Favorable outcomes of allogeneic hematopoietic stem cell transplantation with fludarabine-bendamustine conditioning and posttransplantation cyclophosphamide in classical Hodgkin lymphoma.
Adult
Bendamustine Hydrochloride
Cyclophosphamide
/ therapeutic use
Graft vs Host Disease
/ etiology
Hematopoietic Stem Cell Transplantation
/ adverse effects
Hodgkin Disease
/ drug therapy
Humans
Neoplasm Recurrence, Local
/ drug therapy
Retrospective Studies
Transplantation Conditioning
/ methods
Transplantation, Homologous
/ adverse effects
Vidarabine
/ analogs & derivatives
Allogeneic hematopoietic stem cell transplantation
Hodgkin lymphoma
Immune checkpoint inhibitors
Posttransplantation cyclophosphamide
Reduced-intensity conditioning
Survival outcomes
Journal
International journal of hematology
ISSN: 1865-3774
Titre abrégé: Int J Hematol
Pays: Japan
ID NLM: 9111627
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
15
11
2021
accepted:
12
04
2022
revised:
12
04
2022
pubmed:
6
5
2022
medline:
24
8
2022
entrez:
5
5
2022
Statut:
ppublish
Résumé
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for patients with relapsed and refractory classic Hodgkin lymphoma (rrHL). However, the optimal conditioning regimen and GVHD prophylaxis for rrHL remain undetermined. The aim of this study was to investigate outcomes of allo-HSCT with a fludarabine plus bendamustine (FluBe) conditioning regimen and GVHD prophylaxis with posttransplantation cyclophosphamide (PTCY) in patients with rrHL. Allo-HSCT results in 58 adult patients with rrHL were analyzed retrospectively. Three-year overall survival and event-free survival were 81% (95% CI 65-91) and 55% (95% CI 38-72), respectively. The cumulative incidence of relapse (CIR) at 3 years was 33% (95% CI 13-51). The cumulative incidence of aGVHD grade II-IV and severe aGVHD grade III-IV was 36% (95% CI 22-48) and 22% (95% CI 9-33), respectively. The cumulative incidence of cGVHD was 32% (95% CI 17-45), including moderate or severe cGVHD in 17% (95% CI 4-28). Patients who developed aGVHD after allo-HSCT had significantly lower CIR (24% vs 49%, p = 0.004). The use of PBSC as a graft source also significantly reduced CIR (4% vs 61%, p = 0.002). FluBe-PTCY allo-HSCT facilitates favorable outcomes, low toxicity, and mortality in rrHL.
Identifiants
pubmed: 35511399
doi: 10.1007/s12185-022-03355-3
pii: 10.1007/s12185-022-03355-3
doi:
Substances chimiques
Cyclophosphamide
8N3DW7272P
Bendamustine Hydrochloride
981Y8SX18M
Vidarabine
FA2DM6879K
fludarabine
P2K93U8740
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
401-410Informations de copyright
© 2022. Japanese Society of Hematology.
Références
Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, et al. ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med. 2011;365(3):203–12.
pubmed: 21774708
doi: 10.1056/NEJMoa1100340
Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, et al. Adapted treatment guided by Interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med. 2016;374(25):2419–29.
pubmed: 27332902
pmcid: 4961236
doi: 10.1056/NEJMoa1510093
Afanasyev B, Moiseev I, Alekseev S, Mikhailova B, Kondakova E, Ilyin N, et al. Multicenter prospective escalation-deescalation PET-guided clinical study in classical type Hodgkin disease in the North-West of Russian Federation (RNWOHG-HD1): rationale and design. Cell Ther Transplant. 2017;4(21):76–81.
doi: 10.18620/ctt-1866-8836-2017-6-4-76-81
Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet. 2002;359(9323):2065–71.
pubmed: 12086759
doi: 10.1016/S0140-6736(02)08938-9
Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan A, et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet. 1993;341(8852):1051–4.
pubmed: 8096958
doi: 10.1016/0140-6736(93)92411-L
Tourani JM, Levy R, Colonna P, Desablens B, Leprise PY, Guilhot F, et al. High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin’s disease. J Clin Oncol. 1992;10(7):1086–94.
pubmed: 1607915
doi: 10.1200/JCO.1992.10.7.1086
Sureda A. Autologous and allogeneic stem cell transplantation in Hodgkin’s lymphoma. Hematol Oncol Clin North Am. 2007;21(5):943–60.
pubmed: 17908630
doi: 10.1016/j.hoc.2007.07.008
Majhail NS, Weisdorf DJ, Defor TE, Miller JS, McGlave PB, Slungaard A, et al. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2006;12(10):1065–72.
pubmed: 17084370
doi: 10.1016/j.bbmt.2006.06.006
Shah GL, Yahalom J, Matasar MJ, Verwys SL, Goldman DA, Bantilan KS, et al. Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation. Br J Haematol. 2016;175(3):440–7.
pubmed: 27377168
pmcid: 5554509
doi: 10.1111/bjh.14245
Arai S, Fanale M, DeVos S, Engert A, Illidge T, Borchmann P, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54(11):2531–3.
pubmed: 23617324
doi: 10.3109/10428194.2013.798868
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183–9.
pubmed: 22454421
pmcid: 3646316
doi: 10.1200/JCO.2011.38.0410
Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385(9980):1853–62.
pubmed: 25796459
doi: 10.1016/S0140-6736(15)60165-9
Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562–6.
pubmed: 27432875
pmcid: 5034737
doi: 10.1182/blood-2016-02-699850
Perrot A, Monjanel H, Bouabdallah R, Quittet P, Sarkozy C, Lymphoma Study Association (LYSA), et al. Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program. Haematologica. 2016;101(4):466–73.
pubmed: 26768687
pmcid: 5004383
doi: 10.3324/haematol.2015.134213
Bazarbachi A, Boumendil A, Finel H, Mohty M, Castagna L, Peggs KS, et al. Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party. Br J Haematol. 2018;181(1):86–96.
pubmed: 29468647
doi: 10.1111/bjh.15152
Bazarbachi A, Boumendil A, Finel H, Mohty M, Castagna L, Blaise D, et al. Brentuximab vedotin for recurrent Hodgkin lymphoma after allogeneic hematopoietic stem cell transplantation: a report from the EBMT Lymphoma Working Party. Cancer. 2019;125(1):90–8.
pubmed: 30351488
doi: 10.1002/cncr.31755
Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, et al. Nivolumab for relapsed/refractory classic hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 trial. J Clin Oncol. 2018;36(14):1428–39.
pubmed: 29584546
pmcid: 6075855
doi: 10.1200/JCO.2017.76.0793
Lepik K, Kozlov A, Borzenkova E, Popova M, Moiseev I, Darskaya E, et al. Safety and efficacy of nivolumab applied at different dosage in the patients with relapsing Hodgkin lymphoma after allogeneic hematopoietic stem cell transplantation. Cell Ther Transplant. 2018;7(2):28–35.
doi: 10.18620/ctt-1866-8836-2018-7-2-28-35
Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016;17(9):1283–94.
pubmed: 27451390
pmcid: 5541855
doi: 10.1016/S1470-2045(16)30167-X
Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017;35(19):2125–32.
pubmed: 28441111
pmcid: 5791843
doi: 10.1200/JCO.2016.72.1316
Lepik KV, Mikhailova NB, Moiseev IS, Kondakova EV, Tsvetkova LA, Zalyalov YR, et al. Nivolumab for the treatment of relapsed and refractory classical Hodgkin lymphoma after ASCT and in ASCT-naïve patients. Leuk Lymphoma. 2019;60(9):2316–9.
pubmed: 30712423
doi: 10.1080/10428194.2019.1573368
Sureda A, Domenech E, Schmitz N, Dreger P, Lymphoma Working Party of the European Group for Stem Cell Transplantation. The role of allogeneic stem cell transplantation in Hodgkin’s lymphoma. Curr Treat Options Oncol. 2014;15(2):238–47.
pubmed: 24752768
doi: 10.1007/s11864-014-0287-3
Rashidi A, Ebadi M, Cashen AF. Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma: a systematic review and meta-analysis. Bone Marrow Transplant. 2016;51(4):521–8.
pubmed: 26726948
pmcid: 5092068
doi: 10.1038/bmt.2015.332
Robinson SP, Sureda A, Canals C, Russell N, Caballero D, Bacigalupo A, et al. Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin’s lymphoma: identification of prognostic factors predicting outcome. Haematologica. 2009;94(2):230–8.
pubmed: 19066328
doi: 10.3324/haematol.13441
Ahmed S, Ghosh N, Ahn KW, Khanal M, Litovich C, Mussetti A, et al. Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma. Br J Haematol. 2020;190:573–82 (Epub ahead of print).
pubmed: 32314807
pmcid: 7575614
doi: 10.1111/bjh.16664
Gauthier J, Castagna L, Garnier F, Guillaume T, Socié G, Maury S, et al. Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy. Bone Marrow Transplant. 2017;52(5):689–96.
pubmed: 28067872
doi: 10.1038/bmt.2016.349
Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, et al. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR-ALLO study—a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012;97(2):310–7.
pubmed: 21993674
pmcid: 3269494
doi: 10.3324/haematol.2011.045757
Kanate AS, Mussetti A, Kharfan-Dabaja MA, Ahn KW, DiGilio A, Beitinjaneh A, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donor’s vs HLA-matched unrelated donors. Blood. 2016;127(7):938–47.
pubmed: 26670632
pmcid: 4760094
doi: 10.1182/blood-2015-09-671834
Khouri IF, Champlin RE. Nonmyeloablative allogeneic stem cell transplantation for non-hodgkin lymphoma. Cancer J. 2012;18(5):457–62.
pubmed: 23006952
pmcid: 4454283
doi: 10.1097/PPO.0b013e31826b124c
Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, et al. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014;124(14):2306–12.
pubmed: 25145344
pmcid: 4260365
doi: 10.1182/blood-2014-07-587519
Moskowitz AJ, Hamlin PA Jr, Perales MA, Gerecitano J, Horwitz SM, Matasar MJ, et al. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2013;31(4):456–60.
pubmed: 23248254
doi: 10.1200/JCO.2012.45.3308
Merryman RW, Kim HT, Zinzani PL, Carlo-Stella C, Ansell SM, Perales MA, et al. Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood. 2017;129(10):1380–8.
pubmed: 28073785
pmcid: 5345733
doi: 10.1182/blood-2016-09-738385
Schoch LK, Cooke KR, Wagner-Johnston ND, Gojo I, Swinnen LJ, Imus P, et al. Immune checkpoint inhibitors as a bridge to allogeneic transplantation with posttransplant cyclophosphamide. Blood Adv. 2018;2(17):2226–9.
pubmed: 30190282
pmcid: 6134225
doi: 10.1182/bloodadvances.2018019208
Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, et al. Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations. Eur J Haematol. 2018;100(5):395–402.
pubmed: 29360184
doi: 10.1111/ejh.13030
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825–8.
pubmed: 7581076
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–56.
pubmed: 16338616
doi: 10.1016/j.bbmt.2005.09.004
Martínez C, Gayoso J, Canals C, Finel H, Peggs K, Dominietto A, et al. Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for Hodgkin lymphoma: a registry study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation. J Clin Oncol. 2017;35(30):3425–32.
pubmed: 28846465
doi: 10.1200/JCO.2017.72.6869
Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, et al. Graft-versus-host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Biol Blood Marrow Transplant. 2016;22(6):1037–42.
pubmed: 26970381
doi: 10.1016/j.bbmt.2016.03.004
Sanz J, Galimard JE, Labopin M, Afanasyev B, Angelucci E, Ciceri F, et al. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT. J Hematol Oncol. 2020;13(1):46.
pubmed: 32375860
pmcid: 7201995
doi: 10.1186/s13045-020-00882-6
Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transplant. 2015;50(Suppl 2):S37–9.
pubmed: 26039205
doi: 10.1038/bmt.2015.93
Battipaglia G, Boumendil A, Labopin M, Ciceri F, Tischer J, Stelljes M, et al. Unmanipulated haploidentical versus HLA-matched sibling allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute myeloid leukemia: a retrospective study on behalf of the ALWP of the EBMT. Bone Marrow Transplant. 2019;54(9):1499–510.
pubmed: 30718798
doi: 10.1038/s41409-019-0459-7
Brissot E, Labopin M, Ehninger G, Stelljes M, Brecht A, Ganser A, et al. Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukemia: a report on 1578 patients from the Acute Leukemia Working Party of the EBMT. Haematologica. 2019;104(3):524–32.
pubmed: 30361416
pmcid: 6395335
doi: 10.3324/haematol.2017.187450
Shem-Tov N, Peczynski C, Labopin M, Itälä-Remes M, Blaise D, Labussière-Wallet H, et al. Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT. Leukemia. 2020;34(1):283–92.
pubmed: 31427719
doi: 10.1038/s41375-019-0544-3
Haverkos BM, Abbott D, Hamadani M, Armand P, Flowers ME, Merryman R, et al. PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood. 2017;130(2):221–8.
pubmed: 28468799
pmcid: 5510790
doi: 10.1182/blood-2017-01-761346
De Philippis C, Legrand-Izadifar F, Bramanti S, Giordano L, Montes de Oca C, Duléry R, et al. Checkpoint inhibition before haploidentical transplantation with posttransplant cyclophosphamide in Hodgkin lymphoma. Blood Adv. 2020;4(7):1242–9.
pubmed: 32227210
pmcid: 7160255
doi: 10.1182/bloodadvances.2019001336
Herbaux C, Merryman R, Devine S, Armand P, Houot R, Morschhauser F, et al. Recommendations for managing PD-1 blockade in the context of allogeneic HCT in Hodgkin lymphoma: taming a necessary evil. Blood. 2018;132(1):9–16.
pubmed: 29720488
doi: 10.1182/blood-2018-02-811174
Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800–10.
pubmed: 32320566
doi: 10.1056/NEJMoa1917635
Waller EK, Miklos D, Cutler C, Arora M, Jagasia MH, Pusic I, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy: 1-year update of a phase 1b/2 study. Biol Blood Marrow Transplant. 2019;25(10):2002–7.
pubmed: 31260802
doi: 10.1016/j.bbmt.2019.06.023
Sureda A, Robinson S, Canals C, Carella AM, Boogaerts MA, Caballero D, et al. Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin’s lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26(3):455–62.
pubmed: 18086796
doi: 10.1200/JCO.2007.13.2415
Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT, et al. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008;93(2):257–64.
pubmed: 18223284
doi: 10.3324/haematol.11828
Merryman RW, Castagna L, Giordano L, Ho VT, Corradini P, Guidetti A, et al. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma. Leukemia. 2021;35(9):2672–83.
pubmed: 33658659
doi: 10.1038/s41375-021-01193-6