ASH-CAP Guidelines for the Diagnosis of Acute Leukemia

Taking a step back, one could ask, “Do physicians need such guidelines?” To answer this question, CAP conducted a survey among hematologists/oncologists and pathologists on the current practice of ordering tests for the diagnosis of acute leukemia.⁶  The survey showed that nearly 100 percent of respondents reported performing morphologic assessment and flow cytometry analysis, and 96 percent of respondents reported performing conventional cytogenetics. Surprisingly, far fewer respondents reported performing molecular genetic testing for AML (71%) or for acute lymphoblastic leukemia (ALL; 55%). Limitations of the survey included a preponderance of academic hematopathologists among responders, which could serve as a source of bias and inaccuracy due to self-reporting. The reader could rightly ask, “What are the actual current clinical practice patterns by physicians for patients with acute leukemia?”

An observational cohort study reported at the 2016 ASH Annual Meeting by Dr. Tracy George and colleagues sheds some light onto this topic. The CONNECT MDS/AML Disease Registry (NCT01688011) was used to assess current clinical practice patterns in AML and to compare how these practices align with WHO 2008 recommendations.⁷  The disease registry includes 64 community and 15 academic centers and involves prospective reporting of clinical findings, laboratory results, and pathology test results, which are then centrally reviewed. The data showed that flow cytometry and conventional karyotyping were done in most cases (98% and 92%, respectively), but a manual blast count was performed only in 67 percent of AML patients at diagnosis. Approximately 10 percent of blasts counts were primarily evaluated by flow cytometry, which is highly discouraged per WHO 2008 recommendations, as it may both underestimate and overestimate the blast count. Molecular genetic testing was performed in only 67 percent of patients. A multivariate model identified two independent significant predictors of molecular genetic testing, including age equal to 65 years or younger, and if the patient was enrolled at an academic site. Thus, these results would argue that guidelines are needed for the diagnosis of acute leukemia and the CONNECT AML/MDS disease registry is uniquely positioned to monitor the implementation of the ASH-CAP guidelines.

In studying the ASH-CAP guidelines, their strength lies in the grading of the quality of evidence. Each guideline statement is accompanied by the strength of recommendation allowing the reader to ascertain the impact of each guideline statement. While the initial guideline statements may appear quite obvious to the practicing hematologist and pathologist, they clearly delineate the samples and specimen types necessary for the diagnostic workup. Statement 12 clearly addresses the impact of minimal residual disease testing and statements 13 to 21 offer practical recommendations on the genetic workup of different types of acute leukemia. Survey results and data from the CONNECT AML/MDS registry suggest that physicians are not currently ordering enough genetic testing or the proper genetic tests, so these statements are helpful. The final statements refer to where testing is performed and what results should be reported, including the recommendation that WHO terminology be used for the final diagnosis and classification of acute leukemia.

To summarize, ASH and CAP have published guidelines on testing for the initial workup of acute leukemia that will be helpful in guiding all physicians and allied health professionals on the proper diagnostic workup of acute leukemia. The guidelines are available now on www.archivesofpathology.org. In addition to the full guideline, the recommendations and diagnostic algorithms will also be available in late March 2017 at www.hematology.org/pocketguides, in a printed pocket guide, and digitally in the ASH Pocket Guides app.