S-HAM induction chemotherapy with or without GM-CSF in patients with high-risk myelodysplastic syndromes.
Thirty-one adult patients with high-risk myelodysplastic syndromes (MDS) were enrolled in a prospective randomized double-blind placebo-controlled trial evaluating the efficacy of sequential high-dose Ara C/mitoxantrone chemotherapy with or without GM-CSF. GM-CSF or placebo was given subcutaneously once daily at a dose of 250 micrograms/m2 starting 48 h prior to chemotherapy and continued until neutrophil recovery. This design allowed us to investigate the role of GM-CSF as a priming factor for the leukemic clone, as well as its effect on the recovery of normal hematopoiesis. Twenty-eight patients are currently evaluable for response. The patients reached a complete remission (36%), eight patients had persistent MDS (29%), and ten patients died within 6 weeks after the onset of treatment (early death). Infectious complications during cytopenia were the major cause of death (8/10). Median time to complete hematologic recovery (neutrophils > 500/microliter and platelets 20,000/microliter) and time to neutrophil recovery above 1500/microliter was 29 and 35 days, respectively. Median remission duration was 190 days (6.4 months). Analysis of prognostic subgroups showed a low CR rate (25%) and a high early-death rate (44%) in patients > 55 years of age, suggesting that the intensified treatment approach should be limited to younger patients. No data concerning the influence of GM-CSF on response to chemotherapy or duration of neutropenia are presently available.
Verbeek
W
W
Department of Hematology/Oncology, Georg-August University, Göttingen, Germany.
Wörmann
B
B
Koch
P
P
Aul
C
C
Hinrichs
H
H
Balleisen
L
L
Rowe
J M
JM
Bennett
J
J
Büchner
T
T
Hiddemann
W
W
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001230:Aspergillus / Q000302:isolation & purification; D001769:Blood / Q000382:microbiology; D002175:Candida / Q000302:isolation & purification; D002493:Central Nervous System Diseases / Q000139:chemically induced; D003561:Cytarabine / Q000627:therapeutic use* / Q000633:toxicity; D004311:Double-Blind Method; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000453:epidemiology; D012307:Risk Factors
D000970:Antineoplastic Agents; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone