Monosomal and complex karyotypes as prognostic parameters in patients with International Prognostic Scoring System higher risk myelodysplastic syndrome treated with azacitidine

Kyung-Lim Hwang; Moo-Kon Song; Ho-Jin Shin; Hae-Jung Na; Dong-Hun Shin; Joong-Keun Kim; Joon-Ho Moon; Jae-Sook Ahn; Ik-Chan Song; Junshik Hong; Gyeong-won Lee; Joo-Seop Chung

doi:10.5045/br.2014.49.4.234

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Original Article

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Blood Res 2014; 49(4):

Published online December 31, 2014

https://doi.org/10.5045/br.2014.49.4.234

Monosomal and complex karyotypes as prognostic parameters in patients with International Prognostic Scoring System higher risk myelodysplastic syndrome treated with azacitidine

Kyung-Lim Hwang¹, Moo-Kon Song¹, Ho-Jin Shin¹, Hae-Jung Na¹, Dong-Hun Shin¹, Joong-Keun Kim¹, Joon-Ho Moon², Jae-Sook Ahn³, Ik-Chan Song⁴, Junshik Hong⁵, Gyeong-won Lee⁶, and Joo-Seop Chung^1*

Author Info. +

¹Department of Hematology-Oncology, Pusan National University Hospital, Busan, Korea.

²Department of Hematology, Kyungpook National University Hospital, Daegu, Korea.

³Department of Hematology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

⁴Department of Hematology, Chungnam Nastional Ujnversity Hospital, Daejeon, Korea.

⁵Department of Hematology, Gachon University Gil Medical Center, Incheon, Korea.

⁶Department of Hematology, Gyeong-Sang National University Hospital, School of Medicine, Gyeongsang Natioinal University, Jinju, Korea.

Correspondence to : Correspondence to Joo-Seop Chung, M.D. Department of Hematology-Oncology, School of Medicine, Pusan National University, 179, Gudeok-ro, Seo-gu, Busan 602-739, Korea. Tel: +82-51-240-7225, Fax: +82-51-254-3127, Hemon@pusan.ac.kr

Received: June 12, 2014; Revised: July 11, 2014; Accepted: November 6, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background

Azacitidine (AZA) is standard care for patients with myelodysplastic syndrome (MDS) who have not had allogeneic stem cell transplantation. Chromosomal abnormalities (CA) including complex karyotype (CK) or monosomal karyotype (MK) are associated with clinical outcome in patients with MDS.

Methods

We investigated which prognostic factors including CAs would predict clinical outcomes in patients with International Prognostic Scoring System (IPSS) higher risk MDS treated with AZA, retrospectively. CK was defined as the presence of three or more numerical or structural CAs. MK was defined as the presence of two or more distinct autosomal monosomies or single autosomal monosomy with at least one additional structural CA.

Results

A total of 243 patients who treated with AZA, were enrolled. CK was present in 124 patients and MK was present in 90 patients. Bone marrow blasts ≥15% and CK were associated with poorer response (P=0.038, P=0.007) and overall survival (OS) (P<0.001, P<0.001) independently. Although MK in CK group was not associated with prognosis, non-MK status in non-CK group reflected favorable OS (P=0.005). The group including >3 CAs was associated with poorer OS (group including <3 CAs vs. only three CAs, P=0.001; group with >3 CAs vs. only three CAs, P=0.001).

Conclusion

CK was an important prognostic parameter associated with worse outcome. MK may predict poor survival in only non-CK status. The higher number of CAs was associated with poorer survival.

Keywords Myelodysplastic syndrome, Azacitidine, Complex karyotype, Monosomal karyotype, Chromosomal abnormalities

Article

Original Article

Blood Res 2014; 49(4): 234-240

Published online December 31, 2014 https://doi.org/10.5045/br.2014.49.4.234

Monosomal and complex karyotypes as prognostic parameters in patients with International Prognostic Scoring System higher risk myelodysplastic syndrome treated with azacitidine

¹Department of Hematology-Oncology, Pusan National University Hospital, Busan, Korea.

²Department of Hematology, Kyungpook National University Hospital, Daegu, Korea.

³Department of Hematology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

⁴Department of Hematology, Chungnam Nastional Ujnversity Hospital, Daejeon, Korea.

⁵Department of Hematology, Gachon University Gil Medical Center, Incheon, Korea.

⁶Department of Hematology, Gyeong-Sang National University Hospital, School of Medicine, Gyeongsang Natioinal University, Jinju, Korea.

Correspondence to: Correspondence to Joo-Seop Chung, M.D. Department of Hematology-Oncology, School of Medicine, Pusan National University, 179, Gudeok-ro, Seo-gu, Busan 602-739, Korea. Tel: +82-51-240-7225, Fax: +82-51-254-3127, Hemon@pusan.ac.kr

Received: June 12, 2014; Revised: July 11, 2014; Accepted: November 6, 2014

Abstract

Background

Methods

Results

Conclusion

CK was an important prognostic parameter associated with worse outcome. MK may predict poor survival in only non-CK status. The higher number of CAs was associated with poorer survival.

Keywords: Myelodysplastic syndrome, Azacitidine, Complex karyotype, Monosomal karyotype, Chromosomal abnormalities

Abstract

Fig 1.

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Figure 1.

Comparisons of overall survival (OS) in patients treated with azacitidine according to the presence of a complex karyotype (CK); chromosomal abnormalities [CA] ≥3 (A) and OS according to the presence of a CK (CA≥3) combined with the monosomal karyotype (MK) (B). OS in the group without CK was significantly lower compared to the group with CK in a median follow-up time of 24.2 months (OS, 21.8% in the group with CK, 37.8% in the group without CK, P <0.001) (A). The MK negative status in the group without CK was higher than the other 3 groups (OS of MK +/- in the group without CK, 18.7% vs. 44.8%; MK +/- in the group with CK, 22.2% vs. 21.4%; P <0.001) (B). However, the differences in OS among the other 3 groups were not significant.

Blood Research 2014; 49: 234-240https://doi.org/10.5045/br.2014.49.4.234

Fig 2.

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Figure 2.

Comparisons of overall survival (OS) in patients treated with azacitidine according to the numbers of chromosome abnormalities (CAs); CA <3, CA=3, and CA>3 (A) and OS according to the numbers of CAs combined with the presence or absence of a monosomal karyotype (MK) (B). OS in the group with CA<3 was significantly higher than the other 2 groups (OS, 14.5% in the CA>3 group, 27.9% in the CA=3 group, 37.8% in the CA<3 group; CA<3 vs. CA=3, P=0.001). OS in the CA>3 group was lower than the other 2 groups (CA>3 vs. CA=3, P=0.001) (A). According to the presence or absence of MK combined with the number of CAs, OS was highest in the non-MK group with CA<3 compared to the other 5 groups (OS, 23.3% vs. 50.6% in the CA<3 groups with/without MK, 33.3% vs. 24.4% in the CA=3 groups with/without MK, 11.1% vs. 17.2% in the CA>3 groups with/without MK, P <0.001) (B).

Blood Research 2014; 49: 234-240https://doi.org/10.5045/br.2014.49.4.234

Table 1 . Baseline characteristics of patients..

Abbreviations: RA, refractory anemia; RAEB, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts; RCMD, refractory cytopenia with multilineage dysplasia; IPSS, International Prognostic Scoring System; ECOG PS, Eastern Cooperative Oncology Group Performance Status; ANC, absolute neutrophil count; PLT, platelet; PB, peripheral blood; BM, bone marrow; M/F, male/female; WHO, World Health Organization..

Table 2 . Overall response in patients treated with azacitidine according to International Working Group 2006 response criteria..

Abbreviations: CR, complete response; IWG, International Working Group..

Table 3 . Prognostic factors for overall response and survival in all patients with myelodysplastic syndrome (N=243)..

Abbreviations: AZA, azacitidin; ANC, absolute neutrophil count; Hb, hemoglobin; PLT, platelet; LDH, lactate dehydrogenase; PB, peripheral blood; BM, bone marrow; RAEB, refractory anemia with excess blasts; IPSS, International Prognostic Scoring System; ECOG PS, Eastern Cooperative Oncology Group Performance Status; CK, complex karyotype; MK, monosomal karyotype; HR, hazard ratio; CI, confidence interval..

Table 4 . Prognostic factors for overall survival in patients with myelodysplastic syndrome with or without complex karyotype..

Abbreviations: AZA, azacitidine; ANC, absolute neutrophil count; Hb, hemoglobin; PLT, platelet; LDH, lactate dehydrogenase; PB, peripheral blood; BM, bone marrow; RAEB, refractory anemia with excess blast; IPSS, International Prognostic Scoring System; ECOG PS, Eastern Cooperative Oncology Group Performance Status; CK, complex karyotype; MK, monosomal karyotype; OS, overall survival; HR, hazard ratio; CI, confidence interval..