Azacitidine Use After Allogeneic Stem Cell Transplantation—Results From the Polish Adult Leukemia Group

Drozd-Sokołowska, Joanna; Gil, Lidia; Waszczuk‐Gajda, Anna; Mądry, Krzysztof; Piekarska, Agnieszka; Dutka, Magdalena; Basak, Grzegorz W.; Karakulska-Prystupiuk, Ewa; Dwilewicz‐Trojaczek, Jadwiga

doi:10.1016/j.transproceed.2016.01.078

Cited by 13 publications

(15 citation statements)

References 17 publications

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“…Table 1 summarizes the publications regarding the use of Aza as salvage treatment for relapse after allo-SCT: until now a total of 601 patients with AML, MDS and other related myeloid malignancies have been published with varying schedules and dosages of Aza. These included 3 prospective, non-randomized trials and the majority of patients reported retrospectively [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Furthermore, Aza was the first treatment of relapse and combined with DLI in some of these patients, while other patients had previously received other salvage therapies or did not receive DLI.…”

Section: Azacitidine For the Treatment Of Relapsementioning

confidence: 99%

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation

et al. 2017

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Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT. Furthermore, they have also been incorporated into prophylactic and pre-emptive approaches to avoid haematological relapse. In this review, we summarize the evidence from retrospective studies but also from a few prospective trials regarding the use of HMA after transplant. To aid clinicians in their daily clinical practice, we also comment on some practical aspects such as dosing and schedule, the choice of HMA and the use of complementary cellular therapies. Finally, this review also gives an overview on potential mechanisms mediating the efficacy of HMA after transplant as well as ongoing preclinical research and clinical activities aiming to further improve this treatment approach.

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Section: Azacitidine For the Treatment Of Relapsementioning

confidence: 99%

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation

et al. 2017

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“…Together with the experience from the early retrospective reports this prospective trial demonstrated that the combination of Aza and DLI was safe and effective in patients with AML or MDS who relapse after allo-SCT. Overall, as indicated in Table 1, a total of 215 patients with AML, MDS and other related myeloid malignancies had been reported in the literature until 2015 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)23,25). Treatment schedules and dosages of Aza varied between these reports.…”

Section: Aza For the Treatment Of Relapsementioning

confidence: 99%

Hypomethylating agents after allogeneic blood stem cell transplantation

Schroeder

Rautenberg

Haas

et al. 2016

Stem Cell Investig.

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Allogeneic blood stem cell transplantation (allo-SCT) is a potentially curative treatment for patients with myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), but relapse remains the major cause of treatment failure. So far, therapeutic options for patients with AML or MDS who relapse after allo-SCT generally consisted of palliative care, low-dose or intensive chemotherapy as well as cellular therapies such as donor lymphocyte infusions (DLI) and second transplantation in selected cases. Nevertheless, the prognosis of patients with myeloid malignancies relapsing after allo-SCT remains dismal therefore asking for novel treatment strategies. Considering their wellbalanced profile of good efficacy and moderate toxicity in the non-transplant setting, the hypomethylating agents (HMA) azacitidine (Aza) and decitabine (DAC) have also been tested either alone or in combination with DLI in the post-transplant period. This review summarizes the current knowledge about the use of these two HMA as pre-emptive, salvage or consolidation therapy mostly retrieved from retrospective studies but also from a few prospective trials. Within this review, we also comment on some practical issues such as optimal dose and schedule, the choice of HMA candidates and the role of additional cellular interventions.Finally, we also give an overview on the assumed mode of actions, ongoing research, clinical studies and potential combination partners aiming to improve this treatment approach.

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“…There is no established salvage therapy for relapsed patients . Recently, Azacitidine (AZA) was reported to be a tolerable and promising treatment in patients with relapsed AML or MDS after allo‐HSCT . However, it has not been clearly determined which patients are good candidates for AZA therapy after post‐transplant relapse.…”

Section: Introductionmentioning

confidence: 99%

Azacitidine as salvage therapy for relapsed acute myeloid leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

Ozawa

Fuji²,

Kawashima

et al. 2019

Adv Cell Gene Ther

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Objective: There are no established salvage therapies for relapsed myeloid malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Azacitidine (AZA) has been reported as a promising treatment in such cases. Methods:We conducted a retrospective analysis of patients at our institution who received AZA for relapse after allo-HSCT between 2014 and 2015.Results: Twenty-two patients received AZA as salvage therapy; 19 had acute myeloid leukemia and 3 had myelodysplastic syndrome. The median number of AZA cycles was 2 (range, 1-12). Seventy-seven percent of patients received AZA at a dose of 75 mg/m 2 for either 5 or 7 days. The median interval between each AZA administration was 32 days (20-63 days). Donor lymphocyte infusion (DLI) was administered in 5 patients. The median follow-up period after AZA therapy was 360 days (range, 63-805). The overall response rate was 15% in patients with non-hematological CR (Non-HCR) or hematological relapse (H-Rel) and 56% in patients with molecular relapse (M-Rel). The 1-year overall survival (OS) rates in patients with Non-HCR/H-Rel and M-Rel were 37.3% and 74.1%, respectively (P = 0.30). Patients who received DLI had favorable OS, and those with early H-Rel had poor OS. Grade 3-4 infection occurred in 12 patients. Discussion: Our study suggests that AZA ± DLI is a tolerable and promising treatment in M-Rel patients. The efficacy of AZA in H-Rel patients is limited. K E Y W O R D S acute myeloid leukemia, allogeneic stem cell transplantation, azacitidine, myelodysplastic syndrome, salvage therapy

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Azacitidine Use After Allogeneic Stem Cell Transplantation—Results From the Polish Adult Leukemia Group

Cited by 13 publications

References 17 publications

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation

Hypomethylating agents after allogeneic blood stem cell transplantation

Azacitidine as salvage therapy for relapsed acute myeloid leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

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