RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC-LEUKEMIA OF CHILDHOOD - DETECTION, QUANTITATION, CHARACTERIZATION AND CLINICAL-SIGNIFICANCE

Complete remission is achieved in the majority of children with acute lymphoblastic leukemia (ALL). However, almost one-third of these patie nts have relapses due to persistent indolent disease that is below the level of detection by conventional morphologic methods. Therefore, a major attempt has been made to develop methods that allow us to monito r patients during remission and determine the level of residual diseas e with a higher sensitivity. Residual disease can be detected in ALL p atients at a cellular, chromosomal or molecular level. Among the vario us methods are morphologic, immunologic, clonogenic, cytogenetic and f low cytometry assays. All have limited sensitivity and other various d eficiencies that limit their clinical applications. To overcome these deficiencies the polymerase chain reaction (PCR) has been applied. The PCR technique amplifying leukemia-specific translocations and leukemi a clone-specific immunoglobulin heavy chain and T-cell receptor gene r earrangements detects one leukemia cell among 10(5) normal marrow cell s; however, it cannot provide any information about the growth potenti al of these cells. Therefore, PCR was recently combined with the ALL b last colony assay, which detects ALL progenitors with proliferative an d self-renewal capability. Preliminary results for 30 patients suggest that follow-up studies quantitating changes in the level of residual leukemia may allow prospective assessment of the clinical value of occ ult disease detection.