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Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis

Bone Marrow Transplantation volume 50, pages 40–44 (2015)Cite this article

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Abstract

A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.

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Acknowledgements

We would like to thank Jennifer Rasmussen and Katrina De La Cruz of the UCSF Blood and Marrow Transplant Laboratory for their expert technical assistance with the CD34+ cell viability assays, and Nicole Foley and Sara Halvestine of the UCSF Division of Blood and Marrow Transplantation for their assistance with data management. This work was supported in part by an American Society of Hematology Research Training Award for Fellows (GNM), a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (Clinical Cancer Research 23-004); and the National Cancer Center Research and Development Fund (26-A-24).

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Authors and Affiliations

  1. Division of Hematologic Malignancies and Blood and Marrow Transplantation, Department of Medicine, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

    G N Mannis, A C Logan, R L Olin, L E Damon, C Andreadis, W Z Ai, K M Gaensler, C C Greene, N K Gupta, L D Kaplan, A Mahindra, P H Sayre, C C Smith, J M Venstrom, J L Wolf & T G Martin

  2. Departments of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA

    A D Leavitt & L Caballero

  3. Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan

    M Yanada & N Emi

  4. Department of Biostatistics, University of California, San Francisco, San Francisco, CA, USA

    J Hwang

  5. Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Y Miyazaki

  6. Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    T Naoe

  7. Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan

    S Ohtake

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  1. G N Mannis
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Correspondence to T G Martin.

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Mannis, G., Logan, A., Leavitt, A. et al. Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis. Bone Marrow Transplant 50, 40–44 (2015). https://doi.org/10.1038/bmt.2014.201

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