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A prognostic score system in adult T‐cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 59, pages 496–504 (2024)Cite this article

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Abstract

Adult T-cell acute lymphoblastic leukemia (T-ALL) is highly aggressive with poor prognoses, while hematopoietic stem cell transplantation (HSCT) is a curable option. However, no transplant-specific prognostic model for adult T-ALL is available. We identified 301 adult T-ALL patients who received HSCT at our hospital between 2010 and 2022. These patients were randomly assigned at a 7:3 ratio to a derivation group of 210 patients and a validation group of 91 patients. Next, we developed a prognostic risk score system for adult T-ALL with HSCT, which we named COMM, including 4 predictors (central nervous system involvement, Non-CR1 (CR2+ or NR) at HSCT, minimal residual disease (MRD) ≥ 0.01% after first induction therapy, and MRD ≥ 0.01% before HSCT). Patients were categorized into three risk groups, low-risk (0), intermediate-risk (1–4), and high-risk (5–12), and their 3-year overall survival (OS) were 87.5% (95%CI, 78–93%), 65.7% (95%CI, 53–76%) and 20% (95%CI, 10–20%; P < 0.001), respectively. The area under the subject operating characteristic curve for 2-, 3- or 5-year OS in the derivation cohort and in the validation cohort were all greater than 0.75. Based on internal validation, COMM score system proved to be a reliable prognostic model that could discriminate and calibrate well. We expect that the first prognostic model in adults T-ALL after HSCT can provide a reference of prognostic consultation for patients and families, and also contribute to future research to develop risk adapted interventions for high-risk populations.

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Fig. 1: Overall survival analysis of adult T-ALL patients following HSCT.
Fig. 2: Risk group-based survival outcomes and cumulative relapse mortality.
Fig. 3: The analysis of the COMM model predictive accuracy, calibration plots, and decision curves for adult T-ALL after HSCT.

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Data availability

Because these data contain information about the privacy of the study participants, they are not publicly available. Data on the results of the study can be obtained from the corresponding author, Zhang Xiaohui, PhD, MD.

References

  1. Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N. Engl J Med. 2009;360:2730–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kantarjian HM, O’Brien S, Smith TL, Cortes J, Giles FJ, Beran M, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18:547–61.

    Article  CAS  PubMed  Google Scholar 

  3. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7:e577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, et al. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009;114:5136–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang H, Zhou Y, Huang X, Zhang Y, Qian J, Li J, et al. Minimal residual disease level determined by flow cytometry provides reliable risk stratification in adults with T-cell acute lymphoblastic leukaemia. Br J Haematol. 2021;193:1096–104.

    Article  CAS  PubMed  Google Scholar 

  6. Fuhrmann S, Schabath R, Möricke A, Zimmermann M, Kunz JB, Kulozik AE, et al. Expression of CD56 defines a distinct subgroup in childhood T-ALL with inferior outcome. Results of the ALL-BFM 2000 trial. Br J Haematol. 2018;183:96–103.

    Article  CAS  PubMed  Google Scholar 

  7. Yasuda S, Najima Y, Konishi T, Yamada Y, Nagata A, Takezaki T, et al. Outcome of allogeneic hematopoietic stem cell transplantation for T-cell lymphoblastic leukemia/lymphoma: a single-center study. Leuk Res. 2021;108:106627.

    Article  CAS  PubMed  Google Scholar 

  8. Steimlé T, Dourthe ME, Alcantara M, Touzart A, Simonin M, Mondesir J, et al. Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins. Blood Cancer J. 2022;12:14.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhao P, Wu YJ, He Y, Chong S, Qu QY, Deng RX, et al. A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy. Blood Adv. 2021;5:5479–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Deng RX, Wu YJ, Xu LP, Liu KY, Huang XJ, Zhang XH. Clinical risk factors and prognostic model for idiopathic inflammatory demyelinating diseases after haploidentical hematopoietic stem cell transplantation in patients with hematological malignancies. Am J Hematol. 2021;96:1407–19.

    Article  CAS  PubMed  Google Scholar 

  11. Wang Y, Wang HX, Lai YR, Sun ZM, Wu DP, Jiang M, et al. Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical sibling transplant. Leukemia. 2016;30:2055–63.

    Article  CAS  PubMed  Google Scholar 

  12. Zhao XS, Liu YR, Xu LP, Wang Y, Zhang XH, Chen H, et al. Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts. Am J Hematol. 2019;94:512–21.

    Article  PubMed  Google Scholar 

  13. Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood. 2006;107:3065–73.

    Article  CAS  PubMed  Google Scholar 

  14. Brown PA, Shah B, Advani A, Aoun P, Boyer MW, Burke PW, et al. Acute lymphoblastic leukemia, version 2.2021, NCCN Clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2021;19:1079–109.

    Article  CAS  Google Scholar 

  15. Xu LH, Geng X, Liao N, Yang LH, Mai HR, Wan WQ, et al. Prognostic significance of CNSL at diagnosis of childhood B-cell acute lymphoblastic leukemia: a report from the South China Children’s Leukemia Group. Front Oncol. 2022;12:943761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Genescà E, Morgades M, González-Gil C, Fuster-Tormo F, Haferlach C, Meggendorfer M, et al. Adverse prognostic impact of complex karyotype (≥ 3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL). Leuk Res. 2021;109:106612.

    Article  PubMed  Google Scholar 

  17. Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B, et al. Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). Blood. 2009;113:4153–62.

    Article  CAS  PubMed  Google Scholar 

  18. Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10:147–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  Google Scholar 

  20. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant : J Am Soc Blood Marrow Transplant. 2015;21:389–401.e1.

    Article  Google Scholar 

  21. Shouval R, Fein JA, Labopin M, Kröger N, Duarte RF, Bader P, et al. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 2019;6:e573–e84.

    Article  PubMed  Google Scholar 

  22. Moons KG, Altman DG, Reitsma JB, Ioannidis JP, Macaskill P, Steyerberg EW, et al. Transparent reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med. 2015;162:W1–73.

    Article  PubMed  Google Scholar 

  23. Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ (Clin Res ed). 2015;350:g7594.

    Google Scholar 

  24. Liu GM, Zeng HD, Zhang CY, Xu JW. Identification of a six-gene signature predicting overall survival for hepatocellular carcinoma. Cancer cell Int. 2019;19:138.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wen P, Wen J, Huang X, Wang F. Development and validation of nomograms predicting the 5- and 8-year overall and cancer-specific survival of bladder cancer patients based on SEER program. J Clin Med. 2023;12:1314.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sas V, Moisoiu V, Teodorescu P, Tranca S, Pop L, Iluta S, et al. Approach to the adult acute lymphoblastic leukemia patient. J Clin Med. 2019;8:1175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Aldoss I, Al Malki MM, Stiller T, Cao T, Sanchez JF, Palmer J, et al. Implications and management of central nervous system involvement before allogeneic hematopoietic cell transplantation in acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2016;22:575–8.

    Article  CAS  PubMed  Google Scholar 

  28. Hamdi A, Mawad R, Bassett R, di Stasi A, Ferro R, Afrough A, et al. Central nervous system relapse in adults with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2014;20:1767–71.

    Article  Google Scholar 

  29. Cruz-Chávez DA, López-Pérez BJ, Solórzano-Gómez E, Venta-Sobero JA, Flores-Villegas LV, Toledo-Lozano CG, et al. Neurological involvement in pediatric patients with acute leukemia: a retrospective cohort. Children. 2022;9:1268.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sauter CS, DeFilipp Z, Inamoto Y, Johnston L, Nagler A, Savani BN, et al. ASBMT Statement on routine prophylaxis for central nervous system recurrence of acute lymphoblastic leukemia following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25:e86–e8.

    Article  PubMed  Google Scholar 

  31. Orvain C, Chantepie S, Thomas X, Escofrre-Barbe M, Huguet F, Desbrosses Y, et al. Impact of central nervous system involvement in adult patients with Philadelphia-negative acute lymphoblastic leukemia: a GRAALL-2005 study. Haematologica. 2023;108:3287–329.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Brammer JE, Saliba RM, Jorgensen JL, Ledesma C, Gaballa S, Poon M, et al. Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes. Bone Marrow Transpl. 2017;52:20–7.

    Article  CAS  Google Scholar 

  33. Bakr M, Rasheed W, Mohamed SY, Al-Mohareb F, Chaudhri N, Al-Sharif F, et al. Allogeneic hematopoietic stem cell transplantation in adolescent and adult patients with high-risk T cell acute lymphoblastic leukemia. Biol Blood Marrow Transplant : J Am Soc Blood Marrow Transplant. 2012;18:1897–904.

    Article  Google Scholar 

  34. Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transpl. 2006;12:1–30.

    Article  CAS  Google Scholar 

  35. Chen J, Liu L, Ma R, Pang A, Yang D, Chen X, et al. Comparison of characteristics and outcomes on ETP-ALL/LBL and non-ETP ALL patients receiving allogeneic hematopoietic stem cell transplantation. Front Oncol. 2022;12:1025885.

    Article  PubMed  Google Scholar 

  36. Wang HP, Zhou YL, Huang X, Zhang Y, Qian JJ, Li JH, et al. CDKN2A deletions are associated with poor outcomes in 101 adults with T-cell acute lymphoblastic leukemia. Am J Hematol. 2021;96:312–9.

    Article  CAS  PubMed  Google Scholar 

  37. Mishra V, Jain S, Anand V, Malhotra P, Tejwani N, Kapoor G. Impact of minimal residual disease on relapse in childhood acute lymphoblastic leukemia: Lessons learnt from a tertiary cancer center in India. Pediatr Hematol Oncol. 2023;40:517–28.

    Article  PubMed  Google Scholar 

  38. Bride KL, Vincent TL, Im SY, Aplenc R, Barrett DM, Carroll WL, et al. Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia. Blood. 2018;131:995–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bader P, Kreyenberg H, Henze GH, Eckert C, Reising M, Willasch A, et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. J Clin Oncol. 2009;27:377–84.

    Article  PubMed  Google Scholar 

  40. Brüggemann M, Raff T, Flohr T, Gökbuget N, Nakao M, Droese J, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107:1116–23.

    Article  PubMed  Google Scholar 

  41. Mortuza FY, Papaioannou M, Moreira IM, Coyle LA, Gameiro P, Gandini D, et al. Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol. 2002;20:1094–104.

    Article  PubMed  Google Scholar 

  42. Vidriales MB, Pérez JJ, López-Berges MC, Gutiérrez N, Ciudad J, Lucio P, et al. Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood. 2003;101:4695–700.

    Article  CAS  PubMed  Google Scholar 

  43. Pavlů J, Labopin M, Niittyvuopio R, Socié G, Yakoub-Agha I, Wu D, et al. Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT. J Hematol Oncol. 2019;12:108.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Litzow MR, Ferrando AA. How I treat T-cell acute lymphoblastic leukemia in adults. Blood. 2015;126:833–41.

    Article  CAS  PubMed  Google Scholar 

  45. Paul S, Kantarjian H, Jabbour EJ. Adult acute lymphoblastic leukemia. Mayo Clin Proc. 2016;91:1645–66.

    Article  PubMed  Google Scholar 

  46. Candoni A, Lazzarotto D, Ferrara F, Curti A, Lussana F, Papayannidis C, et al. Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study. Am J Hematol. 2020;95:1466–72.

    Article  CAS  PubMed  Google Scholar 

  47. Alcantara M, Tesio M, June CH, Houot R. CAR T-cells for T-cell malignancies: challenges in distinguishing between therapeutic, normal, and neoplastic T-cells. Leukemia. 2018;32:2307–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bassan R, Bourquin JP, DeAngelo DJ, Chiaretti S. New approaches to the management of adult acute lymphoblastic leukemia. J Clin Oncol. 2018;36:3504–19.

  49. O’Brien S, Schiller G, Lister J, Damon L, Goldberg S, Aulitzky W, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013;31:676–83.

    Article  PubMed  Google Scholar 

  50. Combariza JF, Arango M, Díaz L, Agudelo C, Hernandez S, Madera AM, et al. Measurable residual disease assessment and allogeneic transplantation as consolidation therapy in adult acute lymphoblastic leukemia in Colombia. Clin Lymphoma Myeloma Leuk. 2021;21:e365–e72.

    Article  CAS  PubMed  Google Scholar 

  51. Nagafuji K, Miyamoto T, Eto T, Kamimura T, Taniguchi S, Okamura T, et al. Monitoring of minimal residual disease (MRD) is useful to predict prognosis of adult patients with Ph-negative ALL: results of a prospective study (ALL MRD2002 Study). J Hematol Oncol. 2013;6:14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gökbuget N, Kneba M, Raff T, Trautmann H, Bartram C-R, Arnold R, et al. 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;120:1868–76.

    Article  PubMed  Google Scholar 

  53. Shimizu H, Doki N, Kanamori H, Sakura T, Mori T, Machida S, et al. Prognostic impact of cytogenetic abnormalities in adult patients with Philadelphia chromosome-negative ALL who underwent an allogeneic transplant. Bone Marrow Transpl. 2019;54:2020–6.

    Article  CAS  Google Scholar 

  54. Marks DI, Moorman AV, Chilton L, Paietta E, Enshaie A, DeWald G, et al. The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial. Haematologica. 2013;98:945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Arber DA, Borowitz MJ, Cessna M, Etzell J, Foucar K, Hasserjian RP, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141:1342–93.

    Article  PubMed  Google Scholar 

  56. Gonzalez-Gil C, Morgades M, Lopes T, Fuster-Tormo F, Garcia-Chica J, Zhao R, et al. Genomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials. Haematologica. 2023;108:969–80.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (No. 2021YFC2500304), the Key Program of National Natural Science Foundation of China (No. 82230004), National Natural Science of Foundation of China (No. 81970113) and Capital Health Research and Development of Special (No. 2022-1-4082).

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  1. These authors contributed equally: Mengyu Xiao, Jianying Zhou.

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Mengyu Xiao, Jianying Zhou, Xiaolu Zhu, Yun He, Fengrong Wang, Yuanyuan Zhang, Xiaodong Mo, Wei Han, Jingzhi Wang, Yu Wang, Huan Chen, Yuhong Chen, Xiangyu Zhao, Yingjun Chang, Lanping Xu, Kaiyan Liu, Xiaojun Huang & Xiaohui Zhang

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Contributions

MYX and XHZ contributed to the study design. MYX, JYZ, XLZ, YH, FRW, YYZ, XDM, and WH collected the data. JYZ, JZW, YW, HC, and YHC performed data analysis. MYX drafted and wrote the manuscript. XYZ, YJC, LPX, KYL, and XJH revised it critically. XHZ conceived and directed the study and revised the manuscript. The final version of the manuscript was critically reviewed and approved by all authors.

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Correspondence to Xiaohui Zhang.

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Xiao, M., Zhou, J., Zhu, X. et al. A prognostic score system in adult T‐cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation. Bone Marrow Transplant 59, 496–504 (2024). https://doi.org/10.1038/s41409-024-02211-8

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