T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993)

Blood - Tập 114 Số 25 - Trang 5136-5145 - 2009
David I. Marks1, Elisabeth Paietta2,3, Anthony V. Moorman4, Susan Richards5, Georgina Buck5, Gordon W. Dewald6, Adolfo A. Ferrando7, Adele K. Fielding8, Anthony H. Goldstone8, Rhett P. Ketterling6, Mark R. Litzow6, Selina M. Luger9, Andrew McMillan10, Marc R. Mansour8, Jacob M. Rowe11, Martin S. Tallman12, Hillard M. Lazarus13
1Adult Bone Marrow Transplant Unit, University Hospitals Bristol, National Health Service Foundation Trust, Bristol, United Kingdom.
2Yeshiva University
3Montefiore Medical Center, New York, NY
4Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom
5Clinical Trial Service Unit, Oxford, United Kingdom
6Mayo Clinic, Rochester, MN
7Columbia University, New York, NY
8University College London, London, United Kingdom
9University of Pennsylvania, Philadelphia
10Nottingham City Hospital, Nottingham, United Kingdom
11Rambam Medical Center, Haifa, Israel
12Northwestern University, Chicago, IL; and
13CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OH

Tóm tắt

AbstractThe biology and outcome of adult T-cell acute lymphoblastic leukemia are poorly understood. We present here the clinical and biologic features of 356 patients treated uniformly on the prospective trial (UKALL XII/ECOG 2993) with the aim of describing the outcome and identifying prognostic factors. Complete remission was obtained in 94% of patients, and 48% survived 5 years. Positivity of blasts for CD1a and lack of expression of CD13 were associated with better survival (P = .01 and < .001, respectively). NOTCH1 and CDKN2A mutations were seen in 61% and 42% of those tested. Complex cytogenetic abnormalities were associated with poorer survival (19% vs 51% at 5 years, P = .006). Central nervous system involvement at diagnosis did not affect survival (47% vs 48%, P = not significant). For 99 patients randomized between autograft and chemotherapy, 5-year survival was 51% in each arm. Patients with a matched sibling donor had superior 5-year survival to those without donors (61% vs 46%, χ2, P = .02); this was the result of less relapse (25% vs 51% at 5 years, P < .001). Only 8 of 123 relapsed patients survive. This study provides a baseline for trials of new drugs, such as nelarabine, and may allow risk-adapted therapy in patients with poor-prognosis T-cell ALL.

Từ khóa


Tài liệu tham khảo

Goldstone, 2008, In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/ maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993)., Blood, 111, 1827, 10.1182/blood-2007-10-116582

Vitale, 2006, 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, 107, 473, 10.1182/blood-2005-04-1754

Rowe, 2005, Induction therapy for adults with acute lymphoblastic leukaemia: results of more than 1500 patients from the international ALL trial MRC UKALL XII/ECOG 2993., Blood, 106, 3760, 10.1182/blood-2005-04-1623

Hunault, 2004, 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, 104, 3028, 10.1182/blood-2003-10-3560

Lazarus, 2006, CNS involvement in adult acute lymphoblastic leukaemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG 2993., Blood, 108, 465, 10.1182/blood-2005-11-4666

Fielding, 2007, Outcome of 609 adults after relapse of acute lymphoblastic leukaemia (ALL): an MRC UKALL XII/ECOG 2993 study., Blood, 109, 944, 10.1182/blood-2006-05-018192

Moorman, 2007, Karyotype is an independent prognostic factor in acute lymphoblastic leukaemia: analysis of cytogenetic data from patients treated on the MRC UKALL XII/ECOG 2993 trial., Blood, 109, 3189, 10.1182/blood-2006-10-051912

Early Breast Cancer Trialists' Collaborative Group, 1990, Treatment of Early Breast Cancer: Worldwide Evidence 1985-1990

Borowitz, 2008, T lymphoblastic leukemia/lymphoma., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 176

Sulong, 2009, A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukaemia reveals genomic deletion, copy number neutral loss of heterozygosity and association with specific cytogenetic subgroups., Blood, 113, 100, 10.1182/blood-2008-07-166801

Paietta, 2003, Immunobiology of acute leukemia., Neoplastic Diseases of the Blood, 4th ed, 194

Mansour, 2009, Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia on the MRC UKALLXII/ECOG E2993 protocol., J Clin Oncol, 27, 4352, 10.1200/JCO.2009.22.0996

Asnafi, 2009, NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study., Blood, 113, 3918, 10.1182/blood-2008-10-184069

Riley, 2002, Immunophenotypic analysis of acute lymphocytic leukemia., Hematol Oncol Clin North Am, 16, 245, 10.1016/S0889-8588(02)00004-7

Ferrando, 2004, Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia., Lancet, 363, 535, 10.1016/S0140-6736(04)15542-6

Van Vlierberghe, 2008, Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia., Br J Haematol, 143, 153, 10.1111/j.1365-2141.2008.07314.x

Campana, 2000, Immunophenotyping of leukemia., J Immunol Methods, 243, 59, 10.1016/S0022-1759(00)00228-3

Basso, 2001, New methodologic approaches for immunophenotyping acute leukemias., Haematologica, 86, 675

Del Vecchio, 1996, Immunological classification of acute leukemias: comments on the EGIL proposals., Leukemia, 10, 1832

Czuczman, 1999, Value of immunophenotype in intensively treated adult acute lymphoblastic leukemia: Cancer and Leukemia Group B study 8364., Blood, 93, 3931

Paietta, 2003, How to optimize multiparameter flow cytometry for leukemia/lymphoma diagnosis., Bailliere's Best Practice & Research: Clinical Haematology, Vol 16. Immunophenotyping in Leukemia and Lymphoma, 671

Ludwig, 1996, Routine immunophenotyping of acute leukemias., Blut, 60, 48, 10.1007/BF01720203

Kaleem, 2003, Flow cytometric analysis of acute leukemias: diagnostic utility and critical analysis of data., Arch Pathol Lab Med, 127, 42, 10.5858/2003-127-42-FCAOA

Paietta, 2008, Implications for the use of monoclonal antibodies in future adult ALL trials: analysis of antigen expression in 505 B-lineage (B-Lin) ALL patients (pts) on the MRC UKALLXII/ECOG2993 intergroup trial., Blood, 112, 1907, 10.1182/blood.V112.11.1907.1907

Paietta, 2004, Activating FLT3 mutations in CD117/KIT positive T-cell acute lymphoblastic leukemia., Blood, 104, 558, 10.1182/blood-2004-01-0168

Baldus, 2007, Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favourable outcome., J Clin Oncol, 25, 3739, 10.1200/JCO.2007.11.5253

Bell, 2008, The earliest thymic progenitors for T cells possess myeloid lineage potential., Nature, 452, 764, 10.1038/nature06840

Hawkins, 1991, Evaluation of cytogenetic samples and pertinent technical variables in adult acute lymphocytic leukemia., Cancer Gent Cytogenet, 52, 79, 10.1016/0165-4608(91)90056-Z

Mato, 2006, Autologous stem cell transplant in ALL: who should we be transplanting in first remission?, Bone Marrow Transplant, 37, 989, 10.1038/sj.bmt.1705370

van der Velden, 2007, Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data., Leukemia, 21, 604, 10.1038/sj.leu.2404586

Raff, 2007, Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials., Blood, 109, 910, 10.1182/blood-2006-07-037093

Szczepanski, 2007, Why and how to quantify minimal residual disease in acute lymphoblastic leukemia?, Leukemia, 21, 622, 10.1038/sj.leu.2404603

Bruggemann, 2006, Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia., Blood, 107, 1116, 10.1182/blood-2005-07-2708

Thông tin
Thông tin xuất bản

Blood

Tập 114 Số 25

5136-5145

Thông tin tác giả