Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure.The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10−3 a 10−5), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers.The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL.

Immunophenotypic aberrancies in acute lymphoblastic leukemia from 282 Iraqi patients

“…Such patterns are in contrast to that of hematogones, as they defy normal antigenic evolution of B‐cell precursors and asynchronously co‐express early and late antigens (eg, CD34 and CD20) or over or under‐express others . Such asynchronous expression of early and late B‐cell markers had been reported by many earlier studies on B‐ALL with variable rates . As individual markers, CD10 was the most frequent abnormally expressed marker, followed by nTdT, CD34, CD38, and CD20 (Table ).…”

“…One of the most important findings of the current study is that LAIP was documented in 86.9% of all cases, and such a high rate makes the characterization of LAIP by FC valuable for the purposes of MRD monitoring. The use of FC for the evaluation of MRD yields a sensitivity of 0 −3 ‐10 −4 (in 3‐4 colors FC) and 10 −4 ‐10 −5 (in >6 colors FC), which is approximating the sensitivity achieved by RQ‐PCR of 10 −4 ‐10 −6 . However, FC has the advantage of rapid turnover time of the results, the ability to distinguish viable from apoptotic cells, and being relatively less expensive in comparison with PCR.…”

“…Among the limitations of FC are leukemic phenotypic switches and the frequent lack of standardization of the procedure with its variable sensitivity. In addition, there is no consensus on the extent of panels that should be applied for the initial diagnosis or the detection of MRD …”

“…Several investigators have suggested unfavorable outcomes in T‐ALL with myeloid antigen expression . It is important to note that although the overall frequency LAIP among T‐ALL cases was much less than B‐ALL, the immunophenotype of leukemic T‐lymphoblasts is remarkably different from that of the normal bone marrow and blood T cells, and the detection of dual expression of cCD3 and nTdT and/or cCD3 + /sCD3 − in T‐lymphoblasts in peripheral blood or bone marrow at follow‐up of patients with T‐ALL is regarded as MRD, as T cells with such characteristics are confined to the thymus …”

Simultaneous Inhibition of Protein Kinase CK2 and Dihydrofolate Reductase Results in Synergistic Effect on Acute Lymphoblastic Leukemia Cells

“…Acute lymphoblastic leukemia (ALL) is the most common cancer among children (1), and constitutes approximately 25% of cancer diagnoses among children and teenagers (2). The most common method of treatment of ALL is chemotherapy, divided into several phases, such as: induction phase, consolidation phase, and finally the maintenance phase, while physicians attempt to reduce the possibility of relapse (3).…”