No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease.
In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels </=9.5 microkat/l, bone marrow cellularity </=70%, and WBC counts <4.0 x 10(9)/l, but S-LDH was the only variable independently associated with response by logistic regression analysis. Cox's regression analysis identified four significant prognostic factors for survival: bone marrow cellularity, S-LDH, cytogenetic risk group (International Prognostic Scoring System), and age. Only bone marrow cellularity (P=0.01) and S-LDH (P=0.0003) retained statistical significance in the log-rank test. Severe adverse events were significantly more common in the GM-TAD arm (P=0.01). Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects. We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.
Hast
R
R
Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Hellström-Lindberg
E
E
Ohm
L
L
Björkholm
M
M
Celsing
F
F
Dahl
I-M
IM
Dybedal
I
I
Gahrton
G
G
Lindberg
G
G
Lerner
R
R
Linder
O
O
Löfvenberg
E
E
Nilsson-Ehle
H
H
Paul
C
C
Samuelsson
J
J
Tangen
J-M
JM
Tidefelt
U
U
Turesson
I
I
Wahlin
A
A
Wallvik
J
J
Winquist
I
I
Oberg
G
G
Bernell
P
P
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use*; D003630:Daunorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000473:pathology; D011446:Prospective Studies; D012074:Remission Induction; D015996:Survival Rate; D013866:Thioguanine / Q000009:adverse effects / Q000627:therapeutic use*
D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013866:Thioguanine; D003630:Daunorubicin