1. ¹Departments of Pediatric Blood & Marrow Transplantation, Minneapolis, MN, USA
2. ²Department of Internal Medicine, University of Minnesota, MN, USA

Two sisters with Hurler syndrome underwent allogeneic hematopoietic cell transplantation (HCT) from unrelated donors. After discharge from the inpatient unit, they were simultaneously diagnosed with parainfluenza virus type I (PIV-I) upper respiratory illness (URI), pancytopenia, and severe bone marrow hypoplasia.

Patient 1: At 21 days after HCT, her neutrophil count was >1000/mm³ and peripheral blood showed 100% donor chimerism. On day 40, her white count was 4100/mm³. On day 45, she was readmitted with fever and rhinorrhea; her father and nanny also had URI. Her total white count was <100/mm³. Co-Trimoxazole was discontinued. Nasal wash was positive for PIV-I by heme adsorption and negative for other respiratory viruses (including adenovirus); viral studies in feces, including adenovirus antigen and culture, were negative. Two bone marrow evaluations 1 week apart revealed nearly acellular morphology, with no cells of donor origin; PCR analyses for parvovirus and human herpesvirus-6 (HHV-6) were negative and no virus was isolated in marrow culture. Pancytopenia persisted; on day 67, she received a peripheral blood stem cell 'boost' from her donor, leading to neutrophil recovery with donor-derived engraftment (peripheral blood, 92% donor). After 5 weeks, she developed disseminated adenovirus disease and died.

Patient 2: At 5 months after an uneventful HCT, she developed immune hemolytic anemia (anemia, positive direct antiglobulin test, and reticulocytosis), responsive to prednisone; donor chimerism was 100%. After 1 month, and 3 days after her sister's similar presentation, she presented with URI symptoms and pancytopenia (WBC <100/mm³). Co-Trimoxazole was discontinued. Nasal wash for respiratory viruses isolated PIV-I. No virus was detected in feces culture. Bone marrow was acellular, yet with >90% cells of donor origin; parvovirus and HHV-6 PCR were negative. Owing to persistent pancytopenia, she received a second peripheral blood stem cell graft from the same donor, resulting in full donor-derived hematopoietic recovery. She is alive and well 2 years later.

In this report, we present two sisters who simultaneously developed bone marrow aplasia concomitant with PIV-I infection. Both had undergone allogeneic HCT with complete donor engraftment. The course of events implicates PIV-I as the causative agent for secondary bone marrow failure after HCT in these siblings. While secondary graft failure is a well-known complication after HCT, the cause is often unknown. The differential diagnosis includes viral infections; however, a specific viral etiology (eg HHV-6¹) is identified only occasionally.

Parainfluenza virus URI is primarily a disease of young children, although adults can also be infected and transmit the disease.² While PIV is a recognized cause of respiratory disease and mortality in HCT recipients,^3,4,5 it has not been associated with secondary marrow failure in this patient population. However, there have been reports of allograft rejection associated with PIV (albeit PIV-III) infection in recipients of kidney⁶ and liver⁷ transplants. We recommend that PIV infection be considered as a potential etiology in patients with graft failure following HCT. Bone marrow viral cultures are typically (and at our institution) setup on cell lines to detect herpesviruses and enteroviruses. Isolation of PIV when suspected would require a specific request to the Virology laboratory so that additional cultures on suitable cell lines are included.