Intensive short term therapy with granulocyte-macrophage-colony stimulating factor support, similar to therapy for acute myeloblastic leukemia, does not improve overall results for adults with acute lymphoblastic leukemia. GOELAMS Group.
BACKGROUND
Despite modern treatment programs, less than 20% of adult cases of acute lymphoblastic leukemia (ALL) are cured. For relapsing and/or refractory patients, use of high dose cytosine arabinoside (ara-C) and anthracyclin achieved a complete remission (CR) rate of up to a 75%. The aim of this study was to evaluate in adult patients with ALL 1) the CR rate of a chemotherapy schedule similar to a schedule for acute myeloblastic leukemia (AML) patients, 2) the antileukemic value and the tolerance of 3 intensive stage treatments, and 3) the impact of recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF) on chemotherapy-induced neutropenia and infectious complications, as well as the effect of dose intensity.


METHODS
Between November 1990 and April 1992, 67 patients ages 15-55 years with de novo ALL were randomly assigned to receive either rGM-CSF or placebo. The induction treatment consisted of idarubicin, methylprednisolone, and high dose ara-C. After achieving CR, patients up to age 45 years who had an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation (BMT). All remaining patients received a first course of early intensification with high dose ara-C, mitoxantrone, etoposide, and methylprednisolone, followed by autologous, unpurged BMT.


RESULTS
Of the 64 eligible patients, 50 (78%) achieved CR. Sixteen allogeneic and 18 autologous BMTs were performed. The median survival was 10.2 months. The 4-year survival was 24%. rGM-CSF only improved the incidence of severe mucositis during the induction course (P = 0.003) and probably also improved the median duration of fever (P = 0.07).


CONCLUSIONS
This schedule, similar to that for the treatment of AML patients, with early BMT included, did not prove to be a satisfactory approach to the treatment of most adult ALL patients, although CR was achieved in 78% of cases. In this study, no major improvement was obtained with rGM-CSF therapy.
Ifrah
N
N
Service de Médecine D, CHU, Angers, France.
Witz
F
F
Jouet
J P
JP
François
S
S
Lamy
T
T
Linassier
C
C
Pignon
B
B
Berthou
C
C
Guyotat
D
D
Cahn
J Y
JY
Harousseau
J L
JL
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D011994:Recombinant Proteins; D012074:Remission Induction; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor