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

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the drug. Cerebellar function abnormalities also may occur, and these after high-dose cytarabine plus G-CSF or after G-CSF alone. There is
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require cessation of drug administration. A 1-hour duration infusion of a plateau in the survival curve after autologous stem cell transplantation
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high-dose or reduced-dose (e.g., 2 g/m ) cytarabine may decrease the at about 2.2 years, and there is evidence that autologous transplan-
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likelihood of severe cerebellar toxicity. Older patients and patients tation improves disease-free survival but not overall survival. The
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with renal insufficiency require dose attenuation (i.e., to 1 to 2 g/m ). total number of CD34+ cells infused influences early engraftment, but
durable engraftment is associated more closely with the CD34+/CD38–
Additional Maintenance Therapy subset of cells in the graft. 700
Various forms of less-intensive maintenance chemotherapy have been
attempted after completion of intensive consolidation chemotherapy. Chemoradiotherapy Plus Allogeneic Hematopoietic Stem
Many of the regimens consist of monthly chemotherapy, for example, Cell Transplantation for Consolidation Therapy
low-dose 6-thioguanine or cytarabine. Although improved disease-free General Considerations Utilization of allogeneic HSC transplanta-
survival was noted in some studies, no improvement in overall survival tion for AML is increasing in Europe and the United States. No strict
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has been demonstrated in most studies. Some groups are examining upper-age limit for transplantation exists, but many centers use age
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the role of demethylating agents (e.g., 5-azacytidine or decitabine) as 60 or 65 years for transplantations following ablation of hematopoie-
maintenance therapy. 681 sis and 70 to 75 years for transplantations not preceded by ablation of
Autologous Stem Cell Infusion after Myeloablative Chemo- hematopoiesis (nonmyeloablative or reduced-intensity transplants).
therapy or Chemoradiotherapy for Consolidation Removal and Decisions to proceed to allogeneic transplantation should be individual-
cryopreservation of postremission marrow or collection of mobilized ized, and feasibility depends on (1) the availability of a suitable donor, (2)
blood stem cells from patients with AML and reinfusion of these prod- the recipient’s age and health status, and (3) whether AML is in remission.
ucts following intensive chemotherapy and/or radiotherapy is a form of For full-intensity transplantations, the patient is prepared with a
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postremission therapy (Chap. 23). This approach is loosely referred to regimen that includes total-body irradiation and/or high-dose chemo-
as autologous transplantation but does not cross transplantation barri- therapy, after which the donor stem cells are infused by vein. Patients
ers. Autologous marrow or blood stem cell rescue can be used in patients given allogeneic blood stem cells have more rapid hematopoietic recon-
with AML who achieve a remission, do not have a compatible stem cell stitution than patients given marrow stem cells, but they may have
donor, and are as old as 70 years. With the availability of high-reso- more chronic GVHD and comparable risk of relapse. 703,704 Chapter
lution HLA-matched unrelated donors, cord blood and haploidentical 23 describes the indications, procedure, and preparative regimens for
donors, the number of autologous stem cell transplants used in AML allogeneic stem cell transplantation. In general, no single preparative
has diminished. regimen is superior for patients with AML in first remission. In one
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Various treatment regimens for autologous transplantation in study, cyclophosphamide and total-body irradiation lowered relapse
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AML have been used, such as busulfan-cyclophosphamide, busulfan- risk, but overall results were comparable to conditioning with chemo-
etoposide-cytarabine, high-dose cytarabine-mitoxantrone plus total- therapy alone. Another retrospective study showed outcomes with
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body irradiation, melphalan plus total-body irradiation, and cyclo- intravenous busulfan and cyclophosphamide were not different from
phosphamide plus total-body irradiation. A disease-free survival rate of those with cyclophosphamide and total-body irradiation in AML in
approximately 40 percent at 3 years is average after such regimens in remisison. A retrospective registry analysis showed that leukemia-free
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the age-range treated. 684,685 Long-term disease-free survival can occur and overall survivals were better with busulfan and cyclophosphamide,
in patients who undergo this treatment for AML in second remission. as compared with total body irradiation in AML in first remission.
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Patients older than age 50 years have inferior outcomes, but no strict Postremission consolidation with cytarabine before allogeneic trans-
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upper-age limit for this procedure has been determined. Adminis- plantation for AML in first remission does not improve outcome com-
tration of two or more courses of consolidation chemotherapy prior to pared with immediate transplant after successful induction. It is
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harvest and transplant is associated with decreased relapse rates and unclear that this result will also hold in the setting of reduced-intensity
improved disease-free survival. A marrow nucleated cell dose greater transplants or for transplants performed beyond first remission. 710
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than 2 × 10 /kg improves disease-free survival. Chemotherapy agents Related Donors When matched-sibling transplantation is per-
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such as 4-hydroperoxycyclophosphamide have been used for purging formed for AML in first remission, approximately half of patients have a
residual leukemic cells in marrow before infusion, 689,690 and antisense disease-free survival of 4 years. Small series using T-cell depletion have
agents reportedly diminish leukemic cell contamination. Use of reported 4-year disease-free survival of 65 percent. Leukemia relapses
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marrow grafts purged of residual leukemia cells has not significantly occur in approximately 20 percent of patients who receive an allogeneic
improved the results obtained with unpurged marrow in many stud- transplant. Patients who are alive with good performance status 3 years
ies, suggesting that low proportions of leukemic stem cells may not after transplantation have excellent prospects of long-term survival.
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transplant easily or that they do not survive the freeze–thaw cycle to In the posttransplantation period, approximately one-third of patients
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which autologous marrow is subjected as well as do normal HSCs. die of severe GVHD, opportunistic infection, or interstitial pneumoni-
In addition, residual leukemia in the patient may contribute to relapse. tis. The outlook for long-term survival is improved if (1) the AML is in
For these reasons, marrow purging is rarely used in AML autograft- remission prior to transplantation, (2) grades III to IV acute GVHD
ing (Chap. 23). In long-term cultures from patients newly diagnosed does not occur, and (3) chronic GVHD is low grade. 712,713 For patients
with AML, normal progenitors can be detected, and their numbers with unfavorable cytogenetics, an allogeneic sibling transplantation
are increased by in vitro culture with cytokines. In oligoblastic mye- in first remission is often recommended. Patients with FLT3/ITD-
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logenous leukemia (high-risk myelodysplasia), secondary AML, and positive AML may also benefit from allogeneic HSC transplantation in
therapy-related AML, leukapheresis products obtained after chemo- first remission. 715,716 When AML patients in first remission were com-
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therapy and growth factor treatment contain normal progenitors, pared on a donor versus no donor basis, and more than 80 percent of
indicating mobilized stem cells may be relatively free of leukemic coun- patients with a donor went on to transplantation, patients with a donor
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terparts even in the absence of ex vivo purging. Early mortality may had a significantly better disease-free survival, although treatment-
be decreased using blood stem cells because they engraft more rapidly, related mortality was higher. For patients with intermediate-risk cyto-
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but relapse rates may be higher. Mobilized stem cells can be collected genetics, where the decision is made to delay transplantation until first
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