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Superiority of Reduced-Intensity Conditioning for Hodgkin's Lymphoma

University of Chicago, Chicago, IL

Sureda et al¹ recently reported improved outcomes after nonmyeloablative conditioning for patients with Hodgkin's lymphoma. These conclusions are based on an analysis of registry data collected over a 15-year period.

Registry analyses have contributed to much of our insights in the role of allogeneic transplantation for lymphoma, an area where prospective studies have been notoriously limited. But registry data have their own limitations, including their retrospective nature and lack of central pathology review. To minimize risks of erroneous interpretation, major efforts at obtaining complete information are required, and datasets with excessive amounts of missing data can be unreliable. The data set on which the conclusions of Sureda et al are based seems to have major gaps. For example, in Table 1, patients are divided in three age categories, but only 68 of the 79 recipients of myeloablative transplantation and 75 of the 89 recipients of nonmyeloablative transplantation are thus categorized. Disease stage at diagnosis and cytomegalovirus risk group are known for fewer than half the patients. Seven of 79 patients, but 28% according to Table 1, undergoing myeloablative transplantation had bulky disease at diagnosis. Ten of 89, but 22.2% according to Table 1, undergoing reduced intensity conditioning (RIC) transplantation had bulky disease at transplantation. Are the discrepancies between absolute numbers and percentages typographic errors or do they indicate that disease bulk was not known for many patients? The latter would be a serious problem, given that in multivariate analysis disease bulk is found to be an important risk factor for disease recurrence. How did the authors address such missing data?

A more important issue relates to the definition of what constitutes RIC and to the proportion of patients receiving specific conditioning regimens. The authors state that the carmustine, etoposide, cytarabine, and melphalan conditioning regimen "was included in the RIC group taking into account the results in terms of low NRM [nonrelapse mortality] and good clinical outcome presented by Faulkner et al." This would make it seem that regimens with a good track record were labeled as RIC, and regimens with more previously reported toxicity would be labeled as myeloablative. Such a classification does not take into account the fact that transplantation-related toxicity depends to a large extent on performance status and the presence of comorbidities,^2,3 and it has no biologic underpinnings. Some have argued that the carmustine, etoposide, cytarabine, and melphalan regimen should be considered myeloablative, and one wonders how the results would appear if the patients were recategorized as such.⁴ The authors also conclude that, in multivariate analysis, RIC regimens incorporating total body irradiation are associated with a higher recurrence rate, but no information is provided on the number of patients receiving this type of regimen. Additional information on the distribution of patients receiving particular conditioning regimens and on performance status at transplantation would allow the reader to gain a better understanding of the distribution of patient characteristics and treatments and would further enhance the value of this article.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Sureda A, Robinson S, Canals C, et al: Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: An analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 26:455-462, 2008[Abstract/Free Full Text]

2. Sorror M, Storer B, Sandmaier BM, et al: Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 112:1992-2001, 2008[CrossRef][Medline]

3. Artz A, Pollyea D, Kocherginsky M, et al: Performance status and comorbidity predict transplant related mortality after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 12:954-964, 2006[CrossRef][Medline]

4. Hari P, Carreras J, Zhang MJ, et al: Allogeneic transplants in follicular lymphoma: Higher risk of disease progression after reduced-intensity compared to myeloablative conditioning. Biol Blood Marrow Transplant 14:236-245, 2008[CrossRef][Medline]

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