9/11/2023 0 Comments Prognostic factor![]() ![]() There has also been a lack of consensus regarding the prognostic impact of additional abnormalities accompanying the t(8 21), the outcome of AML with the various translocations involving the MLL locus at 11q23 and the level of cytogenetic complexity considered to confer adverse risk. 1 The relative rarity of some of these abnormalities has presented a challenge in determining their prognostic significance, reflected in inconsistencies in risk assignment between different trial groups ( Table 1). ![]() 1Īlthough karyotype analysis provides a powerful independent prognostic factor for rates of CR, relapse risk and OS in multivariable analyses, there is uncertainty concerning a number of miscellaneous cytogenetic abnormalities that together account for ~10% of AML. 1, 4 Conversely, adults presenting with AML and abnormalities of 3q, deletions of 5q, monosomies of chromosome 5 and/or 7 (−5/−7) or complex karyotype have a very poor prognosis with conventional chemotherapy and are therefore considered candidates for allogeneic transplant and experimental treatment approaches. In this favorable risk group, relapse rates are too low and salvage rates too high for there to be any survival benefit for allogeneic transplantation in first remission. Large multicenter studies have consistently reported that patients with acute promyelocytic leukemia (APL) with the t(15 17)(q22 q12~21) treated on ATRA- and anthracycline-based protocols together with the core binding factor (CBF) leukemias with t(8 21)(q22 q22) or inv(16)(p13q22)/t(16 16)(p13 q22) treated with intensive chemotherapy involving cytarabine at a range of doses are characterized by relatively favorable prognoses 1 ( Figure 1A, Table 1). In multivariable analyses that take into account age, type of AML ( de novo or secondary) and presenting white blood cell count (WBC), diagnostic karyotype emerges as the most significant prognostic factor and accordingly provides the framework for current risk-stratified treatment approaches. Accurate prediction of disease prognosis is therefore invaluable to help inform such treatment decisions, given the considerable expense associated with allogeneic transplantation as well as its longer term impact on health and quality of life. Given the procedure-related mortality associated with allogeneic transplantation, which is influenced by a range of factors, particularly patient age and type of transplant, one could argue that only those individuals at significant risk of relapse might be expected to gain any potential survival benefit from a transplant delivered in first CR. Conventional allografting has been clearly shown to reduce rates of relapse as compared to standard intensive chemotherapy (reviewed in Rowe 2), although the situation regarding overall survival (OS) is less clear. In children and younger adults, one key objective of the diagnostic work-up is to distinguish patients at differing risk of relapse to guide the use of allogeneic transplantation in first complete remission (CR). This could lead to further improvements in outcome and serve to identify in a more reliable fashion those patients most likely to benefit from allogeneic transplant in first remission. These advances present the exciting prospect that panels of pre-treatment parameters affording independent prognostic information can be integrated with precise measurement of treatment response using MRD technologies to provide greater refinement in risk-adapted management of AML. Moreover, there is increasing evidence that risk of relapse and overall survival can be predicted by assessment of kinetics and depth of response following front-line therapy and monitoring of the leukemic burden using molecular or immunological approaches to minimal residual disease (MRD) detection. Defining the individual genetic abnormalities or combinations of markers that provide significant independent prognostic information and establishing their respective relationships to other pre-treatment characteristics that impact on outcome, such as age and presenting white blood cell count, presents a major ongoing challenge. However, it is becoming increasingly apparent that AML is highly heterogeneous at the molecular level. These have not only afforded greater insights into disease biology, but also provided useful information predicting the likelihood of any given patient achieving and maintaining remission following conventional chemotherapy, leading to the development of risk-stratified treatment approaches. Over the last three decades there have been dramatic advances in deciphering the cytogenetic and molecular lesions underlying the pathogenesis of acute myeloid leukemia (AML). ![]()
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