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Current Hematologic Malignancy Reports
Erschienen in: Current Hematologic Malignancy Reports 2/2014

01.06.2014 | Acute Leukemias (R Stone, Section Editor)

Treatment of Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

verfasst von: Amir T. Fathi, Yi-Bin Chen

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 2/2014

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Abstract

Disease relapse remains a major cause of mortality for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Historically, patients who experience disease relapse after HSCT have a dismal prognosis with very few long-term survivors. There is no standard treatment for patients in this situation given the variability in patient characteristics, disease biology, complications such as graft-vs.-host disease (GVHD) and infections, donor availability, and patient choice. Here, we discuss the current options for treatment of relapsed AML after HSCT including conventional chemotherapy, novel agents, donor leukocyte infusion, second allogeneic HSCT, and emerging therapies.
Literatur
1.
2.
Chen YB, Spitzer TR. Current status of reduced-intensity allogeneic stem cell transplantation using alternative donors. Leukemia. 2008;22:31–41.PubMedCrossRef
3.
Ballen KK, Koreth J, Chen YB, et al. Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or haploidentical transplant. Blood. 2012;119:1972–80.PubMedCrossRef
4.
Brunstein CG, Fuchs EJ, Carter SL, et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011;118:282–8.PubMedCentralPubMedCrossRef
5.
Brunner AM, Kim HT, Coughlin E, et al. Outcomes in patients age 70 or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2013;19:1374–80.PubMedCrossRef
6.
Sorror ML, Sandmaier BM, Storer BE, et al. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. JAMA. 2011;306:1874–83.PubMedCentralPubMedCrossRef
7.
van den Brink MR, Porter DL, Giralt S, et al. Relapse after allogeneic hematopoietic cell therapy. Biol Blood Marrow Transplant. 2010;16:S138–45.PubMedCentralPubMedCrossRef
8.
Reese ND, Schiller GJ. High-dose cytarabine (HD araC) in the treatment of leukemias: a review. Curr Hematol Malignancy Rep. 2013;8:141–8.CrossRef
9.
Chevallier P, Prebet T, Pigneux A, et al. Influence of NPM1 and FLT3-ITD status on outcome in relapsed/refractory AML patients receiving salvage therapy including gemtuzumab ozogamicin. Leukemia. 2010;24:467–9.PubMedCrossRef
10.
Kurosawa S, Yamaguchi T, Miyawaki S, et al. Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse. Haematologica. 2010;95:1857–64.PubMedCentralPubMedCrossRef
11.••
Herzig RH, Wolff SN, Lazarus HM, et al. High-dose cytosine arabinoside therapy for refractory leukemia. Blood. 1983;62:361–9. This study, and several which followed it, established the tolerability and efficacy of high-dose cytarabine (HiDAC) as single agent, and subsequently in combination with other cytotoxic agents, in the treatment of relapsed or refractory AML, including those who relapse following transplant. Three decades later, HiDAC is still a commonly used component of re-induction therapies.PubMed
12.
Momparler RL. A model for the chemotherapy of acute leukemia with 1-beta-D-arabinofuranosylcytosine. Cancer Res. 1974;34:1775–87.PubMed
13.
Rudnick SA, Cadman EC, Capizzi RL, et al. High dose cytosine arabinoside (HDARAC) in refractory acute leukemia. Cancer. 1979;44:1189–93.PubMedCrossRef
14.
Early AP, Preisler HD, Slocum H, et al. A pilot study of high-dose 1-beta-D-arabinofuranosylcytosine for acute leukemia and refractory lymphoma: clinical response and pharmacology. Cancer Res. 1982;42:1587–94.PubMed
15.
Gandhi V, Estey E, Keating MJ, et al. Chlorodeoxyadenosine and arabinosylcytosine in patients with acute myelogenous leukemia: pharmacokinetic, pharmacodynamic, and molecular interactions. Blood. 1996;87:256–64.PubMed
16.
Gandhi V, Estey E, Keating MJ, et al. Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol. 1993;11:116–24.PubMed
17.
Pastore D, Specchia G, Carluccio P, et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003;82:231–5.PubMed
18.
Robak T, Wrzesien-Kus A, Lech-Maranda E, et al. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000;39:121–9.PubMedCrossRef
19.
Wierzbowska A, Robak T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008;80:115–26.PubMedCrossRef
20.
Amadori S, Arcese W, Isacchi G, et al. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991;9:1210–4.PubMed
21.
Hiddemann W, Kreutzmann H, Straif K, et al. High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. Blood. 1987;69:744–9.PubMed
22.
Jeha S, Gandhi V, Chan KW, et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103:784–9.PubMedCrossRef
23.
Kantarjian H, Gandhi V, Cortes J, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102:2379–86.PubMedCrossRef
24.
Xie KC, Plunkett W. Deoxynucleotide pool depletion and sustained inhibition of ribonucleotide reductase and DNA synthesis after treatment of human lymphoblastoid cells with 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine. Cancer Res. 1996;56:3030–7.PubMed
25.
Becker PS, Kantarjian HM, Appelbaum FR, et al. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011;155:182–9.PubMedCrossRef
26.
Tse E, Leung AY, Sim J, et al. Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia. Ann Hematol. 2011;90:1277–81.PubMedCentralPubMedCrossRef
27.
Faderl S, Wetzler M, Rizzieri D, et al. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012;30:2492–9.PubMedCrossRef
28.
Patel C, Stenke L, Varma S, et al. Multidrug resistance in relapsed acute myeloid leukemia: Evidence of biological heterogeneity. Cancer. 2013;119:3076–83.PubMedCrossRef
29.
Kantarjian HM, Keating MJ, Walters RS, et al. The characteristics and outcome of patients with late relapse acute myelogenous leukemia. J Clin Oncol. 1988;6:232–8.PubMed
30.
Coral S, Sigalotti L, Gasparollo A, et al. Prolonged upregulation of the expression of HLA class I antigens and costimulatory molecules on melanoma cells treated with 5-aza-2'-deoxycytidine (5-AZA-CdR). J Immunother. 1999;22:16–24.PubMedCrossRef
31.
Pinto A, Maio M, Attadia V, et al. Modulation of HLA-DR antigens expression in human myeloid leukaemia cells by cytarabine and 5-aza-2'-deoxycytidine. Lancet. 1984;2:867–8.PubMedCrossRef
32.
Oran B, de Lima M. Prevention and treatment of acute myeloid leukemia relapse after allogeneic stem cell transplantation. Curr Opin Hematol. 2011;18:388–94.PubMedCrossRef
33.
Goodyear O, Agathanggelou A, Novitzky-Basso I, et al. Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 2010;116:1908–18.PubMedCrossRef
34.
Jabbour E, Giralt S, Kantarjian H, et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer. 2009;115:1899–905.PubMedCrossRef
35.
Bolanos-Meade J, Smith BD, Gore SD, et al. 5-azacytidine as salvage treatment in relapsed myeloid tumors after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2011;17:754–8.PubMedCentralPubMedCrossRef
36.
Lubbert M, Bertz H, Wasch R, et al. Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting. Bone Marrow Transplant. 2010;45:627–32.PubMedCrossRef
37.
Czibere A, Bruns I, Kroger N, et al. 5-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: a retrospective analysis. Bone Marrow Transplant. 2010;45:872–6.PubMedCrossRef
38.
Graef T, Kuendgen A, Fenk R, et al. Successful treatment of relapsed AML after allogeneic stem cell transplantation with azacitidine. Leuk Res. 2007;31:257–9.PubMedCrossRef
39.
Schroeder T, Czibere A, Platzbecker U, et al. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia. 2013;27:1229–35.PubMedCrossRef
40.
Schroeder T, Frobel J, Cadeddu RP, et al. Salvage therapy with azacitidine increases regulatory T cells in peripheral blood of patients with AML or MDS and early relapse after allogeneic blood stem cell transplantation. Leukemia. 2013;27:1910–3.PubMedCrossRef
41.
Blum W, Klisovic RB, Becker H, et al. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J Clin Oncol. 2010;28:4919–25.PubMedCentralPubMedCrossRef
42.
Ford CD, Asch J, Konopa K, et al. CR with lenalidomide in del(5)(q13q33) AML relapsing after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2010;45:403–4.PubMedCrossRef
43.
Attar EC, Amrein PC, Fraser JW, et al. Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Leuk Res. 2013;37:1016–20.PubMedCentralPubMedCrossRef
44.
Chen Y, Kantarjian H, Estrov Z, et al. A phase II study of lenalidomide alone in relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndromes with chromosome 5 abnormalities. Clin Lymphoma Myeloma Leuk. 2012;12:341–4.PubMedCrossRef
45.
Lancet JE, List AF, Moscinski LC. Treatment of deletion 5q acute myeloid leukemia with lenalidomide. Leukemia. 2007;21:586–8.PubMedCrossRef
46.
47.
Gale RE, Green C, Allen C, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 2008;111:2776–84.PubMedCrossRef
48.
Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752–9.PubMedCrossRef
49.
Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–34.PubMedCrossRef
50.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef
51.
Winkler J, Rech D, Kallert S, et al. Sorafenib induces sustained molecular remission in FLT3-ITD positive AML with relapse after second allogeneic stem cell transplantation without exacerbation of acute GVHD: a case report. Leuk Res. 2010;34:e270–2.PubMedCrossRef
52.
Metzelder S, Wang Y, Wollmer E, et al. Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation. Blood. 2009;113:6567–71.PubMedCrossRef
53.•
Metzelder SK, Schroeder T, Finck A, et al. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia. 2012;26:2353–9. Sorafenib was among the first tyrosine kinase inhibitors to be studied as a FLT3 inhibitor in AML, and was demonstrated in this study to be an effective therapy for patients with FLT3-mutant disease who relapse following allogeneic transplantation. Other potent and specific FLT3 inhibitors are currently under study as therapies in those with relapsed disease.PubMedCrossRef
54.
Sharma M, Ravandi F, Bayraktar UD, et al. Treatment of FLT3-ITD-positive acute myeloid leukemia relapsing after allogeneic stem cell transplantation with sorafenib. Biol Blood Marrow Transplant. 2012;17:1874–7.CrossRef
55.
Cortes JE, Kantarjian H, Foran JM, et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013;31:3681–7.PubMedCrossRef
56.
Levis MJ, Perl AE, Dombret H, et al.: Final Results of a Phase 2 Open-Label, Monotherapy Efficacy and Safety Study of Quizartinib (AC220) in Patients with FLT3-ITD Positive or Negative Relapsed/Refractory Acute Myeloid Leukemia After Second-Line Chemotherapy or Hematopoietic Stem Cell Transplantation. Blood (ASH Annual Meeting Abstracts) 120:Abstract 673, 2012.
57.
Levine JE, Braun T, Penza SL, et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol. 2002;20:405–12.PubMedCrossRef
58.
Loren AW, Porter DL. Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation. Bone Marrow Transplant. 2008;41:483–93.PubMedCrossRef
59.•
Schmid C, Labopin M, Nagler A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. 2007;25:4938–45. This is the largest analysis to date of patients who have received DLI for relapsed disease after allogeneic HSCT. It analyzes clinical factors, which predict for an increased success from such a strategy.PubMedCrossRef
60.
Bar M, Sandmaier BM, Inamoto Y, et al. Donor lymphocyte infusion for relapsed hematological malignancies after allogeneic hematopoietic cell transplantation: prognostic relevance of the initial CD3+ T cell dose. Biol Blood Marrow Transplant. 2013;19:949–57.PubMedCrossRef
61.
Tomblyn M, Lazarus HM. Donor lymphocyte infusions: the long and winding road: how should it be traveled? Bone Marrow Transplant. 2008;42:569–79.PubMedCrossRef
62.
Soiffer RJ. Donor lymphocyte infusions for acute myeloid leukaemia. Best Pract Res Clin Haematol. 2008;21:455–66.PubMedCrossRef
63.
Jensen MC, Riddell SR. Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunol Rev. 2014;257:127–44.PubMedCrossRef
64.
Blau IW, Basara N, Bischoff M, et al. Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant. Bone Marrow Transplant. 2000;25:41–5.PubMedCrossRef
65.
Bosi A, Bacci S, Miniero R, et al. Second allogeneic bone marrow transplantation in acute leukemia: a multicenter study from the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO). Leukemia. 1997;11:420–4.PubMedCrossRef
66.
Chiang KY, Weisdorf DJ, Davies SM, et al. Outcome of second bone marrow transplantation following a uniform conditioning regimen as therapy for malignant relapse. Bone Marrow Transplant. 1996;17:39–42.PubMed
67.
Kishi K, Takahashi S, Gondo H, et al. Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. Bone Marrow Transplant. 1997;19:461–6.PubMedCrossRef
68.
Mehta J, Powles R, Treleaven J, et al. Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy. Bone Marrow Transplant. 1997;19:709–19.PubMedCrossRef
69.
Christopoulos P, Schmoor C, Waterhouse M, et al. Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML. Bone Marrow Transplant. 2013;48:901–7.PubMedCrossRef
70.
Leung AY, Tse E, Hwang YY, et al. Primary treatment of leukemia relapses after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning second transplantation from the original donor. Am J Hematol. 2013;88:485–91.PubMedCrossRef
71.•
Christopeit M, Kuss O, Finke J, et al. Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. J Clin Oncol. 2013;31:3259–71. This is the largest analysis to date analyzing any effect of changing donors when undertaking a 2nd allogeneic HSCT for relapsed disease. Perhaps it is limited by numbers, but the data here suggests there is no significant difference when a different donor is used, yet also shows the feasibility of using an unrelated donor for the 2nd HSCT.PubMedCrossRef
Metadaten
Titel
Treatment of Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation
verfasst von
Amir T. Fathi
Yi-Bin Chen
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Current Hematologic Malignancy Reports / Ausgabe 2/2014
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-014-0209-2

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