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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.

Background Clostridium difficile infection (CDI) is a major source of morbidity for patients undergoing autologous and allogeneic hematopoietic stem cell transplantation (HSCT). CDI can complicate gastrointestinal mucositis, lead to mucosal barrier infections or sepsis, and compromise nutrition after HSCT. CDI may contribute to acute gastrointestinal graft-versus-host disease (GI aGVHD) and reduce overall survival in allogeneic HSCT patients. Use of enteral vancomycin as CDI prophylaxis may reduce morbidity and improve outcomes in HSCT recipients. Methods As a quality improvement initiative, enteral vancomycin was instituted as CDI prophylaxis in all autologous and allogeneic HSCT recipients at Methodist Children's Hospital beginning 02/13/19. Patients were prescribed vancomycin 125 mg oral/enteral twice daily (Ganetsky et al. Clin Infect Disease 2019; 68 (12):2003-2009) from HSCT admission to discharge home. Patients readmitted during the first 100 days after HSCT resumed enteral vancomycin while hospitalized. Physicians, advanced practice providers, and pharmacists monitored enteral vancomycin administration. The infectious disease and prevention team monitored CDI and weekly vancomycin resistant enterococcus (VRE) stool testing per institutional policy. Pre- and post-implementation data was retrospectively reviewed (number of HSCT patients, CDI, VRE, adverse events of enteral vancomycin, and GI aGVHD). Two-sided Fisher's exact test was used to compare CDI before and after institution of enteral vancomycin prophylaxis. Results Between 01/05/2018 and 02/12/2019, the rate of CDI was 29% (n=9/31). After implementation of CDI prophylaxis (02/13/19 to 09/16/19), the rate of CDI was 0% (n=0/23). Enteral vancomycin resulted in a significant reduction in the number of CDI cases (p=0.0068). Prior to implementation of CDI prophylaxis, 26% (n=7/27) of allogeneic HSCT recipients developed GI aGVHD. Of the 7 patients that developed GI aGVHD, 6 had a history of CDI. After implementation of CDI prophylaxis, 7% (n=1/14) of allogeneic HSCT recipients developed GI aGVHD. There were no VRE positive screens or infections. There were no adverse events related to enteral vancomycin. Conclusions Enteral vancomycin appears to be safe and effective CDI prophylaxis in pediatric, adolescent, and young adult HSCT recipients. Since institution of enteral vancomycin prophylaxis, there has been a significant reduction of CDI in our HSCT patients. This quality improvement project is ongoing and future analyses will compare GI aGVHD and overall survival with CDI pre- and post-implementation of enteral vancomycin prophylaxis.