Low-dose cytarabine and aclarubicin in combination with G-CSF (CAG) regimen for elderly patients with acute myeloid leukemia and myelodysplastic syndrome: A single institution experience

Abstracts Interventions: Targeted mutational analysis was performed using two different commercially available NGS panels addressed to myeloid malignances using a MiSeq platform (Illumina). Confirmed mutations were then analysed in samples from time of diagnosis or during the chronic phase by means of Sanger sequencing (Applied Byosistems 3500Dx) or massive parallel sequencing (Roche 454). Results: Main results are shown in Table 1. Conclusions: Many genetic alterations are already present in MPN patients at diagnosis or during chronic phase of the disease, and show a higher allele burden at the time of transformation, indicating that the transformation of chronic MPN to AML may be due in part to the expansion of clones bearing additional mutations.

220 Low-dose cytarabine and aclarubicin in combination with G-CSF (CAG) regimen for elderly patients with acute myeloid leukemia and myelodysplastic syndrome: A single institution experience Junko Iwasaki,1 Daisuke Hidaka,1 Shojiro Takahashi,1 Mutsumi Takahata,1 Akio Shigematsu,1 Koichiro Minauchi,1 Masato Obara,1 Shuichi Ota,1 Kiyotoshi Imai,1 Teiichi Hirano,1 Masahiro Ogasawara,1 Naoki Kobayashi,1 Masahiro Imamura1 1

Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Hokkaido, Japan

Table 1

POLYCYTHEMIA VERA

% Chronic % AML Phase Phase

Patient

Mutations

#1

JAK2 p.V617F

78.0

65.0

IDH1 p.R132H

49.5

59.9

RUNX1 p.R201X

4.0

46.0

SRSF2 p.P95R

50.0

45.0

TP53 p.V216E #2

JAK2 p.V617F RUNX1 p.L56S LNK p.R566W

#3

#5 #6

#8

#9

49.6

-

49.7 61.0

ASXL1 p.R634fs

21.7

27.7

TET2 p.Q976X

1.5

37.0

-

48.0

JAK2 p.V617F

82.0

-

DNMT3A p.R771X

-

45.2

DNMT3A p.W330X

-

48.7

IDH2 p.R140Q

-

46.0

NOTCH1 p.L1678P

-

61.0

JAK2 p.V617F JAK2 p.V617F JAK2 p.N1108S

#7

-

94.0

DNMT3A p.R882Ha

ESSENTIAL THROMBOCYTHEMIA

67.0

57.7

JAK2 p.V617F

TP53 p.E286K #4

-

6.0

-

85.6

8.1

ND

47.8

47.0

45.1

FLT3 ITD

ND

IDH2 p.R140Q

ND

41.8

NPM1

ND

positivec

JAK2 p.V617F

58.0

26.0

ASXL1 p.R634fs

22.0

46.0

JAK2 p.V617F

20.3

-

SRSF2 p.R94P

16.0

41.0

0.16b

SRSF2 p.P95H

16.0

41.0

TET2 p.E1215X

27.0

45.0

TET2 p.L1244fs

15.0

41.0

MPL p.W515fs

14.0

38.8

Context: Elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are not eligible for intensive chemotherapy due to high risk of treatment-related mortality. In Asia, less intensive chemotherapy regimen consists of low-dose cytarabine and aclarubicin in combination with G-CSF (CAG) has been used for those elderly AML/MDS patients. Objective: To determine whether CAG is safe and effective regimen for elderly patients with AML or MDS. Design and Setting: Patients with AML or MDS aged 60 years or older who received CAG at our institute between January 2008 and March 2013 were retrospectively analyzed. Results: Total of 140 patients, 19 with MDS and 121 with AML, were analyzed. Median age was 74 (range; 60-91). Of 121 AML patients, 66 patients were diagnosed as AML with MDS-related changes (AML with MRC). According to cytogenetic risk group reported on IPSS for MDS, 78, 30, and 32 patients were categorized to favorable, intermediate, and unfavorable cytogenetic groups, respectively. The treatment was administered as a first-line regimen for 59 patients, while the others received the treatment as a salvage therapy. Overall response rate was 62.1%, including 50% of complete remission cases. With a median follow-up of 284 days, overall survival (OS) at one year was 45.5% (95%CI, 37.0-53.7). Treatment related mortality was 7.1%. No significant difference on response rate was seen between patients received CAG as an initial and salvage therapy (55.9% vs. 66.7%, P¼0.22), or between patients with diagnosis of AML with MRC and other subtypes of AML (56.1% vs. 70.1%, P¼0.13). Patients with unfavorable karyotype had significantly lower response rate and OS compared to the others (response rate, 31.3% vs. 71.7%, P<0.001 ; one-year OS, 9.4% vs. 57.8%, P<0.001). Conclusions: CAG regimen is safe and effective for elderly patients with AML or MDS as initial therapy as well as salvage therapy. More appropriate chemotherapy regimen is required for patients with unfavorable cytogenetics. To determine a useful approach for AML and MDS, prospective studies comparing CAG regimen with other therapies are needed. Keywords: elderly, acute myeloid leukemia, myelodysplastic syndrome, CAG regimen.

ND: not determined aGermline mutation bMutation ratio cUnquantified

Clinical Lymphoma, Myeloma & Leukemia September 2015

- S17