Clinical interventions with the potential to decrease relapse in patients allografted for high-risk AML in the Clinical Case
| Maneuver . | Clinical context . |
|---|---|
| Minimize posttransplant immunosuppression | There is compelling evidence that the risk of relapse is correlated with the intensity of posttransplant immunosuppression. Regular monitoring of posttransplant CsA levels was performed in this patient with the aim of optimizing CsA levels posttransplant. |
| Early immunosuppression taper | No consensus exists concerning the optimal timing of a taper of CsA/tacrolimus in patients allografted for AML in CR1. Such a decision is influenced by a number of factors that include: • Predicted risk of disease relapse • Donor stem cell source • The degree of patient: donor HLA disparity • GVHD prophylaxis regimen adopted—specifically, the use of pretransplant ATG or alemtuzumab • History of GVHD In patients with high-risk AML transplanted using an ATG/alemtuzumab-based GVHD prophylaxis with no history of GVHD, consideration should be given to commencing a rapid (over less than 2 months) CsA/tacrolimus taper on or before day +60. Randomized trials of an early vs late taper of immunosuppression strategy are required. |
| Posttransplant maintenance | Randomized trials demonstrate improved outcomes in patients allografted for Flt3+ AML who receive sorafenib maintenance.24,25 Many patients find it difficult to tolerate sorafenib maintenance, and the results of a recently completed randomized evaluation of posttransplant maintenance with the Flt3 inhibitor gilteritinib are awaited. The patient entered the AMADEUS trial—a randomized comparison of maintenance therapy with CC486, which is an oral preparation of azacitidine. Key considerations in the design of an effective maintenance strategy are (a) patient selection, (b) tolerability of the maintenance agent, (c) when to start maintenance, and (d) duration of therapy. |
| Prophylactic DLI | The only other strategy with the potential to reduce the risk of relapse considered by the transplant team was the administration of prophylactic DLI. This is typically considered in patients with evidence of mixed T-cell chimerism or posttransplant MRD but is associated with a significant risk of GVHD. There are no compelling randomized data to support this strategy, and the results of the recently recruited Pro-DLI trial are awaited. |
| Maneuver . | Clinical context . |
|---|---|
| Minimize posttransplant immunosuppression | There is compelling evidence that the risk of relapse is correlated with the intensity of posttransplant immunosuppression. Regular monitoring of posttransplant CsA levels was performed in this patient with the aim of optimizing CsA levels posttransplant. |
| Early immunosuppression taper | No consensus exists concerning the optimal timing of a taper of CsA/tacrolimus in patients allografted for AML in CR1. Such a decision is influenced by a number of factors that include: • Predicted risk of disease relapse • Donor stem cell source • The degree of patient: donor HLA disparity • GVHD prophylaxis regimen adopted—specifically, the use of pretransplant ATG or alemtuzumab • History of GVHD In patients with high-risk AML transplanted using an ATG/alemtuzumab-based GVHD prophylaxis with no history of GVHD, consideration should be given to commencing a rapid (over less than 2 months) CsA/tacrolimus taper on or before day +60. Randomized trials of an early vs late taper of immunosuppression strategy are required. |
| Posttransplant maintenance | Randomized trials demonstrate improved outcomes in patients allografted for Flt3+ AML who receive sorafenib maintenance.24,25 Many patients find it difficult to tolerate sorafenib maintenance, and the results of a recently completed randomized evaluation of posttransplant maintenance with the Flt3 inhibitor gilteritinib are awaited. The patient entered the AMADEUS trial—a randomized comparison of maintenance therapy with CC486, which is an oral preparation of azacitidine. Key considerations in the design of an effective maintenance strategy are (a) patient selection, (b) tolerability of the maintenance agent, (c) when to start maintenance, and (d) duration of therapy. |
| Prophylactic DLI | The only other strategy with the potential to reduce the risk of relapse considered by the transplant team was the administration of prophylactic DLI. This is typically considered in patients with evidence of mixed T-cell chimerism or posttransplant MRD but is associated with a significant risk of GVHD. There are no compelling randomized data to support this strategy, and the results of the recently recruited Pro-DLI trial are awaited. |
ATG, anti-thymocyte globulin; DLI, donor lymphocyte infusion; HLA, human leukocyte antigen.