Comparison of Conditioning Regimens with or without Antithymocyte Globulin for Unrelated Cord Blood Transplantation in Children with High-Risk or Advanced Hematological Malignancies

Zheng, Changcheng; Zuo, Li; Fang, Jian-Pei; Sun, Xin; Chen, Jing; Li, Chi Kong; Hu, Shaoyan; Zhu, Yiping; Sun, Zimin

doi:10.1016/j.bbmt.2014.12.023

Cited by 27 publications

(21 citation statements)

References 28 publications

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“…In our study, the incidence of aGVHD and cGVHD were lower in the ATG than the non-ATG group; however, this difference was not significant. In line with other studies, the incidences of both CMV and EBV positivity were significantly higher in the ATG than the non-ATG group2627. The transplant-related complication of viral reactivation is thought to be correlated with the delayed immune reconstitution after allo-HSCT.…”

Section: Discussionsupporting

confidence: 84%

Antithymocyte globulin improves the survival of patients with myelodysplastic syndrome undergoing HLA-matched unrelated donor and haplo-identical donor transplants

Wang

Liu

Zhou

et al. 2017

Sci Rep

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Significant advances have been achieved in the outcomes of patients with myelodysplastic syndromes (MDS) after both HLA-matched sibling donor transplants (MSDT) and non-MSDT, the latter including HLA-matched unrelated donor (MUDT) and haplo-identical donor transplants (HIDT). In this retrospective study, we analyzed the data of 85 consecutive patients with MDS who received allogeneic HSCT between Dec 2007 and Apr 2014 in our center. These patients comprised 38 (44.7%) who received MSDT, 29 (34.1%) MUDT, and 18 (21.2%) HIDT. The median overall survival (OS) was 60.2 months, the probabilities of OS being 63%, 57%, and 48%, at the first, second, and fifth year, respectively. Median OS post-transplant (OSPT) was 57.2 months, the probabilities of OSPT being 58%, 55%, and 48% at the first, second, and fifth year, respectively. The survival of patients receiving non-MSDT was superior to that of MSDT, median OSPT being 84.0 months and 23.6 months, respectively (P = 0.042); the findings for OS were similar (P = 0.028). We also found that using ATG in conditioning regimens significantly improved survival after non-MSDT, with better OS and OSPT (P = 0.016 and P = 0.025). These data suggest that using ATG in conditioning regimens may improve the survival of MDS patients after non-MSDT.

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Section: Discussionsupporting

confidence: 84%

Antithymocyte globulin improves the survival of patients with myelodysplastic syndrome undergoing HLA-matched unrelated donor and haplo-identical donor transplants

Wang

Liu

Zhou

et al. 2017

Sci Rep

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“…In this study, we identified that cGvHD or extensive cGvHD was significantly lower in the CBT cohort than in the allo-PBSCT/BMT cohort, even though ATG was omitted in the conditioning regimen. Our previous data also indicated that 20 in patients undergoing unrelated CBT, ATG-containing regimens had no impact on aGvHD or cGvHD compared with patients who did not receive ATG, suggesting that CBT patients cannot obtain additional protection from ATG use. Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML

et al. 2016

Bone Marrow Transplant

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Few studies have presented a comparison of myeloablative cord blood transplantation (CBT) and HLA-identical sibling hematopoietic cell transplantation (HCT) for AML in a disease-specific analysis, and the evaluation of GvHD-free and relapse-free survival (GRFS) in AML patients after unrelated CBT has not been reported. A total of 162 consecutive AML patients receiving intensified myeloablative unrelated CBT (n = 107) or allogeneic PBSC transplantation (allo-PBSCT) or bone marrow transplantation (BMT) from an HLA-identical sibling donor (n = 55) were investigated. Neutrophil or platelet engraftment was slower in the CBT cohort compared with that in the allo-PBSCT/BMT cohort. The incidence of grade II-IV or grade III-IV acute GvHD (aGvHD) and transplant-related mortality (TRM) were not significantly different in the two cohorts. Compared with the allo-PBSCT/BMT cohort, the CBT cohort had a significantly lower rate of chronic GvHD (cGvHD) (13.7% vs 28.3%; P = 0.047) or extensive cGvHD (9.9% vs 24.1%; hazard ratio (HR) = 2.06, P = 0.039). The incidence of relapse at 5 years in the CBT cohort was significantly lower than that in the allo-PBSCT/BMT cohort (15.3% vs 36.1%; HR = 4.62, P = 0.009). The probabilities of overall survival and leukemia-free survival were similar between the two cohorts. The adjusted 5-year probability of GRFS was higher after CBT than that after allo-PBSCT/BMT (55.4% vs 39.2%; HR = 1.63, P = 0.042). The present study suggests that, for AML patients, intensified myeloablative unrelated CBT is associated with less cGvHD and a lower risk of relapse. In addition, these patients do not experience excessive TRM or severe aGvHD that translates into better GRFS compared with those patients who undergo HLA-identical sibling allo-PBSCT/BMT; this observation may reflect the clinical separation between cGvHD and GvL within our CBT protocol. INTRODUCTIONAllogeneic hematopoietic cell transplantation (allo-HCT) is a promising curative approach for treating high-risk or relapsed/ refractory AML. Unrelated cord blood transplantation (CBT) is increasingly being employed as an alternative transplant strategy for AML patients who lack a related or unrelated donor with an identical HLA type. Cord blood (CB) has some potential advantages, including the absence of donor risk, rapid accessibility and less rigorous requirement for HLA compatibility. Recently, reduced-intensity conditioning followed by CBT has been conducted for high-risk AML patients to decrease the early transplant-related mortality (TRM), 1,2 but the incidence of relapse was high (nearly 50%), and the long-term survival was very poor. New strategies should be further investigated to improve the antileukemic effect after CBT. We have reported that myeloablative CBT can result in improved survival and decreased relapse rates in adult or pediatric recipients with hematologic malignancies 3,4 compared with transplants from HLA-matched sibling donors (MSD); however, few studies have presented a comparative analysis of myeloablative CBT and allo-HCT fro...

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“…Several studies have demonstrated the deep impact of ATG on immune reconstitution, alloreactivity, and clinical outcomes [29À34]. Zheng et al [33] retrospectively analyzed post-transplantation outcomes of 207 children with malignant disease who underwent UCBT according to the presence or absence of ATG in the conditioning regimen. They found a higher risk of relapse, a higher viral infection rate, and a lower DFS in those who had received ATG.…”

Section: Discussionmentioning

confidence: 99%

Single-Unit versus Double-Unit Umbilical Cord Blood Transplantation in Children and Young Adults with Residual Leukemic Disease

Balligand

Garrigue

Sîrvent

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C TWe previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single-versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of 10 ¡4 , which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 § 4.4%, and it was not significantly influenced by the MRD level: 70.7 § 5.4% in MRD-negative (<10 ¡4 ) patients (n = 72), 71.1 § 9.4% in MRD-positive patients with 10 ¡4 MRD <10 ¡3 (n = 26) and 58.8 § 11.9% in MRD-positive patients with 10 ¡3 (n = 17). In the MRD-positive group, the mean risk of relapse was significantly lower in the double-UCBT arm compared with the single-UCBT arm (10.5 § 7.2% versus 41.7 § 10.4%; P = .025) leading to a higher mean 3-year survival rate (82.6 § 9.3% versus 53.6 § 10.3%; P = .031). This difference was observed only in patients who had not received antithymocyte globulin during their conditioning regimen. In the MRD-negative group, there was no difference between the single-and the double-UCBT arms. We conclude that even in cases of positive pretransplantation MRD, UCBT in children and young adults with acute leukemia yields a high cure rate, and that a double-unit strategy may enhance the graft-versus-leukemia effect and survival in these patients.

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Comparison of Conditioning Regimens with or without Antithymocyte Globulin for Unrelated Cord Blood Transplantation in Children with High-Risk or Advanced Hematological Malignancies

Cited by 27 publications

References 28 publications

Antithymocyte globulin improves the survival of patients with myelodysplastic syndrome undergoing HLA-matched unrelated donor and haplo-identical donor transplants

Antithymocyte globulin improves the survival of patients with myelodysplastic syndrome undergoing HLA-matched unrelated donor and haplo-identical donor transplants

Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML

Single-Unit versus Double-Unit Umbilical Cord Blood Transplantation in Children and Young Adults with Residual Leukemic Disease

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