Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies

Perić, Zinaida; Mohty, Razan; Bastos, Juliana; Brissot, Éolia; Battipaglia, Giorgia; Belhocine, Ramdane; Sestili, Simona; Giannotti, Federica; Vekhoff, Anne; Legrand, Ollivier; Lapusan, Simona; Isnard, F; Labopin, Myriam; Bonnin, Agnès; Médiavilla, Clémence; Rubio, Marie‐Thérèse; Ruggeri, Annalisa; Duléry, Rémy; Malard, Florent; Mohty, Mohamad

doi:10.1038/s41409-019-0726-7

Cited by 17 publications

(19 citation statements)

References 51 publications

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“…CloB2 conditioning should thus probably not be prescribed for patients receiving a haplo-identical graft. Regarding the TBF regimen, we confirmed a low incidence of relapse [26]. However, NRM was high in this group, resulting in similar OS and DFS compared to CloB2 or Baltimore-based regimens.…”

Section: Discussionsupporting

confidence: 64%

“…Indeed, NRM has been reported to be only of 13% after haplo-Allo-SCT with PTCY and BM as source of graft [15]. Other studies [26,29] have also observed a high incidence of TRM after haplo-Allo-SCT with TBF conditioning, including one showing, as for us, no influence of the intensity of the conditioning regimen [29]. Thus, other regimens with low TRM may be preferred when considering PBSC haplo-Allo-SCT with PTCY, such as a reinforced Baltimorebased regimen with clofarabine (11% of NRM) [13] or treosulfan-based regimen (17% of NRM) [30].…”

Section: Discussionmentioning

confidence: 98%

“…This study thus confirms previous results and indicates that reducing grade 2 aGVHD can be reached using a lower dose of ATG (2.5 mg/ Kg). Indeed, Salas et al [21] have reported an incidence of 21.2% of grade 2-4 aGVHD at day 100 with PTCY þ ATG 4.5 mg/Kg while for Peric at al [26], with 82% of transplants performed with PBSC, this incidence was 30% using ATG at 10 mg/kg. Since reaching grade 2 aGVHD in the particular setting of PBSC haplotransplant with PTCY seems to be of interest, treatments potentially inducing GVHD in patients with grade 0/1 aGVHD might be proposed.…”

Section: Discussionmentioning

confidence: 99%

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Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide

et al. 2020

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide

et al. 2020

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“…In another retrospective study with thiotepa based conditioning and PBSCs as graft in Haplo setting, pre-transplantation ATG (1 mg/kg from day−6 to day−2) and the PT-Cy were used as GVHD prophylaxis. It showed that the 2-year cumulative incidences of III-IV aGVHD, severe cGVHD, NRM and relapse were 16, 16, 26, and 26%, respectively, which compared favorably with those of other reports using BM as graft (21).…”

Section: Discussionsupporting

confidence: 63%

Post-transplantation Cyclophosphamide, Tacrolimus and Low-Dose ATG as GVHD Prophylaxis for Allogeneic Peripheral Stem Cell Transplantation for Adult Patients With Lymphoid Malignancies: A Single Arm Phase II Study

et al. 2021

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The PT-Cy was considered as one of the mainstay protocol for graft verus host disease (GVHD) prophylaxis. Recent study demonstrated that PT-Cy combined with other immunosuppressants could further reduce the incidence of GVHD and improve the GVHD and relapse free survival (GRFS). In this prospective phase II study, we evaluated the effect of a new GVHD prophylaxis consist of PT-Cy combined with tacrolimus and low dose anti-thymoglobulin (ATG). A total of 23 patients were enrolled including 20 patients with acute lymphoblastic leukemia (ALL) and three patients with T cell lymphoma. The median age was 29 years (range, 16~58 years). Patients with HLA-matched related donor (MSD, n=7) received PT-Cy combined with tacrolimus, while patients with HLA matched unrelated (MUD, n = 2) or haplo-identical (Haplo, n = 14) donor received additional ATG at 2.5 mg/kg on day 15 or day 22 after engraftment of neutrophils. As to the acute GVHD (aGVHD), only three patients developed grade I (n = 1) or grade II (n = 2) aGVHD with 100-day incidence of all aGVHD and II-IV aGVHD at 13.0 ± 5.1% and 9.1 ± 6.1% respectively. Only two patients had mild and one had moderate chronic GVHD (cGVHD), with 1-year incidence of cGVHD and moderate/severe cGVHD at 15.2 ± 8.7% and 4.6 ± 4.4% respectively. A high incidence of CMV reactivation was documented (14/16 with MUD/Haplo donor and 2/7 with MSD) with only 1 CMV disease documented. There were two EBV reactivation without post-transplantation lymphoproliferative disease (PTLD) documented. With a median follow-up of 303 days (range, 75~700 days), three patients relapsed leading to 1-year cumulative incidence of relapse (CIR) at 12.8 ± 9.2%. Only one patient died of CMV pneumonia on day 91 with both 100-day and 1-year non-relapse mortality (NRM) at 4.6 ± 4.4%. The 1-year overall survival (OS), event-free survival (EFS) and GRFS were 95.5 ± 4.4%, 82.6 ± 9.5%, and 68.0 ± 11.3% respectively. Based on Simon's stage II design, our primary data showed that the PT-Cy+tacrolimus ± ATG protocol was promising in preventing aGVHD and cGVHD, which may translate into low NRM without increased CIR. Further clinical trial with large number of patients should be warranted. This trial was registered at www.clinicaltrials.gov as #NCT 04118075.

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“…Meanwhile, due to the increasing experience and improvements in transplant outcomes after Haplo-HCT, use of PBSC in this setting has also increased, with favorable outcomes despite the expected higher risk of GVHD [13]. Therefore, implementation of GVHD prophylaxis with the addition of ATG to PTCy and other adjuvant immunosuppressors has been explored when using PBSC [14] [15] [16]. In the current study we sought to compare transplant outcomes of patients receiving PTCy alone or ATG in addition to PTCy in Haplo-HCT with PBSC (Haplo-PBSC).…”

mentioning

confidence: 99%

Impact of the addition of antithymocyte globulin to post-transplant cyclophosphamide in haploidentical transplantation with peripheral blood compared to post-transplant cyclophosphamide alone in acute myeloid leukemia: a retrospective study on behalf of the Acute Leukemia Working Party of the EBMT

Battipaglia

Labopin

Blaise

et al. 2022

Preprint

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Background. Use of haploidentical cell transplantation (Haplo-HCT) with peripheral blood stem cells (PBSC) is increasing for acute myeloid leukemia (AML). We explored whether the addition of antithymocyte globulin (ATG) to post-transplant cyclophosphamide (PTCy) allows better outcomes than PTCy alone in Haplo-PBSC.Methods. We included 441 adult patients undergoing a first Haplo-PBSC for AML in first or second complete remission; graft-versus-host disease (GVHD) prophylaxis contained either PTCy alone (n = 374) or ATG + PTCy (n = 67), in addition to cyclosporine A (CsA) and mycophenolate mofetil (MMF) as other immunosuppressive agents. Transplant period was 2011–2019.Results. No major imbalances were observed between the two groups. Median age was 56 years and median year of Haplo-HCT was 2017 for both groups. Most patients received a reduced-intensity conditioning regimen (57% and 61% in PTCy and ATG + PTCy, respectively; p = 0.54). Median follow-up was 19 versus 15 months in PTCy and ATG + PTCy, respectively (p = 0.59). Neutrophil engraftment occurred in 97% and 98% of PTCy and ATG + PTCy, respectively. In univariate analysis, no statistical differences in transplant outcomes were observed between PTCy and ATG + PTCy. In multivariate analysis ATG + PTCy resulted in a lower risk of chronic GVHD as compared to PTCy alone (HR = 0.46, 95% CI 0.23–0.93; p = 0.03). No differences were observed for the other transplant outcomes.Conclusion. In Haplo-PBSC, addition of ATG to PTCy (with CsA and MMF) is feasible, better at preventing chronic GVHD, and survival and transplant outcomes are comparable to those with PTCy alone, without increasing transplant toxicity, mortality, or relapse incidence.

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Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies

Cited by 17 publications

References 51 publications

Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide

Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide

Post-transplantation Cyclophosphamide, Tacrolimus and Low-Dose ATG as GVHD Prophylaxis for Allogeneic Peripheral Stem Cell Transplantation for Adult Patients With Lymphoid Malignancies: A Single Arm Phase II Study

Impact of the addition of antithymocyte globulin to post-transplant cyclophosphamide in haploidentical transplantation with peripheral blood compared to post-transplant cyclophosphamide alone in acute myeloid leukemia: a retrospective study on behalf of the Acute Leukemia Working Party of the EBMT

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