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Unmanipulated haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in a patient with paroxysmal nocturnal hemoglobinuria and secondary aplastic anemia

Bone Marrow Transplantation volume 51, pages 316–318 (2016)Cite this article

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Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for a variety of malignant and non-malignant hematologic disorders. Unfortunately, only about a third of candidates for alloHSCT have HLA-matched siblings. Haploidentical alloHSCT with post-transplant cyclophosphamide has become a safe and effective procedure for patients without an HLA-matched donor, either related or unrelated. Advantages over other unrelated sources include rapid availability of multiple potential donors, lower costs of graft acquisition, non-inferiority in tumor control and low incidence of chronic GvHD.1 In this report, we present a case of a patient with paroxysmal nocturnal hemoglobinuria (PNH) and severe aplastic anemia without response to eculizumab who was treated with a haploidentical alloHSCT with post-transplant cyclophosphamide with excellent hematological outcome and quality of life.

A 22-year-old man was hospitalized due to fatigue and pallor in November 2012. CBC showed severe and progressive pancytopenia (900 leukocytes/μL, 200 neutrophils/μL, 8 gr hemoglobin/dL with 0.2% reticulocytes and 25 000 platelets/μL), with elevated lactate dehydrogenase and suppressed haptoglobin levels. A bone marrow biopsy showed mild hypoplasia with cellularity between 10 and 50%. Peripheral blood flow cytometry showed a PNH clone (CD16−, CD55− and CD59−) in 5% of erythrocytes, 12% of monocytes and 5% of granulocytes. A new flow cytometric analysis 2 years later showed a PNH clone in 26% of erythrocytes and 72% of monocytes. Constitutional symptoms appeared in the meantime. Eculizumab treatment was initiated at a dose of 600 mg weekly for four doses and then 900 mg every other week. After 2 months of treatment, there was no clinical improvement; however, there was a significant decrease in the lactate dehydrogenase levels, although not to a normal value. We increased eculizumab dose to 1200 mg every other week for 2 months, without any further clinical response. Along with eculizumab, cyclosporine was added with the dose adjusted to maintain serum levels between 250 and 500 ng/μL, but no cell count improvement was observed. The patient had no siblings and unrelated donor search did not identify a suitably matched donor. Hence, we selected his father as a HLA 3/6-compatible haploidentical donor.

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  1. Programa de Trasplantes Hematopoyéticos, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    M Sarmiento & P A Ramírez

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  1. M Sarmiento
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  2. P A Ramírez
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Correspondence to M Sarmiento.

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Sarmiento, M., Ramírez, P. Unmanipulated haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in a patient with paroxysmal nocturnal hemoglobinuria and secondary aplastic anemia. Bone Marrow Transplant 51, 316–318 (2016). https://doi.org/10.1038/bmt.2015.251

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