Although the concept of minimal residual disease (MRD) as an indicator for the quality of treatment response is the same in acute myeloid (AML) and acute lymphoid leukemia (ALL) the practice of measuring MRD levels for monitoring response and guiding post-induction therapy has been implemented much more rapidly in ALL particularly pediatric ALL than in AML. with slow rate of blast clearance during induction. Given the extent of our understanding that MRD has a decisive role in treatment stratification one cannot help but inquire what the reasons are that post-treatment MRD status is not yet used routinely to dictate post-remission therapy in all leukemia subtypes. Indeed in ALL measurement of MRD is usually increasingly used as a tool for adjusting therapy after initial treatment response and for stratifying patients into MRD-risk classes.6 7 The limited success of MRD-based clinical interventions in ALL patients determined high-risk based on unremitting MRD during MRD-guided treatment intensification 8 however suggests that novel treatment strategies are needed to Isochlorogenic acid C overcome the chemoresistance to current therapies as reflected by a persistent positive MRD status. One encouraging innovative modality is usually MRD-targeted therapy with the CD19/CD3-bispecific antibody blinatumomab in B-lineage ALL.11 With respect to MRD-directed therapy in AML robust clinical data are lacking. The pediatric AML02 trial12 failed to reduce MRD levels by intensifying induction therapy but exhibited an MRD-lowering effect of gemtuzumab ozogamicin the anti-CD33 antibody when given after the first course of induction. Strikingly however a high level of MRD after induction 1 was the only significant adverse prognostic factor for outcome. Like the previously listed data in the ALL studies allogeneic stem cell transplantation hasn’t shown to be a panacea for MRD-high risk AML sufferers. Importantly AML02 verified data from retrospective analyses13 which recommended the fact that threshold of prognostically significant MRD was at least 10-moments higher in AML than ALL. Furthermore this research demonstrated that sufferers with low MRD amounts after preliminary treatment did aswell long-term as people that have undetectable MRD regardless of following treatment allocation a acquiring quite not the same as what is observed in ALL where higher degrees of MRD are connected with a proportional upsurge in threat of relapse.14-16 Remarkably the result of MRD pre-transplantation is fairly different in every from AML also;17 while in every survival possibility post transplant was tightly associated with pre-transplant MRD amounts the same had not been the situation in AML.17 18 Quite simply in ALL however not AML increasing MRD amounts ahead of transplantation were connected with increased threat of relapse or death after transplant. In addition to Isochlorogenic acid C these potential biologic disparities between MRD in ALL and Mouse monoclonal to His Tag. AML profound differences exist in available targets for MRD detection and the Isochlorogenic acid C methodologies to monitor them which may explain why the clinical application of MRD to AML treatment is usually lagging behind that in ALL. Conversation A search in PubMed19 in October 2014 yielded >2 0 studies of MRD in ALL and not quite 400 in AML. Though only a rough estimate these numbers clearly demonstrate the fact that much more work is done on MRD in ALL than AML and this is also reflected in the disparate numbers of retrospective clinical trial analyses or prospective MRD-directed interventions. In my opinion before we participate into a conversation of biologic differences of MRD between the two diseases the more mundane issue of MRD measurement should be discussed. When antibodies to hematopoietic antigens became available Bradstock et al20 in 1981 exhibited that several patients in morphologic remission after treatment for all those experienced ‘minimal residual disease’ in their bone marrows based on unique phenotypic aberrations which allowed the variation of leukemic from normal immature cells. Because the first monoclonal antibodies were directed against lymphoid antigens both the immunophenotypic characterization of ALL and the detection of residual lymphoid blasts after treatment Isochlorogenic acid C from the beginning were far ahead of similar efforts in AML. While all methodology for MRD detection relies on the acknowledgement of phenotypic or genotypic differences between normal and leukemia hematopoietic cells there are obvious advantages to measuring MRD in ALL compared with AML which are summarized in Table 1. The fact that the majority of ALL cases have suitable somatic gene rearrangements is probably the most important difference given that AML lacks comparative immunogenotypes. Multiparameter circulation cytometry the quickest and cheapest way to determine MRD is much more straight forward in ALL than AML.