nach oben

Erschienen in:

18.11.2017 | Original Article

Treatment of relapsed AML and MDS after allogeneic stem cell transplantation with decitabine and DLI—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group

verfasst von: Thomas Schroeder, Christina Rautenberg, William Krüger, Uwe Platzbecker, Gesine Bug, Juliane Steinmann, Stefan Klein, Olaf Hopfer, Kathrin Nachtkamp, Mustafa Kondakci, Stefanie Geyh, Rainer Haas, Ulrich Germing, Martin Bornhäuser, Guido Kobbe

Erschienen in: Annals of Hematology | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11). DAC was the first salvage therapy in 16 patients (44%), whereas 20 patients (56%) had previously received 1 to 5 lines of salvage therapy including 16 of them had been treated with Aza. In 22 patients (61%), a median of 2 DLI per patient (range, 1 to 5) was administered in addition to DAC. As a result, overall response rate was 25% including 6 complete remissions (CR, 17%) and 3 partial remissions (PR, 8%). Three patients within the first-line group achieved CR, while also 3 patients receiving DAC as second-line treatment reached CR including 2 patients with previous Aza failure. Median duration of CR was 10 months (range, 2 to 33) and no patient relapsed so far. The 2-year OS rate was 11% (± 6%) without any difference between first-line and pretreated patients. Incidence of acute and chronic graft-versus-host disease was 19 and 5%. Taken together, DAC exerts clinical efficacy in patients with AML or MDS relapsing after allo-SCT and is able to induce durable remissions in individual patients suggesting that DAC may be an alternative to Aza or even a second choice after Aza failure.

de Lima M, Porter DL, Battiwalla M, Bishop MR, Giralt SA, Hardy NM, Kröger N, Wayne AS, Schmid C (2014) Proceedings from the National Cancer Institute’s second international workshop on the biology, prevention, and treatment of relapse after hematopoietic stem cell transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transplant 20(1):4–13. https://doi.org/10.1016/j.bbmt.2013.08.012 CrossRefPubMed

Porter DL, Alyea EP, Antin JH, DeLima M, Estey E, Falkenburg JH et al (2010) NCI first international workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on treatment of relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 16(11):1467–1503. https://doi.org/10.1016/j.bbmt.2010.08.001 CrossRefPubMedPubMedCentral

Craddock C, Labopin M, Robin M, Finke J, Chevallier P, Yakoub-Agha I, Bourhis JH, Sengelov H, Blaise D, Luft T, Hallek M, Kroger N, Nagler A, Mohty M (2016) Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica 101(7):879–883. https://doi.org/10.3324/haematol.2015.140996 CrossRefPubMedPubMedCentral

Czibere A, Bruns I, Kroger N, Platzbecker U, Lind J, Zohren F et al (2010) 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 45(5):872–876. https://doi.org/10.1038/bmt.2009.266 CrossRefPubMed

Graef T, Kuendgen A, Fenk R, Zohren F, Haas R, Kobbe G (2007) Successful treatment of relapsed AML after allogeneic stem cell transplantation with azacitidine. Leuk Res 31(2):257–259. https://doi.org/10.1016/j.leukres.2006.03.003 CrossRefPubMed

Jabbour E, Giralt S, Kantarjian H, Garcia-Manero G, Jagasia M, Kebriaei P, de Padua L, Shpall EJ, Champlin R, de Lima M (2009) Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer 115(9):1899–1905. https://doi.org/10.1002/cncr.24198 CrossRefPubMedPubMedCentral

Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A, Klut IM, Knoth H, Röllig C, Schetelig J, Mohr B, Graehlert X, Ehninger G, Bornhäuser M, Thiede C (2012) Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia 26(3):381–389. https://doi.org/10.1038/leu.2011.234 CrossRefPubMed

Schroeder T, Czibere A, Platzbecker U, Bug G, Uharek L, Luft T, Giagounidis A, Zohren F, Bruns I, Wolschke C, Rieger K, Fenk R, Germing U, Haas R, Kröger N, Kobbe G (2013) Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia 27(6):1229–1235. https://doi.org/10.1038/leu.2013.7 CrossRefPubMed

Schroeder T, Rachlis E, Bug G, Stelljes M, Klein S, Steckel NK, Wolf D, Ringhoffer M, Czibere A, Nachtkamp K, Dienst A, Kondakci M, Stadler M, Platzbecker U, Uharek L, Luft T, Fenk R, Germing U, Bornhäuser M, Kröger N, Beelen DW, Haas R, Kobbe G (2015) Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions—a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant. 21(4):653–660. https://doi.org/10.1016/j.bbmt.2014.12.016 CrossRefPubMed

10.

Steinmann J, Bertz H, Wasch R, Marks R, Zeiser R, Bogatyreva L et al (2015) 5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft. Bone Marrow Transplant 50(5):690–695. https://doi.org/10.1038/bmt.2015.10 CrossRefPubMed

11.

Tessoulin B, Delaunay J, Chevallier P, Loirat M, Ayari S, Peterlin P, le Gouill S, Gastinne T, Moreau P, Mohty M, Guillaume T (2014) Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT. Bone Marrow Transplant 49(4):567–571. https://doi.org/10.1038/bmt.2013.233 CrossRefPubMed

12.

Woo J, Deeg HJ, Storer B, Yeung C, Fang M, Mielcarek M, Scott BL (2017) Factors determining responses to azacitidine in patients with myelodysplastic syndromes and acute myeloid leukemia with early post-transplantation relapse: a prospective trial. Biol Blood Marrow Transplant. 23(1):176–179. https://doi.org/10.1016/j.bbmt.2016.10.016 CrossRefPubMed

13.

Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C (2012) Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30(21):2670–2677. https://doi.org/10.1200/JCO.2011.38.9429 CrossRef

14.

Ganguly S, Amin M, Divine C, Aljitawi OS, Abhyankar S, McGuirk JP (2013) Decitabine in patients with relapsed acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). Ann Hematol 92(4):549–550. https://doi.org/10.1007/s00277-012-1607-y CrossRefPubMed

15.

Phillips CL, Davies SM, McMasters R, Absalon M, O'Brien M, Mo J, Broun R, Moscow JA, Smolarek T, Garzon R, Blum W, Schwind S, Marcucci G, Perentesis JP (2013) Low dose decitabine in very high risk relapsed or refractory acute myeloid leukaemia in children and young adults. Br J Haematol 161(3):406–410. https://doi.org/10.1111/bjh.12268 CrossRefPubMed

16.

Wang B, Jin X, Wang Q, Jing Y (2016) Decitabine+ CAG +DLI in relapsed acute myeloid leukemia after allogeneic stem cell transplantation. Journal of BUON: Official Journal of the Balkan Union of Oncology 21(1):280–281

17.

Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447. https://doi.org/10.1182/blood-2016-08-733196 CrossRefPubMedPubMedCentral

18.

Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SMM, Miyazaki Y, Pfeilstocker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120(12):2454–2465. https://doi.org/10.1182/blood-2012-03-420489 CrossRefPubMedPubMedCentral

19.

Bolanos-Meade J, Smith BD, Gore SD, McDevitt MA, Luznik L, Fuchs EJ et al (2011) 5-azacytidine as salvage treatment in relapsed myeloid tumors after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 17(5):754–758. https://doi.org/10.1016/j.bbmt.2010.10.008 CrossRefPubMed

20.

Ghobadi A, Choi J, Fiala MA, Fletcher T, Liu J, Eissenberg LG, Abboud C, Cashen A, Vij R, Schroeder MA, Pusic I, Stockerl-Goldstein K, Jacoby M, Uy G, DiPersio J, Westervelt P (2016) Phase I study of azacitidine following donor lymphocyte infusion for relapsed acute myeloid leukemia post allogeneic stem cell transplantation. Leuk Res 49:1–6. https://doi.org/10.1016/j.leukres.2016.07.010 CrossRefPubMedPubMedCentral

21.

Lubbert M, Bertz H, Wasch R, Marks R, Ruter B, Claus R et al (2010) 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 45(4):627–632. https://doi.org/10.1038/bmt.2009.222 CrossRefPubMed

22.

Bejanyan N, Weisdorf DJ, Logan BR, Wang HL, Devine SM, de Lima M, Bunjes DW, Zhang MJ (2015) Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transplant. 21(3):454–459. https://doi.org/10.1016/j.bbmt.2014.11.007 CrossRefPubMed

23.

Schmid C, Labopin M, Nagler A, Niederwieser D, Castagna L, Tabrizi R, Stadler M, Kuball J, Cornelissen J, Vorlicek J, Socie G, Falda M, Vindelov L, Ljungman P, Jackson G, Kroger N, Rank A, Polge E, Rocha V, Mohty M, on behalf of the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) (2012) Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood 119(6):1599–1606. https://doi.org/10.1182/blood-2011-08-375840 CrossRefPubMed

24.

Christopeit M, Kuss O, Finke J, Bacher U, Beelen DW, Bornhauser M et al (2013) Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 31(26):3259–3271. https://doi.org/10.1200/JCO.2012.44.7961 CrossRef

25.

Duong VH, Bhatnagar B, Zandberg DP, Vannorsdall EJ, Tidwell ML, Chen Q, Baer MR (2015) Lack of objective response of myelodysplastic syndromes and acute myeloid leukemia to decitabine after failure of azacitidine. Leukemia & lymphoma 56(6):1718–1722. https://doi.org/10.3109/10428194.2014.966708 CrossRef

26.

Harel S, Cherait A, Berthon C, Willekens C, Park S, Rigal M, Brechignac S, Thépot S, Quesnel B, Gardin C, Adès L, Fenaux P, Braun T (2015) Outcome of patients with high risk myelodysplastic syndrome (MDS) and advanced chronic myelomonocytic leukemia (CMML) treated with decitabine after azacitidine failure. Leuk Res 39(5):501–504. https://doi.org/10.1016/j.leukres.2015.02.004 CrossRefPubMed

27.

Dohner H, Weisdorf DJ, Bloomfield CD (2015) Acute myeloid leukemia. N Engl J Med 373(12):1136–1152. https://doi.org/10.1056/NEJMra1406184 CrossRefPubMed

28.

Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Döhner K, Schlenk RF, Döhner H, Campbell PJ (2016) Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 374(23):2209–2221. https://doi.org/10.1056/NEJMoa1516192 CrossRefPubMedPubMedCentral

29.

Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS et al (2016) TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med 375(21):2023–2036. https://doi.org/10.1056/NEJMoa1605949 CrossRefPubMedPubMedCentral

30.

Woo J, Howard NP, Storer BE, Fang M, Yeung CC, Scott BL, Deeg HJ (2017) Mutational analysis in serial marrow samples during azacitidine treatment in patients with post-transplant relapse of acute myeloid leukemia or myelodysplastic syndromes. Haematologica 102(6):e216–e218. https://doi.org/10.3324/haematol.2016.162909 CrossRefPubMedPubMedCentral

31.

Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas A et al (2007) 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 25(31):4938–4945. https://doi.org/10.1200/JCO.2007.11.6053 CrossRef

32.

Schroeder T, Frobel J, Cadeddu RP, Czibere A, Dienst A, Platzbecker U et al (2013) 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 27(9):1910–1913. https://doi.org/10.1038/leu.2013.64 CrossRefPubMed

33.

Schroeder T, Rautenberg C, Haas R, Kobbe G (2016) Hypomethylating agents after allogeneic blood stem cell transplantation. Stem cell investigation 3:84. https://doi.org/10.21037/sci.2016.11.04 CrossRefPubMedPubMedCentral

Titel: Treatment of relapsed AML and MDS after allogeneic stem cell transplantation with decitabine and DLI—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group
verfasst von: Thomas Schroeder
Christina Rautenberg
William Krüger
Uwe Platzbecker
Gesine Bug
Juliane Steinmann
Stefan Klein
Olaf Hopfer
Kathrin Nachtkamp
Mustafa Kondakci
Stefanie Geyh
Rainer Haas
Ulrich Germing
Martin Bornhäuser
Guido Kobbe
Publikationsdatum: 18.11.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 2/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-017-3185-5

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Treatment of relapsed AML and MDS after allogeneic stem cell transplantation with decitabine and DLI—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

Simultaneous point-of-care detection of anemia and sickle cell disease in Tanzania: the RAPID study

PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas

PET-positive bone lesion due to Langerhans cell histiocytosis after BEACOPP therapy for Hodgkin lymphoma: how anamnesis, histopathological accuracy, and molecular analysis could resolve a clinical dilemma

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience

Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin