Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome.
BACKGROUND
To the authors' knowledge, the natural history of myelosuppression and infectious complications associated with the use of standard cytarabine (ARA-C) plus daunorubicin ("7 + 3") remission-induction therapy for adult acute myeloid leukemia (AML) and high dose ARA-C (HDARA-C) consolidation has not been described completely.


METHODS
A retrospective study of untreated adult AML patients receiving standard 7 + 3 induction followed by "5 + 2" and HDARA-C consolidation was undertaken to describe the relationship of the myelosuppression profiles, blood product use, and infectious morbidity, and to correlate this finding with the outcome of antileukemic therapy. Multivariate techniques were used to evaluate variables of prognostic importance.


RESULTS
Fifty-nine percent of the patients achieved remission after a median of 35 days; almost half (48%) of these patients required more than one 7 + 3 induction course. For one, two, and three induction courses, the mean number of days the patients experienced severe neutropenia (< 0.5 x 10(9)/l) were 22.5 +/- 10.9, 39.3 +/- 14.3, and 47.4 +/- 9.7 days (P < 0.001), respectively, and the infection rates were 1.45, 2.45, and 3 infections per course (P < 0.0001), respectively. The pattern of blood product use was similar. HDARA-C consolidation was the most significant factor related to prolonged disease free survival, however the myelosuppression profiles and infection rates were surprisingly similar to those for the single 7 + 3 induction courses.


CONCLUSIONS
The 7 + 3 induction regimen used in this center provided only limited antileukemic activity, while requiring multiple induction courses in a high proportion of patients. The use of multiple induction courses had consequences of prolonged myelosuppression, increased blood product use, and incremental risks of infectious complications. HDARA-C consolidation for those who experienced complete remission appeared to improve disease free survival with myelosuppression comparable with that of patients who received primary induction therapy. The infection risk was acceptable, with only a marginal increase in bacteremic and fungal infections.
Bow
E J
EJ
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Kilpatrick
M G
MG
Scott
B A
BA
Clinch
J J
JJ
Cheang
M S
MS
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007239:Infections / Q000150:complications* / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008350:Manitoba; D008875:Middle Aged; D015999:Multivariate Analysis; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D003561:Cytarabine; D003630:Daunorubicin