Abstract
Abstract 3445
Relapsing AML/MDS after HSCT has a dismal prognosis, with few patients achieving long-term control of the malignancy. AZA is a hypomethylating agent that is moderately active against AML/MDS, and may have beneficial immunomodulatory effects after HSCT. We have shown that a significant minority of patients with recurrent disease respond to this drug. Here, we present long-term follow-up after salvage treatment regimens that included AZA, to treat AML/MDS that recurred after HSCT.
Twenty-three patients received low-dose AZA for recurrence. Decision to use AZA was based on clinical assessment of slow progression of disease and relatively slower disease ‘tempo' and relatively small AML bulk. AZA cohort preparative regimens for 1st HSCT were myeloablative in 12 cases, and of reduced intensity in 11 cases. AZA was used prior to or without a 2nd HSCT (n=17), or after a 2nd HSCT (n=6). Outcomes were compared to controls (n=18) that relapsed ≥ 8 months after HSCT, and did not receive AZA (8 months representing the median disease free survival (DFS) for AZA-treated patients). The control group included all patients that relapsed ≥ 8 months after allogeneic HSCT using myeloablative busulfan 130 mg/m2 and fludarabine 40 mg/m2 for 4 days. AZA was studied as a time dependent variable. AZA and controls had similar baseline characteristics as described in the Table, although median DFS after the first HSCT was 8 (range: 2–51) and 17 (range: 7–59) months, favoring the control group (p=0.08). AZA was administered outpatient, with good tolerance. Fatigue and nausea were commonly observed toxicities. Doses were 8 mg/m2 (n=1), 16 mg/m2 (n=3), 24 mg/m2 (n=10), 32 mg/m2 (n=5), 40 mg/m2 (n=2), and 75 mg/m2 (n=2), administered subcutaneously for 5 days, in 28–32-day cycles.
Median number of cycles was 4 (range, 1–44). With a median follow-up of 18 months for AZA and control patients, median survival after relapse was 17 versus 6 months, respectively for AZA and control patients. 11 (48%) AZA patients are alive, while 2 (11%) control patients are alive. Two-year overall survival (OS) for AZA and control groups was 40% and 10%, respectively. AZA and controls had similar baseline characteristics as described in the Table.
Low-dose AZA was a well tolerated outpatient treatment that may improve survival after AML/MDS recurrence in selected cases. Major determinants of survival in this setting, however, were remission duration after HSCT, and use of a 2nd HSCT.
| . | Vidaza (N=23) . | Control (n=18)≥ 8 months DFS . | p . |
|---|---|---|---|
| Age at 1st HSCT, years | 47 (21–66) | 39 (25–60) | 0.3 |
| Age at 1st relapse, years | 51 (21–67) | 41 (25–62) | 0.3 |
| Time: diagnosis to 1st HSCT, months | 10 (1–248) | 12 (3–33) | 0.3 |
| . | Vidaza (N=23) . | Control (n=18)≥ 8 months DFS . | p . |
|---|---|---|---|
| Age at 1st HSCT, years | 47 (21–66) | 39 (25–60) | 0.3 |
| Age at 1st relapse, years | 51 (21–67) | 41 (25–62) | 0.3 |
| Time: diagnosis to 1st HSCT, months | 10 (1–248) | 12 (3–33) | 0.3 |
| . | N° of patients . | % . | N° of patients . | % . | . |
|---|---|---|---|---|---|
| Diagnosis | |||||
| AML | 19 | 83% | 16 | 89% | |
| MDS | 4 | 17% | 2 | 11% | |
| Cytogenetic before 1st HSCT | |||||
| Good | 2 | 9% | 0 | 0% | |
| Intermediate | 13 | 56% | 10 | 56% | |
| Bad | 8 | 35% | 6 | 33% | |
| Unknown | 0 | 0% | 2 | 11% | |
| Disease status at 1st HSCT | |||||
| Complete remission | 9 | 39% | 7 | 39% | |
| Active disease | 14 | 61% | 11 | 61% | 0.9 |
| Donor type | |||||
| Matched sibs | 6 | 26% | 12 | 67% | |
| Other | 17 | 74% | 6 | 33% | 0.01 |
| DFS after 1st HSCT | |||||
| <8 months | 10 | 43% | |||
| ≥8 months | 13 | 57% | 18 | 100% | 0.02 |
| Median DFS after 1st HSCT | 8 month | (2–51) | 17 month | (7–59) | 0.08 |
| Median WBC at 1st relapse | 3.3 (n=21) | (1.2–8.4) | 4.6 | (0.8–242) | 0.05 |
| Presence of peripheral blood blasts at 1st relapse | 6 (n=21) | 29% | 6 | 33% | |
| Median Bone Marrow blast at 1st relapse | 13% (n=19) | (1–60) | 23% | (0–95) | 0.4 |
| GVHD at relapse | 2 | 9% | 2 | 11% | |
| Outcomes since 1st relapse | |||||
| Patients alive | 11 | 48% | 2 | 11% | |
| Median follow up of survivors | 19 months | (5–61) | 18 months | (16,21) | |
| Median OS | 17 months | 6 months | |||
| OS at 2 years | 40% | (17–62) | 10% | (1–33) | *0.2 |
| . | N° of patients . | % . | N° of patients . | % . | . |
|---|---|---|---|---|---|
| Diagnosis | |||||
| AML | 19 | 83% | 16 | 89% | |
| MDS | 4 | 17% | 2 | 11% | |
| Cytogenetic before 1st HSCT | |||||
| Good | 2 | 9% | 0 | 0% | |
| Intermediate | 13 | 56% | 10 | 56% | |
| Bad | 8 | 35% | 6 | 33% | |
| Unknown | 0 | 0% | 2 | 11% | |
| Disease status at 1st HSCT | |||||
| Complete remission | 9 | 39% | 7 | 39% | |
| Active disease | 14 | 61% | 11 | 61% | 0.9 |
| Donor type | |||||
| Matched sibs | 6 | 26% | 12 | 67% | |
| Other | 17 | 74% | 6 | 33% | 0.01 |
| DFS after 1st HSCT | |||||
| <8 months | 10 | 43% | |||
| ≥8 months | 13 | 57% | 18 | 100% | 0.02 |
| Median DFS after 1st HSCT | 8 month | (2–51) | 17 month | (7–59) | 0.08 |
| Median WBC at 1st relapse | 3.3 (n=21) | (1.2–8.4) | 4.6 | (0.8–242) | 0.05 |
| Presence of peripheral blood blasts at 1st relapse | 6 (n=21) | 29% | 6 | 33% | |
| Median Bone Marrow blast at 1st relapse | 13% (n=19) | (1–60) | 23% | (0–95) | 0.4 |
| GVHD at relapse | 2 | 9% | 2 | 11% | |
| Outcomes since 1st relapse | |||||
| Patients alive | 11 | 48% | 2 | 11% | |
| Median follow up of survivors | 19 months | (5–61) | 18 months | (16,21) | |
| Median OS | 17 months | 6 months | |||
| OS at 2 years | 40% | (17–62) | 10% | (1–33) | *0.2 |
HR=0.6, (95%CI= 0.3–1.3)
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
