Abstract
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan–cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10−5 and 10−4, respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34–0.86), P=0.01) and overall survival (HR=0.54 (0.34–0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.
This is a preview of subscription content, access via your institution
Access options
Similar content being viewed by others
References
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 4th edn. IARC: Lyon, 2008.
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: 5136–5145.
Vitale A, Guarini A, Ariola C, Mancini M, Mecucci C, Cuneo A et al. Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol. Blood 2006; 107: 473–479.
Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengline E et al. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. J Clin Oncol 2013; 31: 4333–4342.
Jain P, Kantarjian H, Ravandi F, Thomas D, O'Brien S, Kadia T et al. The combination of Hyper-CVAD plus nelarabine as frontline therapy in adult T cell acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (LL)-MD Anderson cancer center experience. Leukemia 28: 973–975 2013.
Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S 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: 4134–4140.
Gokbuget N, Basara N, Baurmann H, Beck J, Bruggemann M, Diedrich H et al. High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood 2011; 118: 3504–3511.
Ribera JM . Advances in acute lymphoblastic leukemia in adults. Curr Opin Oncol 2011; 23: 692–699.
Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, 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: 1868–1876.
Dhedin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V et al. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood 2015; 125: 2486–2496 quiz 2586.
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 2012; 18: 1897–1904.
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 2009; 15: 1628–1633.
Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004; 22: 4075–4086.
Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 2005; 106: 3760–3767.
Scrucca L, Santucci A, Aversa F . Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant 2007; 40: 381–387.
Grambsch PM, Therneau TM . Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994; 81: 515–526.
Andersen PK, Klein JP, Zhang MJ . Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med 1999; 18: 1489–1500.
Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB et al. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 1983; 309: 1347–1353.
Tutschka PJ, Copelan EA, Klein JP . Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood 1987; 70: 1382–1388.
Marks DI, Forman SJ, Blume KG, Perez WS, Weisdorf DJ, Keating A et al. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant 2006; 12: 438–453.
Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 2004; 104: 3028–3037.
Shigematsu A, Kondo T, Yamamoto S, Sugita J, Onozawa M, Kahata K et al. Excellent outcome of allogeneic hematopoietic stem cell transplantation using a conditioning regimen with medium-dose VP-16, cyclophosphamide and total-body irradiation for adult patients with acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2008; 14: 568–575.
Granados E, de La Camara R, Madero L, Diaz MA, Martin-Regueira P, Steegmann JL et al. Hematopoietic cell transplantation in acute lymphoblastic leukemia: better long term event-free survival with conditioning regimens containing total body irradiation. Haematologica 2000; 85: 1060–1067.
Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X et al. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood 2013; 122: 3863–3870.
Bredeson C, LeRademacher J, Kato K, Dipersio JF, Agura E, Devine SM et al. Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation. Blood 2013; 122: 3871–3878.
Bunin N, Aplenc R, Kamani N, Shaw K, Cnaan A, Simms S . Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant 2003; 32: 543–548.
Davies SM, Ramsay NK, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 2000; 18: 340–347.
Eroglu C, Pala C, Kaynar L, Yaray K, Aksozen MT, Bankir M et al. Comparison of total body irradiation plus cyclophosphamide with busulfan plus cyclophosphamide as conditioning regimens in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplant. Leuk Lymphoma 2013; 54: 2474–2479.
Tang W, Wang L, Zhao WL, Chen YB, Shen ZX, Hu J . Intravenous busulfan-cyclophosphamide as a preparative regimen before allogeneic hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2011; 17: 1555–1561.
Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.
Litzow MR, Ferrando AA . How we treat T-cell acute lymphoblastic leukemia in adults. Blood 2015; 126: 833–841.
Lazarus HM, Richards SM, Chopra R, Litzow MR, Burnett AK, Wiernik PH et al. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood 2006; 108: 465–472.
Acknowledgements
We thank all EBMT participating centers (listed in Supplementary Data), especially physicians and data managers for providing data. We also thank Leila Moukhtari and Hervé Finel for excellent data management.
Author contributions
XC, JE, SG and MM designed the study, analyzed data and wrote the manuscript; ML performed statistical analysis and helped writing the manuscript; EP coordinated data collection and management; HS provided and analyzed data; MA, SK-K, GS, ME, FB, DB, SV, MM, MS, TZ, JF, JP, IY-A, DN, GS and AN provided data and commented on the manuscript. All authors approved submission of the manuscript for publication purposes.
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
This work was presented in part at the ASH 2012 meeting as an oral presentation.
Supplementary Information accompanies this paper on Bone Marrow Transplantation website
Supplementary information
Rights and permissions
About this article
Cite this article
Cahu, X., Labopin, M., Giebel, S. et al. Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT. Bone Marrow Transplant 51, 351–357 (2016). https://doi.org/10.1038/bmt.2015.278
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2015.278
This article is cited by
-
Thiotepa, busulfan and fludarabine conditioning-regimen is a promising approach for older adult patients with acute lymphoblastic leukemia treated with allogeneic stem cell transplantation
Bone Marrow Transplantation (2023)
-
Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT
Bone Marrow Transplantation (2023)
-
Whole body irradiation with intensity-modulated helical tomotherapy prior to haematopoietic stem cell transplantation: analysis of organs at risk by dose and its effect on blood kinetics
Journal of Cancer Research and Clinical Oncology (2023)
-
Helical versus static approaches to delivering tomotherapy to the junctional target for patients taller than 135 cm undergoing total body irradiation
European Journal of Medical Research (2022)
-
Lung sparing and ribcage coverage in total body irradiation delivered by helical tomotherapy
European Journal of Medical Research (2022)