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  • 1
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3445-3445
    Abstract: Abstract 3445 Background: 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. Patients and Methods: 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. Results: 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. Conclusion: 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. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 2
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3471-3471
    Abstract: Abstract 3471 AML with the internal tandem duplication of the Fms-Like Tyrosine kinase-3 gene (FLT3-ITD) has a poor prognosis, with high relapse rates. Sorafenib is an oral multikinase inhibitor of tyrosine kinases including Flt-3 with activity in AML. We used this drug to treat patients relapsing after allogeneic HSCT and herein present the results. Patients and Methods. We retrospectively evaluated 16 patients with FLT3-ITD AML that received sorafenib for at least a 7-day course either alone (n=8; 50%) or in combination (n=8; 50%) to treat AML relapsing at a median of 3 months (range, 1–7) after HSCT. Median age was 34 years (range, 20–603). Cytogenetics was diploid in 69%, high-risk in 19% and unknown in 12%. Treatment history prior to HSCT included sorafenib in 38% of the cases, and 30% were status post a 2nd HSCT. Donors were related (50%) or unrelated (50%). Seven patients (44%) received and failed other salvage chemotherapy prior to starting sorafenib (median=2 treatments; range, 1–5). At start of sorafenib salvage treatment, median WBC was 22.5 K/mm3 (range, 0.6–119), and median bone marrow blast was 58% (range, 12–88%), while 75% of the patients had circulating blasts. Sorafenib doses were as follows: 400 mg (n=3) or 800 mg daily (n=4) in combination to idarubicin/Ara-C, or 800 mg daily with 5-azacitidine (n=1); single agent: 800 mg (n=6) or 1200 mg (n=2) daily. Median duration of sorafenib single agent therapy was 39.5 days (range, 10–100), and in combination it was 7 days (range, 7–32). Complete remission (CR) rate was zero; 2 patients achieved a PR. Median reduction in bone marrow (n=9) and peripheral blood (n=12) blasts was 0% (range, 0–46), and 50% (range, 0–88), respectively. Two patients were ‘bridged’ to a 2nd HSCT, which led to CR durations of 53 and 106 days. Median survival after sorafenib initiation was 81 days and it was similar with single agent versus combination therapy (Figure 1 and 2). All patients have died. Conclusions. Treatment of overt AML relapse with sorafenib was unsuccessful as described here. It is possible that ‘pre-emptive’ treatment in the presence of minimal residual disease will be more effective, but this remains to be proven. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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