Hematopoietic Cell Transplantation and Outcomes Related to Human Papillomavirus Disease in GATA2 Deficiency: Running title: HPV in GATA2 after Transplantation

Abstract Background GATA2 deficiency is a bone marrow failure syndrome effectively treated with hematopoietic cell transplantation (HCT), which also addresses the predisposition to many infections (prominently mycobacterial). However, many GATA2-deficient persons who come to HCT also have prevalent and refractory human papilloma virus disease (HPVD), which can be a precursor to cancer. Objective We analyzed 75 HCT recipients for the presence of HPVD to identify patient characteristics and transplant results that influence HPVD outcomes. Study Design We assessed the impact of cellular recovery and iatrogenic post-transplant immunosuppression, as per protocol (PP) or intensified/prolonged (IP) graft-versus-host disease (GVHD) prophylaxis or treatment, on the persistence or resolution of HPVD. Results Our HCT experience with 75 recipients shows a prevalence of 49% with anogenital HPVD, which was either a contributing or primary factor in the decision to proceed to HCT. Of 24 recipients with sufficient follow-up, 13 had resolution of HPVD, 8 with IP and 5 PP. Eleven recipients had persistent HPVD, 5 with IP and 6 with PP immunosuppression. No plausible cellular recovery group (NK cells or T-cells) showed a significant difference between HPV outcomes. One recipient died of metastatic squamous cell carcinoma, presumably of anogenital origin, 33 months post-transplant after prolonged immunosuppression for chronic GVHD. Conclusion Individual cases demonstrate the need for continued aggressive monitoring, especially in the context of disease that is prevalent at transplant or prior malignancy. HCT proved curative in many cases in which HPVD was refractory and recurrent prior to transplant, supporting a recommendation that HPVD should be considered an indication rather than contraindication to HCT, but post-transplant monitoring should be prolonged with a high level of vigilance for new or recurrent HPVD.