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Clinically significant adverse events after major ABO mismatch BMT

Bone Marrow Transplantation volume 51, pages 148–149 (2016)Cite this article

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It is well known that RBCs present in a major ABO mismatch bone marrow transplant (BMT) can cause clinical hemolysis. To prevent this infusion complication, the volume of RBCs in the bone marrow (BM) graft can be reduced via various RBC depletion techniques. This management of major ABO mismatch BMT varies considerably due to the lack of strong evidence-based guidelines.1 In particular, it is not known what volume of residual incompatible RBCs is safe, especially for smaller pediatric patients. Patrick et al.2 attempted to address this important question in the recent article Major ABO incompatible BMT in children: determining what residual volume of donor red cells can safely be infused following red cell depletion. Through a retrospective chart review of 78 children who underwent major ABO mismatch BMT (most after RBC depletion with pentaspan sedimentation), they identified only two patients who had clinically significant adverse events related to the infusion of ABO-incompatible BM. These two patients, who both developed significant renal impairment, received 3.66 and 3.9 ml of incompatible RBCs per patient kg (compared with the median volume of 1.6 ml/kg). The authors implied that clinically significant adverse events following major ABO-incompatible BMT only occur when patients receive >3 ml/kg of incompatible RBCs. This idea is inaccurate as we have observed clinically significant adverse events related to the infusion of major ABO-incompatible BM in patients who received <3 ml/kg of incompatible RBCs. Here we report the details of this observation in one pediatric and one adult patient (Table 1).

Table 1 Summary of reported patients with clinically significant adverse events
Full size table

Patient 1 was a 45 kg 13-year-old female with treatment-related AML. Pre-BMT glomerular filtration rate was abnormal at 82 ml/min/1.73 m2 body surface area, but her serum creatinine was normal at 0.5 mg/dL. She received busulfan and fludarabine as a reduced intensity conditioning regimen. The patient was O+, while the 8/8 HLA-matched unrelated donor was A+. After RBC depletion with hydroxyethyl starch sedimentation, the RBC volume in the BMT product was reduced from 458 to 51 ml (1.1 ml/kg). Hydration with 2x maintenance IV fluids was started 4 h before infusion and acetaminophen, diphenhydramine and hydrocortisone were administered as infusion premedications. The BM graft was infused over 4.4 h (0.26 ml/kg/h RBCs) and the patient received a dose of IV furosemide following the infusion. No significant adverse event occurred during the infusion. Post infusion the patient began to have hemoglobinuria. At 6 h post-infusion serum creatinine increased to 1.6 mg/dL with an elevated potassium of 5.4 mmol/L and bilirubin of 2.2 mg/dL. Given the patient’s evolving renal impairment which included decreased urine output, she was given IV furosemide and started on a renal dose dopamine infusion. At 9 h post-infusion, creatinine peaked at 1.7 mg/dL (340% above baseline). Cyclosporine, valacylovir, voriconazole and day +1 methothrexate were held. Mycophenolate mofetil was started as an alternative GvHD prophylaxis agent. Hyperhydration was continued as the patient continued to have hemoglobinuria. On day +4, hemoglobinuria resolved and creatinine stabilized at 0.9 m/dL. Previously held nephrotoxic medications were resumed, but methotrexate was given at 50% dosing on day +3 and day +6. She engrafted and was discharged from the hospital on day +27.

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References

  1. Raimondi R, Soli M, Lamparelli T, Bacigalupo A, Arcese W, Belloni M et al. ABO-incompatible bone marrow transplantation: a GITMO survey of current practice in Italy and comparison with the literature. Bone Marrow Transplant 2004; 34: 321–329.

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Authors and Affiliations

  1. Department of Pathology, Center for Transfusion and Cellular Therapy, Emory University, Atlanta, GA, USA

    R S Nickel & E K Waller

  2. Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA

    R S Nickel, M Qayed & K-Y Chiang

  3. Division of Hematology, Children’s National Health System, Washington, DC, USA

    R S Nickel

  4. Division of Stem Cell Transplantation and Immunotherapy, Emory University, Atlanta, GA, USA

    E K Waller

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  1. R S Nickel
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Correspondence to R S Nickel.

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Nickel, R., Waller, E., Qayed, M. et al. Clinically significant adverse events after major ABO mismatch BMT. Bone Marrow Transplant 51, 148–149 (2016). https://doi.org/10.1038/bmt.2015.230

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