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Successful mobilization and transplantation of filgrastim mobilized hematopoietic stem cells in sickle cell-hemoglobin C disease

Bone Marrow Transplantation volume 37, pages 1065–1066 (2006)Cite this article

With improved life expectancy to a median age of 48 years in sickle-cell disease and to a median of 68 years in sickle-cell-hemoglobin C disease,1 patients with these diagnoses are increasingly developing both hematologic malignancy and other neoplasms.2, 3, 4 Many of these malignancies may benefit from autologous hematopoietic stem cell transplantation. However, filgrastim administered to mobilize hematopoietic stem cells may precipitate severe and sometimes fatal sickle crisis in patients with sickle-cell anemia or complex sickle-cell hemoglobinopathies.5, 6 A previous single report describes successful autologous marrow transplantation in a patient with sickle-cell disease and diffuse large-cell lymphoma.2 Filgrastim was used to support initial chemotherapy and was also administered post transplantation without clinical evidence of sickle-cell crisis. We now report a successful filgrastim mobilized hematopoietic stem cell transplantation for diffuse large-cell lymphoma in a patient with sickle-cell hemoglobin C disease.

A 22-year-old male with a history of hemoglobin SC disease (HbSC) (1–2 mild-to-moderate sickle-cell pain crisis per year and recent penile prosthesis for recurrent priapism) was diagnosed with stage IV large-cell B-cell non-Hodkin's lymphoma with a high International Prognostic Index score (LDH-691, performance status–2, stage IV). He had persistent disease after seven cycles of rituximab, cyclophosphamide, adriamycin, vincristine and prednisone (R-CHOP) chemotherapy. While receiving prophylactic doses of filgrastim during the first two cycles of R-CHOP chemotherapy, he experienced severe sickle pain crises requiring hospitalization. Filgrastim was therefore not used in subsequent cycles. Two cycles of salvage rituximab, etoposide, cisplatin, cytarabine and methylprednisone (R-ESHAP) chemotherapy established that his disease was chemo-sensitive and an autologous hemopoietic stem cell transplant was planned. Given the history of sickle crisis with previous use of filgrastim, he was monitored after chemotherapy alone but mobilized insufficient CD34+ cells. We therefore performed an exchange transfusion using 10 units of peripheral red blood cells before stem cell mobilization with filgrastim, lowering HbS from 20 to 6%. Following rebound from ifosphamide and etoposide chemotherapy (third salvage cycle), filgrastim was initiated in a split dose schedule (total dose, 10 μg/kg divided in to two equal doses administered twice a day) in order to minimize the risk of hyperleucocytosis. The total white blood cell count following 5 days of filgrastim was 18.7 × 109/l and CD34+ cells 29/μl. A total of 6.8 × 106/kg CD34+ cells were collected through 2 apheresis procedures. He then received high-dose chemotherapy with rituximab 375 mg/m2 × 1 day, carmustine 300 mg/m2 × 1 day, cytarabine 400 mg/m2 × 4 days, etoposide 400 mg/m2 × 4 days and melphalan 140 mg/m2 × 1 day (R-BEAM) and had rapid and sustained myeloid and platelet engraftment on days 9 and 10, respectively, without post transplant filgrastim. Engraftment was complicated by a moderately severe pain crisis similar to his previous filgrastim related crises that improved over 7 days. Of note, he developed hypophosphatemia at engraftment that required intensive replacement therapy. Post transplant restaging revealed a residual 2.5 cm lesion in the pelvis with no other evidence of disease; he is currently undergoing external beam radiation to the residual site.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, TX, Houston, USA

    R T Kamble & G Carrum

  2. Texas Oncology, PA, TX, Houston, USA

    C K Tin-U

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  1. R T Kamble
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  2. C K Tin-U
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Correspondence to R T Kamble.

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Kamble, R., Tin-U, C. & Carrum, G. Successful mobilization and transplantation of filgrastim mobilized hematopoietic stem cells in sickle cell-hemoglobin C disease. Bone Marrow Transplant 37, 1065–1066 (2006). https://doi.org/10.1038/sj.bmt.1705376

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