CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(01): 071-076
DOI: 10.1055/s-0041-1729730
Trainees’ Corner

Minimal Residual Disease in Acute Lymphoblastic Leukemia

Pratik P. Patil
1   Department of Medical Oncology, Max Super Speciality Hospital, New Delhi, India
,
Esha Jafa
2   Department of Medical Oncology, Super Speciality Cancer Institute, Lucknow, Uttar Pradesh, India
,
Mayank Aggarwal
1   Department of Medical Oncology, Max Super Speciality Hospital, New Delhi, India
› Institutsangaben

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children accounting for 25 and 75% of childhood cancers and leukemia, respectively, citied as the major success stories in the world of oncology where the cure rates have gone up to 80% (event-free survival [EFS]) from literally zero in the 1950s.[1] [2] [3] Prognostic factors play an important role in the strategic standard management of ALL wherein minimal residual disease (MRD) is now widely regarded as a clinically significant tool. A meta-analysis has proven that MRD negativity is directly proportional to the powerful predictors of disease-free survival (DFS) (hazard ratio [HR]: 0.23, [95% Bayesian credible interval [BCI]: 0.18–0.28] for pediatric patients and 0.28 [95% BCI: 0.24–0.33] for adults) and overall survival (OS) (HR: 0.28, [95% BCI: 0.19–0.41] and 0.28 [95% BCI: 0.20–0.39] for children and adults with ALL, respectively).[4]

It now provides information depending on when the MRD assessment was performed: after induction therapy, after consolidation therapy (CT), or before and after stem cell transplant (SCT) and genomic information for targetable therapies available today, as shown in [Table 1]. As of today, for the management of ALL, induction therapy to aim complete hematological recovery and complete remission (CR), followed by CT after attainment of CR, with standard central nervous system (CNS) prophylaxis, is imperative. It is followed by SCT in few subsets. Mostly all pediatric and adult ALL guidelines have introduced informative checkpoints during the management of ALL. For pediatric subgroup, MRD negativity on day 15 of induction chemotherapy defines excellent outcomes, wherein in adults, MRD is taken later in the course at 4 weeks of starting induction chemotherapy and defines better survival rates.[5] [6]

Table 1

Genetic classification by prognosis of B-cell acute lymphoblastic leukemia

Good prognosis

Intermediate prognosis

Poor prognosis

Undetermined prognosis

Abbreviations: ALL, acute lymphoblastic leukemia; MLL, mixed-lineage leukemia.

at(5; 14); IL3-IGH is a World Health Organization-classified acute leukemia and prognosis data has not been determined.

Hyperdiploid karyotypes

t(1; 19); TCF3-PBX1

Hypodiploid karyotypes

t(5; 14); IL3-IGHa

t(12; 21); ETV6-RUNX1 (TEL-AML1)

t(9; 22); BCR-ABL

Philadelphia-like ALL

11q23 MLL arrangements



Publikationsverlauf

Artikel online veröffentlicht:
28. Mai 2021

© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Gaynon PS. Childhood acute lymphoblastic leukaemia and relapse. Br J Haematol 2005; 131 (05) 579-587
  • 2 Chessells JM, Hardisty RM, Richards S. Long survival in childhood lymphoblastic leukaemia. Br J Cancer 1987; 55 (03) 315-319
  • 3 Shanta V, Maitreyan V, Sagar TG, Gajalakshmi CK, Rajalekshmy KR. Prognostic variables and survival in pediatric acute lymphoblastic leukemias: cancer institute experience. Pediatr Hematol Oncol 1996; 13 (03) 205-216
  • 4 Berry DA, Zhou S, Higley H. et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA Oncol 2017; 3 (07) e170580
  • 5 Basso G, Veltroni M, Valsecchi MG. et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol 2009; 27 (31) 5168-5174
  • 6 Šálek C, Folber F, Froňková E. et al. Czech Leukemia Study Group - for Life. Early MRD response as a prognostic factor in adult patients with acute lymphoblastic leukemia. Eur J Haematol 2016; 96 (03) 276-284
  • 7 Trautmann H, Bautz J, Kruse AW, Kneba M, Brüggemann M. Molecular Characterization of Immune Gene Rearrangement Profiles in Acute Lymphoblastic Leukemia (ALL) using QIAxcel® Advanced Department of Internal Medicine II, Christian Albrechts University. Campus Kiel, Germany: University Medical Center Schleswig Holstein. Available from:https://www.qiagen.com/us/resources/download.aspx?id= 8878bf26–9da2–435c-9160–551fbc5351b7&lang=en. Accessed April 13, 2021
  • 8 Coustan-Smith E, Sancho J, Hancock ML. et al. Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. Blood 2002; 100 (07) 2399-2402
  • 9 Brisco MJ, Sykes PJ, Hughes E. et al. Monitoring minimal residual disease in peripheral blood in B-lineage acute lymphoblastic leukaemia. Br J Haematol 1997; 99 (02) 314-319
  • 10 van der Velden VH, Jacobs DC, Wijkhuijs AJ. et al. Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL. Leukemia 2002; 16 (08) 1432-1436
  • 11 van Dongen JJ, Seriu T, Panzer-Grümayer ER. et al. Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet 1998; 352 (91/42) 1731-1738
  • 12 van Dongen JJ, van der Velden VH, Brüggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood 2015; 125 (26) 3996-4009
  • 13 Ribera JM, Oriol A, Morgades M. et al. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol 2014; 32 (15) 1595-1604
  • 14 Dhédin N, Huynh A, Maury S. et al. GRAALL group. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood 2015; 125 (16) 2486-2496, quiz 2586
  • 15 Bassan R, Masciulli A, Intermesoli T. et al. Final results of Northern Italy Leukemia Group (NILG) trial 10/07 combining pediatric-type therapy with minimal residual disease study and risk-oriented hematopoietic cell transplantation in adult acute lymphoblastic leukemia (ALL). Blood 2016; 128: 176
  • 16 Gökbuget N, Kneba M, Raff T. et al. German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood 2012; 120 (09) 1868-1876
  • 17 Chalandon Y, Thomas X, Hayette S. et al. Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood 2015; 125 (24) 3711-3719
  • 18 Foà R, Vitale A, Vignetti M. et al. GIMEMA Acute Leukemia Working Party. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 2011; 118 (25) 6521-6528
  • 19 Yoon JH, Yhim HY, Kwak JY. et al. Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Ann Oncol 2016; 27 (06) 1081-1088
  • 20 Maino E, Sancetta R, Viero P. et al. Current and future management of Ph/BCR-ABL positive ALL. Expert Rev Anticancer Ther 2014; 14 (06) 723-740
  • 21 Pfeifer H, Wassmann B, Bethge W. et al. GMALL Study Group. Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR-ABL1-positive acute lymphoblastic leukemia. Leukemia 2013; 27 (06) 1254-1262
  • 22 Chiaretti S, Vitale A, Vignetti M. et al. A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study. Haematologica 2016; 101 (12) 1544-1552
  • 23 Lee S, Kim DW, Cho BS. et al. Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia. Leukemia 2012; 26 (11) 2367-2374
  • 24 Lussana F, Intermesoli T, Gianni F. et al. Achieving molecular remission before allogeneic stem cell transplantation in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: impact on relapse and long-term outcome. Biol Blood Marrow Transplant 2016; 22 (11) 1983-1987
  • 25 Nishiwaki S, Imai K, Mizuta S. et al. Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT. Bone Marrow Transplant 2016; 51 (01) 43-50
  • 26 Hovorkova L, Zaliova M, Venn NC. et al. Monitoring of childhood ALL using BCR-ABL1 genomic breakpoints identifies a subgroup with CML-like biology. Blood 2017; 129 (20) 2771-2781
  • 27 Cazzaniga G, De Lorenzo P, Alten J. et al. Predictive value of minimal residual disease in Philadelphia-chromosome-positive acute lymphoblastic leukemia treated with imatinib in the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia, based on immunoglobulin/T-cell receptor and BCR/ABL1 methodologies. Haematologica 2018; 103 (01) 107-115
  • 28 Clappier E, Kim R, Cayuela JM, et al. Persistent BCR-ABL1 Clonal Hematopoiesis after Blast Clearance Identifies a CML-Like Subgroup of Patients with Philadelphia Chromosome-positive (Ph+) ALL: Interim Results from GRAAPH-2014 Trial. Stockholm: 23th EHA Annual Congress Stockholm; 2018. p. S1568
  • 29 Huguet F, Leguay T, Raffoux E. et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol 2009; 27 (06) 911-918
  • 30 Jain N, Roberts KG, Jabbour E. et al. Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults. Blood 2017; 129 (05) 572-581
  • 31 Buckley SA, Appelbaum FR, Walter RB. Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia. Bone Marrow Transplant 2013; 48 (05) 630-641
  • 32 Campana D, Leung W. Clinical significance of minimal residual disease in patients with acute leukaemia undergoing haematopoietic stem cell transplantation. Br J Haematol 2013; 162 (02) 147-161
  • 33 Bassan R, Spinelli O, Oldani E. et al. Different molecular levels of post-induction minimal residual disease may predict hematopoietic stem cell transplantation outcome in adult Philadelphia-negative acute lymphoblastic leukemia. Blood Cancer J 2014; 4: e225
  • 34 Hoelzer D. Personalized medicine in adult acute lymphoblastic leukemia. Haematologica 2015; 100 (07) 855-858
  • 35 Zhou Y, Slack R, Jorgensen JL. et al. The effect of peritransplant minimal residual disease in adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk 2014; 14 (04) 319-326
  • 36 Shen Z, Gu X, Mao W. et al. Influence of pre-transplant minimal residual disease on prognosis after Allo-SCT for patients with acute lymphoblastic leukemia: systematic review and meta-analysis. BMC Cancer 2018; 18 (01) 755
  • 37 Bar M, Wood BL, Radich JP. et al. Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia. Leukemia Res Treat 2014; 2014: 421723
  • 38 Terwey TH, Hemmati PG, Nagy M. et al. Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for adult acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2014; 20 (10) 1522-1529
  • 39 Eckert C, Flohr T, Koehler R. et al. Very early/early relapses of acute lymphoblastic leukemia show unexpected changes of clonal markers and high heterogeneity in response to initial and relapse treatment. Leukemia 2011; 25 (08) 1305-1313
  • 40 Szczepanski T, van der Velden VH, Waanders E. et al. Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition. J Clin Oncol 2011; 29 (12) 1643-1649
  • 41 Beldjord K, Chevret S, Asnafi V. et al. Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood 2014; 123 (24) 3739-3749
  • 42 Sutton R, Venn NC, Law T. et al. A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children. Br J Haematol 2018; 180 (04) 550-562
  • 43 Löffler A, Gruen M, Wuchter C. et al. Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct. Leukemia 2003; 17 (05) 900-909
  • 44 Leone P, Shin EC, Perosa F, Vacca A, Dammacco F, Racanelli V. MHC class I antigen processing and presenting machinery: organization, function, and defects in tumor cells. J Natl Cancer Inst 2013; 105 (16) 1172-1187
  • 45 Brandl C, Haas C, d’Argouges S. et al. The effect of dexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific single-chain antibody construct. Cancer Immunol Immunother 2007; 56 (10) 1551-1563
  • 46 Topp MS, Gökbuget N, Zugmaier G. et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol 2014; 32 (36) 4134-4140
  • 47 Topp MS, Gökbuget N, Stein AS. et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2015; 16 (01) 57-66
  • 48 Kantarjian H, Stein A, Gökbuget N. et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017; 376 (09) 836-847
  • 49 Zugmaier G, Gökbuget N, Klinger M. et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood 2015; 126 (24) 2578-2584
  • 50 Gökbuget N, Zugmaier G, Klinger M. et al. Long-term relapse-free survival in a phase 2 study of blinatumomab for the treatment of patients with minimal residual disease in B-lineage acute lymphoblastic leukemia. Haematologica 2017; 102 (04) e132-e135
  • 51 Gökbuget N, Dombret H, Bonifacio M. et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood 2018; 131 (14) 1522-1531
  • 52 Kantarjian H, Thomas D, Jorgensen J. et al. Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer 2013; 119 (15) 2728-2736
  • 53 Kantarjian HM, DeAngelo DJ, Stelljes M. et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med 2016; 375 (08) 740-753
  • 54 Davila ML, Riviere I, Wang X. et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014; 6 (224) 224ra25
  • 55 Lee DW, Kochenderfer JN, Stetler-Stevenson M. et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015; 385 (99/67) 517-528
  • 56 Gardner RA, Finney O, Annesley C. et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood 2017; 129 (25) 3322-3331
  • 57 Brentjens RJ, Davila ML, Riviere I. et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013; 5 (177) 177ra38