Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993.
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.
Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. hillard.lazarus@case.edu
Hillard M
HM
Lazarus
Susan M
SM
Richards
Raj
R
Chopra
Mark R
MR
Litzow
Alan K
AK
Burnett
Peter H
PH
Wiernik
Ian M
IM
Franklin
Martin S
MS
Tallman
Lucy
L
Cook
Georgina
G
Buck
I Jill
IJ
Durrant
Jacob M
JM
Rowe
Anthony H
AH
Goldstone
D000293:Adolescent; D000328:Adult; D001215:Asparaginase / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012074:Remission Induction; D015996:Survival Rate
D001215:Asparaginase; D008727:Methotrexate