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Allogeneic hematopoietic stem cell transplantation for 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement: a case report and literature review

Bone Marrow Transplantation volume 54, pages 326–329 (2019)Cite this article

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The 8p11 myeloproliferative syndrome is a rare hematologic malignancy associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene located at chromosome 8p11-12 [1]. Cases can present as a myeloproliferative neoplasm or (upon transformation) as acute myeloid leukemia, T- or B-lymphoblastic leukemia/lymphoma, or mixed-phenotype acute leukemia. Depending on the partner chromosome, a variety of fusion genes incorporating part of FGFR1 can form. To date, 15 genes have been shown by sequence analysis to fuse with FGFR1 [2]. Among them, translocations involving 22q11 that result in a BCR-FGFR1 fusion have a distinct phenotype mimicking chronic myelogenous leukemia (CML) with a predilection toward developing B-lymphoblastic lymphoma, mixed-phenotype B/myeloid acute leukemia, or even trilineage T/B/myeloid mixed-phenotype acute leukemia [3]. Although the prognosis in patients with 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement is very poor despite intensive chemotherapy and the only curative option is thought to be allogeneic hematopoietic stem cell transplantation (HSCT), the role of allogeneic HSCT remains elusive in terms of disease status at the time of HSCT and selection of stem cell donor source [3]. Here, we present a case of 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement that was successfully treated with allogeneic HSCT from a human leukocyte antigen (HLA)-DR one allele-mismatched unrelated donor. We also comprehensively reviewed the literature and identified an additional 10 cases of 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement who underwent allogeneic HSCT [1, 3,4,5,6,7,8,9,10,11,12]. The application of allogeneic HSCT has a relevant role in managing 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement, even for patients with active disease. We also noticed that patients who received stem cells from HLA-identical matched sibling donors experienced disease persistence or disease relapse. Our observations suggest a possible dependence on the graft-versus-leukemia (GvL) effect for achieving disease-free survival (DFS) after allogeneic HSCT for these patients with 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement.

The patient underwent initial treatment with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (the hyper-CVAD/MA regimen) therapy. Despite initial cytoreduction resulting in complete hematological remission, he experienced disease progression immediately after MA therapy. Then, he commenced two courses of mitoxantrone, etoposide, and intermediate-dose cytarabine therapy and achieved complete cytogenetic response (CCyR). Subsequently, he underwent allogeneic bone marrow transplantation from an HLA-DR one allele-mismatched unrelated donor. He received a conditioning regimen including cyclophosphamide (60 mg/kg on days −5 and −4) and total-body irradiation (2 Gy twice daily on days −3 to −1). Graft-versus-host disease (GvHD) prophylaxis consisted of tacrolimus, mycophenolic acid, and methotrexate (5 mg/m2 on days 1, 3, and 6). Engraftment was achieved on day 21. Acute GvHD grade II (skin; stage 1, gut; stage 1) was observed on day 55 and was successfully treated with prednisolone. Twenty-eight months after allogeneic HSCT, the patient is well and remains in CCyR.

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Acknowledgements

We are grateful to the medical, nursing, and laboratory staff of the participating departments for their contributions to this study.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yoshinobu Konishi, Tadakazu Kondo, Yasuyuki Otsuka, Momoko Nishikori, Masakatsu Hishizawa, Kouhei Yamashita & Akifumi Takaori-Kondo

  2. Department of Hematology and Oncology, Shiga General Hospital, Shiga, Japan

    Kensuke Nakao & Kohusuke Asagoe

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  1. Yoshinobu Konishi
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Correspondence to Tadakazu Kondo.

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Konishi, Y., Kondo, T., Nakao, K. et al. Allogeneic hematopoietic stem cell transplantation for 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement: a case report and literature review. Bone Marrow Transplant 54, 326–329 (2019). https://doi.org/10.1038/s41409-018-0287-1

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