Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin

Duval, Michel; Pédron, Béatrice; Rohrlich, Pierre‐Simon; Legrand, Faézeh; Faye, Albert; Lescoeur, Brigitte; Bensaïd, Philippe; Larchee, R; Sterkers, Ghislaine; Vilmer, E

doi:10.1038/sj.bmt.1703680

Cited by 33 publications

(27 citation statements)

References 18 publications

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“…2,14 The propensity of patients receiving 10 mg/kg ATG to contract severe virus-related infections is associated with significantly lower lymphocyte counts on day 30. Duval et al 22 reported similar results. Although it was not prospectively subject to any hypothesis, the clinical significance of this result deserves further prospective investigation.…”

Section: Discussionsupporting

confidence: 77%

Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial

Wang

et al. 2013

Bone Marrow Transplant

104

131

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To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III-IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1-23.1%) than in the ATG-10 group (4.5%, CI, 0.7-8.3%, P ¼ 0.005, 95% CI for the difference, À 19.4% to À 3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1-33.5%) than in the ATG-6 group (9.6% (4.0-15.2%), P ¼ 0.001). The 1-year disease-free survival rates were 84.3% (77.3-91.3%) and 86.0% (79.2-92.8%) for the ATG-6 group and ATG-10 groups, respectively (P ¼ 0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD. INTRODUCTIONAntithymocyte globulin (ATG) has been used in the conditioning regimen to prevent severe GVHD in haploidentical hematopoietic SCT (HSCT), and our previous study presented encouraging results. 1 However, the limitations associated with the use of ATG as a regimen for in vivo T-cell depletion (TCD) include the occurrence of delayed immune reconstitution and an increased risk of severe infections, depending on the dose of ATG administered. 2 Several previous studies have suggested suitable doses of ATG in matched unrelated transplantations. 3,4 However, to date, the optimal dose of ATG with respect to the prevention of severe GVHD following the haploidentical transplantation is unknown.In our recently reported retrospective study, we reduced the total dose of ATG from the traditional 10 mg/kg in our classic regimen to 6 mg/kg for refractory/relapsed patients undergoing haploidentical HSCT. We observed that the reduction of the total dose of ATG to 6 mg/kg produced similar rates of engraftment, GVHD and survival compared with the 10 mg/kg dose of ATG. 5 Based on these findings, we set out to extend the use of 6 mg/kg ATG to standard-risk patients. Therefore, we initiated the current prospective randomized study to evaluate the effect of the two different doses of ATG in conditioning regimens on graft failure, GVHD, relapse and survival among standard-risk patients receiving haploidentical HSCT. We postulated that the use of 6 mg/kg ATG might reduce adverse events without increasing the risk of GVHD.

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Section: Discussionsupporting

confidence: 77%

Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial

Wang

et al. 2013

Bone Marrow Transplant

104

131

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“…The median time to CD3 þ count of 41000/ml was 7 months in patients who received 7.5 mg/ kg of rATG in Duval's study, 25 compared to 5.3 months in our study. Duval indicated that the time to recovery of T cell immunity was related to the rATG dose.…”

Section: Discussionmentioning

confidence: 75%

“…Immune reconstitution in children undergoing unmanipulated unrelated and mismatched related donor transplants receiving different doses of rATG was studied by Duval et al 25 In their study, a higher dose of rATG (median 15.5 mg/kg) was related to significant delay in immune reconstitution. The median time to CD3 þ count of 41000/ml was 7 months in patients who received 7.5 mg/ kg of rATG in Duval's study, 25 compared to 5.3 months in our study.…”

Section: Discussionmentioning

confidence: 99%

“…11 In an effort to minimize toxicity, we combined targeted intravenous busulfan with a new immunosuppressive antimetabolite (fludarabine) and a more potent anti-thymocyte globulinrATG (Thymoglobulin, SangStat), and studied it prospectively in a pediatric patient population. 12,13 We describe the engraftment rate, chimerism, immune reconstitution, and toxicities of this reduced intensity conditioning regimen when used in children with a variety of nonmalignant disorders, myelodysplastic syndrome (MDS) and CML.…”

Section: Introductionmentioning

confidence: 99%

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Reduced intensity conditioning using intravenous busulfan, fludarabine and rabbit ATG for children with nonmalignant disorders and CML

Horn

Englert

et al. 2005

Bone Marrow Transplant

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“…Many protocols have been used, and some comparisons made in non-randomized studies. [24][25][26][27][28] However, the impact of different protocols on lymphoid depletion and recovery has not been properly evaluated, 29 although some differences in lymphocyte recovery have been noted. 25,26 We prospectively evaluated three different serotherapy schedules with a single prospective protocol on adjusted conditioning of 69 patients with a median age of 54 years, and mainly with high-risk hematological malignancies, in a single institution.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival

Juliusson

Theorin

Karlsson

et al. 2006

Bone Marrow Transplant

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Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled in a single-institution protocol for allogeneic transplantation with adjusted non-myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg Â 3 days), the subsequent 26 had Campath 30 mg Â 3 days subcutaneously, and the final cohort of 14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and risk factors. Campath-patients had no acute toxicity, fewer days with fever and antibiotics, and required fewer transfusions than ATG-treated patients. 3-d-Campath patients showed lower lymphocyte counts from day þ 4, and CD4 þ , CD8 þ , CD19 þ and NK cells recovered slower than in ATG-treated patients. More Campath patients developed mixed chimerism that required DLI. 3-d-Campath induced more serious and opportunistic infections than ATG, which resulted in a greater non-relapse mortality and an impaired overall survival despite a low tumor-related mortality. The change of the Campath dosing schedule to one dose abrogated the deleterious effect of 3-d-Campath on immune recovery, severe infections and survival. Subcutaneous Campath is simple and provides strong immune suppression with no early toxicity, but dose limitation to 30 mg once is recommended.

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Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin

Cited by 33 publications

References 18 publications

Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial

Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial

Reduced intensity conditioning using intravenous busulfan, fludarabine and rabbit ATG for children with nonmalignant disorders and CML

Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival

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