Page 1109 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 61 Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults 979

survival in patients with AML and MDS after transplantation, and pathophysiology of MDS and AML and suggest routes for targeted
5
this was largely attributable to increased treatment-related mortality. therapy. However, in many circumstances targeted therapy may not
Similarly, a prospective single-institution study of 190 adult patients be feasible, and thus the utility of molecular prognostic indicators is
undergoing MAC HSCT demonstrated that elevated pretransplanta- to identify patients who will benefit from early transplantation.
tion serum ferritin level was associated with increased risk for 100-day
mortality, acute GVHD, and bloodstream infections or death as a
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composite endpoint. It has now been recognized that elevated REFERENCES
ferritin level can predict inferior outcomes even after RIC transplan-
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tation. As a laboratory prognostic factor, ferritin should be consid- For the complete list of references, log on to www.expertconsult.com.
ered a marker of comorbidity, because ferritin is a marker of
inflammation. As such, ferritin levels could influence the decision to
pursue high-intensity or reduced-intensity HSCT. Optimally, if high- SUGGESTED READINGS
intensity HSCT is planned, proceeding before the accumulation of
a critical amount of iron should be pursued, or, alternatively, chela- Alessandrino EP, Della Porta MG, Bacigalupo A, et al: WHO classifica-
tion therapy before HSCT can be considered, although this latter tion and WPSS predict posttransplantation outcome in patients with
approach has not yet been demonstrated to be effective in prospective myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto
clinical trials. di Midollo Osseo (GITMO). Blood 112:895, 2008.
Bornhauser M, Kienast J, Trenschel R, et al: Reduced-intensity conditioning
versus standard conditioning before allogeneic haemopoietic cell trans-
Pretransplantation Therapy plantation in patients with acute myeloid leukaemia in first complete
remission: a prospective, open-label randomised phase 3 trial. Lancet
The role of cytoreductive chemotherapy before HSCT for MDS Oncol 13:1035, 2012.
remains controversial. Many analyses have demonstrated that out- Brunstein CG, Fuchs EJ, Carter SL, et al: Alternative donor transplantation:
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comes are improved with lower disease burden at the time of HSCT, results of parallel phase II trials using HLA-mismatched related bone
but previously only conventional chemotherapy was offered. The marrow or unrelated umbilical cord blood grafts. Blood 118:282, 2011.
analyses that compare chemotherapy to no chemotherapy before Burnett A, Wetzler M, Lowenberg B: Therapeutic advances in acute myeloid
HSCT are inherently biased, because patients who do poorly or leukemia. J Clin Oncol 29:487, 2011.
expire with chemotherapy are not included in HSCT outcome data Cutler CS, Lee SJ, Greenberg P, et al: A decision analysis of allogeneic
and might have had favorable outcomes if not exposed to cytotoxic bone marrow transplantation for the myelodysplastic syndromes: delayed
agents. On the other hand, responsiveness to chemotherapy may transplantation for low-risk myelodysplasia is associated with improved
indicate more favorable disease biology and this has been correlated outcome. Blood 104:579, 2004.
with improved outcomes after HSCT. 108 Dohner H, Estey EH, Amadori S, et al: Diagnosis and management of acute
With the advent of DNA hypomethylating therapy, the use of myeloid leukemia in adults: recommendations from an international
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effect of DNA hypomethylating therapy on HSCT outcomes has 2010.
recently been studied by several groups. 94–96 Compared retrospectively, Eapen M, Rocha V, Sanz G, et al: Effect of graft source on unrelated donor
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offers a survival advantage, but these agents continue to be used retrospective analysis. Lancet Oncol 11:653, 2010.
widely to prevent disease progression and to reduce transfusion needs Farag SS, Maharry K, Zhang MJ, et al: Comparison of reduced-intensity
while donor selection is performed in patients destined to undergo hematopoietic cell transplantation with chemotherapy in patients aged
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tional chemotherapy with hypomethylating therapy prior to trans- Blood Marrow Transplant 2011.
plantation. In the smaller of the two analyses, there was no advantage Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al: Efficacy of azacitidine
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to hypomethylating therapy over conventional chemotherapy, compared with that of conventional care regimens in the treatment of
while in the larger of the two, the use of both chemotherapy and higher-risk myelodysplastic syndromes: a randomised, open-label, phase
hypomethylating therapy prior to transplantation was associated with III study. Lancet Oncol 10:223, 2009.
adverse outcomes, presumably on the basis of identifying subjects Greenberg P, Cox C, LeBeau MM, et al: International scoring system for
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with more aggressive disease biology. Only a prospective random- evaluating prognosis in myelodysplastic syndromes. Blood 89:2079, 1997.
ized trial with survival measured from the time of randomization to Gupta V, Tallman MS, He W, et al: Comparable survival after HLA-well-
pretransplant therapy can rationally answer the question as to the matched unrelated or matched sibling donor transplantation for acute
most appropriate pretransplant therapy. myeloid leukemia in first remission with unfavorable cytogenetics at
There may be some advantage to the use of these agents before diagnosis. Blood 116:1839, 2010.
HSCT, because DNA hypomethylating therapy has been shown to Gupta V, Tallman MS, Weisdorf DJ: Allogeneic hematopoietic cell transplan-
upregulate the expression of cancer-testis antigens, 112,113 killer tation for adults with acute myeloid leukemia: myths, controversies, and
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immunoglobulin-like receptor (KIR) ligands, HLA molecules, unknowns. Blood 117:2307, 2011.
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and other minor antigens on tumor cells, all of which may enhance Koreth J, Schlenk R, Kopecky KJ, et al: Allogeneic stem cell transplantation
graft-versus-MDS effects. Hypomethylating agents have been used for acute myeloid leukemia in first complete remission: systematic review
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after transplantation to reduce the risk for relapse, but more studies and meta-analysis of prospective clinical trials. JAMA 301:2349, 2009.
will need to be undertaken before this type of therapy can be routinely Lee JH, Lim SN, Kim DY, et al: Allogeneic hematopoietic cell transplantation
recommended. for myelodysplastic syndrome: prognostic significance of pre-transplant
IPSS score and comorbidity. Bone Marrow Transplant 45:450, 2010.
Lim Z, Brand R, Martino R, et al: Allogeneic hematopoietic stem-cell trans-
FUTURE DIRECTIONS plantation for patients 50 years or older with myelodysplastic syndromes
or secondary acute myeloid leukemia. J Clin Oncol 28:405, 2010.
Despite the progress that has been made in conventional therapy for Litzow MR, Tarima S, Perez WS, et al: Allogeneic transplantation for
both AML and MDS, allogeneic HSCT has the best track record for therapy-related myelodysplastic syndrome and acute myeloid leukemia.
curing the disease. Although HSCT has limitations, reductions in Blood 115:1850, 2010.
toxicity, improvements in donor availability, and new strategies to Luger SM, Ringden O, Zhang MJ, et al: Similar outcomes using myeloabla-
enhance GVL while limiting GVHD promise to further improve tive vs reduced-intensity allogeneic transplant preparative regimens for
survival. Advances in mutation analysis provide insights into the AML or MDS. Bone Marrow Transplant 47:203, 2012.