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Pretransplant hepatomegaly is linked to relapse in patients with leukemia and myelodysplastic syndrome not in remission

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Abstract

Hepatomegaly is an extramedullary disease (EMD) manifestation of hematological malignancy. Although EMD before allogeneic hematopoietic stem cell transplantation (allo-HCT) is a risk factor for relapse in patients not in complete remission (NonCR) patients, the significance of hepatomegaly to allo-HCT is unclear. We conducted a single-center retrospective observational study of 140 patients with acute leukemia and myelodysplastic syndrome who underwent allo-HCT at our institution from 2014 to 2019. Hepatomegaly was assessed by ultrasonography using the liver index (LI). In the univariable analysis, the LI/height ratio was significantly associated with relapse (hazard ratio [HR] per standard deviation [sd]: 1.51, 95% confidence interval [CI] 1.18–1.93, p = 0.001, sd = 13.8) in NonCR patients (n = 62), but showed no significant association in CR patients (n = 78) (HR per sd: 0.95, 95% CI 0.64–1.39, p = 0.780, sd = 8.7). In multivariable analysis, the LI/height ratio was significantly associated with relapse (HR per sd: 1.34, 95% CI 1.02–1.78, p = 0.037) after adjusting for the refined disease risk index and conditioning intensity. Interaction analysis showed a noteworthy but not statistically significant association between the LI/height ratio and CR status (p = 0.110). In conclusion, our findings suggest that the LI may be a risk factor for relapse in NonCR patients after allo-HCT.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

The authors thank S. Ishikawa for her valuable secretarial assistance.

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Authors and Affiliations

  1. Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno, Osaka, 545-8585, Japan

    Yusuke Okayama, Naonori Harada, Yosuke Makuuchi, Masatomo Kuno, Teruhito Takakuwa, Hiroshi Okamura, Asao Hirose, Mitsutaka Nishimoto, Yasuhiro Nakashima, Masayuki Hino & Hirohisa Nakamae

  2. Department of Hematology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Yusuke Okayama

  3. Department of Hematology, Fuchu Hospital, Osaka, Japan

    Naonori Harada

  4. Department of Laboratory Medicine and Medical Informatics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Mika Nakamae

  5. Department of Preventive Medicine and Environmental Health, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Hideo Koh

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  1. Yusuke Okayama
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Correspondence to Naonori Harada.

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Conflict of interest

There are no conflicts of interest related to the submitted work. Dr. Makuuchi, Dr. Kuno, and Dr. Hirose stated no conflicts of interest. Dr. Okayama has received honoraria from Sanofi K.K. Dr. Harada has received honoraria from Chugai Pharmaceutical Co., Ltd., Sanofi K.K., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Meiji Seika Pharma Co., Ltd., and Nippon Shinyaku Co., Ltd. Dr. Takakuwa has received honoraria from AbbVie GK, Kyowa Kirin Co., Ltd., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., Bristol-Myers Squibb K.K., and Janssen Pharmaceutical K.K., has received research funding from AbbVie GK, GlaxoSmithKline K.K., Pfizer Japan Inc., and Bristol-Myers Squibb K.K., and has received consulting fees from Sanofi K.K. Dr. Okamura has received honoraria from Nippon Shinyaku Co., Ltd. Dr. Mika Nakamae has received research funding from VERITAS Corporation, and her family received honoraria (see Dr. Hirohisa Nakamae’s honoraria). Dr. Nishimoto has received honoraria from Kyowa Kirin Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., and Nippon Shinyaku Co., Ltd., and has received research funding from Janssen Pharmaceutical K.K., Pfizer Japan Inc., and Astellas Pharma Inc. Dr. Nakashima has received honoraria from Amgen Inc., Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., Bristol-Myers Squibb K.K., and Janssen Pharmaceutical K.K., has received research funding from Astellas Pharma Inc., AbbVie GK, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., and Bristol-Myers Squibb K.K., and has received advisory fees from Amgen Inc. and Novartis Pharma K.K. Dr. Koh has received honoraria from Sumitomo Pharma Co., Ltd., MSD K.K., and Novartis Pharma K.K. and has received research funding from Amgen Inc. Dr. Hino has received honoraria from Meiji Seika Pharma Co., Ltd., Astellas Pharma Inc., AbbVie GK, Amgen Inc., Otsuka Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., and MSD K.K., has received consulting fees from DAIICHI SANKYO COMPANY, the LIMITED., has received research funding from Nippon Shinyaku Co., Ltd., Pfizer Japan Inc., and Bristol-Myers Squibb K.K., and has received advisory fees from Otsuka Pharmaceutical Co., Ltd. and Kyowa Kirin Co., Ltd., and has donations from JCR Pharmaceuticals Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., DAIICHI SANKYO COMPANY, the LIMITED., Chugai Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., and Sumitomo Pharma Co., Ltd. Dr. Hirohisa Nakamae has received honoraria from Astellas Pharma Inc., Amgen Inc., Otsuka Pharmaceutical Co., Ltd., DAIICHI SANKYO COMPANY, the LIMITED., Sumitomo Pharma Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Bristol-Myers Squibb K.K., and Janssen Pharmaceutical K.K., has received advisory fees from Novartis Pharma K.K., and has received research funding from Meiji Seika Pharma Co., Ltd., Novartis Pharma K.K., and Bristol-Myers Squibb K.K. (none of which are related to the submitted work). Authorship statement: Y.O., N.H., M.H., and H.N. conceptualized and designed the study. A.H. and M. Nakamae acquired data. Y.O. and N.H. analyzed the data, interpreted the results, and wrote the manuscript. Y.M., M.K., T.T., H.O., A.H., M. Nakamae, M. Nishimoto, Y.N., H.K., M.H., and H.N. interpreted the results and critically reviewed and revised the manuscript. All authors read and approved the final version of the manuscript.

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Supplementary file1 (DOCX 66 KB)

12185_2023_3707_MOESM2_ESM.tif

Supplementary file2 (TIF 3596 KB) Supplemental Fig. S1. Differences in the LI and SI based on the presence of EMD before allo-HCT in NonCR patients. The LI and SI were significantly higher in patients with EMD before allo-HCT (median LI: 101.4 [range: 69.2-185.5] cm2, median SI: 56.8 [range: 15.5-138.6] cm2) than in patients without EMD before allo-HCT (median LI: 82.6 [range: 43.3-122.5] cm2, median SI: 34.0 [range: 17.9-66.7] cm2) (p < 0.001 and p < 0.001, respectively). LI, liver index; SI, spleen index; EMD, extramedullary disease

12185_2023_3707_MOESM3_ESM.tif

Supplementary file3 (TIF 3480 KB) Supplemental Fig. S2. Differences in the LI and SI based on the presence of EMD relapse in NonCR patients. The LI and SI were not significantly different in patients with EMD relapse (median LI: 103.0 [range: 50.0-120.2] cm2, median SI: 37.4 [range: 17.9-133.4] cm2) and in patients without EMD relapse (median LI: 89.2 [range: 66.9-185.5] cm2, median SI: 39.0 [range: 21.5-138.6] cm2) (p = 0.218 and p = 1.000, respectively). LI, liver index; SI, spleen index; EMD, extramedullary disease

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Supplementary file4 (TIF 3599 KB) Supplemental Fig. S3. Differences in the LI based on the presence of pretransplant liver dysfunction. The LI did not significantly differ between individuals with and without pretransplant liver dysfunction among NonCR patients (median LI: 94.3 [59.8-185.5] cm2 and 87.7 [range: 43.3-139.2] cm2, respectively, p = 0.301), and CR patients (median LI: 86.8 [range: 65.0-119.4] cm2 and 85.0 [range: 55.2-122.8] cm2, respectively, p = 0.814). LI, liver index; NonCR, noncomplete remission; CR, complete remission

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Okayama, Y., Harada, N., Makuuchi, Y. et al. Pretransplant hepatomegaly is linked to relapse in patients with leukemia and myelodysplastic syndrome not in remission. Int J Hematol 119, 316–326 (2024). https://doi.org/10.1007/s12185-023-03707-7

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