Page 1423 - Williams Hematology ( PDFDrive )

1398 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1399

cytarabine with glucocorticoids can be considered. Systemic relapse chemotherapy have led to comparable overall survival rates. However,
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commonly follows relapse in the meninges, and concurrent systemic leukemia-free survival was greater after allogeneic transplantation. In
treatment usually is indicated. Long-term success is unusual unless allo- the last decade, treatment-related mortality from transplantation has
geneic HSC transplantation is possible. Unless the patient has neuro- declined and matched unrelated donor transplantations are as effective
logic symptoms, lumbar puncture generally is deferred until blood blast as those from a matched sibling donor, so currently, transplantation
cells have cleared. No consensus exists on a trigger for platelet transfu- is recommended for all but good-prognosis patients (CBF leukemias
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sion in adults with AML undergoing lumbar puncture, but a platelet or those with NPM1 mutation without a FLT3 mutation). A Markov
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count less than 20 × 10 /L has been proposed as such a trigger, but decision analysis has shown that patients treated with allogeneic HSC
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many therapists use a higher platelet count (e.g., 50 × 10 /L) as a safety transplantation have a longer life expectancy compared with those
threshold for lumbar puncture. treated with chemotherapy among patients with an intermediate- or
Management of Nonleukemic Myeloid Sarcoma Some patients unfavorable-risk prognosis. A prospective matched-pairs analysis has
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present with myeloid (granulocytic) sarcomas without evidence of leu- also concluded that allogeneic HSC transplantation is the most effective
kemia in the blood or marrow (see “Myeloid [Granulocytic] Sarcoma” postremission therapy for AML, especially for those 45 to 59 years of
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earlier). Myeloid sarcoma may be the presenting finding in approxi- age and/or with high-risk cytogenetics. When quality of life was mea-
mately 1 percent of patients with AML. Such patients should receive sured for patients in complete remission for 1 to 7 years, those treated
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intensive AML induction therapy. Intensive therapy results in a lon- with chemotherapy had the highest quality of life, whereas those who
ger nonleukemic period than patients who have undergone surgical underwent allogeneic HSC transplantation had the lowest. 662
resection or resection followed by local irradiation. Whether such The decision to utilize autologous or allogeneic HSC transplanta-
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patients should undergo allogeneic HSC transplantation in first remis- tion or high-dose cytarabine alone for consolidation should be individ-
sion irrespective of other factors has not been determined. 653,654 Median ualized, based on the patient’s age and other prognostic factors, such
relapse-free survival is approximately 12 months after AML-type as high-risk cytogenetic findings and antecedent hematologic disease.
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chemotherapy. Patients with trisomy 8 have poorer survival rates. 260 Patients with good-risk cytogenetics should receive up to four cycles
of high-dose cytarabine. Patients with poor-risk cytogenetics should
POSTREMISSION THERAPY be considered for allogeneic HSC transplantation as soon as feasible. A
meta-analysis has also shown that compared with nonallogeneic thera-
Cytotoxic Therapy pies, allogeneic HSC transplantation has superior relapse-free survival
General Considerations Postremission therapy is intended to pro- and overall survival for cases of AML classified intermediate and poor-
long remission duration and overall survival, but no consensus exists risk, but not for cases considered good-risk AML in first remission. 663
regarding the best approach. Postremission chemotherapy that does not Intensive Consolidation Therapy For patients who do not
produce profound prolonged cytopenias, closely simulating intensive receive high-dose chemotherapy with autologous or allogeneic trans-
induction therapy, has produced on average only slight prolongation plantation in first remission, consolidation chemotherapy regimens
of remission or life. Regimens that fall between these intensities have containing high-dose cytarabine provide better results than inter-
been used, with equivocal results. Intensive consolidation therapy after mediate-dose cytarabine, 664,665 but these regimens are not universally
remission results in a somewhat longer remission duration and, more accepted. Patients who are to have allogeneic HSC transplantation do
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significantly, a subset of patients who have a remission of more than not require four cycles of high-dose cytarabine, and may not benefit
3 years. The issue of postremission therapy and its impact is compli- from even one, if a donor is readily available. RAS mutations are asso-
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cated by the large proportion of patients with AML who are older than ciated with benefit from high-dose cytarabine therapy. Patients with
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60 years of age and have limited tolerance for intensive therapy. In addi- CBF leukemias such as t(8;21) also have particularly favorable responses
tion, a very small pool of leukemic stem cells may sustain the process, to repetitive cycles of high-dose cytarabine. In patients who received
and elimination of these cells may require approaches other than inten- three or more cycles, a relapse rate of 19 percent was reported. 669
sive chemotherapy, especially in adults. Other regimens, such as those containing gemtuzumab ozogamicin
Several randomized trials have studied whether AML patients and fludarabine, have been used in postremission therapy, but whether
in first remission should receive consolidation chemotherapy alone, they provide benefit over use of high-dose cytarabine has not been
autologous transplantation, or allogeneic HSC transplantation, with- studied. Long-term disease-free survival at 5 years generally is approx-
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out reaching a consensus. Allogeneic transplantation was compared to imately 30 percent when two to four cytarabine-containing regimens are
autologous transplantation using unpurged marrow and two courses of administered. 671,672 Adding mitoxantrone or amsacrine to high-doses
intensive chemotherapy in 623 patients who had a complete remission cytarabine has not improved treatment outcomes in consolidation,
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after induction chemotherapy. Disease-free survival was 53 percent and timed sequential chemotherapy used in consolidation did not
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at 4 years for those receiving allogeneic transplantation, 48 percent for improve outcome as compared with high-dose cytarabine. Most cen-
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those receiving autologous transplantation, and 30 percent for patients ters use four cycles of therapy. A cycle is 3 g/m twice daily on days 1,
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receiving intensive chemotherapy. Overall survival after complete 3, and 5, providing six doses per cycle, with cycle durations dependent
remission was similar in all three groups because patients who relapsed on normal blood count recovery. The optimal number of cycles for this
after chemotherapy could be rescued with allogeneic HSC transplan- therapy is not known. High-dose cytarabine can be administered at a
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tation. No significant difference in the 4-year disease-free survival dose of 3 g/m in a 1- to 3-hour intravenous infusion every 12 hours for
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between allogeneic HSC transplantation (42 percent) and other types up to 6 days (12 doses), but this schedule is almost never used because of
of intensive postremission therapy (40 percent) has been found. In its toxicity. There is some evidence that two cycles of intermediate-dose
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another study, only patients younger than 35 years of age with poor-risk cytarabine (1 g/m every 12 hours for 6 days) may be a viable alterna-
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cytogenetics had improved disease-free survival if they had a sibling tive to the 3 g/m for six doses schedules. When 36 g/m total dosing
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donor and underwent allogeneic transplantation (43.5 percent vs. 18.5 was compared with 12 g/m dosing in the first consolidation, there was
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percent at 4 years). Thus, in several studies, the early mortality after no improvement in treatment outcomes. High-dose cytarabine fre-
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allogeneic HSC transplantation and the chemotherapy-induced remis- quently causes conjunctivitis and photophobia, and glucocorticoid eye
sions in patients who relapse following autologous transplantation or drops are usually used every 6 hours until 24 hours after the last dose of
Kaushansky_chapter 88_p1373-1436.indd 1398 9/21/15 11:01 AM