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Clinical Trial
. 2015 Feb 6:8:4.
doi: 10.1186/s13045-014-0098-9.

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

Frédéric Baron  1 , Pierre Zachée  2 , Johan Maertens  3 , Tessa Kerre  4 , Aurélie Ory  5 , Laurence Seidel  6 , Carlos Graux  7 , Philippe Lewalle  8 , Michel Van Gelder  9 , Koen Theunissen  10 , Evelyne Willems  11 , Marie-Paule Emonds  12 , Ann De Becker  13 , Yves Beguin  14
Affiliations
Clinical Trial

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

Frédéric Baron et al. J Hematol Oncol. .

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) .

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Figures

Figure 1
Figure 1
Hematologic recovery in the 2 groups the first year after transplantation. A) Neutrophil count (ANC), B) lymphocyte count (ALC), C) hemoglobin (Hb) levels and D) platelet levels.
Figure 2
Figure 2
Chimerism levels in Flu-TBI (black boxes) and TLI-ATG (white boxes) patients. A) T cell chimerism levels, and B) Bone marrow (BM) chimerism levels.
Figure 3
Figure 3
Transplantation outcomes. A) 180-day cumulative incidence of grade II-IV acute GVHD. B) 5-year cumulative incidence of moderate/severe chronic GVHD. C) 100-day cumulative incidence of CMV reactivation. D) 5-year cumulative incidence of progression. E) 5-year progression-free survival. F) 5-year overall survival. Broken line: fludarabine (90 mg/m2) plus 2 Gy total body irradiation; continuous line = 8 Gy total lymphoid irradiation plus ATG thymoglobulinR (7.5 mg/kg).
See this image and copyright information in PMC

References

    1. Baron F, Sandmaier BM. Current status of hematopoietic stem cell transplantation after nonmyeloablative conditioning. Curr Opin Hematol. 2005;12:435–43. doi: 10.1097/01.moh.0000177830.63033.9d. - DOI - PubMed
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    1. 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. doi: 10.1200/JCO.2005.08.136. - DOI - PubMed
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    1. 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. doi: 10.1182/blood.V97.11.3390. - DOI - PubMed

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