Successful Full-Term Live Birth in an Allogeneic Stem Cell Transplant Patient with Active Extensive Chronic Graft-Versus-Host Disease.
Authors: Shah Heather , Salzman Donna , Ashraf Khaleel , Vaughan William 
Published: October 2019

Abstract
Objective: Little information exists regarding pregnancy after allogeneic stem cell transplantation. Pregnancy in the setting of active graft-versus-host disease (GVHD) is even less common. We report an interesting case of a patient with active GVHD who had a spontaneous pregnancy four years after allogeneic stem cell transplant and whose GVHD remained stable during her pregnancy.
Patient information: Our patient is a 27 year-old African-American female who was diagnosed with aplastic anemia in January 2002. She was initially treated with anti-thymocyte gamma globulin (ATG) and cyclosporine with minimal response. She was red blood cell and platelet transfusion dependent during this time. She was referred to the UAB Bone Marrow Transplant Center for evaluation for allogeneic stem cell transplant in June 2002. Her conditioning regimen included cyclophosphamide and ATG. She received her stem cell transplant on July 30, 2002 and was no longer transfusion dependent seven months after her transplant. In January 2003, the patient was diagnosed with GVHD of her oropharynx and skin. She was treated with cyclosporine and oral solumedrol initially. By February 2003, mycophenolate mofetil was added to her regimen. She was tapered off of the solumedrol by day +366 and maintained on cyclosporine and mycophenolate. Tapering of her immunosuppressive medication was attempted multiple times unsuccessfully. Unfortunately, she progressed to sclerodermatous changes of the skin that were confirmed as GVHD by biopsy. She started psoralen and UVA light therapy (PUVA) in August 2004. Subsequently, she was treated with topical hydroquinone and FK-506 along with photopheresis and physical and occupational therapy. Pentoxifylline and vitamin E were added in August 2005. By August 2006, photopheresis had been decreased to every month and she was controlled on mycophenolate and photopheresis. Planned immunosuppressant taper at four years post-transplant was complicated by an unplanned pregnancy at that time. The patient’s photopheresis was discontinued because of concerns for teratogenicity with psoralens. During her pregnancy, the patient was maintained on full dose mycophenolate and low dose oral FK-506. Of note, the patient was not on any estrogen supplementation at the time of conception. The patient was monitored by the transplant team serially throughout her pregnancy. Her GVHD did not progress objectively, and the patient reported subjective improvement. The patient went on to deliver a healthy female infant at term via C-section.
Conclusions: Ours is the first reported case of pregnancy and successful delivery of a healthy infant in a patient with active extensive chronic GVHD. On review of the literature, only a few cases of spontaneous pregnancies after allogeneic stem cell transplant have been reported, and they typically involve reduced dose intensity chemoradiotherapy or occur in premenarchal patients. There are twenty unconfirmed cases of pregnancy in the transplant registry. More cases have been reported in solid organ transplant patients on immunosuppressive medications. As transplants for non-malignant disorders and the use of nonmyeloablative transplants increase, we expect to see more cases of pregnancy after transplant. Attention to fertility issues and monitoring for pregnancy in potentially fertile patients needs to be considered. Also, further research into the altered immune state during pregnancy may lead to further understanding of the mechanism of GVHD and possibly novel treatments.