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 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.
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.
Pat. Nr. | age | Diagnosis | HLA match | Conditioning regimen | GvHD prophylaxis | time to GI aGvHD (d) |
1 | 43 | Follicular lymphoma | 10/10 | BEAM Mini Seattle | CyA, Mycophenolat, ATG | 20 |
2 | 64 | Plasmacell leukemia | 10/10 | Flu/TBI | CyA Mycophenolat | 100 |
3 | 32 | Morbus Hodgkin | 10/10 | BEAM Mini-Seattle | CyA Mycophenolat | 6 |
4 | 65 | MDS | 10/10 | Flu/Bu | CyA, ATG MTX | 38 |
5 | 69 | AML | 10/10 | Flu/TBI | CyAMycophenolat | 70 |
6 | 46 | ALL | 10/10 | Cy/TBI | CyA, MTX | 8 |
7 | 64 | MDS | 10/10 | Cy/Bu | CyA, MTX | 19 |
8 | 30 | AML | 9/10 | Cy/Bu | CyA, MTX. ATG | 19 |
9 | 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 | 7 |
Pat. Nr. | age | Diagnosis | HLA match | Conditioning regimen | GvHD prophylaxis | time to GI aGvHD (d) |
1 | 43 | Follicular lymphoma | 10/10 | BEAM Mini Seattle | CyA, Mycophenolat, ATG | 20 |
2 | 64 | Plasmacell leukemia | 10/10 | Flu/TBI | CyA Mycophenolat | 100 |
3 | 32 | Morbus Hodgkin | 10/10 | BEAM Mini-Seattle | CyA Mycophenolat | 6 |
4 | 65 | MDS | 10/10 | Flu/Bu | CyA, ATG MTX | 38 |
5 | 69 | AML | 10/10 | Flu/TBI | CyAMycophenolat | 70 |
6 | 46 | ALL | 10/10 | Cy/TBI | CyA, MTX | 8 |
7 | 64 | MDS | 10/10 | Cy/Bu | CyA, MTX | 19 |
8 | 30 | AML | 9/10 | Cy/Bu | CyA, MTX. ATG | 19 |
9 | 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 | 7 |
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.
Pat. Nr. | Response (GI) | GI-aGvHD grade at response |
1 | Partial | + |
2 | Complete | 0 |
3 | Complete | 0 |
4 | Complete | 0 |
5 | Complete | 0 |
6 | Partial | ++ |
7 | Partial | ++ |
8 | Partial | ++ |
9 | Partial | ++ |
10 | Partial | ++ |
11 | No response | Death |
12 | No response | +++ |
Pat. Nr. | Response (GI) | GI-aGvHD grade at response |
1 | Partial | + |
2 | Complete | 0 |
3 | Complete | 0 |
4 | Complete | 0 |
5 | Complete | 0 |
6 | Partial | ++ |
7 | Partial | ++ |
8 | Partial | ++ |
9 | Partial | ++ |
10 | Partial | ++ |
11 | No response | Death |
12 | No response | +++ |
Abbreviations: aGvHD, acute graft-versus-host disease; GI, gastrointestinal.
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.
No relevant conflicts of interest to declare.
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