Background

Acute gastrointestinal GvHD (GI-aGvHD) refractory to first line treatment with systemic corticosteroids is resulting in death in the majority of patients. Intra-arterial local dose intensification in the gut has been reported in pediatric but not in adult patients. We prospectively assessed the feasibility and efficacy of regional intra-arterial steroid treatment in adult patients with severe (>= grade III) GI-aGvHD not responding to first line treatment.

Patients and Methods

Patients with more than +++ GI-aGvHD not responding to intravenous methylprednisolone at a dose of 2 mg/kg/day within 14 days were eligible for inclusion. Catheter guided intra-arterial steroid administration (IASA) was performed by accessing the right or left common femoral artery; a 4 Fr angiography catheter was used to locate and select the superior and inferior mesenteric artery and, in patients with upper gastrointestinal symptoms into the celiac trunk (9 patients) and the left gastric artery (2 patients). The mean total dose of methylprednisolone administered over 1 minute was 180 mg (120-240 mg). In 7 patients with persistent or recurring symptoms, IASA was repeated within 14 days. Response assessment was at 28 days after IASA. CR was defined as complete resolution of GI symptoms; partial response was defined as reduction of GI score from +++ to ++. Non-response was defined as the same grade of aGvHD, progression of symptoms or death within 28 days after IASA.

Results

Between January 2010 and June 2012, 12 consecutive patients with steroid-refractory GI-aGvHD received IASA as second line treatment. The patient's baseline characteristics are summarized in Table 1. The mean patient's age was 53 years (range 30 - 69), 9 were male and 3 female. All patients received peripheral blood stem cells as stem cell source. All 12 patients had grade III GI-aGvHD. At time of initial IASA, 4 patients had skin (grade + - +++) and 2 patients had liver (grade +) involvement. In all patients the overall grade of aGvHD was III. The median time from HSCT to onset of GI-aGvHD was 20 days (range 6 - 278). The median time from onset of GI-aGvHD to initial IASA was 19 days (range 9 - 41). 7 patients not responding to the first IASA received a second IASA (median period of time between IASA was 13 days, range 6 - 14). 83% of patients had gastrointestinal response including four patients (33%) with complete response at 28 days after IASA (Table 2). 6/12 patients were alive at a median time of 531 days (389 – 1362) after IASA. During IASA no technical complications occurred. There was one duodenal ulcer in one patient two days after second IASA that resolved after treatment.

Table 1

Patient's baseline characteristics.

Pat. Nr. age Diagnosis HLA match Conditioning regimen GvHD prophylaxis time to GI aGvHD (d) 
43 Follicular lymphoma 10/10 BEAM Mini Seattle CyA, Mycophenolat, ATG 20 
64 Plasmacell leukemia 10/10 Flu/TBI CyA Mycophenolat 100 
32 Morbus Hodgkin 10/10 BEAM Mini-Seattle CyA Mycophenolat 
65 MDS 10/10 Flu/Bu CyA, ATG MTX 38 
69 AML 10/10 Flu/TBI CyAMycophenolat 70 
46 ALL 10/10 Cy/TBI CyA, MTX 
64 MDS 10/10 Cy/Bu CyA, MTX 19 
30 AML 9/10 Cy/Bu CyA, MTX. ATG 19 
67 Plasmacell myeloma 10/10 Flu/TBI CyA, Mycophenolat 278 
10 59 Mantle cell lymphoma 9/10 BEAM Mini-Seattle CyA, Mycophenolat 83 
11 45 Lymphoplamocytic lymphoma 10/10 BEAM Mini-Seattle CyA, ATG Mycophenolat 10 
12 49 T-lymphoblastic lymphoma 10/10 Cy/TBI CyA, ATG MTX 
Pat. Nr. age Diagnosis HLA match Conditioning regimen GvHD prophylaxis time to GI aGvHD (d) 
43 Follicular lymphoma 10/10 BEAM Mini Seattle CyA, Mycophenolat, ATG 20 
64 Plasmacell leukemia 10/10 Flu/TBI CyA Mycophenolat 100 
32 Morbus Hodgkin 10/10 BEAM Mini-Seattle CyA Mycophenolat 
65 MDS 10/10 Flu/Bu CyA, ATG MTX 38 
69 AML 10/10 Flu/TBI CyAMycophenolat 70 
46 ALL 10/10 Cy/TBI CyA, MTX 
64 MDS 10/10 Cy/Bu CyA, MTX 19 
30 AML 9/10 Cy/Bu CyA, MTX. ATG 19 
67 Plasmacell myeloma 10/10 Flu/TBI CyA, Mycophenolat 278 
10 59 Mantle cell lymphoma 9/10 BEAM Mini-Seattle CyA, Mycophenolat 83 
11 45 Lymphoplamocytic lymphoma 10/10 BEAM Mini-Seattle CyA, ATG Mycophenolat 10 
12 49 T-lymphoblastic lymphoma 10/10 Cy/TBI CyA, ATG MTX 

Abbreviations: aGvHD, acute graft-versus-host disease; ATG, anti T-cell globulin; BEAM Mini-Seattle (Carmubris, Cytarabin, Etoposid, Fludara, Melphalan); Bu, Busulfan; Cy, cyclophosphamide; CyA, cyclosporine A; Flu, fludarabine; GI, gastrointestinal; IASA, intra-arterial steroid administration; MTX, methotrexate; TBI, total body irradiation.

Table 2

Response 28 days after intra-arterial steroid administration.

Pat. Nr. Response (GI) GI-aGvHD grade at response 
Partial 
Complete 
Complete 
Complete 
Complete 
Partial ++ 
Partial ++ 
Partial ++ 
Partial ++ 
10 Partial ++ 
11 No response Death 
12 No response +++ 
Pat. Nr. Response (GI) GI-aGvHD grade at response 
Partial 
Complete 
Complete 
Complete 
Complete 
Partial ++ 
Partial ++ 
Partial ++ 
Partial ++ 
10 Partial ++ 
11 No response Death 
12 No response +++ 

Abbreviations: aGvHD, acute graft-versus-host disease; GI, gastrointestinal.

Conclusion

Regional treatment of severe GVHD with IASA treatment seems to be a safe and effective second line treatment for steroid-refractory GI-aGvHD in adult patients. Our results compare favorably with reported results of steroid-refractory GI-aGvHD.

Disclosures:

No relevant conflicts of interest to declare.

Sign in via your Institution