Impact of rabbit ATG-containing myeloablative conditioning regimens on the outcome of patients undergoing unrelated single-unit cord blood transplantation for hematological malignancies

Pascal, Laurent; Mohty, Mohamad; Ruggeri, Annalisa; Tucunduva, Luciana; Milpied, Noël; Chevallier, Patrice; Tabrizi, Reza; Labalette, Myriam; Gluckman, Éliane; Labopin, Myriam; Yakoub-Agha, Ibrahim

doi:10.1038/bmt.2014.216

Cited by 48 publications

(35 citation statements)

References 33 publications

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“…The current study also confirmed a detrimental impact of ATG on NRM as recently reported in a study including data from patents given UCB after MAC conditioning [25] or RIC in the double UCBT setting [26]. Further, despite ATG not only induces in vivo T-cell depletion of the graft but also promotes the generation of regulatory T cells [27, 28], ATG failed to prevent GVHD in the current study.…”

Section: Discussionsupporting

confidence: 89%

RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT

et al. 2016

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Nonrelapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditioning (RIC) regimens have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of the current retrospective study was to compare transplantation outcomes of acute myeloid leukemia (AML) patients given UCBT after either RIC or MAC. Data from 894 adults with AML receiving a single or double UCBT as first allograft from 2004 to 2013 at EBMT centers were included in this study. 415 patients were given UCBT after RIC while 479 patients following a MAC. In comparison to MAC recipients, RIC recipients had a similar incidence of neutrophil engraftment and of acute and chronic graft-versus-host disease (GVHD). However, RIC recipients had a higher incidence of disease relapse and a lower NRM, translating to comparable leukemia-free (LFS), GVHD-free, relapse-free survival (GRFS) and overall survival (OS). These observations remained qualitatively similar after adjusting for differences between groups in multivariate analyses. In conclusion, these data suggest that LFS and OS are similar with RIC or with MAC in adults AML patients transplanted with UCBT. These observations could serve as basis for a future prospective randomized study.

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Section: Discussionsupporting

confidence: 89%

RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT

et al. 2016

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“…Another important difference is the use of ATG, mainly in patients undergoing SUCBT. Retrospective analyses have found ATG to be associated with worse outcomes after myeloablative and reduced intensity conditioning in the setting of UCBT [42–44]; possibly due to a delayed immune recovery with ATG and increased incidence of post-transplantation lymphoproliferative disorder and infections [43, 45–48]. …”

Section: Discussionmentioning

confidence: 99%

Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine

et al. 2018

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BackgroundThiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established.MethodsThis was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics.ResultsSUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002).ConclusionsOur results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0655-8) contains supplementary material, which is available to authorized users.

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“…In the largest retrospective study, survival was lower with ATG (w10 mg/kg between day -5 and 0) than without ATG (61% versus 71%), however, this was not statistically significant [83]. In the second largest retrospective study, survival was significantly lower with ATG (median 5 mg/kg between approximately day -6 and -5) than without ATG (38% versus 57%; P ¼ .02) [86].…”

Section: Impact Of Atg In Conditioning On Gvhd Relapse Infections Amentioning

confidence: 94%

Rabbit Anti–T Cell Globulin in Allogeneic Hematopoietic Cell Transplantation

Storek

Mohty²,

Boelens

2015

Biology of Blood and Marrow Transplantation

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Anti-T cell globulin (ATG) is polyclonal IgG from rabbits immunized with human thymocytes or a human T cell line. Prophylaxis using ATG infused with conditioning for adult marrow or blood stem cell transplantation reduces both acute and chronic graft-versus-host disease (GVHD). However, ATG is not or minimally efficacious in steroid refractory GVHD treatment. Regarding preemptive therapy, ATG is promising; however, further work is needed on establishing adequate biomarkers to be used as triggers for preemptive therapy before it can be used routinely. Relapse is not increased by ATG, except possibly in the setting of reduced-intensity conditioning. Infections are probably increased when using high but not low-dose ATG, except for Epstein-Barr virus-driven post-transplantation lymphoproliferative disorder, which may be increased even with low-dose ATG. Survival is not improved with ATG; however, survival free of immunosuppressive therapy is improved. Pharmacokinetics of ATG are highly variable, resulting in highly variable areas under the time-concentration curves. Optimized dosing of ATG might improve transplantation outcomes. In conclusion, ATG reduces GVHD and, thus, may improve quality of life, without compromising survival.

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Impact of rabbit ATG-containing myeloablative conditioning regimens on the outcome of patients undergoing unrelated single-unit cord blood transplantation for hematological malignancies

Cited by 48 publications

References 33 publications

RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT

RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT

Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine

Rabbit Anti–T Cell Globulin in Allogeneic Hematopoietic Cell Transplantation

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