Allogeneic hematopoietic stem cell transplantation for adult patients with B-cell acute lymphoblastic leukemia harboring t(1;19)(q23;p13.3); comparison with normal karyotype

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Abstract

There are few reports on allogeneic hematopoietic stem cell transplantation (allo-HSCT) for adult B-cell acute lymphoblastic leukemia (B-ALL) harboring t(1;19)(q23;p13.3). We used nationwide registry data of Japan for 2003–2016 to evaluate transplant outcomes and clarified prognostic factors among adult allo-HSCT recipients with B-ALL harboring t(1;19)(q23;p13.3) (n = 125). Compared with cytogenetically normal (CN) B-ALL patients (n = 1057), their 3-year overall survival (OS) rates were comparable (55.4% for t(1;19) and 54.4% for CN; P = 0.76). Considering only patients in first complete hematological remission (CR1), the 3-year OS rates remained comparable (70.5% for t(1;19) and 67.8% for CN; P = 0.86). For t(1;19) patients in CR1, minimal residual disease (MRD) at transplantation was associated with relatively worse outcomes. The 3-year OS rates were 43.6% for patients with MRD and 77.4% for those without it (P = 0.016). The 3-year relapse rates were 54.5% for patients with MRD and 12.8% for those without it (P < 0.001). Multivariate analyses revealed that MRD at transplantation was a significant risk factor for OS and relapse. In the high-intensity chemotherapy era, t(1;19)(q23;p13.3) did not have a poorer posttransplant prognosis than the normal karyotype. However, even for patients in CR1, MRD at transplantation was associated with comparatively worse OS and higher relapse rates.

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References

  1. 1.

    Lafage-Pochitaloff M, Baranger L, Hunault M, Cuccuini W, Lefebvre C, Bidet A, et al. Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia. Blood. 2017;130:1832–44.

  2. 2.

    Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109:3189–97.

  3. 3.

    Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Francais de Cytogenetique Hematologique. Blood. 1996;87:3135–42.

  4. 4.

    Hunger SP, Galili N, Carroll AJ, Crist WM, Link MP, Cleary ML. The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias. Blood. 1991;77:687–93.

  5. 5.

    Moorman AV, Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ. A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood. 2010;115:206–14.

  6. 6.

    Murre C. Regulation and function of the E2A proteins in B cell development. Adv Exp Med Biol. 2007;596:1–7.

  7. 7.

    Fu X, McGrath S, Pasillas M, Nakazawa S, Kamps MP. EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1. Oncogene. 1999;18:4920–9.

  8. 8.

    Kamps MP. E2A-Pbx1 induces growth, blocks differentiation, and interacts with other homeodomain proteins regulating normal differentiation. Curr Top Microbiol Immunol. 1997;220:25–43.

  9. 9.

    Moorman AV, Ensor HM, Richards SM, Chilton L, Schwab C, Kinsey SE, et al. Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. Lancet Oncol. 2010;11:429–38.

  10. 10.

    Kager L, Lion T, Attarbaschi A, Koenig M, Strehl S, Haas OA, et al. Incidence and outcome of TCF3-PBX1-positive acute lymphoblastic leukemia in Austrian children. Haematologica. 2007;92:1561–4.

  11. 11.

    Vey N, Thomas X, Picard C, Kovascovicz T, Charin C, Cayuela JM, et al. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia. 2006;20:2155–61.

  12. 12.

    Garg R, Kantarjian H, Thomas D, Faderl S, Ravandi F, Lovshe D, et al. Adults with acute lymphoblastic leukemia and translocation (1;19) abnormality have a favorable outcome with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine chemotherapy. Cancer. 2009;115:2147–54.

  13. 13.

    Burmeister T, Gokbuget N, Schwartz S, Fischer L, Hubert D, Sindram A, et al. Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia. Haematologica. 2010;95:241–6.

  14. 14.

    Gupta V, Richards S, Rowe J. Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. Blood. 2013;121:339–50.

  15. 15.

    Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, et al. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014;123:3739–49.

  16. 16.

    Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.

  17. 17.

    Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

  18. 18.

    Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.

  19. 19.

    Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

  20. 20.

    Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

  21. 21.

    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

  22. 22.

    Hayakawa F, Sakura T, Yujiri T, Kondo E, Fujimaki K, Sasaki O, et al. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group. Blood Cancer J. 2014;4:e252.

  23. 23.

    Sakura T, Hayakawa F, Sugiura I, Murayama T, Imai K, Usui N, et al. High-dose methotrexate therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG. Leukemia. 2018;32:626–32.

  24. 24.

    Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375:740–53.

  25. 25.

    Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836–47.

  26. 26.

    Jabbour E, Short NJ, Ravandi F, Huang X, Daver N, DiNardo CD, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol. 2018;5:e618–e27.

  27. 27.

    Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48.

  28. 28.

    Park JH, Riviere I, Gonen M, Wang X, Senechal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–59.

  29. 29.

    Zhang J, Yang F, Qiu HY, Wu Q, Kong DQ, Zhou J, et al. Anti-CD19 chimeric antigen receptors T cells for the treatment of relapsed or refractory E2A-PBX1 positive acute lymphoblastic leukemia: report of three cases. Leuk Lymphoma. 2019;60:1454–61.

  30. 30.

    Eldfors S, Kuusanmaki H, Kontro M, Majumder MM, Parsons A, Edgren H, et al. Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia. Leukemia. 2017;31:51–7.

  31. 31.

    Familiades J, Bousquet M, Lafage-Pochitaloff M, Bene MC, Beldjord K, De Vos J, et al. PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study. Leukemia. 2009;23:1989–98.

  32. 32.

    Asai D, Imamura T, Yamashita Y, Suenobu S, Moriya-Saito A, Hasegawa D, et al. Outcome of TCF3-PBX1 positive pediatric acute lymphoblastic leukemia patients in Japan: a collaborative study of Japan Association of Childhood Leukemia Study (JACLS) and Children’s Cancer and Leukemia Study Group (CCLSG). Cancer Med. 2014;3:623–31.

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Acknowledgements

We are grateful to all physicians and staff at the transplant centers who provided clinical data to the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. We also express gratitude to the staff at the Japan Society of Hematopoietic Cell Transplantation and the Japanese Data Center for Hematopoietic Cell Transplantation for their dedication to the organization and management of the data.

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Correspondence to Satoshi Kaito.

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Kaito, S., Najima, Y., Harada, K. et al. Allogeneic hematopoietic stem cell transplantation for adult patients with B-cell acute lymphoblastic leukemia harboring t(1;19)(q23;p13.3); comparison with normal karyotype. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-0816-6

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