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

David I. Marks, Anthony V. Moorman, Lucy Chilton, Elisabeth M. Paietta, Amir Enshaie, Gordon de Wald, Christine J. Harrison, Adele K. Fielding, Letizia Foroni, Anthony H. Goldstone, Mark R. Litzow, Selina M. Luger, Andrew K. McMillan, Janis Racevskis, Jacob M. Rowe, Martin S. Tallman, Peter Wiernik, Hillard M. Lazarus

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Abstract

The biology and outcome of adult t(4;11)(q21;q23)/MLL-AFF1 acute lymphoblastic leukemia are poorly understood. We describe the outcome and delineate prognostic factors and optimal post-remission therapy in 85 consecutive patients (median age 38 years) treated uniformly in the prospective trial UKALLXII/ECOG2993. The immunophenotype of this leukemia was pro-B (CD10NEG). Immaturity was further suggested by high expression of the stem-cell antigens, CD133 and CD135, although CD34 expression was significantly lower than in t(4;11)- negative patients. Complete remission was achieved in 77 (93%) patients but only 35% survived 5 years (95% CI: 25-45%); the relapse rate was 45% (95% CI: 33-58%). Thirty-one patients underwent allogeneic transplantation in first remission (15 sibling donors and 16 unrelated donors): with 5-year survival rates of 56% and 67% respectively, only 2/31 patients relapsed. This compares with a 24% survival rate and 59% relapse rate in 46 patients who received post-remission chemotherapy. A major determinant of outcome was age with 71% of patients aged <25 years surviving. Younger patients had lower relapse rates (19%) but most received allografts in first complete remission. In conclusion, multivariate analysis did not demonstrate an advantage of allografting over chemotherapy but only five younger patients received chemotherapy. Prospective trials are required to determine whether poor outcomes in older patients can be improved by reduced-intensity conditioning allografts. NCT00002514 www.clinicaltrials.gov.

Original languageEnglish (US)
Pages (from-to)945-952
Number of pages8
JournalHaematologica
Volume98
Issue number6
DOIs
StatePublished - 2013

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Therapeutics
Homologous Transplantation
Recurrence
Drug Therapy
Allografts
fms-Like Tyrosine Kinase 3
Survival Rate
Unrelated Donors
Siblings
Leukemia
Stem Cells
Multivariate Analysis
Tissue Donors

ASJC Scopus subject areas

  • Hematology

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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. / Marks, David I.; Moorman, Anthony V.; Chilton, Lucy; Paietta, Elisabeth M.; Enshaie, Amir; de Wald, Gordon; Harrison, Christine J.; Fielding, Adele K.; Foroni, Letizia; Goldstone, Anthony H.; Litzow, Mark R.; Luger, Selina M.; McMillan, Andrew K.; Racevskis, Janis; Rowe, Jacob M.; Tallman, Martin S.; Wiernik, Peter; Lazarus, Hillard M.

In: Haematologica, Vol. 98, No. 6, 2013, p. 945-952.

Research output: Contribution to journalArticle

Marks, DI, Moorman, AV, Chilton, L, Paietta, EM, Enshaie, A, de Wald, G, Harrison, CJ, Fielding, AK, Foroni, L, Goldstone, AH, Litzow, MR, Luger, SM, McMillan, AK, Racevskis, J, Rowe, JM, Tallman, MS, Wiernik, P & Lazarus, HM 2013, '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, vol. 98, no. 6, pp. 945-952. https://doi.org/10.3324/haematol.2012.081877
Marks, David I. ; Moorman, Anthony V. ; Chilton, Lucy ; Paietta, Elisabeth M. ; Enshaie, Amir ; de Wald, Gordon ; Harrison, Christine J. ; Fielding, Adele K. ; Foroni, Letizia ; Goldstone, Anthony H. ; Litzow, Mark R. ; Luger, Selina M. ; McMillan, Andrew K. ; Racevskis, Janis ; Rowe, Jacob M. ; Tallman, Martin S. ; Wiernik, Peter ; Lazarus, Hillard M. / 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. In: Haematologica. 2013 ; Vol. 98, No. 6. pp. 945-952.
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abstract = "The biology and outcome of adult t(4;11)(q21;q23)/MLL-AFF1 acute lymphoblastic leukemia are poorly understood. We describe the outcome and delineate prognostic factors and optimal post-remission therapy in 85 consecutive patients (median age 38 years) treated uniformly in the prospective trial UKALLXII/ECOG2993. The immunophenotype of this leukemia was pro-B (CD10NEG). Immaturity was further suggested by high expression of the stem-cell antigens, CD133 and CD135, although CD34 expression was significantly lower than in t(4;11)- negative patients. Complete remission was achieved in 77 (93{\%}) patients but only 35{\%} survived 5 years (95{\%} CI: 25-45{\%}); the relapse rate was 45{\%} (95{\%} CI: 33-58{\%}). Thirty-one patients underwent allogeneic transplantation in first remission (15 sibling donors and 16 unrelated donors): with 5-year survival rates of 56{\%} and 67{\%} respectively, only 2/31 patients relapsed. This compares with a 24{\%} survival rate and 59{\%} relapse rate in 46 patients who received post-remission chemotherapy. A major determinant of outcome was age with 71{\%} of patients aged <25 years surviving. Younger patients had lower relapse rates (19{\%}) but most received allografts in first complete remission. In conclusion, multivariate analysis did not demonstrate an advantage of allografting over chemotherapy but only five younger patients received chemotherapy. Prospective trials are required to determine whether poor outcomes in older patients can be improved by reduced-intensity conditioning allografts. NCT00002514 www.clinicaltrials.gov.",
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T1 - 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

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AU - Moorman, Anthony V.

AU - Chilton, Lucy

AU - Paietta, Elisabeth M.

AU - Enshaie, Amir

AU - de Wald, Gordon

AU - Harrison, Christine J.

AU - Fielding, Adele K.

AU - Foroni, Letizia

AU - Goldstone, Anthony H.

AU - Litzow, Mark R.

AU - Luger, Selina M.

AU - McMillan, Andrew K.

AU - Racevskis, Janis

AU - Rowe, Jacob M.

AU - Tallman, Martin S.

AU - Wiernik, Peter

AU - Lazarus, Hillard M.

PY - 2013

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N2 - The biology and outcome of adult t(4;11)(q21;q23)/MLL-AFF1 acute lymphoblastic leukemia are poorly understood. We describe the outcome and delineate prognostic factors and optimal post-remission therapy in 85 consecutive patients (median age 38 years) treated uniformly in the prospective trial UKALLXII/ECOG2993. The immunophenotype of this leukemia was pro-B (CD10NEG). Immaturity was further suggested by high expression of the stem-cell antigens, CD133 and CD135, although CD34 expression was significantly lower than in t(4;11)- negative patients. Complete remission was achieved in 77 (93%) patients but only 35% survived 5 years (95% CI: 25-45%); the relapse rate was 45% (95% CI: 33-58%). Thirty-one patients underwent allogeneic transplantation in first remission (15 sibling donors and 16 unrelated donors): with 5-year survival rates of 56% and 67% respectively, only 2/31 patients relapsed. This compares with a 24% survival rate and 59% relapse rate in 46 patients who received post-remission chemotherapy. A major determinant of outcome was age with 71% of patients aged <25 years surviving. Younger patients had lower relapse rates (19%) but most received allografts in first complete remission. In conclusion, multivariate analysis did not demonstrate an advantage of allografting over chemotherapy but only five younger patients received chemotherapy. Prospective trials are required to determine whether poor outcomes in older patients can be improved by reduced-intensity conditioning allografts. NCT00002514 www.clinicaltrials.gov.

AB - The biology and outcome of adult t(4;11)(q21;q23)/MLL-AFF1 acute lymphoblastic leukemia are poorly understood. We describe the outcome and delineate prognostic factors and optimal post-remission therapy in 85 consecutive patients (median age 38 years) treated uniformly in the prospective trial UKALLXII/ECOG2993. The immunophenotype of this leukemia was pro-B (CD10NEG). Immaturity was further suggested by high expression of the stem-cell antigens, CD133 and CD135, although CD34 expression was significantly lower than in t(4;11)- negative patients. Complete remission was achieved in 77 (93%) patients but only 35% survived 5 years (95% CI: 25-45%); the relapse rate was 45% (95% CI: 33-58%). Thirty-one patients underwent allogeneic transplantation in first remission (15 sibling donors and 16 unrelated donors): with 5-year survival rates of 56% and 67% respectively, only 2/31 patients relapsed. This compares with a 24% survival rate and 59% relapse rate in 46 patients who received post-remission chemotherapy. A major determinant of outcome was age with 71% of patients aged <25 years surviving. Younger patients had lower relapse rates (19%) but most received allografts in first complete remission. In conclusion, multivariate analysis did not demonstrate an advantage of allografting over chemotherapy but only five younger patients received chemotherapy. Prospective trials are required to determine whether poor outcomes in older patients can be improved by reduced-intensity conditioning allografts. NCT00002514 www.clinicaltrials.gov.

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