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Immunohistochemical and FISH analyses identify synovitis associated with chronic GVHD after allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 42, pages 289–291 (2008)Cite this article

Chronic GVHD (cGVHD) is a common complication of allogeneic hematopoietic SCT, which affects 40–70% of recipients in skin, mucosae, liver and lung.1 Arthralgia and arthritis with synovitis are rare features of cGVHD, being occasionally associated with the presence of autoantibodies.2 FISH analysis for sex chromosome in sex-mismatched transplant has been proposed for the genotypic characterization of mononuclear cells infiltrate, supporting cGVHD diagnosis. We report the first case of a 33-year-old male patient developing arthritis and synovitis following a second allogeneic gender-mismatched hematopoietic SCT from HLA-identical sibling; FISH analysis demonstrated the donor origin of the inflammatory infiltrate within the synovial tissues, thus confirming the diagnosis of cGVHD.

A 33-year-old male patient affected by AML M2 FAB, FLT3 internal tandem duplication (ITD) negative, intermediate risk karyotype and hyperleucocytosis at the onset received in the first CR an autologous transplantation due to HLA-identical sibling donor transient unavailability. After disease relapse, the patient received a reinduction therapy without response and then underwent an allogeneic transplantation of PBSC from his HLA-identical sister. The conditioning regimen consisted of TBI (1320 cGy) and CY (120 mg/kg) followed by CsA and short course MTX as GVHD prophylaxis. At 100 days from transplant, the patient experienced extensive cGVHD involving lungs and liver successfully treated with CsA, steroids and extracorporeal photopheresis. During immunosuppressive therapy, the patient developed hematological and extra hematological (gingival and testicular) relapse. After chemotherapy reinduction, he achieved a second CR with fully donor chimerism demonstrated by both FISH and short tandem repeat (STR) and persistence of liver cGVHD was consolidated with a second PBSC allogeneic transplant from the same donor after conditioning with thyotepa 15 mg/kg and CY 120 mg/kg. The engraftment was prompt and sustained and the patient was discharged from the hospital showing a full chimerism. At day +48 on CsA treatment, the patient developed a painful tenosynovitis of bilateral coxa joints. BM aspirate evaluation confirmed the CR and the chimerism was fully donor both on peripheral blood and BM. Abdominal and pelvis CT scan revealed synovial fluid with increased synovial thickness of both coxa joints. After a few days, the patient developed painful tenosynovitis in both knee joints and severe functional impairment. Electromyography showed no significant sensory or motor deficit. The knee synovial fluid was clear, without cells and normal proteins. Autoantibodies were negative, including antinuclear antibodies (ANA), extractable nuclear antigen (ENA) and anti-smooth muscle antibodies (ASMA), circulating immunocomplexes. Multiple synovial biopsies were taken.

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Authors and Affiliations

  1. Department of Hematology, University of Florence, Florence, Italy

    C Nozzoli, S Guidi, R Saccardi & A Bosi

  2. Department of Human Pathology and Oncology, University of Florence, Florence, Italy

    M Paglierani, E Wnekowicz, M Santucci & D Massi

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  1. C Nozzoli
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  2. S Guidi
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  3. M Paglierani
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  4. E Wnekowicz
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  7. M Santucci
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  8. D Massi
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Correspondence to D Massi.

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Nozzoli, C., Guidi, S., Paglierani, M. et al. Immunohistochemical and FISH analyses identify synovitis associated with chronic GVHD after allogeneic hematopoietic SCT. Bone Marrow Transplant 42, 289–291 (2008). https://doi.org/10.1038/bmt.2008.161

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