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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research

Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society

Authors: Frédéric Baron, Pierre Zachée, Johan Maertens, Tessa Kerre, Aurélie Ory, Laurence Seidel, Carlos Graux, Philippe Lewalle, Michel Van Gelder, Koen Theunissen, Evelyne Willems, Marie-Paule Emonds, Ann De Becker, Yves Beguin

Published in: Journal of Hematology & Oncology | Issue 1/2015

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Abstract

Background

Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT).

Methods

Here, we report the results of a phase II multicenter randomized study comparing non-myeloablative allo-HCT from HLA-identical siblings (n = 54) or from 10/10 HLA-matched unrelated donors (n = 40) with either fludarabine plus 2 Gy total body irradiation (Flu-TBI arm; n = 49) or 8 Gy TLI + anti-thymocyte globulin (TLI-ATG arm; n = 45) conditioning.

Results

The 180-day cumulative incidences of grade II-IV acute GVHD (primary endpoint) were 12.2% versus 8.9% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Two-year cumulative incidences of moderate/severe chronic GVHD were 40.8% versus 17.8% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Five Flu-TBI patients and 10 TLI-ATG patients received pre-emptive DLI for low donor chimerism levels, while 1 Flu-TBI patient and 5 TLI-ATG patients (including 2 patients given prior pre-emptive DLIs) received a second HCT for poor graft function, graft rejection, or disease progression. Four-year cumulative incidences of relapse/progression were 22% and 50% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Four-year cumulative incidences of nonrelapse mortality were 24% and 13% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Finally, 4-year overall (OS) and progression-free survivals (PFS) were 53% and 54%, respectively, in the Flu-TBI arm, versus 54% (P = 0.9) and 37% (P = 0.12), respectively, in the TLI-ATG arm.

Conclusions

In comparison to patients included in the Flu-TBI arm, patients included in the TLI-ATG arm had lower incidence of chronic GVHD, higher incidence of relapse and similar OS.

Trial registration

The study was registered on ClinicalTrial.gov (NCT00603954) and EUDRACT (2010-024297-19).
Appendix
Available only for authorised users
Literature
1.
Baron F, Sandmaier BM. Current status of hematopoietic stem cell transplantation after nonmyeloablative conditioning. Curr Opin Hematol. 2005;12:435–43.CrossRefPubMed
2.
Sorror ML, Sandmaier BM, Storer BE, Franke GN, Laport GG, Chauncey TR, et al. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. J Am Med Assoc. 2011;306:1874–83.CrossRef
3.
Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol. 2005;23:1993–2003.CrossRefPubMed
4.
Storb R, Gyurkocza B, Storer BE, Sorror ML, Blume K, Niederwieser D, et al. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2013;31:1530–8.CrossRefPubMedCentralPubMed
5.
McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97:3390–400.CrossRefPubMed
6.
Maris MB, Sandmaier BM, Storer BE, Maloney DG, Shizuru JA, Agura E, et al. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing. Biol Blood Marrow Transplant. 2006;12:454–65.CrossRefPubMed
7.
Blaise D, Tabrizi R, Boher JM, Le Corroller-Soriano AG, Bay JO, Fegueux N, et al. Randomized study of 2 reduced-intensity conditioning strategies for human leukocyte antigen-matched, related allogeneic peripheral blood stem cell transplantation: prospective clinical and socioeconomic evaluation. Cancer. 2013;119:602–11.CrossRefPubMed
8.
Kornblit B, Maloney DG, Storer BE, Maris MB, Vindelov L, Hari P, et al. A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after nonmyeloablative unrelated donor transplantation. Haematologica. 2014;99(10):1624–31.CrossRefPubMedCentralPubMed
9.
Baron F, Sandmaier BM, Storer BE, Maris MB, Langston AA, Lange T, et al. Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2007;13:1041–8.CrossRefPubMedCentralPubMed
10.
Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V, et al. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013;19:1340–7.CrossRefPubMedCentralPubMed
11.
Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA, et al. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005;353:1321–31.CrossRefPubMed
12.
Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, et al. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009;114:1099–109.CrossRefPubMedCentralPubMed
13.
Benjamin J, Chhabra S, Kohrt HE, Lavori P, Laport GG, Arai S, et al. Total Lymphoid Irradiation-Antithymocyte Globulin Conditioning and Allogeneic Transplantation for Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms. Biol Blood Marrow Transplant. 2014;20(6):837–43.CrossRefPubMed
14.
Messina G, Giaccone L, Festuccia M, Irrera G, Scortechini I, Sorasio R, et al. Multicenter experience using total lymphoid irradiation and antithymocyte globulin as conditioning for allografting in hematological malignancies. Biol Blood Marrow Transplant. 2012;18:1600–7.CrossRefPubMed
15.
Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, et al. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012;119:6145–54.CrossRefPubMedCentralPubMed
16.
17.
Kahl C, Storer BE, Sandmaier BM, Mielcarek M, Maris MB, Blume KG, et al. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood. 2007;110:2744–8.CrossRefPubMedCentralPubMed
18.
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.CrossRefPubMedCentralPubMed
19.
McSweeney P, Abhyankar S, Petersen F, Devetten M, Arcaroli J, Zeng C, et al. Tacrolimus and mycophenolate mofetil for GVHD prevention after unrelated donor transplants. Blood. 2003;102(Part 1):717a. #2654.
20.
Socie G, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011;117:6375–82.CrossRefPubMed
21.
Baron F, Labopin M, Blaise D, Lopez-Corral L, Vigouroux S, Craddock C, et al. Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2014;49:389–96.CrossRefPubMed
22.
Deeg HJ, Storer BE, Boeckh M, Martin PJ, McCune JS, Myerson D, et al. Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen. Biol Blood Marrow Transplant. 2006;12:573–84.CrossRefPubMed
23.
Hannon M, Humblet-Baron S, Graux C, Maertens J, Kerre T, Theunissen K, et al. Comparison of immune reconstitution after hematopoietic stem cell transplantation with Flu-TBI versus TLI-ATG conditioning. Haematologica. 2012;97:s180.
24.
Chawla S, Dharmani-Khan P, Liu Y, Prokopishyn N, Amlish Munir M, Griffiths C, et al. High serum level of antithymocyte globulin immediately before graft infusion is associated with a low likelihood of chronic, but not acute, graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20:1156–62.CrossRefPubMed
25.
Mohty M, Avinens O, Faucher C, Viens P, Blaise D, Eliaou JF. Predictive factors and impact of full donor T-cell chimerism after reduced intensity conditioning allogeneic stem cell transplantation. Haematologica. 2007;92:1004–6.CrossRefPubMed
26.
Baron F, Petersdorf EW, Gooley T, Sandmaier BM, Malkki M, Chauncey TR, et al. What is the role for donor natural killer cells after nonmyeloablative conditioning? Biol Blood Marrow Transplant. 2009;15:580–8.CrossRefPubMedCentralPubMed
27.
Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C, et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia. 2012;26:2462–8.CrossRefPubMed
28.
Thepot S, Zhou J, Perrot A, Robin M, Xhaard A, de Latour RP, et al. The graft-versus-leukemia effect is mainly restricted to NIH-defined chronic graft-versus-host disease after reduced intensity conditioning before allogeneic stem cell transplantation. Leukemia. 2010;24:1852–8.CrossRefPubMed
29.
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;11:945–56.CrossRefPubMed
30.
Kahl C, Maris M, Storer B, Mielcarek M, Sandmaier B, Maloney D, et al. Relapse risk after nonmyeloablative hematopoietic cell transplantation for malignant diseases. Blood. 2005;106(Part 1):207a. #703.
Metadata
Title
Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society
Authors
Frédéric Baron
Pierre Zachée
Johan Maertens
Tessa Kerre
Aurélie Ory
Laurence Seidel
Carlos Graux
Philippe Lewalle
Michel Van Gelder
Koen Theunissen
Evelyne Willems
Marie-Paule Emonds
Ann De Becker
Yves Beguin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-014-0098-9

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