Parvovirus B19-Associated Graft Failure after Allogeneic Hematopoietic Stem Cell Transplantation

Background Parvovirus B19 (PVB19) is a single-stranded DNA virus that infects erythroid progenitor cells, classically causing a pure red cell aplasia, but sometimes causing fulminant pancytopenia. PVB19 has been implicated in solid organ allograft failure, but no such literature exists for allogeneic hematopoietic stem cell transplantation (allo-HSCT). PVB19 may be an underappreciated complication in allo-HSCT. Methods Retrospective report of two pediatric patients diagnosed with PVB19 infection and allo-HSCT graft failure. Results Case #1: 1 year-old male with leukocyte adhesion deficiency (LAD) received reduced intensity conditioning with alemtuzumab, fludarabine, thiotepa, and melphalan, followed by a 10/10 HLA- matched, ABO-compatible, sibling donor bone marrow graft (4.85 × 108 TNC/kg and 9.74 × 106 CD34+ cells/kg). He achieved neutrophil and platelet engraftment by days +23 and +25, respectively. Day +29 chimerism was 100% donor unseparated. Patient had biopsy-proven acute GI GVHD at day +77, responsive to systemic steroids. Evaluation for unexplained transfusion-dependent normocytic normochromic anemia at day +88 revealed PVB19 by PCR (3900 copies/mL). Patient had history of intermittent, non-palpable, and non-specific blanching erythematous rash. At day +105, donor chimerism decreased to 9% unseparated and 5% myeloid engraftment. Flow cytometry revealed repopulation of original LAD phenotype, confirming secondary graft failure. The patient received a second allo-HSCT using the same donor at day +225. Case #2: 13 year-old male with acute myeloid leukemia received myeloablative conditioning with fludarabine and busulfan followed by a T cell-replete, 5/10 HLA-mismatched, ABO-compatible, sibling bone marrow graft (3.60 × 108 TNC/kg and 4.51 × 106 CD34+ cells/kg). GVHD prophylaxis included post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil. He achieved neutrophil engraftment by day +16. Patient had non-specific blanching rash with bone pain during the post-HSCT recovery period. Patient had low level CMV viremia treated with ganciclovir and valganciclovir early post-HSCT. Day +26 donor chimerism showed 89% unseparated and 100% myeloid engraftment. Patient developed pancytopenia unresponsive to G-CSF. Bone marrow exam on day +40 showed mixed chimerism, no recurrent AML, but detectable PVB19 by PCR. Blood PVB19 PCR was positive (312 copies/mL). The patient was diagnosed with secondary graft failure with persistent severe pancytopenia. He received a rescue allo-HSCT from the same donor at day + 69. Conclusions There are many risk factors and potential confounders in determining the exact etiology of graft failure after allo-HSCT. These two cases highlight the importance of including PVB19 PCR in the diagnostic evaluation for graft failure. PVB19 infection may be an important risk factor for allo-HSCT graft failure.