Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: Results from the international ALL trial MRC UKALL XII/ECOG E2993

Hillard M. Lazarus, Susan M. Richards, Raj Chopra, Mark R Litzow, Alan K. Burnett, Peter H. Wiernik, Ian M. Franklin, Martin S. Tallman, Lucy Cook, Georgina Buck, I. Jill Durrant, Jacob M. Rowe, Anthony H. Goldstone

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Abstract

Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with L-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)-positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy.

Original languageEnglish (US)
Pages (from-to)465-472
Number of pages8
JournalBlood
Volume108
Issue number2
DOIs
StatePublished - Jul 15 2006

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Neurology
Stem cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Central Nervous System
Stem Cell Transplantation
Chemotherapy
Unrelated Donors
Consolidation
Tissue Donors
Asparaginase
Autografts
Chromosomes
Leukemia
Methotrexate
Transplantation
Maintenance Chemotherapy
Philadelphia Chromosome
Central Nervous System Diseases
Disease-Free Survival
Maintenance

ASJC Scopus subject areas

  • Hematology

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Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis : Results from the international ALL trial MRC UKALL XII/ECOG E2993. / Lazarus, Hillard M.; Richards, Susan M.; Chopra, Raj; Litzow, Mark R; Burnett, Alan K.; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Jill Durrant, I.; Rowe, Jacob M.; Goldstone, Anthony H.

In: Blood, Vol. 108, No. 2, 15.07.2006, p. 465-472.

Research output: Contribution to journalArticle

Lazarus, HM, Richards, SM, Chopra, R, Litzow, MR, Burnett, AK, Wiernik, PH, Franklin, IM, Tallman, MS, Cook, L, Buck, G, Jill Durrant, I, Rowe, JM & Goldstone, AH 2006, 'Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: Results from the international ALL trial MRC UKALL XII/ECOG E2993', Blood, vol. 108, no. 2, pp. 465-472. https://doi.org/10.1182/blood-2005-11-4666
Lazarus, Hillard M. ; Richards, Susan M. ; Chopra, Raj ; Litzow, Mark R ; Burnett, Alan K. ; Wiernik, Peter H. ; Franklin, Ian M. ; Tallman, Martin S. ; Cook, Lucy ; Buck, Georgina ; Jill Durrant, I. ; Rowe, Jacob M. ; Goldstone, Anthony H. / Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis : Results from the international ALL trial MRC UKALL XII/ECOG E2993. In: Blood. 2006 ; Vol. 108, No. 2. pp. 465-472.
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AU - Burnett, Alan K.

AU - Wiernik, Peter H.

AU - Franklin, Ian M.

AU - Tallman, Martin S.

AU - Cook, Lucy

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AU - Rowe, Jacob M.

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N2 - Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with L-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)-positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy.

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