Hematology, Oncology & Immunology · Topic 24 of 26

Hematopoietic Stem Cell Transplant

Transplant · stem cell and bone marrow

Hematopoietic Stem Cell Transplant

Autologous grafts bring neutropenia without GVHD; allogeneic grafts add graft-versus-tumor and GVHD. Watch the calendar: engraftment, SOS, then acute GVHD.

Key numbers

Engraftment: ANC above 500/µLANC > 500/µL

Acute GVHD: skin, gut, liver≤ 100 days

Grade ≥ 2 GVHD: methylprednisolone 2 mg/kg2 mg/kg/day

SOS: bilirubin ≥ 2, tender liverbilirubin ≥ 2 mg/dL

01 · Defined byEngraftment: ANC above 500/µL

Neutrophil engraftment means ANC above 500/µL (platelet engraftment above 20,000/µL), typically about 10–20 days after infusion and faster with peripheral blood grafts; until then the patient is profoundly neutropenic.

02 · GiveGrade ≥ 2 GVHD: methylprednisolone 2 mg/kg

Treat grade ≥ 2 acute GVHD with methylprednisolone 2 mg/kg/day (skin-only grade 1 gets topical steroids); about half respond. Steroid-refractory disease gets ruxolitinib, the FDA-approved second-line therapy.

03 · Defined bySOS: bilirubin ≥ 2, tender liver

Sinusoidal obstruction syndrome (veno-occlusive disease), usually within 3 weeks: bilirubin ≥ 2 mg/dL plus ≥ 2 of painful hepatomegaly, weight gain > 5% and ascites. Defibrotide is the only FDA-approved therapy for severe SOS.

Causes & risk factors

Why it happens

Day 0–30, 30–100, after 100: different threatsDays 0–30: conditioning toxicity, SOS, engraftment syndrome and infection during profound neutropenia. Days 31–100: CMV and other infections, acute GVHD, transplant TMA. After day 100: chronic GVHD, opportunistic infection, bronchiolitis obliterans.

Fungal risk: neutropenia early, GVHD laterInvasive fungal infection follows pre-engraftment neutropenia or severe GVHD treatment after engraftment; Candida causes most yeast infections and Aspergillus most mold infections, so recipients get antifungal prophylaxis.

Presentation

What you'll see

Acute GVHD: skin, gut, liver must knowAcute GVHD — donor T cells attacking recipient tissue — classically appears within 100 days of allogeneic HSCT and targets the skin (rash), gastrointestinal tract (diarrhea) and liver.

Engraftment syndrome: fever, rash, infiltrates at count recoveryEngraftment syndrome occurs with neutrophil recovery after autologous or allogeneic HSCT: noninfectious fever, rash, weight gain and pulmonary infiltrates or edema. Exclude infection and acute GVHD; give corticosteroids for severe cases.

Do right now

In this order

First moves

Pre-engraftment fever: antibiotics within 1 hour

→

Irradiated blood products for every HSCT patient

→

Grade ≥ 2 GVHD: methylprednisolone 2 mg/kg2 mg/kg/day

Why each step

Pre-engraftment fever: antibiotics within 1 hourFever before engraftment is neutropenic fever: draw cultures and give broad-spectrum antibiotics within 1 hour (see Neutropenic Fever); neutropenic sepsis drives early ICU admission.

Irradiated blood products for every HSCT patientGive HSCT recipients irradiated cellular blood products (red cells, platelets) to prevent transfusion-associated GVHD, which is more than 90% fatal; routine solid-organ immunosuppression alone is not an indication.

Grade ≥ 2 GVHD: methylprednisolone 2 mg/kgTreat grade ≥ 2 acute GVHD with methylprednisolone 2 mg/kg/day (skin-only grade 1 gets topical steroids); about half respond. Steroid-refractory disease gets ruxolitinib, the FDA-approved second-line therapy.

Management

Orders

CMV-positive allogeneic recipients: letermovir prophylaxisCMV-seropositive allogeneic recipients get letermovir prophylaxis for about 100 days — it avoids the myelosuppression of ganciclovir and valganciclovir but has no HSV activity, so acyclovir prophylaxis continues.

GVHD prophylaxis: calcineurin inhibitor plus antimetaboliteStandard GVHD prophylaxis pairs a calcineurin inhibitor (tacrolimus or cyclosporine) with methotrexate or mycophenolate, with or without antithymocyte globulin; post-transplant cyclophosphamide is increasingly used, especially for haploidentical donors.

Red flags & don'ts

Avoid harm

Alveolar hemorrhage: progressively bloodier BAL complicationDiffuse alveolar hemorrhage (median about day 30, near engraftment) causes bilateral infiltrates and rapid respiratory failure; serial lavage returns get progressively bloodier, with ≥ 20% hemosiderin-laden macrophages.

Transplant TMA: reduce the calcineurin inhibitor complicationTransplant-associated thrombotic microangiopathy (median about day 86 after allogeneic HSCT) is managed by withdrawing or reducing the calcineurin inhibitor, with complement inhibition (eculizumab) for severe disease.

Bronchiolitis obliterans: new airflow obstruction late complicationBronchiolitis obliterans syndrome — new obstructive airflow limitation after allogeneic HSCT and a chronic GVHD complication — is the hardest late lung problem; screen with spirometry every 3 months after day 100 for 2 years.

Engraftment syndrome or acute GVHD?

Commonly confused

Timing	Around neutrophil recovery
Transplant type	Autologous or allogeneic
Features	Noninfectious fever, rash, weight gain, pulmonary infiltrates
Treatment	Supportive; corticosteroids if severe

More detail

Reference

Show 8 reference facts

Ruxolitinib, belumosudil and ibrutinib are approved for steroid-refractory chronic GVHD.

For gastrointestinal acute GVHD, nonabsorbable oral steroids (budesonide or beclomethasone) are added to systemic methylprednisolone; steroid-refractory GI GVHD carries median survival under 12 months.

SOS affects about 2–15% of allogeneic recipients, and severe SOS is highly lethal. Modified Seattle criteria: 2 of bilirubin > 2 mg/dL, hepatomegaly or RUQ pain, weight gain > 2%, within 20 days.

ICU admission follows 16–30% of allogeneic and 3–8% of autologous transplants, most often for respiratory failure or sepsis.

Idiopathic pneumonia syndrome (median about day 19) is noninfectious multilobar lung injury treated with high-dose corticosteroids (methylprednisolone 2 mg/kg/day), with etanercept as an established add-on.

Within 100 days of allogeneic HSCT, GVHD is the third leading cause of nonrelapse death (about 15%), after infection and organ failure.

In diffuse alveolar hemorrhage after HSCT, systemic corticosteroids have been linked to worse outcomes in some cohorts; inhaled tranexamic acid shows promise but lacks randomized data.

Stem cells come from bone marrow, peripheral blood (apheresis) or umbilical cord blood; peripheral blood grafts engraft faster than marrow.

Pearl

Autologous means no GVHD — and no graft-versus-tumor effect either.

Sources · Specific factors influence the success of autologous and allogeneic hematopoietic stem cell transplantation. Oxid Med Cell Longev 2009 (PMC2763249; engraftment definitions) · ADLM Pearls of Laboratory Medicine — Transfusion Support in Hematopoietic Cell Transplant · Critical care in hematopoietic stem cell transplantation: Common complications and management. World J Crit Care Med 2026;15:113235 (PMC13010842) · Recent advances in acute gastrointestinal graft versus host disease (aGvHD): aspects of steroid-resistant disease. Ann Hematol 2025 (PMC11971137) · Utility of the refined EBMT diagnostic and severity criteria 2023 for sinusoidal obstruction syndrome/veno-occlusive disease. Bone Marrow Transplant 2024 (PMC10994840) · Engraftment syndrome following hematopoietic stem cell transplantation: a systematic approach toward diagnosis and management. Med Oncol 2022 (PMC9718873) · Merck Manual Professional — Complications of Transfusion (transfusion-associated GVHD and irradiation) · Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients. J Clin Med 2020 (PMC7141503) · Noninfectious pulmonary complications of haematopoietic stem cell transplantation. Eur Respir Rev 2020 (PMC9488720) · Novel Pharmacological Treatment Options of Steroid-Refractory Graft-versus-Host Disease. Adv Hematol 2023 (PMC10718798) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).