LAUSR

To the Editor, Steroid-refractory gastrointestinal tract (GIT) acute graft-versus-host disease (SR-aGVHD) remains one the most lethal complications of allogeneic hematopoietic cell transplantation (HCT), with a mortality rate upwards of 75% [1, 2]. Despite the utility of various therapies, complete remission rates can average only at 30% [3]. Affected patients are treated with alternative and higher intensity immunosuppressive drugs to prevent tissue injury caused by immune attack mostly by alloreactive T cells. However, these patients have also deficiency in tissue regeneration and repair. It has been shown that severe GVHD is characterized by an imbalance of circulating tissue repair factors, with elevated amphiregulin and very low (<10 pg/ml) plasma epidermal growth factor (EGF). In addition to this, a urinary-derived preparation of human chorionic gonadotropin (hCG) improved chronic GVHD involving the skin and GIT [4]. The authors found that the expression of indoleamine-2,3-dioxygenase, and regulatory T cells (Tregs) were expanded [4]. Holtan et al. recently used human chorionic gonadotropin [Pregnyl (EGF and hCG)], in a phase I study for treatment of steroid refractory acute GVHD [5]. At day 28 of study, responses for initial therapy were 8/13 CR (62%), 0/13 PR (0%), and 5/13 NR (38%). Increased serum hCG, estradiol, and testosterone plasma EGF Treg expansion were observed in patients compared with baseline. GIT GVHD is one of the proteinlosing enteropathies associated with mucosal erosions [6, 7]. Albumin levels are consistently very low in these patients and hence also useful in predicting the occurrence of severe aGVHD [8], as well as its outcome (e.g., mortality) [9]. We present a case that demonstrates that the recovery of GIT of injury, tissue healing, and regeneration from GIT GVHD is a very slow and difficult process and takes long-time. A 53-year-old male with high-risk myelodysplastic syndrome received stem cells from his HLA-identical brother after conditioning with busulfan and fludarabine (BuFlu4). GVHD prophylaxis was comprised of minimethotrexate and tacrolimus. He had no acute complications and engrafted on day +15. Day +30 donor chimerism was 100% in myeloid cells both in peripheral blood and bone marrow, but 80% in T cells in peripheral blood. He developed severe neutropenia and thrombocytopenia, etiology unknown, but with no evidence of relapse. He was treated conservatively with growth factor support, transfusions, and the dose of tacrolimus was lowered to target lower levels (~5 ng/mL). His counts improved over time and T cell chimerism reached 100% 3 months after HCT. Day +89 the patient developed severe abdominal pain associated with large volume (>3 L) and bloody diarrhea. Mucosal sloughing was severe and easily noticeable. Sigmoidoscopy revealed severely ulcerated, erythematous, and congested rectal mucosa. Biopsy showed apoptosis with loss of crypts consistent with grade IV GVHD. He failed standard methylprednisolone, therefore a course of antiTNF and ATG therapy was initiated in combination with Pregnyl. Steroid therapy was rapidly tapered off given the lack of response. Although the abdominal pain improved and hemorrhage resolved, the stool volume continued to be high. Ruxolitinib, a second course of ATG and * Celalettin Ustun [email protected]