Comparison of Myeloablative versus Reduced-Intensity Conditioning Regimens in Allogeneic Stem Cell Transplantation Recipients with Acute Myelogenous Leukemia with Measurable Residual Disease-Negative Disease at the Time of Transplantation: A Retrospective Cohort Study

Yu, James; Du, Yi; Ahmad, Sarfraz; Patel, Rushang D.; Varela, Juan Carlos; Chang, Chung‐Che; Mori, Shahram

doi:10.1016/j.jtct.2021.04.017

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…The relatively low incidence of relapse (16% at 2 years) reported in the present study, despite the considerable number of patients transplanted with active disease (15%) or ≥CR2 (19%), should be highlighted. Although conflicting results have been reported by other authors regarding the impact of conditioning intensity on the risk of relapse [ 55 – 58 ], our GvHD prophylaxis in combination with myeloablative conditioning showed potent antileukemic efficacy and was well tolerated even in older patients with comorbidities. Other alternative or complementary explanations to consider could be the possible synergistic effect of Sir-PTCy on the in vivo expansion of regulatory T cells in order maintain a balance between GvHD and disease recurrence [ 15 , 59 ] or the potential antileukemic effect of sirolimus [ 60 ].…”

Section: Discussionmentioning

confidence: 70%

Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia

Lazzari

Balaguer‐Roselló

Montoro

et al. 2022

Bone Marrow Transplant

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Post-transplant cyclophosphamide (PTCy) has emerged as a promising graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no studies have reported the efficacy of a GvHD prophylaxis based on PTCy with sirolimus (Sir-PTCy) in patients with acute myeloid leukemia (AML). In this retrospective study, we analyze the use of sirolimus in combination with PTCy, with or without mycophenolate mofetil (MMF), on 242 consecutive adult patients with AML undergoing a myeloablative first allo-HSCT from different donor types, in three European centers between January 2017 and December 2020. Seventy-seven (32%) patients received allo-HSCT from HLA-matched sibling donor, 101 (42%) from HLA-matched and mismatched unrelated donor, and 64 (26%) from haploidentical donor. Except for neutrophil and platelet engraftment, which was slower in the haploidentical cohort, no significant differences were observed in major transplant outcomes according to donor type in univariate and multivariate analysis. GvHD prophylaxis with Sir-PTCy, with or without MMF, is safe and effective in patients with AML undergoing myeloablative allo-HSCT, resulting in low rates of transplant-related mortality, relapse/progression, and acute and chronic GvHD in all donor settings.

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Section: Discussionmentioning

confidence: 70%

Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia

Lazzari

Balaguer‐Roselló

Montoro

et al. 2022

Bone Marrow Transplant

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“…The intensity of the conditioning regimens was associated with the incidence of cGVHD ( 28 , 34 , 35 ). Grade 3-4 aGVHD and moderate/severe cGVHD were more common in the MAC group than in RIC group ( 36 ). In our study, all patients were in CR before the second transplant and received the MAC allo-HSCT, which may partially explain the different occurrence of GVHD between our center and the other centers.…”

Section: Discussionmentioning

confidence: 99%

Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant

et al. 2023

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BackgroundChimeric antigen receptor (CAR) T-cell therapy has demonstrated high initial complete remission (CR) rates in B-cell acute lymphoblastic leukemia (B-ALL) patients, including those who relapsed after transplant. However, the duration of remission requires improvements. Whether bridging to a second allogeneic hematopoietic stem cell transplant (allo-HSCT) after CAR-T therapy can improve long-term survival remains controversial. We retrospectively analyzed long-term follow-up data of B-ALL patients who relapsed post-transplant and received CAR-T therapy followed by consolidation second allo-HSCT to investigate whether such a treatment sequence could improve long-term survival.MethodsA single-center, retrospective study was performed between October 2017 and March 2022, involving 95 patients who received a consolidation second transplant after achieving CR from CAR-T therapy.ResultsThe median age of patients was 22.8 years (range: 3.3-52.8) at the second transplant. After the first transplant, 71 patients (74.7%) experienced bone marrow relapse, 16 patients (16.8%) had extramedullary relapse, 5 patients (5.3%) had both bone marrow and extramedullary relapse and 3/95 patients (3.2%) had positive minimal residual disease (MRD) only. Patients received autologous (n=57, 60.0%) or allogeneic (n=28, 29.5%) CAR-T cells, while 10 patients (10.5%) were unknown. All patients achieved CR after CAR-T therapy. Before second HSCT, 86 patients (90.5%) were MRD-negative, and 9 (9.5%) were MRD-positive. All second transplant donors were different from the first transplant donors. The median follow-up time was 623 days (range: 33-1901) after the second HSCT. The 3-year overall survival (OS) and leukemia-free survival (LFS) were 55.3% (95%CI, 44.3-66.1%) and 49.8% (95%CI, 38.7-60.9%), respectively. The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 10.5% (95%CI, 5.6-19.6%) and 43.6% (95%CI, 33.9-56.2%), respectively. In multivariate analysis, the interval from CAR-T to second HSCT ≤90 days was associated with superior LFS(HR, 4.10, 95%CI,1.64-10.24; p=0.003) and OS(HR, 2.67, 95%CI, 1.24-5.74, p=0.012), as well as reduced NRM (HR, 2.45, 95%CI, 1.14-5.24, p=0.021).ConclusionsOur study indicated that CAR-T therapy followed by consolidation second transplant could significantly improve long-term survival in B-ALL patients who relapsed post-transplant. The second transplant should be considered in suitable patients and is recommended to be performed within 90 days after CAR-T treatment.

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“…Nonetheless, in the BMT CTN 0901 Clinical Trial, patients younger than 65 years who received RIC instead of MAC had a higher relapse incidence (HR: 4.06, 95% CI: 2.59-6.35), a lower OS and RFS but a significantly lower 4-year transplant-related mortality (9.9 vs. 25.1%) [107,108]. Few studies have reported pre-transplant MRD, but retrospective data show that those patients in CR1 with negative MRD have similar outcomes irrespective of conditioning intensity [109][110][111]. However, RIC regimens appear less likely to clear a positive pre-transplant MRD than MAC [82].…”

Section: Conditioning Intensitymentioning

confidence: 99%

Optimal Post-Remission Consolidation Therapy in Patients with AML

Jimenez-Chillon,

Dillon,

Russell

2023

Acta Haematol

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Background: Despite recent advances, 40–85% of patients with acute myeloid leukaemia (AML) achieve complete remission after intensive chemotherapy. However, without optimal treatment after remission, the risk of relapse remains high. Summary: A variable number of consolidation cycles consisting of intermediate doses of cytarabine are the most commonly used regimens in low-intermediate-risk AML, while patients at higher risk of relapse should consolidate response by proceeding to HSCT. Different post-consolidation (maintenance therapies) have demonstrated their benefit in prolonging relapse-free survival, and others are still under investigation. Careful consideration should be given to which patients benefit most from each of these interventions, considering that the risk of relapse is dynamic. Key Messages: Patients consolidated with chemotherapy should receive either 2 courses of HDAC or no more than 3–4 cycles of IDAC with dose reduction in patients over 60 years. Patients with mutated FLT3 AML benefit from post-consolidation maintenance with FLT3 inhibitors, and selected patients not fit for adequate consolidation may benefit from CC-468 maintenance. Patients at higher risk of relapse should proceed to allogeneic SCT as soon as possible, opting for a more intensive conditioning in patients younger than 55 years. However, autologous HSCT may still have role in favourable-risk MRD-negative AML. Multiple treatment options targeting MRD are emerging, either as definitive treatment or as a bridge to allogeneic transplantation, and are likely to become increasingly relevant.

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Comparison of Myeloablative versus Reduced-Intensity Conditioning Regimens in Allogeneic Stem Cell Transplantation Recipients with Acute Myelogenous Leukemia with Measurable Residual Disease-Negative Disease at the Time of Transplantation: A Retrospective Cohort Study

Cited by 8 publications

References 32 publications

Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia

Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia

Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant

Optimal Post-Remission Consolidation Therapy in Patients with AML

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