/L. [DOI] /j.issn Medicine School of South China University of Technology, Guangzhou , China

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1 Med J Chin PLA, Vol. 43, No. 3, March 1, [ ]1 (DAC) (MDS) DAC DAC MDS MDS (AML) 35 1 DAC 28~35d (H-Lym /L)(L-Lym /L) Pearson χ 2 t 1 DAC Kaplan-Meier (PFS) log-rank 35 H-Lym 15 L-Lym 20(P 0.05) 10%(P 0.05) H-Lym 1 DAC (P 0.05) L-Lym (P 0.05) H-Lym (80.0%) L-Lym (40.0%) (P 0.05) H-Lym PFS 10 L-Lym 7.6 (P 0.05)MDS (P 0.05) 1 DAC /L [ ] [ ] R [ ] A [ ] (2018) [DOI] /j.issn The absolute value of lymphocyte counts and the response to decitabine treatment in patients with myelodysplastic syndrome PANG Yan-bin 1, ZHAO Song-ying 1, XUE Hua 1, GUO Hui-mei 1, HUA Luo-ming 1, FAN Li-xia 1*, LUO Jian-min 2, DU Xin 3 1 Department of Hematology, Affiliated Hospital of Hebei University, Baoding, Hebei , China 2 Department of Hematology, Second Hospital of Hebei Medical University, Shijiazhuang , China 3 Department of Hematology, Guangdong General Hospital Guangdong Academy of Medical Sciences, First Clinical Hospital of Medicine School of South China University of Technology, Guangzhou , China * Corresponding author, @qq.com [Abstract] Objective To investigate the relations of absolute lymphocyte counts (ALC) to the therapeutic responses in patients with myelodysplastic syndrome (MDS) after the first course of decitabine (DAC) treatment. Methods Clinical data of 35 patients with MDS and MDS-derived secondary acute myeloid leukemia (AML) who were admitted in the Affiliated Hospital of Hebei University from Jan to Dec and treated with DAC were included in the present study. The patients were grouped into high lymphocyte group (H-Lym, ALC /L) and low lymphocyte group (L-Lym, ALC< /L) based on the ALC in days after the first course of DAC treatment. The baseline data of both groups were compared with Pearson χ 2 analysis, while t test was used to analyze the changes of lymphocyte number before and after the first course of DAC treatment. Progressionfree survival (PFS) was estimated with Kaplan-Meier method, and the cumulative survival (CS) was compared between the two groups using log-rank test. Results Of the 35 patients, 15 were in H-Lym group and 20 in L-Lym group. No significant difference existed in the baseline lymphocyte levels between the two groups (P>0.05). The statistically significant differences (P<0.05) existed [ ] [ ] () ( ) / ( ) [ ] @qq.com

2 only in the patients of the two groups who were with the proportion of bone marrow blasts 10%. The ALC in H-Lym group were slightly higher after the first course of DAC treatment than that at the time of diagnosis, but with no statistically significant (P>0.05). However, the ALC in L-Lym group were significantly lower after the first course of DAC treatment than that at the time of diagnosis (P<0.05). Patients had higher overall response rate (ORR) in H-Lym group than in L-Lym group (80% vs. 40%, P<0.05). The median PFS was 10 months in H-Lym group and 7.6 months in L-Lym group (P<0.05). Univariate analysis showed that the low ALC was a poor prognostic factor for the progression of MDS (P<0.05). Conclusion Patients with ALC /L after the first course of DAC treatment will have better ORR and longer PFS. [Key words] decitabine; myelodysplastic syndromes; lymphocyte; progression-free survival (myelodysplastic syndromes MDS) (acute myeloid leukemia AML) [1-2] MDS MDS [3] (hypomethylating agents HMAs) (decitabine DAC) MDS [1] HMAs HMAs [4-5] MDS [6] DAC 1 DAC 28~35d (Lym) MDS MDS MDS [7] MDS2 DAC 35 42~83( 66) 26 (74.3%) 9 (25.7%) MDS (22.9%) - 12 (34.3%) - 6 (17.1%) MDS AML 9 (25.7%) 35 (international prognostic scoring system IPSS) - ( ) 9 (25.7%) - ( ) 17 (48.6%) 1.2 [8] 1 DAC /L (H-Lym) (n=15) /L (L-Lym) 10% 10% IPSS (secondary acute myeloid leukemia saml) 1.3 DAC 15~20mg/(m 2.d) 1~5d(d1 5) 28d MDS (International Working Group IWG) MDS [7] (CR) 5% /L /L (PR) 50% 5%PR (HI) 110g/L 15g/L /L /L /L /L /L /L /L 100% (PD) 50% 50% 20g/L (ORR) CR PR (PFS) PD MDS DAC 30d 1.5 H-Lym L-Lym 1 DAC 1 DAC 28~35d

3 Med J Chin PLA, Vol. 43, No. 3, March 1, DAC 1.6 H-Lym L-Lym DAC 2 DAC IWG MDS 1 DAC 28~35d IPSS 1.7 H-Lym L-Lym PFS 2 DAC IWG MDS 1 DAC 28~35d IPSS DAC 1.8 SPSS 20.0 x±s t Pearson χ 2 Kaplan- Meier PFS log-rank P DAC 2~10 ( 4 ) H-Lym ( ) 10 9 /L L-Lym ( ) 10 9 /L (P= ) ( 1) H-Lym 10% L-Lym (P= ) 2.21 DAC 1 DAC 28~35d H-Lym ( ) 10 9 /L ( ) 10 9 /L (P=0.072) L-Lym ( ) 10 9 /L ( /L) (P=0.006) 2.31 DAC H-Lym ORR 80.0%(12/15) L-Lym ORR 40.0%(8/20) (P=0.018) 2 DAC 1 Tab. 1 Baseline data and mortality after entire courses of DAC therapy of two groups Characteristic L-Lym(n=20) H-Lym(n=15) P Age [year, median (range)] 66(42-83) 66(53-80) Gender [n(%)] Male 15(66.7) 11(73.3) Female 5(33.3) 4(26.7) IPSS risk category [n(%)] Lower risk group 8(40.0) 1(6.7) Higher risk group 8(40.0) 9(60.0) saml 4(20.0) 5(33.3) Complete blood count at diagnosis Neutrophils (x±s, 10 9 /L) Lymphocytes (x±s, 10 9 /L) Hemoglobin (x±s, g/l) Platelet (x±s, 10 9 /L) Treatment related death [n(%)] Death 2(10.0) 2(13.3) Survive 18(90.0) 13(86.7) Bone marrow blasts [n(%)] % 15(75.0) 5(33.3) 10% 5(25.0) 10(66.7) Cytogenetics risk [n(%)] Favorable/ Intermediate 18(87.5) 10(66.7) Unfavorable 2(12.5) 5(33.3) saml. Secondary acute myeloid leukemia 1 DAC (P<0.05) IPSS MDS saml DAC MDS (69.6% vs. 33.3% P=0.04) ( 2) H-Lym PFS 10 (95%CI 7.6~12.4) L-Lym 7.6 (95%CI 3.5~11.6) (P= ) 10% PFS 10% (P=0.411) (P=0.708) IPSS (P=0.236) PFS ( 3) (P<0.05) 3 MDS [9-10] MDS

4 MDS Tab. 2 Relationship between clinical parameters and the therapeutic response of MDS patients Responsive to Item decitabine (DAC) P Yes No Lymphocyte count after the first cycle DAC treatment [n(%)] L-Lym 8(40.0) 12(60.0) H-Lym 12(80.0) 3(20.0) Bone marrow blasts [n(%)] % 9(45.0) 11(55.0) 10% 11(73.3) 4(26.7) Cytogenetics risk [n(%)] Favorable/Intermediate 14(50.0) 14(50.0) Unfavorable 6(85.7) 1(14.3) IPSS level [n(%)] 0.04 MDS Low/Intermediate-1 4(33.3) 8(66.7) MDS Intermediate-2/High/sAML 16(69.6) 7(30.4) IPSS. International prognostic scoring system; saml. Secondary acute myeloid leukemia Progression free survival (1) H-Lym L-Lym Time (month) 1 H-Lym L-Lym Fig. 1 Survival curves of patients in H-Lym and L-Lym group (1)P< MDS PFS Tab. 3 Univariate analysis for the risk factors influencing the progression-free survival of MDS patients Item PFS[months (95% CI)] P Lymphocyte count after the first cycle DAC treatment L-Lym 10.0( ) H-Lym 7.6( ) Bone marrow blasts % 8.1( ) 10% 8.9( ) Cytogenetics risk Favorable/Intermediate 8.3( ) Unfavorable 8.5( ) IPSS level MDS Low/Intermediate-1 7.6( ) MDS Intermediate-2 /High/sAML 8.8( ) IPSS. International prognostic scoring system; saml. Secondary acute myeloid leukemia MDS [3] MDS IPSS IPSS [8] (HMAs) DAC MDS MDS AML [6,11] DAC 28~35d 1 DAC 28~35d H-Lym DAC PFS L-Lym (P 0.05) H-Lym L-Lym (P 0.05) H-Lym L-Lym (P 0.05) DAC Saeed [8] 889 MDS PFS (35 vs 26 P 0.05) 1.3 (95%CI 1.2~1.6 P 0.05) AML Behl [12] 103 AML DAC DAC HMAs (endogenous retrovirus EDV) HMASs EDV RNA RNA(dsRNA) dsrna To l l 3(TLR-3) 5(MDA5) (MAVS) (IRF)3 IRF7 B(NF- B) [4-5] JAK/STAT T [4-5,13] DAC H-Lym MDS saml L-Lym (P 0.05) MDS

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