were randomized was rather small, but the results were such (and still are) that a substantial benefit from ASCT was extremely unlikely. Our study was probably the first that questioned the value of ASCT; ever since, other reports of randomized trials for various malignancies have also failed to show a benefit for ASCT.³-⁷

A decade ago, the general feeling was that ASCT was an important step forward in the treatment of various malignancies. Regrettably, it probably is not better than intensive chemotherapy for the vast majority of patients.

REFERENCES

1. Shipp MA, Abeloff MD, Antman KH, et al: International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin's lymphomas: Report of the jury. J Clin Oncol 17:423-429, 1999[Free Full Text]

2. Verdonck LF, van Putten WL, Hagenbeek A, et al: Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin's lymphoma. N Engl J Med 332:1045-1051, 1995[Abstract/Free Full Text]

3. Ravindranath Y, Yeager AM, Chang MN, et al: Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med 334:1428-1434, 1996[Abstract/Free Full Text]

4. Santini G, Salvagno L, Leoni P, et al: VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: Results of a prospective randomized trial by the non-Hodgkin's lymphoma cooperative study group. J Clin Oncol 16:2796-2802, 1998[Abstract]

5. Gherlinzoni F: Early autologous stem cell transplantation versus conventional first-line chemotherapy in high-risk aggressive non-Hodgkin's lymphomas (NHL): An Italian multicenter randomized trial. Blood 92:726a, 1998 (abstr 2980)

6. Rodenhuis S, Richel DJ, Elsken van der Wall et al: Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 352:515-521, 1998[Medline]

7. Cassileth PA, Harrington DP, Appelbaum FR, et al: Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 339:1649-1656, 1998[Abstract/Free Full Text]

High-Dose Therapy With Autologous Stem-Cell Transplantation in Aggressive Non-Hodgkin's Lymphoma

For the Jury, International Consensus Conference on High Dose Therapy With Hematopoietic Stem Cell Transplantation in Aggressive Non-Hodgkin's Lymphomas

In Reply: The authors of a Dutch cooperative group trial¹ comparing the efficacy of CHOP chemotherapy to that of autologous bone marrow transplantation in slowly responding patients with aggressive non-Hodgkin's lymphoma express concern regarding the review of their study in the recent international consensus conference jury report.² Jury members noted that it was not possible to distinguish complete responders with residual masses from partial responders with persistent viable tumor using only standard radiographic criteria in this study.² In addition, they noted that the majority (56%) of randomized patients on this trial had only low or low/intermediate-risk disease as assessed by the International Prognostic Index.² They also noted that the sample size was too small (69 randomized patients) and that the randomized groups included different percentages of patients with specific subtypes of aggressive NHL.² These methodologic issues led the jury to conclude that additional studies were needed on the role of high-dose therapy with stem-cell support in patients with slow or incomplete responses to induction therapy.²

REFERENCES

1. Verdonck LF, van Putten WL, Hagenbeek A, et al: Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin's lymphoma. N Engl J Med 332:1045-1051, 1995

2. Shipp MA, Abeloff MD, Antman KH, et al: International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin's lymphomas: Report of the jury. J Clin Oncol 17:423-429, 1999

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Verdonck, L. F. Articles by Shipp, M. A. Search for Related Content PubMed PubMed Citation Articles by Verdonck, L. F. Articles by Shipp, M. A. Social Bookmarking                            What's this?