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Haploidentical allogeneic stem cell transplantation with post-transplant cyclophosphamide and subsequent kidney transplant for patients with severe sickle cell disease with end-stage kidney disease (ESKD)

Bone Marrow Transplantation volume 58, pages 835–838 (2023)Cite this article

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Adult patients with sickle cell disease (SCD) and end-stage kidney disease (ESKD) have limited curative options as many are deemed not to be candidates for stem cell transplantation (HCT) or gene-therapy trials. Furthermore, many patients lack a matched donor. Haploidentical (haplo)-HCT with post-transplant cyclophosphamide (PTCy) has improved access for patients [1]. Mitigating the risk of graft loss for SCD patients undergoing haplo-HCT that cannot tolerate myeloablative conditioning, two groups have reported successful engraftment with modified non-myeloablative (NMA) conditioning regimens using PTCy (50 mg/kg on days +3 and +4) in combination with anti-thymocyte globulin (ATG) (0.5 mg/kg on day −9 and 2 mg/kg on days −8 and −7) after fludarabine (Flu 30 mg/m2 on days −6 to −2), cyclophosphamide (Cy 14.5 mg/kg on days −6 and −5) and TBI 400 cGy (on day-1) or similar Flu/Cy with the addition of Thiotepa (10 mg/kg on day −7) and TBI 200cGy [2, 3]. Here we report who we believe to be the first patient with SCD and ESKD undergoing a haplo-HCT Flu/Cy/TBI 400 cGy and review the considerations for future patients.

A 26-year-old male (B+, CMV-) with SCD (Hb SS) and sickle-cell-nephropathy on hemodialysis, was referred for evaluation for HCT. He was diagnosed at newborn screening. On his first adult visit at age 21, he was controlled on hydroxyurea, but with occasional vaso-occlusive crises, recurrent priapism, and stage 2 chronic kidney disease (CKD). He had had two episodes of acute-chest-syndrome. A kidney biopsy showed focal-segmental-glomerulosclerosis. Over the next 4-years, his CKD progressed with recurrent hyperkalemia, acidosis, and anemia requiring 2-3 transfusions monthly. Between ages 24-25, he had 7 hospitalizations including 2 to the ICU. He developed atrial flutter requiring ablation and started therapy for tachycardia-induced non-ischemic cardiomyopathy (NICM). At age 25, he was started on hemodialysis. He was trying to complete college and his quality-of-life was severely affected.

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Fig. 1: Treatment Schema.
Fig. 2: Bone marrow biopsy demonstrating histologic features of hyperparathyroidism (renal osteodystrophy in the setting of renal failure).

Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We would like to thank the patient and his family for their trust in our team.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, NY, USA

    Alexandra Gomez-Arteaga, Nina Orfali, Inna Guindine, Jingmei Hsu, Sebastian A. Mayer, Adrienne A. Phillips, Tsiporah B. Shore, Sung Yoon & Koen van Besien

  2. Department of Haematology, St James Hospital, Dublin, Ireland

    Nina Orfali

  3. Department of Pharmacy, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, NY, USA

    Michelle Pasciolla

  4. Division of Hematology and Oncology, NewYork-Presbyterian Hospital Brooklyn Methodist Hospital, Brooklyn, NY, USA

    Ayanna Baptiste

  5. Division of Nephrology, Department of Medicine, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, NY, USA

    Jonathan Lin & Thangamani Muthukumar

  6. The Rogosin Institute, New York, NY, USA

    Jonathan Lin & Thangamani Muthukumar

  7. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, NY, USA

    Paul D. Simonson

  8. Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY, USA

    Edward DiCarlo

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  1. Alexandra Gomez-Arteaga
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Contributions

AG: was responsible for the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. NO contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. MP contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. AB contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. IG contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. JH contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. JL contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. SAM contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. AAP contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. TBS contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. PDS contributed to analyzing and interpreting the pathology and writing the report. ED contributed to analyzing and interpreting the pathology and writing the report. SY contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. TM contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results. KV contributed to the patient’s plan of care, writing the report, extracting, and analyzing data, interpreting results.

Corresponding author

Correspondence to Alexandra Gomez-Arteaga.

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The patient provided informed consent for publication.

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Gomez-Arteaga, A., Orfali, N., Pasciolla, M. et al. Haploidentical allogeneic stem cell transplantation with post-transplant cyclophosphamide and subsequent kidney transplant for patients with severe sickle cell disease with end-stage kidney disease (ESKD). Bone Marrow Transplant 58, 835–838 (2023). https://doi.org/10.1038/s41409-023-01981-x

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