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AML

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Chemotherapy choices for
1. AML
2. MDS-RAEBT
3. CML-blast crisis

Prognosis in AML based on cytogenetics

ARAC-DNR for 59 yrs. or younger


INDUCTION (7+3):
Cytarabine 100-200 mg/m2 CIV days 1-7
Daunorubicin 30- 45 mg/m2 IVB* days 1-3
*Daunorubicin dose is 30 mg/m2 for patients 60 years of age and older, and 45 mg/m2 for those under 60.

If leukemia is persistant, additional induction cycles are given:
Cytarabine 100 mg/m2 CIV days 1-5
Daunorubicin 30 or 45 mg/m2 IVB* days 1 & 2

Maintenance is complex; see reference for details.

Ref: Yates J, et al: Blood 60:454 (1982).

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Other 7+3 Regimen:

CYTARABINE 100 mg/m2 CI DAYS 1-7
IDARUBICIN 12 mg/m2 IV DAYS 1-3

CYTARABINE 100 mg/m2 CI DAYS 1-7
MITOXANTRONE 12 mg/m2 IV DAYS 1-3


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5+2 INDUCTION Regimen:
REF:Fisher DS. Knobf MT, Durivage HJ, eds. The Cancer Chemotherapy Handbook, 4th ed. St. Louis, MO:CV MOSBY 1993:314-315


CYTARABINE 100 mg/m2 CI DAYS 1-5
DAUNARUBICIN 45 mg/m2 IV DAYS 1-2

OR

CYTARABINE 100 mg/m2 CI DAYS 1-5
MITOXANTRONE 12 mg/m2 IV DAYS 1-2


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MTZ-ARAC

INDUCTION
Mitoxantrone 12 mg/m2 IV/30min days 1-3
Cytarabine 100 mg/m2 CIV days 1-7

if complete remission is not achieved, give:

Mitoxantrone 12 mg/m2 IV/30min days 1 & 2
Cytarabine 100 mg/m2 CIV days 1-5

REF: Arlin ZA: Novantrone: Worldwide Clinical Experience. Symposium, December (1988) (abstract).


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IDA-ARAC (Induction)

INDUCTION
Idarubicin 12 mg/m2 IV days 1-3
Cytarabine 100 mg/m2 CIV days 1-7

Repeat if luekemia persists on day 14 bone marrow.

CONSOLIDATION
Thioguanine 100 mg/m2 PO q12h X 10 doses
Cytarabine 100 mg/m2 IV q12h X 10 doses
Idarubicin 15 mg/m2 IV day 1 of each program

Repeat cycle every 21 to 28 days.

MAINTENANCE
Cytarabine 100 mg/m2 CIV days 1-5
Idarubicin 12 mg/m2 IV days 1 & 2

Repeat cycle every 13 weeks for 4 cycles.

Ref: Volger WR, et al: Semin Oncol 16:21 (1989).

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High Dose ARAC + DNR


Cytarabine 2000-3000 mg/m2 IV q12h
days 1-4 or 5
Daunorubicin 30- 45 mg/m2 IVB days 4-6

Ref: Herzig RH, et al: Blood 62:361 (1983).
Herzig RH, et al: J Clin Oncol 5:927 (1987).
Hoaglund HC, et al: JAMA 235:1888 (1976).

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High Dose ARAC for consolidation

Cytarabine 3000 mg/m2 IV q12h days 1, 3& 5


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CMA-676

Acetaminophen 650 mg orally and diphenhydramine 25 to 50 mg intravenously 15-30 minutes before infusion of CMA-676

CMA-676 9-mg/m2 2-hour intravenous infusion

Blood, Vol. 93 No. 11 (June 1), 1999: pp. 3678-3684
.
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ARSENIC
ARSENIC TRIOXIDE 0.15 mg/kg IV QD until remission, not to exceed 60 doses.

REF: Cell Therapeutics, INC, Trioxide package insert. 2000

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ATRA
All-trans-retinoic acid (ATRA) 45 mg/m2/day PO (1 or 2 divided doses)
Start 2 days before induction chemotherapy

REF:Blood 85:2643, 1995

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Journal of Clinical Oncology, Vol 20, Issue 15 (August), 2002: 3249-3253

Phase I Study of Temozolomide in Relapsed/ Refractory Acute Leukemia

20 patients (16 with AML, 2 with ALL, & 2 with CML in blastic phase) received 43 cycles of temozolomide. Patients began treatment at 2 different dose levels: 200 mg/m2/d x 7 days or 200 mg/m2/d x 9 days.

RESULTS: Prolonged aplasia was the dose-limiting toxicity, and the maximum-tolerated dose was 7 days of temozolomide. Overall treatment was well tolerated: hospitalization was required in only nine of 43 courses, & there were no treatment-related deaths. 2 patients obtained a complete response, and two others met criteria for complete response except for platelet recovery. Overall, 9 of 20 patients had a significant decrease in bone marrow blasts after temozolomide treatment.

CONCLUSION: Temozolomide was well tolerated & had significant antileukemic activity when given as a single agent. Further studies of temozolomide in hematologic malignancies are indicated

FAVORABLE PROGNOSIS CYTOGENETICS:
REF: Blood, Vol. 92 No. 7 (October 1), 1998: pp. 2322-2333

t(8;21)
t(15;17)
inv(16)
Whether alone or in conjunction with other abnormalities.

INTERMEDIATE PROGNOSIS CYTOGENETICS:
Normal
+8
+21
+22
del(7q)
del(9q)
Abnormal 11q23
All other structural/numerical abnormalities ie, Cytogenetic abnormalities not classified as favorable or adverse. Lack of additional favorable or adverse cytogenetic changes.

ADVERSE PROGNOSIS CYTOGENETICS:
5
7
del(5q)
Abnormal 3qComplex
Whether alone or in conjunction with intermediate-risk or other adverse-risk abnormalities.

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