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. 2023 Dec 18;27(2):62.
doi: 10.3892/ol.2023.14193. eCollection 2024 Feb.

Clinical impacts of severe thrombocytopenia in the first cycle of azacitidine monotherapy and cytogenetics in patients with myelodysplastic syndrome: The Kyoto Conditional Survival Scoring System

Yu Inoue  1 , Haruya Okamoto  1 , Akihiro Miyashita  1 , Yuka Kawaji-Kanayama  1 , Shotaro Chinen  1 , Takahiro Fujino  1 , Taku Tsukamoto  1 , Yuji Shimura  1 , Shinsuke Mizutani  1 , Hiroto Kaneko  2 , Saeko Kuwahara-Ota  3 , Shin-Ichi Fuchida  3 , Daichi Nishiyama  4 , Koichi Hirakawa  4 , Hitoji Uchiyama  5 , Nobuhiko Uoshima  6 , Eri Kawata  7 , Junya Kuroda  1
Affiliations

Clinical impacts of severe thrombocytopenia in the first cycle of azacitidine monotherapy and cytogenetics in patients with myelodysplastic syndrome: The Kyoto Conditional Survival Scoring System

Yu Inoue et al. Oncol Lett. .

Abstract

Azacitidine (AZA) has been one of the standard treatments for transplantation-ineligible patients with myelodysplastic syndrome (MDS); however, hematological toxicities frequently cause treatment interruption in the early phase of the therapy. The present study conducted a multicenter retrospective study to investigate the prognostic impacts of various factors, including factors included in the Revised International Prognostic Scoring System (IPSS-R) and severe cytopenia in the early phase of AZA monotherapy in 212 patients with MDS. Severe cytopenia was evaluated after the initiation of therapy by absolute neutrophil counts on the 29th day after AZA (ANC29) initiation, and red cell concentrates (RCC) and platelet concentrate (PC) transfusion units required within 28 days from the start of AZA, designated in the present study as RCC28 and PC28, respectively. The survival period was determined from the 29th day of AZA treatment to death from any cause as the conditional survival period after the first cycle of AZA (CS-AZA1). Multivariate analysis demonstrated that severe thrombocytopenia defined by >30 units of PC28 and very poor risk cytogenetics according to IPSS-R were independent prognostic factors for CS-AZA1. The Kyoto Conditional Survival Scoring System was subsequently developed by incorporating severe thrombocytopenia defined by PC28 and very poor risk cytogenetics, which successfully stratified the risks of the patients in CS-AZA1. In conclusion, extreme PC transfusion dependency during the first cycle of AZA and very poor risk cytogenetics are important prognostic factors in AZA monotherapy for MDS.

Keywords: azacitidine; cytogenetics; cytopenia; myelodysplastic syndrome; platelet concentrate; transfusion.

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Conflict of interest statement

TF has received honoraria from Takeda Pharmaceutical; TT has received honoraria from Bristol Myers Squibb (BMS), Janssen Pharmaceutical, Sanofi, Kyowa Kirin and Chugai Pharmaceutical; YS has received honoraria from Ono Pharmaceutical, BMS, Janssen Pharmaceutical, Sanofi, Kyowa Kirin, Takeda Pharmaceutical and Chugai Pharmaceutical; SM has received honoraria from Sanofi and Ono Pharmaceutical; and NU has received honoraria from BMS and Takeda. JK is a consultant for Janssen Pharmaceutical, Abbvie and BMS; has received research funding from Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Shionogi and BMS; and has received honoraria from Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi and BMS. None of the pharmaceutical companies aforementioned benefited from the present research or played any role in our study. All other authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Survival curves of CS-AZA1 and CLFS-AZA1 stratified according to disease risk and treatment intensity. (A) CS-AZA1 and (B) CLFS-AZA1 in the entire training set. (C) CS-AZA1 and (D) CLFS-AZA1 were stratified by the Revised International Prognostic Scoring System in the training set. RDI-AZA1 had no prognostic impact on (E) CS-AZA1 and (F) CLFS-AZA1. CS-AZA1, conditional survival period after the first cycle of azacitidine treatment; CLFS-AZA1, conditional leukemia-free survival period after the first cycle of azacitidine treatment; RDI-AZA1, relative dose intensity in the first cycle of azacitidine treatment.
Figure 2.
Figure 2.
Prognostic impact of the transfusion units required within 28 days from the start of AZA with PC28. (A) CS-AZA1, (B) CLFS-AZA-1 and (C) cumulative incidence of progression to AML based on severe thrombocytopenia defined by PC28 or not. The causes of death in patients with (D) severe thrombocytopenia and (E) those without who died within the follow-up period. CS-AZA1, conditional survival period after the first cycle of azacitidine treatment; CLFS-AZA1, conditional leukemia-free survival period after the first cycle of azacitidine treatment; AML, acute myeloid leukemia; PC28, platelet concentrate transfusion units required within 28 days from the start of AZA.
Figure 3.
Figure 3.
CS-AZA1 and CLFS-AZA1 stratified according to the KCSS. (A) Patient distribution of IPSS-R and KCSS. (B-E) Survival curves based on KCSS. KCSS stratified (B) CS-AZA1 and (C) CLFS-AZA1 in the training set, and KCSS stratified (D) CS-AZA-1 and (E) CLFS-AZA-1 in the validation set. CS-AZA1, conditional survival period after the first cycle of azacitidine treatment; CLFS-AZA1, conditional leukemia-free survival period after the first cycle of azacitidine treatment; IPSS-R, Revised International Prognostic Scoring System; KCSS, Kyoto Conditional Survival Scoring System.
Figure 4.
Figure 4.
Prognostic value of KCSS. C-indices of Revised International Prognostic Scoring System and KCSS in the (A) training set and the (B) validation set. (C) Box plot of the number of AZA cycles based on KCSS. KCSS, Kyoto Conditional Survival Scoring System; AZA, azacytidine.
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