Second allogeneic haematopoietic cell transplantation using HLA‐matched unrelated <i>versus</i> T‐cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia

Kharfan‐Dabaja, Mohamed A.; Labopin, Myriam; Brissot, Éolia; Finke, Jürgen; Ciceri, Fabio; Deconinck, Eric; Blaise, Didier; Chevallier, Patrice; Gramatzki, Martin; Ganser, Arnold; Stelljes, Matthias; Edinger, Matthias; Savani, Bipin N.; Ruggeri, Annalisa; Sanz, Jaime; Nagler, Arnon; Mohty, Mohamad

doi:10.1111/bjh.17426

Cited by 19 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our decision to change the donor for 2nd allogeneic transplantation was based on theoretical considerations for a different immune system. This is supported by one multicenter retrospective analysis finding a benefit [ 8 ], but not in other publications [ 5 , 9 , 24 , 25 ]. Several immune-escape mechanism have been described in AML relapse, among other loss of HLA in mismatched transplantation, further supporting a change of donor [ 26 ].…”

Section: Discussionmentioning

confidence: 79%

Thiotepa–fludarabine–treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial

Finke

Schmoor

Stelljes

et al. 2022

Bone Marrow Transplant

Self Cite

View full text Add to dashboard Cite

Therapeutic options for patients with AML relapsing after allogeneic HCT range from chemotherapy or hypomethylating agents with or without donor lymphocyte infusions to a 2nd allogeneic HCT. Available data are based on retrospective single center or registry studies. The aim of this multicenter trial was to investigate prospectively intensive conditioning with Thiotepa, Fludarabine and Treosulfan (TFT) for 2nd allogeneic HCT from an alternative unrelated donor in patients with AML relapse > 6 months after a 1st allogeneic HCT. Primary endpoint was disease-free survival (DFS) at one year after 2nd HCT. 50 patients median age 53.5 years, in CR/PR (34%) or active relapse (66%) were included. 33 of 38 patients (86.8%) with available data achieved CR 100 days post transplant. 23 patients were alive and free of relapse at primary endpoint one year after 2nd HCT (DFS rate 0.46, 95%-CI (0.32–0.61). Three-year rates of DFS, relapse, non-relapse mortality, and overall survival were 0.24, 95%-CI (0.13–0.36); 0.36 (0.25–0.52); 0.40 (0.29–0.57); and 0.24 (0.13–0.37). Second HCT with TFT conditioning is feasible and has high anti-leukemic efficacy in chemosensitive or refractory AML relapse after prior allogeneic HCT. Still, relapse rates and NRM after 2nd allogeneic HCT remain a challenge. The trial is registered in the German Clinical Trials Registry (number DRKS00005126).

show abstract

Section: Discussionmentioning

confidence: 79%

Thiotepa–fludarabine–treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial

Finke

Schmoor

Stelljes

et al. 2022

Bone Marrow Transplant

Self Cite

View full text Add to dashboard Cite

show abstract

“…NRM was 26% vs. 27% ( p = 0.53). A longer OS was associated again with relapse later than one year after the first transplant ( p < 0.0001) and with CR-status at the second transplant ( p = 0.02) [ 97 ].…”

Section: Treatment Of Aml Relapsed After Hsctmentioning

confidence: 99%

Prevention and Treatment of Acute Myeloid Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The State of the Art and Future Perspectives

Leotta

Condorelli

Sciortino

et al. 2022

JCM

View full text Add to dashboard Cite

Allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk acute myeloid leukemia (AML) represents the only curative option. Progress has been made in the last two decades in the pre-transplant induction therapies, supportive care, selection of donors and conditioning regimens that allowed to extend the HSCT to a larger number of patients, including those aged over 65 years and/or lacking an HLA-identical donor. Furthermore, improvements in the prophylaxis of the graft-versus-host disease and of infection have dramatically reduced transplant-related mortality. The relapse of AML remains the major reason for transplant failure affecting almost 40–50% of the patients. From 10 to 15 years ago to date, treatment options for AML relapsing after HSCT were limited to conventional cytotoxic chemotherapy and donor leukocyte infusions (DLI). Nowadays, novel agents and targeted therapies have enriched the therapeutic landscape. Moreover, very recently, the therapeutic landscape has been enriched by manipulated cellular products (CAR-T, CAR-CIK, CAR-NK). In light of these new perspectives, careful monitoring of minimal-residual disease (MRD) and prompt application of pre-emptive strategies in the post-transplant setting have become imperative. Herein, we review the current state of the art on monitoring, prevention and treatment of relapse of AML after HSCT with particular attention on novel agents and future directions.

show abstract

“…Similar to DLI, a second allogeneic transplant produces the best outcomes when performed in remission and in patients with a longer duration of remission following their initial transplant. In an EBMT registry study including 455 patients with relapsed AML following allo-HCT who received a second transplant from a matched unrelated or haploidentical donor, the two factors that predicted poorer leukemia-free survival (LFS) following second transplant were transplant with active disease versus CR (HR 1.48, p=0.004) and duration of remission >13.2 months following the first transplant (HR 0.53, p<0.0001) without appreciable differences based on donor type ( 115 ). Unsurprisingly, the clinical factors that predict outcome following a second allo-HCT are similar to those that predict outcome after DLI.…”

Section: Immunotherapymentioning

confidence: 99%

Treatment of AML Relapse After Allo-HCT

2021

View full text Add to dashboard Cite

With advances in allogeneic hematopoietic stem cell transplant (allo-HCT), disease relapse has replaced transplant-related mortality as the primary cause of treatment failure for patients with acute myeloid leukemia (AML). The efficacy of allo-HCT in AML is a consequence of a graft-versus-leukemia (GVL) effect that is mediated by T lymphocytes, and unique mechanisms of immune evasion underlying post-allo-HCT AML relapses have recently been characterized. Relapsed AML following allo-HCT presents a particularly vexing clinical challenge because transplant-related toxicities, such as graft-versus-host (GVHD) and infections, increase the risk of treatment-related morbidity and mortality. In general, the prognosis of relapsed AML following allo-HCT is poor with most patients failing to achieve a subsequent remission and 2-year survival consistently <15%. The two factors that have been found to predict a better prognosis are a longer duration of post-transplant remission prior to relapse and a lower disease burden at the time of relapse. When considered in combination with a patient’s age; co-morbidities; and performance status, these factors can help to inform the appropriate therapy for the treatment of post-transplant relapse. This review discusses the options for the treatment of post-transplant AML relapse with a focus on the options to achieve a subsequent remission and consolidation with cellular immunotherapy, such as a second transplant or donor lymphocyte infusion (DLI). While intensive reinduction therapy and less intensive approaches with hypomethylating agents have long represented the two primary options for the initial treatment of post-transplant relapse, molecularly targeted therapies and immunotherapy are emerging as potential alternative options to achieve remission. Herein, we highlight response and survival outcomes achieved specifically in the post-transplant setting using each of these approaches and discuss how some therapies may overcome the immunologic mechanisms that have been implicated in post-transplant relapse. As long-term survival in post-transplant relapse necessarily involves consolidation with cellular immunotherapy, we present data on the efficacy and toxicity of both DLI and second allo-HCT including when such therapies are integrated with reinduction. Finally, we provide our general approach to the treatment of post-transplant relapse, integrating both novel therapies and our improved understanding of the mechanisms underlying post-transplant relapse.

show abstract

Second allogeneic haematopoietic cell transplantation using HLA‐matched unrelated versus T‐cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia

Cited by 19 publications

References 20 publications

Thiotepa–fludarabine–treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial

Thiotepa–fludarabine–treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial

Prevention and Treatment of Acute Myeloid Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The State of the Art and Future Perspectives

Treatment of AML Relapse After Allo-HCT

Contact Info

Product

Resources

About