Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation

Pascal, Laurent; Tucunduva, Luciana; Ruggeri, Annalisa; Blaise, Didier; Céballos, Patrice; Chevallier, Patrice; Cornelissen, Jan J.; Maillard, Natacha; Tabrizi, Reza; Petersen, Eefke; Linkesch, Werner; Sengeloev, Henrik; Kenzey, Chantal; Pagliuca, Antonio; Holler, Ernst; Einsele, Hermann; Gluckman, Éliane; Rocha, Vanderson; Yakoub‐Agha, Ibrahim; Eurocord,; Transplantation, Marrow

doi:10.1182/blood-2014-09-599241

Cited by 71 publications

(52 citation statements)

References 30 publications

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“…Predominant T‐cell reconstitution in the early post‐transplant period is mediated by the CB‐derived naïve T cells which are at a small number and easily rejected 10. The use of ATG could impair the early development of donor‐derived T cells due to the persistence of these antibodies in the patient for several weeks after administration especially if given too close to graft infusion 11. Similarly, use of MTX is also associated with delayed engraftment and increased risk of graft failure 14, 15.…”

Section: Discussionmentioning

confidence: 99%

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

Sun

Liu

Luo

et al. 2018

Intl Journal of Cancer

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Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study including 58 patients who underwent CBT with MAC or MMAC from 2000 to 2011. Neutrophil and platelet engraftment rate, overall survival (OS) and disease free survival (DFS) were significantly higher in the MMAC group (adjusted hazard ratio [HR], 2.58, 2.43, 0.36 and 0.37; p < 0.01, p = 0.01, p = 0.02 and p = 0.02, separately). Nonrelapse mortality (NRM) was comparable (p = 0.183). To validate the outcomes noted in the MMAC group, we conducted a prospective single‐arm clinical trial including 188 patients who underwent CBT with MMAC from 2011 to 2015. Engraftment rate, survival and NRM of the MMAC group in the prospective trail (MMAC‐P) were similar to the MMAC group in the retrospective study (MMAC‐R). This study is the first to demonstrate the superiority of MMAC to MAC in CBT for hematological malignancies.

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Section: Discussionmentioning

confidence: 99%

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

Sun

Liu

Luo

et al. 2018

Intl Journal of Cancer

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“…37 ATG prophylaxis is likely to have detrimental effects after single CBT due to increased risks of death and relapse, a result that agrees with a recent study using the European transplant registry database. 38 This study has several limitations. First, poor GRFS may not justify avoidance of a particular graft source, since the absence of significant GvHD may not be a long-term goal for some patients.…”

Section: Discussionmentioning

confidence: 99%

Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups

Inamoto¹,

Kimura

Kanda

et al. 2016

Haematologica

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G raft-versus-host disease-free relapse-free survival, which is defined as the absence of grade III-IV acute graft-versus-host disease, systemically treated chronic graft-versus-host disease, relapse, and death, is a novel, meaningful composite end point for clinical trials. To characterize risk factors and differences in graft-versus-host disease-free relapse-free survival according to a variety of graft sources, we analyzed 23,302 patients with hematologic malignancy that had a first allogeneic transplantation from 2000 through 2013 using the Japanese national transplant registry database. The 1-year graft-versus-host disease-free relapsefree survival rate was 41% in all patients. The rate was higher after bone marrow transplantation than after peripheral blood stem cell transplantation due to the lower risks of III-IV acute and chronic graft-versus-host disease. The rate was highest after HLA-matched sibling bone marrow transplantation. The rate after single cord blood transplantation was comparable to that after HLA-matched unrelated bone marrow transplantation among patients aged 20 years or under, and was comparable or better than other alternative graft sources among patients aged 21 years or over, due to the low risk of chronic graft-versus-host disease. Other factors associated with better graft-versus-host disease-free relapse-free survival include female patients, antithymocyte globulin prophylaxis (for standard-risk disease), recent years of transplantation, sex combinations other than from a female donor to a male patient, the absence of prior autologous transplantation, myeloablative conditioning, negative cytomegalovirus serostatus, and tacrolimus-based prophylaxis. These results provide important information to guide the choice of graft sources and are benchmarks for future graft-versus-host disease prophylaxis studies.

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“…Several studies demonstrated that the use of ATG was associated with increased TRM and decreased survival in CBT, which was mainly due to the higher incidence of infection [48,49]. Therefore, patients who received ATG in conditioning regimen were excluded in this study.…”

Section: Discussionmentioning

confidence: 99%

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

et al. 2016

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Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n 5 319), MSD peripheral blood stem cell transplantation (PBSCT) (n 5 462), or unrelated CBT (n 5 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P 5 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P 5 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.Am. J. Hematol. 91:E284-E292,

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Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation

Abstract: Key Points When possible, ATG should be avoided in adults undergoing UCBT following Cy/Flu/TBI200 regimen.

Cited by 71 publications

References 30 publications

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

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