Page 1425 - Williams Hematology ( PDFDrive )

1400 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1401

relapse and second remission, physicians should identify a source of a donors in AML gave similar rates of leukemia-free survival. In a
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HSC graft and ensure that careful monitoring of the patient occurs so multivariate analysis, active disease at transplant and development
that transplantation can be instituted as quickly as possible. 718 of grades II to IV GVHD after transplantation had a negative impact
In an attempt to decrease the relapse rate after stem cell transplan- on survival in reduced-dose-intensity transplantations. Reduced-
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tation for advanced acute leukemia, I-labeled anti-CD45 antibody to intensity transplantations are feasible in elderly patients with both flu-
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deliver radiation to leukemic cells, followed by a standard transplant darabine and low-dose total-body irradiation and with fludarabine
preparative regimen, has been used. With this regimen, more radiation and IV busulfan but donor availability and coexisting medical prob-
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can be delivered to hematopoietic tissues compared with liver, lung, or lems often limit its use. 744
kidney, which may improve the efficacy of the transplant. 719 Use of Transplantation in Relapsed Patients Some form of
Unrelated Donors Approximately 70 percent of all patients with allograft usually is recommended for patients in early first relapse or
AML are older than 50 years of age, and the current mean family size second remission, because long-term survival with chemotherapy alone
in the United States is slightly more than two children per family. Thus, is improbable, whereas histocompatible sibling transplants in these sit-
only approximately 10 to 15 percent of subjects with AML are within uations have a 25 percent survival rate. For patients who lack a sibling
the age-range and have a sibling donor for marrow transplantation. The donor, matched-unrelated donor transplantations can be effective, but
ability to extend the proportion of patients who can be transplanted treatment-related mortality is high, suggesting that patients with unfa-
has led to histocompatible, unrelated donors or HLA type-mismatched vorable cytogenetics should undergo a matched-unrelated donor trans-
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sibling or parent (haploidentical) donor transplants. More than plantation in first complete remission, if an acceptable donor can be
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70 percent of patients of European descent can find a suitable unrelated found. However, when transplantation was compared to chemother-
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-matched donor in the available donor registries, and another study apy for AML in second remission, the 3-year probability of event-free
showed that the majority of patients with AML in first remission for survival was 17 percent with chemotherapy and 16 percent with trans-
whom transplantation is recommended are able to undergo the proce- plantation. Patients younger than 30 years of age who were in remis-
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dure; the main barriers to transplantation are relapse of disease while sion for at least 1 year fared best. Development of chronic GVHD,
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awaiting a donor and poor performance status. Molecular matching an unrelated donor, a young age of donor, and blast cell count less than
of classes I and II HLA alleles adds to the clinical success of unrelated 30 percent at transplantation were found in another series to be favor-
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donor transplantations, but makes finding a donor more difficult. able predictors of survival for transplantations performed in leukemia
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Using such typing, studies have demonstrated that use of matched- relapse. Another study found that those with a remission duration
unrelated donors as compared with matched-related donors result in of less than 6 months, circulating blasts, donor other than an HLA-
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similar survival times in AML. Transplantation benefits younger matched sibling, poor-performance status, and poor-risk cytogenetics
adults in first remission, but no difference in outcome between matched- were adverse pretransplantation variables for those in relapse or pri-
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related donors and matched unrelated donors. HLA-matched or HLA- mary induction failure. Patients with extramedullary sites of leukemia
mismatched cord blood stem cells can be used in adults with acute leu- are more likely to relapse after allogeneic transplantation. 749
kemia but generally not for patients in first remission. 726,727 In adults, the Patients with AML who relapse after allogeneic stem cell trans-
numbers of stem cells available in a single cord product may not result plantation can have a long-term remission, if they undergo retransplan-
in engraftment, which has led to the use of two-cord blood units for tation. A second stem cell transplantation can induce 2-year overall
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grafting (Chap. 23). 728 survival in approximately 25 percent of patients and is effective after
Reduced-Intensity and Nonmyeloablative Transplantation either related or unrelated donor transplantations. A clear advantage
Patients who, based upon comorbidities or performance status, are of changing the donor for the second transplantation has not been
deemed too old or too ill to undergo a full-intensity (myeloablative) demonstrated. 751
allogeneic stem cell transplantation may be offered a reduced- The mechanism of benefit of allogeneic stem cell transplantation
intensity transplantation procedure or a nonmyeloablative condition- was thought to result from high-dose ablative chemoradiotherapy fol-
ing regimen, provided a suitable donor is available. Reduced-intensity lowed by marrow “rescue.” The increased relapse rate of AML in patients
transplant results in some degree of myeloablation but in non-ablative transplanted with marrow from identical twins, compared to noniden-
transplants, autologous stem cell recovery would occur in the case of tical siblings, or transplanted with T-lymphocyte–depleted marrow
graft failure. 729,730 This type of transplantation for AML and closely has indicated that an immunologic effect of donor lymphocytes may
related hematologic malignancies relies upon the graft-versus-leukemia determine the results of transplantation. This immunologic response,
effect as primary therapy. 731–733 These regimens have moderate hema- referred to as graft-versus-leukemia effect, may play a role in preventing
tologic and nonhematologic toxicity, and often can be performed on leukemia relapses. 752
an outpatient basis. Engraftment and establishment of complete donor Donor Leukocyte Infusion In an attempt to enhance graft-
chimerism are successful in most patients. GVHD rates have been versus-leukemia effects, adoptive immunotherapy with donor mononu-
variable, and the ultimate risk of acute and chronic GVHD with these clear cell infusions is sometimes used to treat relapse of leukemia after
regimens is unclear. A variety of low-intensity regimens have been allografting. 753,754 These infusions have been successful in only a minor-
proposed. In AML in first remission, the 1-year progression-free sur- ity of patients with AML, but given the high mortality associated with
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vival is approximately 55 percent. 735,736 The role of this approach in the alternative procedures such as a second transplantation, the infusions
treatment of AML remains to be defined, and comparative trials with are a reasonable approach for patients who relapse after allogeneic trans-
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longer followup are needed. Nonmyeloablative conditioning with unre- plantation. GVHD and marrow aplasia are the major complications of
lated donors has been used successfully. 737,738 Although randomized this form of treatment. The graft-versus-leukemia reaction is thought
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trials of ablative versus reduced dose-intensity conditioning regimens to be directed against minor histocompatibility antigens on the cell sur-
for transplantation of AML patients in first remission have not been face of hematopoietic cells, but reactions against leukemia-specific anti-
done, there is evidence that reduced dose intensity is an inferior option gens are possible. Relapses after donor leukocyte infusions for recurring
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for disease control, but that disadvantage is offset by the decreased acute leukemia have a higher probability of being extramedullary.
treatment-related mortality. One study found that reduced-intensity con- Donor lymphocyte infusions are most effective in early relapses and in
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ditioning compared with myeloablative conditioning using unrelated the absence of extensive of chronic GVHD. Some patients also enter a
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