Chapter 34, Ep 2 of 4: Hematopoietic Cell Transplant Gut GVHD

Episode two takes the other host state hiding behind the word transplant: the hematopoietic cell transplant recipient whose donor immune system attacks the host. The post-transplant timeline organizes everything, with the first twenty-one days belonging to conditioning toxicity rather than graft-versus-host disease, so the timeline decides which diagnosis is even allowed. Gut disease is staged by daily stool volume on the Glucksberg-Seattle thresholds, the histology anchors on crypt apoptosis, and the biopsy-bench differential always includes CMV because apoptosis is not pathognomonic. Treatment is methylprednisolone first and ruxolitinib second on the strength of a randomized trial, and the shared move across both host states is to pair every immunosuppression escalation with an infectious workup.   Topics covered The post-transplant timeline and conditioning toxicity Sinusoidal obstruction syndrome and defibrotide Acute GVHD target organs and prognosis Glucksberg-Seattle gut staging by stool volume Crypt apoptosis histology and the Lerner system The biopsy-bench differential and CMV overlap Steroids first and steroid-refractory definition Ruxolitinib and mechanism-matched later agents   Key decisions Read gut symptoms against the timeline: the first twenty-one days belong to conditioning toxicity, which mimics graft-versus-host disease but does not need graft-versus-host therapy. Stage gut GVHD by daily stool volume, with stage four defined by output greater than two thousand milliliters per day, severe pain, ileus, or hematochezia. Include CMV polymerase chain reaction and tissue immunohistochemistry in every suspected gut GVHD workup, because crypt apoptosis is not pathognomonic and CMV coexists often. Start intravenous methylprednisolone two milligrams per kilogram per day with the calcineurin inhibitor continued, reserving budesonide for upper-gut-only mild disease. Classify non-response at day five to seven as steroid-refractory and move to ruxolitinib rather than pushing methylprednisolone to four milligrams per kilogram or to colectomy. Give ruxolitinib five to ten milligrams twice daily as the first-line second therapy, matching later agents like vedolizumab or infliximab to the dominant tissue and cytokine. When CMV reactivates during a steroid course, treat with intravenous ganciclovir and hold immunosuppression escalation until viremia clears rather than reading it as GVHD progression.   For the full chapter with MCQs, tables, and primary-guideline references, visit www.boardpearls.com. Questions or feedback: [email protected]. (00:00) - The other transplant and the post-transplant timeline (00:44) - Timeline windows and sinusoidal obstruction syndrome (01:59) - Acute GVHD target organs and prognosis (03:01) - Staging gut disease by stool volume (03:59) - Crypt apoptosis and the biopsy-bench differential (05:44) - Steroids first and the steroid-refractory line (07:06) - Ruxolitinib and the later mechanism-matched agents (08:58) - Pairing immunosuppression escalation with infectious workup