Minimal residual disease (MRD) is an im-
IntroductionThe presence of minimal residual disease (MRD) following therapy for acute lymphoblastic leukemia (ALL) has been shown to be an important prognostic marker in many studies. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] MRD is typically detected either by polymerase chain reaction (PCR) amplification of clonotypic immunoglobulin or T-cell receptor gene rearrangements [20][21][22][23][24][25][26] or by flow cytometry, 27-41 the latter based on the principle that leukemic cells express combinations of antigens that are different from those present on normal bone marrow cells. The former technique can be more sensitive, though to achieve adequate sensitivity it is necessary to synthesize optimized clonespecific reagents. As a consequence, it is difficult to obtain real-time data that could be used for early intervention.Molecular detection of MRD has been well standardized. 25,[42][43][44] Though less widely standardized, 37,45 flow cytometry is faster, generally less expensive, and provides informative results in a higher percentage of patients than molecular methods. For these reasons, flow-based MRD assessment has the potential for rapidly identifying patients at increased risk of relapse, allowing for prompt changes in therapy, including earlier intensification. 7 Both PCR and flow have successfully been used to help risk-stratify patients, and while there is generally concordance between the methods in direct comparisons, 46,47 individual patients may not always be classified in the same way by each method. 48 Although the prognostic significance of MRD in ALL is well established, and is used as a criterion for risk stratification in many current studies, 49,50 most published studies have been relatively small. In childhood ALL in particular, the value of MRD must be weighed against other well-established prognostic variables, including age, white blood cell count, cytogenetic features of blasts, and conventional assessment of response to therapy. [50][51][52][53][54][55][56][57] Although MRD has been shown to retain prognostic significance after adjusting for some common risk factors, 4,6,19 the relationship between MRD and other prognostic factors has been incompletely explored. It is not clear if MRD by itself is all that is needed to predict outcome, if other risk factors add additional information to that obtained by MRD, or whether there are complex interactions between MRD and other factors. For example, we previously showed a difference between the frequency of positive MRD results at end induction in patients with the 2 most common The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From favorable genetic lesions: the TEL-AML1 translocation and simultaneous trisomies of chromosomes 4 and 10, w...