Intensive postremission chemotherapy without maintenance therapy in adults with acute lymphoblastic leukemia. Dutch Hemato-Oncology Research Group.
OBJECTIVE
To investigate the value of intensive consolidation chemotherapy not followed by maintenance therapy in adult acute lymphoblastic leukemia (ALL).


METHODS
A multicenter phase II trial was conducted in 130 adult patients with ALL between 16 and 60 years of age. After standard induction therapy, postinduction chemotherapy was given: three courses of high-dose cytarabine (2,000 mg/m2 every 12 hours for four doses) in combination with amsacrine (course one), mitoxantrone (course two), and etoposide (course three). CNS prophylaxis consisted of 10 injections of intrathecal methotrexate (IT MTX). Patients younger than 50 years with an HLA-identical sibling were eligible to receive allogeneic bone marrow transplantation (BMT).


RESULTS
Ninety-five patients (73%) achieved complete remission (CR); 82% were younger than 50 years and 41% were older than 50 years. Seventeen patients (13%) were resistant to chemotherapy, and 18 (14%) died during induction treatment. Only age and performance status were significantly associated with response (P<.001 and .03, respectively). Death during consolidation occurred in four patients. The estimated 5-year overall survival (OS) was 22% for the entire group and 26% for patients younger than 35 years. Disease-free survival (DFS) at 5 years was 28% +/- 6 for patients younger than 35 years, 25% +/- 9 for patients between 35 and 50 years, and 0% for patients older than 50 years. Increasing age (P<.01) and expression of CD34 (P<.01) were adverse factors. Only three patients (3%) developed an isolated CNS relapse.


CONCLUSIONS
Intensive consolidation including high-dose cytarabine not followed by maintenance therapy provides an outcome for adult patients with ALL that may be worse or even inferior compared with studies using long-term maintenance therapy. High-dose cytarabine in combination with IT MTX was effective for CNS prophylaxis.
Dekker
A W
AW
Department of Hematology, University Hospital Utrecht, the Netherlands. j.vd.velde@digd.azu.nl
van't Veer
M B
MB
Sizoo
W
W
Haak
H L
HL
van der Lelie
J
J
Ossenkoppele
G
G
Huijgens
P C
PC
Schouten
H C
HC
Sonneveld
P
P
Willemze
R
R
Verdonck
L F
LF
van Putten
W L
WL
Löwenberg
B
B
D000293:Adolescent; D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009426:Netherlands; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012074:Remission Induction; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000677:Amsacrine; D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone