Non-intensive treatment with low-dose 5-aza-2′-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients

The role of hypomethylating agent therapy (HMT) as a bridge to allogeneic hematopoietic cell transplantation (alloHCT) in patients with myelodysplastic syndrome (MDS) remains undetermined. We investigated the feasibility of HMT followed by alloHCT in patients with MDS. In all, 19 patients who received HMT followed by alloHCT were analyzed. A total of 7 patients were classified as low-risk and 12 as high-risk, based on World Health Organization (WHO) classification at the time of HMT. HMT consisted of decitabine in 9 patients and azacitidine in 10. After HMT, two patients achieved CR, six mCR, three hematologic improvement alone, and six SD in terms of best response. HMT did not alter WHO classification in 15 patients (79%), whereas 1 patient (5%) improved and 3 (16%) progressed to AML. Most patients (95%) received a non-myeloablative conditioning regimen based on fludarabine/BU/anti-thymocyte globulin, and peripheral blood-mobilized stem cells. Neutrophil and platelet engraftments were achieved in 95 and 79% of patients, respectively. The incidences of acute and chronic GVHD were 42 and 26%, respectively. In all, 2-year OS rates were 68%, and the overall outcomes of those who achieved CR/mCR with HMT tended to be superior to those without CR/mCR. HMT followed by alloHCT was a feasible and effective treatment strategy for patients with MDS.

Section: Discussionmentioning

confidence: 99%

Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome

Kim

Lee

Park

et al. 2011

“…A CR was defined as o5% blasts in a BM of adequate cellularity and no Auer rods, absence of leukemic blasts in the peripheral blood, an ANC of ⩾ 1000/μL, platelets of ⩾ 100 000/μL and transfusion independence. 9 Patients not fulfilling CR criteria were scored as having achieved temporary disease control when the mixed chimerism in the peripheral blood remained stable, without evidence of increasing leukocytosis, for at least 4 weeks (chimerism was routinely monitored every 1-2 weeks in the peripheral blood). Patients were scored as treatment failure when no temporary disease control was achieved.…”

Section: Response Criteria and Evaluationmentioning

confidence: 99%

5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft

Steinmann

Bertz

Wäsch

et al. 2015

Self Cite

DNA-hypomethylating agents are a viable treatment option for AML/myelodysplastic syndrome (MDS) relapse after allograft by upregulating Ags on blasts before DLI. Seventy-two patients with relapsed AML (n = 62), MDS (n = 8) and other myeloid neoplasms (n = 2) after allograft were treated with low-dose 5-azacytidine and, if feasible, DLI. Patient characteristics: median age 62 years (range 20-75), 42% with adverse cytogenetics, 82% not in remission at transplant and 83% received fludarabine-based reducedtoxicity conditioning. Median duration from transplant to 5-azacytidine was 289 days (range 59-2133). Response criteria: CR, temporary disease control or treatment failure. A median of 2.7 courses (range 1-10) were administered; 65 out of 72 patients also received DLI (41 already before 5-azacytidine). Ten patients developed acute GVHD and two succumbed to treatment-related sepsis. CR rate was 9.7% (in two patients lasting 45 years), 44% had temporary disease control (median duration 71 days, range 31-380). Median survival from 5-azacytidine was 108 days, 21 patients proceeded to subsequent transplant. In multivariate analysis, peripheral blood blasts o 1% were predictive of longer OS (P = 0.03). Taken together, long-term remissions can be induced by this well-tolerated outpatient treatment, particularly in patients without peripheral blood blasts.

“…A CR was defined as o5% blasts in a BM of adequate cellularity and no Auer rods, absence of leukemic blasts in the peripheral blood, an ANC of X1000/ml, plts of X100 000/ml and transfusion independence. 19 Patients not fulfilling CR criteria were scored as having achieved temporary disease control when the mixed chimerism in the peripheral blood remained stable, without evidence of increasing leukocytosis, for at least 4 weeks (chimerism was routinely monitored every 1-2 weeks in the peripheral blood). When no temporary disease control was achieved, the patient was scored as a treatment failure.…”

Section: Response Criteria and Evaluationmentioning

confidence: 99%

Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting

Lübbert

Bertz

Wäsch

et al. 2009

Self Cite

We have piloted a low-dose schedule of 5-azacytidine followed by donor lymphocyte infusions (DLIs) in patients with relapse of AML or chronic myelomonocytic leukemia (CMMoL) after allografting. Of the 26 patients (median age 62 years, range 28-75) with relapsed AML (n ¼ 24) or CMMoL (n ¼ 2), 11 (42%) had poor-risk cytogenetics. Twenty-three patients had received fludarabinebased reduced-toxicity conditioning regimens, and three had received conventional myeloablative conditioning. Patients received 5-azacytidine s.c., at a total daily dose of 100 mg, on days 1-3, to be followed by DLI on day 10, with the next course of treatment to be started on day 22. A total of 60 courses of 5-azacytidine were administered, with a median of 2 courses (range: 1-10). In 44 courses, 5-azacytidine was followed by DLI, and thus 19/26 (73%) patients received at least one course of this combined treatment. Clinically relevant neutropenic infections not associated with progressive disease developed in four patients, one of them succumbing to sepsis. Only two patients developed de novo acute GvHD after the combination of 5-azacytidine and DLI. Overall, 66% of the patients benefited from this treatment, with continued CRs achieved in 4 (16%) patients, lasting a median of 525 days (range: 450 þ to 820 þ ), and a 50% rate of temporary disease control with stable mixed chimerism (median duration 72 days). The median survival from the start of 5-azacytidine treatment was 136 days (range: 23 to 873 þ ), with an estimated 2-year survival probability of 16%. In conclusion, this non-intensive outpatient regimen of 5-azacytidine followed by DLI is feasible, with a very low aGVHD rate. Objective responses, including continuous complete donor chimerism, occurred also in patients with poor-risk cytogenetics.