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Medullar toxicity after prolonged nitrous oxide exposure: an unexpected cause of bone marrow failure post allogeneic transplant

Bone Marrow Transplantation volume 51, pages 876–878 (2016)Cite this article

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Here, we describe the case of a 16 year-old girl who presented with secondary bone marrow failure following allogeneic haplo-identical stem cell transplant (SCT). The patient, an 11-year old girl was treated for AML with normal karyotype, and underwent a first SCT from her brother, after obtaining a first CR. Two years later, as the disease relapsed, the patient received a salvage regimen (gemtuzumab, Ara-C and fludarabine), leading to a second CR. Two years later, at the age of 16, a second relapse occurred and, after salvage chemotherapy, she underwent a second SCT from a haplo-identical donor. Pretransplant bone marrow analysis showed CR. The conditioning regimen was based on thiotepa, IV busulfan and fludarabine. Graft versus host–disease prophylaxis consisted of cyclosporine, mycophenolate mofetil and post-transplant cyclophosphamide. A total of 7.54 × 106 CD34+ cells per kg, obtained by apheresis from her haplo-identical mother, were infused. Engraftment was enhanced with GCSF from day 6 until neutrophils were up to 1 × 109/L. Engraftment occurred on day 18 (neutrophils>0.5 × 109/L). Chimerism evaluation on day 30 was full donor type. Bone marrow evaluation at day 30 showed a normal cellularity with no blast excess.

A bone marrow analysis performed on day 55 revealed a normal cellularity with no excess of blasts, excluding a disease relapse. The erythroid lineage was abnormal, showing hyperplasia and megaloblastosis. The granulocytic compartment was characterized by a relative excess of myelocytes and promyelocytes without maturation blockade. Blood tests showed a moderate deficiency of vitamin B12 (142 pg/mL, normal range: 180–820 pg/mL), and the patient did receive a systemic treatment with folate. The homocystein level was not measured. Bone marrow revealed megaloblastic anemia, which cannot be explained by a moderate vitamin B12 deficiency. As the presentation contrasted with the relatively modest degree of cobalamine deficiency, we suspected it could represent an adverse effect of NO. MEOPA administration was then stopped at day 54 and IV vitamin B12 supplement was started. As shown on Figure 2, 3 days after NO was stopped, the reticulocyte and neutrophil counts increased and reached >30 × 109/L and 1 × 109/L on day 59, respectively. Bone marrow control, performed 3 weeks later, did not show any sign of megaloblastosis. The quick hematologic improvement after stopping NO gas exposure argued for its causality.

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Authors and Affiliations

  1. Service d’hématologie, Hôpital Saint Antoine, Paris, France

    A Vozy, M T Rubio, M Mohty & A-C Mamez

  2. Centre d’évaluation et de traitement de la douleur, Hôpital Saint Antoine, Paris, France

    M Cohen & S Rostaing-Rigattieri

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  1. A Vozy
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  2. M Cohen
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Correspondence to A-C Mamez.

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AV collected the data and wrote the manuscript. AV, MC, MTR, SRR, MM were responsible for patient care. ACM was responsible for data collection, review and manuscript preparation. All the authors read and approved the final manuscript.

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Vozy, A., Cohen, M., Rubio, M. et al. Medullar toxicity after prolonged nitrous oxide exposure: an unexpected cause of bone marrow failure post allogeneic transplant. Bone Marrow Transplant 51, 876–878 (2016). https://doi.org/10.1038/bmt.2015.314

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