Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

Brissot, Éolia; Labopin, Myriam; Моисеев, И С; Cornelissen, Jan J.; Meijer, Ellen; Gorkom, Gwendolyn Van; Rovira, Montserrat; Ciceri, Fabio; Griškevičius, Laimonas; Blaise, Didier; Forcade, Édouard; Mistrík, Martin; Mielke, Stephan; Bulabois, Claude Eric; Niittyvuopio, Riitta; Deconinck, Eric; Ruggeri, Annalisa; Sanz, Jaime; Spyridonidis, Alexandros; Savani, Bipin N.; Giebel, Sebastian; Nagler, Arnon; Mohty, Mohamad

doi:10.1186/s13045-020-00923-0

Cited by 57 publications

(53 citation statements)

References 43 publications

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“…Nevertheless, a comparison of ATG to PT-Cy as GVHD prophylaxis might be of interest. So far, only retrospective comparisons have been reported (26) (27) (28). Results, however, need confirmation in prospective randomized controlled trials.…”

Section: Discussionmentioning

confidence: 99%

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial

et al. 2022

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Graft versus host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase III trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse free survival (GRFS) as compared to the combination of CsA and mycophenolic acid (MPA) after non-myeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018, 160 patients diagnosed with a high-risk hematological malignancy and having a matched related or at least 8 out of 8 HLA matched unrelated donor were randomized and allocated in a 1:2 ratio to CsA/MPA or PT-Cy/CsA. A total of 151 patients was transplanted (52 versus 99 patients). The cumulative incidence of grade II-IV acute GVHD at six months was 48% in recipients of CsA/MPA versus 30% following PT-Cy/CsA (Hazard ratio (HR): 0.48, 95% confidence interval (CI): 0.29-0.82, p=0.007). The two-year cumulative incidence of chronic extensive GVHD was 48% versus 16% (HR: 0.36, 95%CI: 0.21-0.64, p<0.001). The one-year estimate of GRFS was 21% (11%-32%) versus 45% (35%-55%), p<0.001. With a median follow-up of 56.4 months, relapse incidence, progression-free and overall survival were not significantly different between the two treatment arms. PT-Cy combined with a short course of CsA after NMA matched alloHSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD. The trial was registered as number NL2128 in the Dutch trial registry (www.trialregister.nl).

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Section: Discussionmentioning

confidence: 99%

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial

et al. 2022

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“…Another option to improve GRFS in HLA‐identical HSCT could be the addition of ATG, as we did not use this in most of our patients. However, in most studies ATG only lowers GVHD and does not impact OS [33, 34] and gives similar results to PTCY [35].…”

Section: Discussionmentioning

confidence: 94%

Real‐world experience: Introduction of T cell replete haploidentical transplantations in a single center

Gorkom

Billen

Elssen

et al. 2021

eJHaem

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Objectives The aim of this study was to describe real‐world data on outcomes of T cell replete haploidentical hematopoietic stem cell transplantation (HSCT) after the introduction of this modality in a single center and to compare them with different donor types. Method Outcomes of 30 consecutive patients with hematological malignancies that received T cell replete haploidentical HSCT with posttransplantation cyclophosphamide (PTCY) from 2016 to 2018 in our center were analyzed and compared to the outcome of human leukocyte antigen (HLA)‐related and unrelated matched donor HSCT (n = 97) and to a historical cohort of T cell depleted haploidentical HSCT (n = 11). Results One year graft‐versus‐host‐free, relapse‐free survival in haploidentical HSCT was comparable with other donor types (haplo 40%, matched related donor [MRD] 33%, matched unrelated donor [MUD] 25%, p = 0.55). Non relapse mortality was high in haploidentical HSCT (50%), mostly due to infectious complications. However, relapse rates were only 3%, and OS and progression‐free survival after 1 year were 47% and thereby also similar to HLA‐matched HSCT in our center (MRD 53%, MUD 48%). Conclusion Our data show that T cell replete haploidentical HSCT has similar outcomes to HLA identical HSCT after introduction in our center. More strict adaptation on infection prevention was a crucial aspect of our learning curve. Overall, this type of transplantation is a feasible option when lacking an HLA‐identical donor. This option has advantages over an unrelated donor as it brings less logistical challenges than MUD transplantations.

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“…Infections following PT-CY are common, albeit, non-lethal 27 . ATG when compared with PT-CY retrospectively yields equivalent outcomes in MUD recipients 28 . Prospective study of ATG vs. PT-CY have failed to identify significant differences in clinical outcomes in single locus HLA mismatched unrelated donor transplants 29 .…”

Section: Discussionmentioning

confidence: 96%

Dynamical Systems Modeling of Early-Term Immune Reconstitution with Different Anti-Thymocyte Globulin (ATG) Administration Schedules in Allogeneic Stem Cell Transplantation

Zelikson

Toor

Simmons

et al. 2021

Preprint

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Alloreactivity forms the basis of allogeneic hematopoietic cell transplantation (HCT), with donor derived T cell response to recipient antigens mediating clinical responses either in part or entirely. These encompass the different manifestations of graft vs. host disease (GVHD), infection risk as well as disease response. Whilst the latter is contingent upon disease biology and thus may be less predictable, the former two are more likely to be directly proportional to the magnitude of donor derived T cell recovery. Herein we explore the quantitative aspects of immune cell recovery following allogeneic HCT and clinical outcomes in two cohorts of HLA matched allograft recipients who received rabbit anti-thymocyte globulin (ATG) on different schedules (days -9 to -7 vs. -3 to -1). Monocyte as well as donor derived T cell (ddCD3) recovery was superior in those given ATG early in their course (days -9/-7). This difference was related to a more rapid rate of ddCD3 recovery, largely driven by CD3+/8+ cells in the first month following transplantation. Early monocyte recovery was associated with later T cell recovery, improved survival, and less chronic GVHD. In contrast rapid and early ddCD3 expansion out of proportion to monocyte recovery was associated with a high likelihood of acute GVHD and poor survival. This analytic methodology demonstrates that modeling 'early-term immune reconstitution' following HCT yields insights that may be useful in management of post-transplant immunosuppression and adaptive cellular therapy to optimize clinical outcomes.

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Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

Cited by 57 publications

References 43 publications

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial

Real‐world experience: Introduction of T cell replete haploidentical transplantations in a single center

Dynamical Systems Modeling of Early-Term Immune Reconstitution with Different Anti-Thymocyte Globulin (ATG) Administration Schedules in Allogeneic Stem Cell Transplantation

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