Immunologic monitoring in adults with acute lymphoblastic leukemia

Abstract

Investigation of minimal residual disease (MRD) by immunophenotyping and molecular techniques has proven to be a powerful approach for disease monitoring in patients with acute leukemia. Multiparameter flow cytometry, through the use of triple or quadruple marker combinations, identifies aberrant or uncommon phenotypic profiles in more than 90% of adult patients with acute lymphoblastic leukemia (ALL) at diagnosis. These profiles allow identification of residual leukemic cells in bone marrow or peripheral blood once morphologic complete remission is achieved. Until now, most immunophenotypic MRD studies in ALL have focused on children. In contrast, information on the value of MRD in adults with ALL is scanty and usually restricted to polymerase chain reaction studies. In this review, we focus on technical aspects of MRD detection by flow cytometry and on the clinical data concerning the value of immunologic MRD studies as a tool for relapse prediction in adult ALL. Although prospective studies are needed, we assert that immunophenotypic MRD studies are clinically useful. Such studies should be incorporated into the routine management of adult ALL patients for identification of those at high risk of relapse, who could benefit from new alternative therapeutic approaches, and to distinguish these patients from others who could be cured with more conventional approaches.

Immunophenotyping of acute leukemias and myelodysplastic syndromes

“…For many years, the use of single stainings analyzed by fluorescence microscopy or flow cytometry have restricted the routine applications of immunophenotyping in MDS to the characterization of blast cell populations after transformation into AL (24,25). These studies confirmed that almost every AL following an MDS corresponded to an AML, B-and T-lymphoid blast crisis being either rare or exceptional, respectively (87).…”

“…More recently, it has also proven to be of great help for the screening of genetic abnormalities (14 -22), the follow-up of minimal residual disease (MRD) (23)(24)(25), monitoring of patient-specific therapies (26,27), and the study of MDS (28,29). These new applications of flow cytometry immunophenotyping mainly rely on the concept that even if neoplastic cells show a great similarity to normal hematopoietic precursors, they frequently display aberrant phenotypes that allow their specific identification and discrimination from normal cells, even when present at very low frequencies (23)(24)(25). To a large extent, such aberrant phenotypes would be a consequence of the genetic abnormalities accumulated by the neoplastic cell (14 -22).…”

2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: Medical indications

“…Assessment of response to therapy (including “minimal residual disease” testing) and persistence of FCI‐detectable MRD following therapy, which is often an adverse prognostic factor. However, the optimal frequency of such monitoring has not been established (112, 137–163). Documentation of progression or relapse. Diagnosis of additional intercurrent hematolymphoid neoplasm, either treatment‐ related (such as MDS/AML or PTLD) or coincidental (164–170).…”

Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] MRD is typically detected either by polymerase chain reaction (PCR) amplification of clonotypic immunoglobulin or T-cell receptor gene rearrangements [20][21][22][23][24][25][26] or by flow cytometry, [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] the latter based on the principle that leukemic cells express combinations of antigens that are different from those present on normal bone marrow cells. The former technique can be more sensitive, though to achieve adequate sensitivity it is necessary to synthesize optimized clonespecific reagents.…”