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Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia

For the Acute Myeloid Leukemia Committee of the International Berlin-Frankfurt-Münster Study Group, Münster, Germany
For the Acute Myeloid Leukemia Committee of the International Berlin-Frankfurt-Münster Study Group, VU University Medical Center, Amsterdam, the Netherlands

To the Editor:

First, we would like to thank our colleagues Cheson et al for revising the response criteria and other definitions in acute myeloid leukemia (AML) that have been the basis for reports since 1990.^1,2

We appreciate that the definitions of response and treatment failures in AML have been clarified and that the category of treatment failure due to complications from aplasia is now included. The latter was lacking in the definition of 1990, and helps to distinguish patients who are not in complete remission into those with persistent AML and others with aplasia in a morphologic leukemia-free state. In addition, early treatment assessment is a valuable contribution.

However, the AML committee of the International Berlin-Frankfurt-Münster (BFM) Study Group at their recent annual meeting discussed two remarks concerning the definitions, based on their experience in pediatric AML. First, there is a category of treatment failure due to indeterminate cause. This relates to patients who died less than 7 days post-therapy, patients who died more than 7 days post-therapy with no peripheral blood blasts but no bone marrow examination, and patients who did not complete the first course of therapy. Most of these patients would have been included previously in the category of early death. Now, this is a mixed category including patients of whom data are lacking. Our proposal is to resume a definition of early death, including all patients dying before day 15 of treatment. In general, this is the same definition as surviving less than 7 days after chemotherapy. However, we propose to include patients dying after more than 7 days after chemotherapy in the aplastic death category because at least the data of neutrophils and platelets will be available, and by far most of them will be aplastic. In pediatric AML, a day 15 bone marrow puncture will almost always be performed; therefore, patients without information on response will be rare. A second topic is the definition of morphologic complete remission (CR), which is easier now because it does not require a 4-week duration of complete response as given in the previous guidelines. However, a problem from a pediatric point of view is that CR, by definition, requires more than 1,000/µL neutrophils and more than 100,000/µL platelets. Often, such a recovery is not awaited and additional intensive chemotherapy will be continued. In approximately 10% of our patients, CR by this definition will not be achieved even after four or five courses of intensive chemotherapy. Additional medication (such as for prophylaxis for infections) and intercurrent viral infections may also play a role. However, these patients have achieved remission, and most of them stay in remission. Therefore, we suggest that in addition to the conventional CR rate (with a neutrophil count of > 1,000/µL and platelets > 100,000/µL), morphologic CR with incomplete blood count recovery (CRi) become a well-recognized category. Overall remission rate will then relate to CR and CRi patients. Cheson et al recommended this CRi status only for patients of phase I and II studies, and state that they should not be included in the CR group. We think that, at least in our pediatric trials, some patients surviving in remission would be in an incorrect category.

On the basis of these remarks and some other points not discussed here, the AML committee of the International BFM Study Group is currently preparing pediatric guidelines for definitions of treatment response in pediatric AML.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Cheson BD, Bennett JM, Kopecky KJ, et al: Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 21:4642–4649, 2003[Abstract/Free Full Text]

2. Cheson BD, Cassileth PA, Head DR, et al: Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 8:813–819, 1990[Abstract]

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• Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia
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  JCO 2003 21: 4642-4649 [Abstract] [Full Text]

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