Correlation between Bone Marrow Morphology & Minimal Residual Disease Level at Day 15 during Induction Chemotherapy in Patients with Precursor B – Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (B-ALL) is the most common type of leukemia especially in children. The effective treatment of ALL is one of the great successes of Clinical Hematology, achieving survival rates of 80-85%. However, disease relapse remains the most common cause of treatment failure (15-20%).

The term "minimal residual disease, MRD" describes a disease that is detected only by laboratory techniques more sensitive than morphology, such as flow cytometry (FCM) for immunologic MRD, or polymerase chain reaction (PCR) for molecular MRD. This residual disease is believed to be minimal, being found in the absence of clinical signs or symptoms. The MRD testing in acute leukemia is used for measuring early treatment response, and identifying patients who achieved morphologic remission, but still harbor considerable levels of disease. The ultimate goal of MRD assays is to guide therapeutic decisions by distinguishing patients in whom therapy must be continued or intensified to minimize the likelihood of clinical relapse and to minimize treatment when not required to avoid treatment related toxicity.

The quantification of MRD by FCM is based on identification of markers defining a leukemia-associated phenotype (LAP), which is expressed on leukemic B- lymphoblasts, absent on hematogones, and ideally stable during therapy and at relapse. As phenotypic switch is common during treatment, multiple LAPs must be available and used for MRD detection over time. In MRD measurement, the FCM is frequently used being sensitive, rapid, widely applicable and relatively inexpensive.

In this study simplified detection of MRD at day 15 was performed on (50) newly diagnosed pre-B ALL patients, aiming to (1) evaluate the relationship between MRD and morphology as a prognostic factor in B-ALL. (2) Importance of MRD at early day point (day 15) post induction to pick up high risk patients as early as possible to avoid toxic effect of ineffective treatment. (3) The role of CD38 and CD58 in differentiation between blast cells and HGs.