Outcome prediction by immunophenotypic minimal residual disease detection in adult T‐cell acute lymphoblastic leukaemia

Abstract

Summary. Flow-cytometric detection of minimal residual disease (MRD) identifies patients with high relapse risk in childhood acute lymphoblastic leukaemia (ALL). We studied the efficacy of this method in adult T-ALL treated with the Italian co-operative GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) LAL0496 protocol. Bone marrow samples from 53 patients were taken at fixed treatment time points and MRD was analysed using a leukaemiaspecific immunophenotype (cytoplasmic-CD3/nuclear-terminal desoxynucleotidyl transferase). The median follow-up was 17 months (range 3-61) and a median of 4AE5 analyses/ patient was performed (range 3-12). Six out of 53 (11AE3%) patients were refractory to treatment, 30/53 (56AE6%) relapsed and 17/53 (32AE1%) remain in continuous complete remission. The probability of relapse at 2 years for MRDpositive patients at preconsolidation was 81AE5% vs 38AE9% for MRD-negative patients (P ¼ 0AE00078). This risk was still 54AE5% for MRD-positive vs 15AE8% for MRD-negative patients pre-third reinduction (P ¼ 0AE0098) and 50AE0% for MRDpositive vs 16AE4% for MRD-negative patients pre-sixth reinduction (P ¼ 0AE032). The relapse-predicting value of MRD did not depend on features at diagnosis such as age, sex and leucocyte count. Our data suggest that immunophenotypic MRD monitoring in the first year of treatment is a useful outcome predictor for adult T-ALL patients.

Monitoring of T-cell acute lymphoblastic leukemia by flow cytometry

“…Thus combination of an early marker (TdT, CD34, CD99) with a T-cell marker (CD2, CD3, CD5, CD7) is used for T-ALL MRD detection most widely, such as: TdT/CD5/cCD3 and CD34/CD5/cCD3 in Campana's study [17]; TdT/CD7/sCD3/cCD3, CD99/CD7/sCD3/ cCD3 and CD99/CD7/CD5/CD3 in Dworzak's study [14]; or cCD3/TdT in Krampera's study [18].…”

New markers for minimal residual disease detection in acute lymphoblastic leukemia

“…27 Flow cytometric detection of leukemia-specific markers has been shown to predict outcome in numerous clinical correlative studies. 7,9,10,13,14,17,18,20 The method holds potential for wider applicability than molecular techniques because flow cytometric methods for leukemia diagnosis are already established at most cancer centers worldwide. 5 MRD studies by flow cytometry rely on panels of Abs to define unique immunophenotypic signatures of leukemic cells which must distinguish leukemic blasts from their normal counterparts, the CD19 ϩ CD10 ϩ lymphoid progenitors of the BM ("hematogones").…”

“…5 MRD is currently the most powerful prognostic indicator in childhood ALL, [6][7][8][9][10][11][12][13][14][15][16] and there is strong evidence supporting its prognostic significance in adult ALL. [17][18][19][20][21] Thus, MRD monitoring has been introduced into many contemporary treatment protocols for risk assignment and selection of therapeutic regimens. [1][2][3][4] MRD measurements are also clinically useful in patients with relapsed ALL who achieve a second remission, [22][23][24] can help optimize the timing of hematopoietic stem cell transplantation, 25 and guide decisions about donor lymphocyte infusion posttransplantation.…”

Minimal residual disease detection in childhood precursor–B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] MRD may be detected at a sensitivity of at least 10 À4 either by molecular means, generally based on polymerase chain reaction (PCR) amplification of rearranged immunoglobulin (Ig) or T-cell receptor genes 13,14,[16][17][18][19][20] or by multiparameter flow cytometry. 1,2,[8][9][10]15,[21][22][23][24][25][26] The latter approach is based on the fact that leukemic cells express aberrant phenotypic combinations of antigens that are not present on normal bone marrow cells. 9,22,[27][28][29] Both methods are generally recognized as useful, although they have different advantages and disadvantages.…”