Transcript Presentation Title

Treatment of AML in
the Elderly
Gayle Marble BSN, RN, OCN
Banner Health Clinical Education
Oncology
Dallas, TX • November 2–4, 2012
EFFECT OF AGING
• Cancer is a disease of the aged
• Over 65 years from 5.8 million in 2010
– to 8.7 million in 2030.6
– In 2050, this group is projected to reach 19
million. (3)
• 85 and over are projected to account for 4.3%
in U.S.
• Age range 10 yrs to 90 yrs
– Survival worsens 1% per year of age
attained (7)
Dallas, TX • November 2–4, 2012
Dallas, TX • November 2–4, 2012
TELEMERES
http://www.ncbi.nlm.nih.gov/
pubmed/16281260
Dallas, TX • November 2–4, 2012
Acute Leukemia
• Leukemia Overall Prevalence
– 47,150  new cases in 2012/ 23,540 ↑
deaths
– 50% mortality rate equal to 50% survival
• AML represents 80% of all adult leukemia's
– Males slightly higher rate
– 10 times greater occurrence for adults
• AML 13,780 ↑ new cases with 10,200 
deaths
– 74% mortality rate equal to 26% survival
– SEER reports only 5-10% survival if > 60 years
(Surveillance, Epidemiology and End Result)
Dallas, TX • November 2–4, 2012
Acute Myeloid Leukemia
• AML
– Acute Myelocytic Leukemia
– Acute Myeloid Leukemia
• ANLL
– Acute Non-Lymphocytic Leukemia
• AGL
– Acute Granulocytic Leukemia
Dallas, TX • November 2–4, 2012
Leukemia or white blood
• Greek word for white: Leukos
• Greek word for blood: Heima
• Velpeau and Bennett described the
disease process Leucocythemia
• Rudolf Virchow in 1856 defined as
leukemia
http://www.news-medical.net/health/Acute-Myeloid-Leukemia-History.aspx
Dallas, TX • November 2–4, 2012
Leukemia
• Proliferation of immature WBCs leads to
suppression of development of other blood
cells
– Results in bone marrow failure
• Death
– Symptoms related to cytopenias
• Infection
• Fatigue
• Bruising/bleeding
– Or too much proliferation of the malignant clone
• Bone Pain
Dallas, TX • November 2–4, 2012
FAB subtype
Name
% of adult AML
patients
Prognosis compared
to average for AML
M0
Undifferentiated acute
myeloblastic leukemia
5%
Worse
M1
Acute myeloblastic
leukemia with minimal
maturation
15%
Average
M2
Acute myeloblastic
leukemia with maturation
25%
Better
M3
Acute promyelocytic
leukemia (APL)
10%
Best
M4
Acute myelomonocytic
leukemia
20%
Average
M4 eos
Acute myelomonocytic
leukemia with eosinophilia
5%
Better
M5
Acute monocytic leukemia
10%
Average
M6
Acute erythroid leukemia
5%
Worse
M7
Acute megakaryoblastic
leukemia
5%
Worse
Dallas, TX • November 2–4, 2012
http://www.cancer.org/Cancer/Leukemia-AcuteMyeloidAML/DetailedGuide/leukemia-acute-myeloid-myelogenous-classified
Accessed August 27, 2012
Hematopoiesis
Lymphoid
B Cell
Pleuropotent
Stem Cell
T Cell
Progenitor
Lymphocyte
Monocyte
Myeloid
Myelocyte
Erythrocyte
Megakaryocyte
Dallas, TX • November 2–4, 2012
Hematopoiesis
ALL
B Cell
Pleuropotent
Stem Cell
Lymphoid
T Cell
Progenitor
Lymphocyte
M0
M5
M4
M1
Monocyte
Myeloid
M2
M3
M6
M7
Myelocyte
Erythrocyte
Megakaryocyte
Dallas, TX • November 2–4, 2012
Treatment for AML
• Goal is to render the marrow aplastic
with out depleting the stem cells.
• 7 + 3:
– Anthracycline X IVP once daily for 3 Days
• Daunorubicin 45-50 mg/M2
• Idarubicin 12 mg/M2
– Cytosine Arabinacide IV infusion Daily X 7
Days
• Cytarabine (ARA-C) 100-200 mg/M2
• Cytarabine (ARA-C) 3 grams/M2 For HiDAC RX
Dallas, TX • November 2–4, 2012
Anthracyclines in AML
• Antitumor antibiotics
– Daunorubicin
– Idarubicin
• Major Nursing concerns
– Cardiotoxicity
– Vesicant potential
– Melosuppression
– Alopecia
Dallas, TX • November 2–4, 2012
Cytarabine
• Pyridimine analogue that inhibits DNA synthesis
• Myelosuppression
• GI symptoms
– Nausea and Vomiting
– Diarrhea
• Chemical conjuctivitis
– Prophylactic dexamethasone eye drops
• 20% incidence of cerebellar and cerebral dysfunction
– Greatest occurrence in folks older than 50 yrs
•
•
•
•
Slurring of speech
Ataxia
Confusion
Coma
Dallas, TX • November 2–4, 2012
Side Effects of Treatment
• Myelosuppression by Day 3
– Neutropenia ↑ Infections ↑ Antibiotics
– Thrombocytopenia ↑ Bleeding ↑Platelet transfusion
– Anemia ↑ fatigue, hypoxia, potential for falls
• Mucositis
• Nausea and Vomiting
• Dermatologic
– Alopecia
– Rash (hand and foot)
Dallas, TX • November 2–4, 2012
Consolidation Therapy
• Repeat of same drugs: intensification
– Different doses: consolidation
• Use of different drugs
• Without Consolidation 100% of AML will
recur
• Toxicities are compounded with each
successive therapy given
Dallas, TX • November 2–4, 2012
Who should be treated?
• Variables to consider
– Type of Presentation
 De Novo
 Following an antecedent hematologic disorder
– Cytogenetics
 t(8;21), (q22;q22), t(15;17)(q22;q21), or
inv(16)(p13q22) were favorable
 Monosomies of 5 or 7 (-5,-7) or deletions of long
arm chromosomes were unfavorable
 MDR1 or multidrug resistance
Dallas, TX • November 2–4, 2012
Variables to consider
cont’d
– Pre-existing organ toxicity
– Presence of infection
– Performance status
• Karnofsky’s 100 (ADL independent)- 0 (dead)
• ECOG
0 (Fully independent)- 5 (dead)
– Age
– WBC >50,000
– LDH
Dallas, TX • November 2–4, 2012
Clinical Trials for Elderly
AML Patients
•
•
•
•
Clofarabine: CR 38% TID 10% (n=112)
Decitabine: CR 24% TID 4% (n=55)
3 + 7: CR 41% TID 18% (n=600)
Laromustine: CR+CRp 33% OS@1year
20%
• LDAC (low dose cytarabine) CR+CRp
23%
OS @ 1 year 25% (n61)
Dallas, TX • November 2–4, 2012
Hematopoietic Stem Cell
Transplant
• Autologous: promotes disease free
survival but does not cure.
– 5-10% mortality
• Allogeneic: Potential cure
– 50% mortality
• Both processes require myeloablation
Dallas, TX • November 2–4, 2012
Myeloablation
• Complete emptying of the bone marrow
• Unable to grow back without rescue of
stem cells
• Transplants rely on total myeloablation
B
Ce T
• Achieved through
ll Ce
ll
– Hi dose chemo
– TBI
• Stem Cell Rescue
Megak
aryocyt
e
Erythr
ocyte
Myel
ocyte
Dallas, TX • November 2–4, 2012
Non-myeloablative
Allogeneic BMT
• Elderly unable to tolerate assault to vital
organs
• Submyeloblative Transplant: Allogeneic
– Preferred for patients >60 yrs
– Less organ toxicity due to lower chemo
doses
– Graft versus leukemia effect
– Non-curative
• Increase disease free survival
Dallas, TX • November 2–4, 2012
Case Study
• 63 YO male with AML
– Karnofsky PS 100
– Well nourished
• 1998: Induction therapy
• Prior to consolidation Relapsed
– Induction again
• Remission lasted 3 mos
– Referred for BMT assessment
• Non myeloablative Transplant
Dallas, TX • November 2–4, 2012
Case Study Cont’d
• Three years of disease free survival
– Devoted a portion of his life to promoting HLA
typing through the National Marrow Donor
Program
– Arranged his considerable finances to promote
further participation and research for patients with
poor prognosis
– His final comment to me was:
“I would like more time, but I’ve had 3 years I
wouldn’t have had without the treatment I was
provided. Help my sister be okay with it”
Dallas, TX • November 2–4, 2012
Old age is not a disease - it is strength and
survivorship, triumph over all kinds of
vicissitudes and disappointments, trials and
illnesses.
Maggie Kuhn
Dallas, TX • November 2–4, 2012
References
1.
http://joe.endocrinology-journals.org/content/173/3/387.full.pdf Accessed August 24, 2012
2.
http://www.ncbi.nlm.nih.gov/pubmed/16281260 Abstract accessed August 24, 2012
3.
http://www.aoa.gov/aoaroot/aging_statistics/future_growth/DOCS/p25-1138.pdf accessed August 24
2012
4. C. P. Leith, K. J. Kopecky, J. Godwin, et al., “Acute myeloid leukemia in the elderly: assessment of
multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct
responses to standard chemotherapy. A Southwest Oncology Group Study,” Blood, vol. 89, no. 9, pp.
3323–3329, 1997
5.
F. Ferrara and A. Pinto, “Acute myeloid leukemia in the elderly: current therapeutic results and
perspectives for clinical research,” Reviews on Recent Clinical Trials, vol. 2, no. 1, pp. 33–41, 2007.
6.
S. Fröhling, R. F. Schlenk, S. Kayser, et al., “Cytogenetics and age are major determinants of outcome
in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML
HD98-B,” Blood, vol. 108, no. 10, pp. 3280–3288, 2006
7.
J. K. Weick, K. J. Kopecky, F. R. Appelbaum, et al., “A randomized investigation of high-dose versus
standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid
leukemia: a Southwest Oncology Group study,” Blood, vol. 88, no. 8, pp. 2841–2851, 1996.
8.
Estey, E AML and MDS in older patients. J Clin Onc 2007;25:1908-15.
9.
The Length of A Human DNA Molecule,” The Physics Factbook, Edited by Glenn Elert.
10.
http://bloodjournal.hematologylibrary.org/content/98/5/1312.full.pdf+html Accessed August 30, 2012
Dallas, TX • November 2–4, 2012