Top

Published in:

01-11-2018 | Original Article

Efficacy of haploidentical hematopoietic stem cell transplantation compared to HLA-matched transplantation for primary refractory acute myeloid leukemia

Authors: Bin Gu, Xiang Zhang, Guanghua Chen, Xiaojin Wu, Xiao Ma, Suning Chen, Depei Wu

Published in: Annals of Hematology | Issue 11/2018

Abstract

Newly diagnosed acute myeloid leukemia (AML) failed to achieve complete remission after two courses of intensive chemotherapy. This was considered as primary refractory AML (PRR-AML), and still has a dismal prognosis. Allogeneic hematopoietic stem cell transplantation could be the only cure for these patients. However, the role of haploidentical hematopoietic stem cell transplantation (HID-HCT) for PRR-AML is still undetermined. We retrospectively analyzed the outcomes of 45 adult patients with PRR-AML who underwent HID-HCT, and compared it with the result of 53 patients who received HLA-matched related or unrelated donor transplantation (MD-HCT) during the same treatment period. The 3-year overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) rates in the HID-HCT group were 19.0, 16.5, 70.0, and 35.2%, respectively, but showed no significant differences from the results of MD-HCT. Multivariate analysis showed that complex karyotype with del(7) and time > 6 months from diagnosis to transplantation were associated with lower OS and LFS, and chronic GVHD demonstrated better OS and LFS in the entire cohort. Complex karyotype with del(7) was related with higher CIR and chronic GVHD with lower CIR. In conclusion, HID-HCT could be an alternative treatment strategy to improve the long-term survival in PRR-AML adult patients who have no HLA-matched donors.

Brissot E, Labopin M, Stelljes M, Ehninger G, Schwerdtfeger R, Finke J, Kolb HJ, Ganser A, Schäfer-Eckart K, Zander AR, Bunjes D, Mielke S, Bethge WA, Milpied N, Kalhs P, Blau IW, Kröger N, Vitek A, Gramatzki M, Holler E, Schmid C, Esteve J, Mohty M, Nagler A (2017) Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the acute leukemia working party of the EBMT. J Hematol Oncol 10:130CrossRef

Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28(23):3730–3738CrossRef

Nagler A, Savani BN, Labopin M, Polge E, Passweg J, Finke J, Kyrcz-Krzemien S, Volin L, Anagnostopoulos A, Aljurf M, Beelen DW, Vigouroux S, Milpied N, Suarez F, Mohty M (2015) Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. Lancet Haematol 2(9):e384–e392CrossRef

Gyurkocza B, Lazarus HM, Giralt S (2017) Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission: potentially curative therapy. Bone Marrow Transplant 52(8):1083–1090CrossRef

Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a southwest oncology group/eastern cooperative oncology group study. Blood 96(13):4075–4083PubMed

Fröhling S, Schlenk RF, Kayser S, Morhardt M, Benner A, Döhner K, Döhner H, German-Austrian AML Study Group (2015) Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood 108(10):3280–3288CrossRef

Thol F, Schlenk RF, Heuser M, Ganser A (2015) How I treat refractory and early relapsed acute myeloid leukemia. Blood 126(3):319–327CrossRef

Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD, International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia (2003) Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 21(24):4642–4649CrossRef

Ferguson P, Hills RK, Grech A, Betteridge S, Kjeldsen L, Dennis M, Vyas P, Goldstone AH, Milligan D, Clark RE, Russell NH, Craddock C, UK NCRI AML Working Group (2016) An operational definition of primary refractory acute myeloid leukemia allowing early identification of patients who may benefit from allogeneic stem cell transplantation. Haematologica 101(11):1351–1358CrossRef

10.

Ravandi F (2011) Primary refractory acute myeloid leukaemia—in search of better definitions and therapies. Br J Haematol 155(4):413–419CrossRef

11.

Fung HC, Stein A, Ml S, O'donnell MR, Snyder DS, Cohen S, Smith D, Krishnan A, Spielberger R, Bhatia R, Bhatia S, Falk P, Molina A, Nademanee A, Parker P, Rodriguez R, Rosenthal J, Sweetman R, Kogut N, Sahebi F, Popplewell L, Vora N, Somlo G, Margolin K, Chow W, Smith E, Forman SJ (2003) A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome. Biol Blood Marrow Transplant 9(12):766–771CrossRef

12.

Biggs JC, Horowitz MM, Gale RP, Ash RC, Atkinson K, Helbig W, Jacobsen N, Phillips GL, Rimm AA, Ringdén O (1992) Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 80(4):1090–1093PubMed

13.

Michallet M, Thomas X, Vernant JP, Kuentz M, Socié G, Espérou-Bourdeau H, Milpied N, Blaise D, Rio B, Reiffers J, Jouet JP, Cahn JY, Bourhis JH, Lioure B, Leporrier M, Sotto JJ, Souillet G, Sutton L, Bordigoni P, Dreyfus F, Tilly H, Gratecos N, Attal M, Leprise PY, Déméocq F, Michel G, Buzyn A, Delmas-Marsalet B, Bernaudin F, Ifrah N, Sadoun A, Guyotat D, Cavazzana-Cavo M, Caillot D, De Revel T, Vannier JP, Baruchel A, Fegueux N, Tanguy ML, Thiébaut A, Belhabri A, Archimbaud E (2000) Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant 26(11):1157–1163CrossRef

14.

Mehta J, Powles R, Horton C, Milan S, Treleaven J, Tait D, Catovsky D (1994) Bone marrow transplantation for primary refractory acute leukaemia. Bone Marrow Transplant 14(3):415–418PubMed

15.

Craddock C, Labopin M, Pillai S, Finke J, Bunjes D, Greinix H, Ehninger G, Steckel NK, Zander AR, Schwerdtfeger R, Buchholz S, Kolb HJ, Volin L, Fauser A, Polge E, Schmid C, Mohty M, Rocha V (2011) Factors predicting outcome after unrelated donor stem cell transplantation in primary refractory acute myeloid leukaemia. Leukemia 25(5):808–813CrossRef

16.

Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, Chen H, Chen YH, Wang FR, Wang JZ, Sun YQ, Huang XJ (2013) Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer 119(5):978–985CrossRef

17.

Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, Bregante S, Van Lint MT, Varaldo R, Ghiso A, Gobbi M, Carella AM, Signori A, Galaverna F, Bacigalupo A (2014) Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant 20(10):1573–1579CrossRef

18.

Chen H, Liu KY, Xu LP, Chen YH, Han W, Zhang XH, Wang Y, Qin YZ, Liu YR, Huang XJ (2015) Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Biol Blood Marrow Transplant 21(6):1110–1116CrossRef

19.

Shen Y, Chen J, Liu Y, Wu D (2014) Addition of cladribine to idarubicin and cytarabine during induction increases the overall efficacy rate in adult patients with acute myeloid leukemia: a matched-pair retrospective comparison. Chemotherapy 60(5–6):368–374CrossRef

20.

Wang Y, Chen F, Han Y, Fu ZZ, Tang XW, Miao M, Qiu HY, Jin ZM, Sun AN, Wu DP (2009) Partially matched related hematopoietic stem cell transplantation without ex vivo T cell depletion compared with matched unrelated transplantation in adult patients with hematologic malignancies. Biol Blood Marrow Transplant 15(10):1258–1264CrossRef

21.

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED (1995) 1994Consensus conference on acute GVHD grading. Bone Marrow Transplant 15(6):825–828PubMed

22.

Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB, Schubert MM, Atkinson K, Thomas ED (1981) Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 57(2):267–276PubMed

23.

Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Chen YH, Han W, Shi HX, Huang XJ (2011) Superior graft-versus-leukemia effect associated with transplantation of haplo-identical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historical comparison. Biol Blood Marrow Transplant 17(6):821–830CrossRef

24.

Ringdén O, Labopin M, Ciceri F, Velardi A, Bacigalupo A, Arcese W, Ghavamzadeh A, Hamladji RM, Schmid C, Nagler A, Mohty M (2016) Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings? Leukemia 30(2):447–455CrossRef

25.

Ringdén O, Pavletic SZ, Anasetti C, Barrett AJ, Wang T, Wang D, Antin JH, Di Bartolomeo P, Bolwell BJ, Bredeson C, Cairo MS, Gale RP, Gupta V, Hahn T, Hale GA, Halter J, Jagasia M, Litzow MR, Locatelli F, Marks DI, McCarthy PL, Cowan MJ, Petersdorf EW, Russell JA, Schiller GJ, Schouten H, Spellman S, Verdonck LF, Wingard JR, Horowitz MM, Arora M (2009) The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation. Blood 113(13):3110–3118CrossRef

26.

Xiao-Jun H, Lan-Ping X, Kai-Yan L, Dai-Hong L, Yu W, Huan C, Yu-Hong C, Wei H, Jing-Zhi W, Yao C, Xiao-Hui Z, Hong-Xia S, Feng-Rong W, Fei-Fei T (2009) Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies. Clin Cancer Res 15(14):4777–4783CrossRef

27.

Barrett AJ, Battiwalla M (2010) Relapse after allogeneic stem cell transplantation. Expert Rev Hematol 3(4):429–441CrossRef

28.

Kumar AJ, Hexner EO, Frey NV, Luger SM, Loren AW, Reshef R, Boyer J, Smith J, Stadtmauer EA, Levine BL, June CH, Porter DL, Goldstein SC (2013) Pilot study of prophylactic ex vivo costimulated donor leukocyte infusion after reduced-intensity conditioned allogeneic stem cell transplantation. Biol Blood Marrow Transplant 19(7):1094–1101CrossRef

29.

Craddock C, Jilani N, Siddique S, Yap C, Khan J, Nagra S, Ward J, Ferguson P, Hazlewood P, Buka R, Vyas P, Goodyear O, Tholouli E, Crawley C, Russell N, Byrne J, Malladi R, Snowden J, Dennis M (2016) Tolerability and clinical activity of post-transplantation azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA trial. Biol Blood Marrow Transplant 22(2):385–390CrossRef

30.

Pusic I, Choi J, Fiala MA, Gao F, Holt M, Cashen AF, Vij R, Abboud CN, Stockerl-Goldstein KE, Jacoby MA, Uy GL, Westervelt P, DiPersio JF (2015) Maintenance therapy with decitabine after allogeneic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant 21(10):1761–1769CrossRef

31.

Battipaglia G, Ruggeri A, Massoud R, El Cheikh J, Jestin M, Antar A, Ahmed SO, Rasheed W, Shaheen M, Belhocine R, Brissot E, Dulery R, Eder S, Giannotti F, Isnard F, Lapusan S, Rubio MT, Vekhoff A, Aljurf M, Legrand O, Mohty M, Bazarbachi A (2017) Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia. Cancer 123(15):2867–2874CrossRef

32.

Rautenberg C, Nachtkamp K, Dienst A, Schmidt PV, Heyn C, Kondakci M, Germing U, Haas R, Kobbe G, Schroeder T (2017) Sorafenib and azacitidine as salvage therapy for relapse of FLT3-ITD mutated AML after allo-SCT. Eur J Haematol 98(4):348–354CrossRef

33.

Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E, Bunjes D, Harsdorf SV, Scheid C, Holtick U, Greinix H, Keil F, Schneider B, Sandherr M, Bug G, Tischer J, Ledderose G, Hallek M, Hiddemann W, Kolb HJ (2006) Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 108(3):1092–1099CrossRef

34.

Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK, on behalf of the National Cancer Research Institute Adult Leukaemia Working Group (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116(3):354–365CrossRef

35.

Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, Adorno G, Angelini S, Andreani M, De Felice L, Rapanotti MC, Sarmati L, Bavaro P, Papalinetti G, Di Nicola M, Papola F, Montanari M, Nagler A, Arcese W (2013) Haploidentical unmanipulated G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood 121(5):849–857CrossRef

36.

Peccatori J, Forcina A, Clerici D, Crocchiolo R, Vago L, Stanghellini MT, Noviello M, Messina C, Crotta A, Assanelli A, Marktel S, Olek S, Mastaglio S, Giglio F, Crucitti L, Lorusso A, Guggiari E, Lunghi F, Carrabba M, Tassara M, Battaglia M, Ferraro A, Carbone MR, Oliveira G, Roncarolo MG, Rossini S, Bernardi M, Corti C, Marcatti M, Patriarca F, Zecca M, Locatelli F, Bordignon C, Fleischhauer K, Bondanza A, Bonini C, Ciceri F (2015) Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors. Leukemia 29(2):396–405CrossRef

37.

Todisco E, Ciceri F, Boschini C, Giglio F, Bacigalupo A, Patriarca F, Donnini I, Alessandrino EP, Arcese W, Iori AP, Marenco P, Cavattoni I, Chiusolo P, Terruzzi E, Castagna L, Santoro A, Bosi A, Oldani E, Bruno B, Bonifazi F, Rambaldi A (2017) Factors predicting outcome after allogeneic transplant in refractory acute myeloid leukemia: a retrospective analysis of Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Bone Marrow Transplant 52(7):955–961CrossRef

38.

Ravandi F, Cortes J, Faderl S, O'Brien S, Garcia-Manero G, Verstovsek S, Santos FP, Shan J, Brandt M, de Lima M, Pierce S, Kantarjian H (2010) Characteristics and outcome of patients with acute myeloid leukemia refractory to 1 cycle of high dose cytarabine-based induction chemotherapy. Blood 116(26):5818–5823CrossRef

39.

Wong R, Shahjahan M, Wang X, Thall PF, De Lima M, Khouri I, Gajewski J, Alamo J, Couriel D, Andersson BS, Donato M, Hosing C, Komanduri K, Anderlini P, Molldrem J, Ueno NT, Estey E, Ippoliti C, Champlin R, Giralt S (2015) Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant 11(2):108–114CrossRef

40.

Jabbour E, Daver N, Champlin R, Mathisen M, Oran B, Ciurea S, Khouri I, Cornelison AM, Ghanem H, Cardenas-Turanzas M, Popat U, Ravandi F, Giralt S, Garcia-Manero G, Cortes J, Kantarjian H, de Lima M (2014) Allogeneic stem cell transplantation as initial salvage for patients with acute myeloid leukemia refractory to high-dose cytarabine-based induction chemotherapy. Am J Hematol 89(4):395–398CrossRef

41.

Rambaldi A, Bacigalupo A, Fanin R, Ciceri F, Bonifazi F, Falda M, Lambertenghi-Deliliers G, Benedetti F, Bruno B, Corradini P, Alessandrino PE, Iacopino P, Arcese W, Scimè R, Raimondi R, Sica S, Castagna L, Lamparelli T, Oneto R, Lombardini L, Pollichieni S, Algarotti A, Carobbio A, Sacchi N, Bosi A, Gruppo Italiano Trapianto di Midollo Osseo, GITMO (2012) Outcome of patients activating an unrelated donor search: the impact of transplant with reduced intensity conditioning in a large cohort of consecutive high risk patients. Leukemia 26(8):1770–1785CrossRef

42.

Weisdorf DJ, Millard HR, Horowitz MM, Hyare PS, Champlin R, Ho V, Mielcarek M, Rezvani A, Stockerl-Goldstein K, Khoury HJ, De Lima M, Saber W, Sandmaier B, Zhang MJ, Eapen M (2017) Allogeneic transplantation for advanced acute myeloid leukemia: the value of complete remission. Cancer 123(11):2025–2034CrossRef

43.

Pfeiffer T, Schleuning M, Mayer J, Haude KH, Tischer J, Buchholz S, Bunjes D, Bug G, Holler E, Meyer RG, Greinix H, Scheid C, Christopeit M, Schnittger S, Braess J, Schlimok G, Spiekermann K, Ganser A, Kolb HJ, Schmid C (2013) Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse. Haematologica 98(4):518–525CrossRef

Title: Efficacy of haploidentical hematopoietic stem cell transplantation compared to HLA-matched transplantation for primary refractory acute myeloid leukemia
Authors: Bin Gu
Xiang Zhang
Guanghua Chen
Xiaojin Wu
Xiao Ma
Suning Chen
Depei Wu
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 11/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-018-3428-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Efficacy of haploidentical hematopoietic stem cell transplantation compared to HLA-matched transplantation for primary refractory acute myeloid leukemia

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 11/2018

Successful treatment of refractory/relapsed acquired pure red cell aplasia with sirolimus

Features of vascular adverse events in Japanese patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a retrospective study of the CML Cooperative Study Group database

Rabbit antithymocyte globulin dose does not affect response or survival as first-line therapy for acquired aplastic anemia: a multicenter retrospective study

The role of bortezomib in newly diagnosed diffuse large B cell lymphoma: a meta-analysis

Drug-induced liver failure due to rivaroxaban

PD-1 genotype of the donor is associated with acute graft-versus-host disease after HLA-identical sibling donor stem cell transplantation

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page