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1408 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1409

TREATMENT OF OLDER PATIENTS cytarabine with etoposide and G-CSF. 1041 Temozolomide has been used
Biologic Features in this age group, 1042 and clofarabine is also being tested in patients
In one study of clofarabine in older patients
1043
age 60 years and older.
Approximately 65 percent of patients with AML are older than age who were deemed unfit for 7-plus-3 chemotherapy, a 5-day clofarabine
60 years at the time of diagnosis. 1018 The disease in this age group is regimen resulted in a 48 percent response rate, and 18 percent died
less responsive to therapy, and this age group has a higher propor- within 30 days. 1044 Another study in those older than 60 years showed a
tion of patients who have oligoblastic myelogenous leukemia (MDS); response rate of 46 percent and an overall median survival of 41 weeks
an antecedent clonal myeloid disease; prior chemotherapy for cancer and a 30-day all-cause mortality of approximately 10 percent. 1045 Several
of another site; and comorbid conditions that decrease the tolerance investigational therapies, including 5-azacytidine, decitabine, clore-
to intensive chemotherapy programs. 1019–1022 The AML cells of elderly tazine, and depsipeptide, are also being studied. There are also several
patients often have more CD34 expression, suggesting origin from a reports concerning addition of other agents to standard chemotherapy
more primitive multipotential (? stem) cell. This finding is thought to to improve responses. These include bevacizumab, 1046 sorafenib, 1047 and
contribute to longer duration of postchemotherapy aplasia and to the gemtuzumab ozogamicin. 1048,1049 Thus far, none of these drugs have
increased risk of induction deaths in this age group. 1023 Patients older resulted in improvement in overall survival.
than age 60 years also have a high frequency of unfavorable cytogenetic
findings (32 percent) and higher MDR1 expression (71 percent) and
functional drug efflux (58 percent). 1024,1025 Autologous Stem Cell Infusion or Nonmyeloablative Alloge-
neic Transplantation
Autologous stem cell transplantation has been used in fit patients older
Chemotherapy than age 60 years. 1050 The incidence of relapse is lower when marrow
The therapist and patient determine whether a standard regimen, a stan- stem cells are used compared to blood stem cells. Some patients older
dard regimen with dose reductions, or a special regimen is used. 1026,1027 than age 60 years may be eligible for reduced-intensity allogeneic stem
Decisions based on chronologic age should be supplanted by mea- cell transplantation from related or unrelated donors, but more data
surements of cognitive, neurologic, and physical fitness used by geri- regarding outcomes are needed. 1051 In a large registry study, examin-
atricians to evaluate the wisdom of considering intensive treatment. 1028 ing reduced-intensity allogeneic HSC transplantation for older patients
These are often not well-validated in geriatric AML populations, but with AML and MDS in first remission, older age was not found to affect
there is evidence that assessments focused on cognition and objective 2-year nonrelapse mortality, disease-free or overall survival. 1052
measures of physical function may predict for overall survival in those
older than age 60 years who undergo standard induction chemother- Postremission Therapy in Older Patients
apy. 1029 In patients older than age 60 years who are fit and otherwise are No consensus exists regarding the best regimen or the number of treat-
considered good candidates, standard two-drug therapy can be used: ment cycles for postremission therapy in older adults. Regardless of the
cytarabine and an anthracycline antibiotic, and on some occasions the consolidation regimen, the duration of the leukemia-free survival is
addition of a third drug, etoposide. Remission rates of approximately longer with high-dose cytarabine and autologous stem cell transplanta-
35 to 45 percent can be achieved. Based on case studies, those who are tion, just as it is in younger patients, 1042 but fewer older patients can tol-
able to receive induction chemotherapy may have a median survival erate this degree of therapeutic intensity. Higher-dose cytarabine can be
slightly better than those who receive supportive care alone, 1030,1031 but used in older adults with AML, but usually at a reduced dose. 1053 Older
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there are no randomized trials that address this issue. 1032 Patients older patients treated with attenuated high-dose cytarabine at 750 mg/m
than 70 years (median: 74; range: 70 to 88) may not have much ben- intravenously for 12 doses and then consolidated with four to six doses
efit from intensive chemotherapy with an 8-week mortality of greater had an approximately 50 percent remission rate with a median duration
than 30 percent and a median survival of less than 6 months. 1033 Some of remission of 326 days. 1054 Fifty-one percent of 110 patients older than
investigators have proposed waiting for cytogenetic information before 60 years of age had a 9-month median remission duration when con-
therapy decisions are made in older patients. Those with unfavorable solidated with high-dose cytarabine. 1055 Older patients are at higher risk
cytogenetics and two or more other criteria including age older than for relapse despite successfully completing intensive consolidation ther-
75 years, poor performance status, and WBC greater than 50 × 10 /L apy, regardless of whether other adverse prognostic features are present.
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were found not to benefit from chemotherapy. 1034 Chemotherapy has Cytarabine as maintenance therapy may prolong disease-free survival
been combined with growth factor support to accelerate neutrophil but does not improve overall survival. 1056 Decitabine and 5-azacytidine
recovery in older patients. 1035 In a study in which patients older than age are also being examined for maintenance therapy. In one randomized
55 years were randomized to receive either placebo or G-CSF after study, those receiving consolidation therapies had more hospitalizations
induction therapy, no reduction in the duration of hospitalization, sur- and more transfusion requirements. 1057
vival prolongation, or cost of supportive care was noted. 1036 In previously Patients older than 80 years of age do not tolerate treatments well.
untreated elderly patients with AML, mitoxantrone induction therapy Remission rates are approximately 30 percent, but the median survival
produces a slightly higher remission rate than did daunorubicin, but of treated patients is approximately 1 month. Less than 10 percent of
had no significant effect on remission duration and survival. 1037 Oral patients survive for 1 year. 1058
idarubicin alone has been used with success. 1038 Unlike the case in younger patients, the treatment outcomes for
Attenuated standard regimens can be used in older patients. An older patients have not improved over the last two decades. 1059 Treat-
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example of an attenuated regimen is cytarabine 100 mg/m subcutane- ment options in older patients include (1) no treatment, (2) supportive
ously every 12 hours for 10 doses on days 1 through 5 and daunorubicin care, (3) palliative low-dose chemotherapy, (4) attenuated induction
30 mg/m IV on days 1 through 3 of treatment. One induction regimen chemotherapy, or (5) high-dose chemotherapy regimens. Investigative
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is not superior to another in older patients. Outcomes achieved with agents should also be given strong consideration in this population. 1060
cytarabine and daunorubicin are comparable to results with mitox- Comorbidities are independent predictors of complete remission and
antrone and etoposide. 1039 Other regimens for older patients include should be taken into account during decision making, 1061 as should
lower total doses of idarubicin, etoposide, and cytarabine (DIVA performance status. 1062 Some argue that the approximately 15 percent
regimen) 1040 and a combination of continuous infusion low-dose rate of death in those older than 60 years of age in the first month after

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