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Previous Volume 333:595-596 August 31, 1995 Number 9 Next

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To the Editor: Inaccuracies in our paper "Interferon Alfa-2a Therapy for Life-Threatening Hemangiomas of Infancy"¹ prompted a careful review. On the basis of our reanalysis and an interim review by a standing faculty committee of the Harvard Medical School, we submitted a revised Table 1, published as a correction notice.² The final review of this committee concluded that ambiguities in method, presentation, and conclusions should be clarified and that errors remained that should be corrected.

In our original description of the assessment of outcomes, we never stated that lesions were measured; however, the use of the terms "dimensions" in the Methods section and "percentages" in the Methods section and the table could have implied a quantitative method. It is not possible to quantify precisely the tumors we were describing, because of their heterogeneity in size, shape, and anatomical location. Therefore, the Methods section should have read: "Premature regression was defined as an obvious decrease of 50 percent or more in the size [not dimensions] of the hemangioma." We estimated the percent change by comparing pretreatment photographs, radiographs, or endoscopic examinations with those obtained after treatment; the assessment was adjusted according to clinical status for most patients. We used the combination of methods appropriate for each patient but did not weight the contributions of each method formally. For example, in Patient 2, who had Kasabach–Merritt syndrome, 70 percent regression was estimated subjectively on the basis of the reduction in the size of the lesion as shown by photography, the diminished turgor of the lesion, and reversal of coagulopathy. In Patient 14, 60 percent regression was estimated subjectively on the basis of the 100 percent regression of the airway lesion shown by endoscopy and magnetic resonance imaging (MRI), modified because of residual mediastinal disease (seen on MRI) and the patient's clinical status. For clarification, we now include a table showing the methods used to estimate the response in each patient (Table 1).

View this table: [in this window] [in a new window]   Table 1. Methods Used to Assess Outcomes of Interferon Alfa Treatment.

 
In all patients, the period of assessment began at the start of interferon treatment. In the Methods section of our paper, we stated incorrectly, "Premature regression . . . was sustained for at least six months during treatment or after the withdrawal of the medication."¹ To clarify: Patients 8, 16, 19, and 20 required less than 6 months of treatment; they were assessed at 3 months, 3 months, 4 months, and 5.25 months, respectively. Follow-up procedures were not performed if they required general anesthesia and were not clinically indicated — i.e., MRI was not performed for Patients 4 and 20, and endoscopy was not performed for Patient 8. Clinical assessments alone were used, in these instances, to document sustained regression.

We also stated incorrectly in the Methods section, "To be eligible for the study, infants had to have a life-threatening or vision-threatening hemangioma that failed to respond to a two-week course of corticosteroid therapy. . . ."¹ Therapeutic doses of corticosteroids were given before interferon therapy to 15 patients, for one month during interferon therapy to Patient 1, and for seven weeks during interferon therapy to Patient 12.² Patient 1 died and Patient 12's hemangioma grew while she was receiving both drugs. Patients 3 and 14 began receiving interferon after 12 days of corticosteroids, not 14 days, because of their worsening conditions. Interferon alone was given to Patients 10, 13, and 16.² In 15 patients for whom corticosteroids failed, interferon was initiated during the period when the dose of corticosteroid was being tapered, since it was not considered safe to discontinue the latter abruptly.

We stated incorrectly in the Methods section, "A complete blood count and tests of hepatic . . . function were performed monthly." We were unable to obtain monthly laboratory studies for 18 patients; therefore, we cannot reach any conclusions about toxic effects. We must add to the record, however, that four patients, not one, had transient neutropenia, and eight patients had liver aminotransferase levels two to five times their pretreatment levels. Patient 15 was hyperactive for one day after receiving a gradually escalated dose of interferon to 6 million units per square meter of body-surface area. Furthermore, Patient 14 missed 13 doses of interferon during six months of therapy.

We are embarrassed by our errors and regret them. We apologize to the readers for any misunderstanding and thank our colleagues for their assistance in correcting our report.

Alan Ezekowitz, M.B., Ch.B., D.Phil.
John Mulliken, M.D.
Judah Folkman, M.D.
Children's Hospital
Boston, MA 02115

References

1. Ezekowitz RAB, Mulliken JB, Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1992;326:1456-1463. [Abstract]
2. Correction to: Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1994;330:300-300. [Free Full Text]

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