ASH Clinical News September 2015 | Page 66

Minimal Residual Disease: ALL It’s Cracked Up to Be? Monitoring minimal residual disease (MRD) has become the standard of care in pediatric patients with acute lymphocytic leukemia (ALL) based on evidence that it is a strong prognostic factor for patient outcomes – patients who test negative for MRD have better outcomes than those who test positive. However, MRD monitoring isn’t a panacea. There are still many unanswered questions about what MRD is able to tell us, and what it isn’t – especially in adult patients with ALL. The use of MRD monitoring in adult patients is much less prevalent due to a lack of clear evidence and inconsistencies among the labs that conduct the tests. Despite some lingering questions, there is no doubt that the movement toward MRD monitoring is in full swing. ASH Clinical News spoke with several experts about MRD monitoring in pediatric and adult ALL, its role in signaling a relapse, and whether its results can help doctors avoid overtreating low-risk patients and identifying high-risk patients who would benefit from more intensive therapy. Measuring MRD In the pediatric realm, MRD measurement is replacing routine bone marrow tests as 64 ASH Clinical News the standard in assessing persistent disease, even as oncologists place less emphasis on the results from what has in the past been the standard of bone marrow biopsies. “I don’t trust it,” Ching-Hon Pui, MD, chair of the department of oncology at St. Jude Children’s Research Hospital in Memphis, Tennessee, told ASH Clinical News. “I don’t rely on my eye to tell me whether or not a patient has a leukemic cell.” Although he still performs morphologic bone marrow tests, Dr. Pui no longer depends on them. MRD monitoring is able to provide greater sensitivity and identify disease not found on bone marrow tests, without adding significant costs. There are several ways to test for MRD, and often the technique chosen depends on the lab where the test is being conducted. In the United States, the most common method for detecting MRD is flow cytometry: leukemia-associated immunophenotypes that are not found on normal hematopoietic cells are identified through a process of reacting live cells with inked antibodies that fluoresce when illuminated with a laser. In Europe, the common approach is using polymerase chain reaction (PCR) to screen and amplify a DNA in the immuglobulin gene or Tcell receptor to identify a clone associated with leukemia. Next, specific primers or molecules that will only bind to this clone are made to test later samples for the presence of this clone. So, the test is only looking for that specific clone present in that particular leukemia. Each method has its own set of advantages and disadvantages. Flow cytometry, for instance, is less expensive, can often report quantitative results within a day, and has a larger evidence base (having been used in most U.S.-based trials). PCR is said to be more sensitive, although researchers say it isn’t clear yet how critical it is to have that lower detection. “Studies have compared these two methods head-to-head, and they are quite concordant, particularly in higher levels of MRD,” said Stephen Hunger, MD, chief of the division of pediatric oncology and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. There is an emerging technique on the horizon: next-generation sequencing. Essentially, it works on the same principle as PCR but, instead of only amplifying one sequence and making a specific primer, next-generation se- September 2015