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Myeloablative immunosuppressive treatment with autologous haematopoietic stem cell transplantation in a patient with psoriatic arthropathy and monoclonal gammopathy of undetermined significance
  1. M Mohren,
  2. T Daikeler,
  3. D Benz,
  4. I Günaydin,
  5. L Kanz,
  6. I Kötter
  1. Department of Haematology, Oncology, Immunology and Rheumatology, Tübingen University Hospital, Tübingen, Germany
  1. Correspondence to:
    Dr I Kötter
    Department of Internal Medicine II, Haematology/Oncology, Immunology and Rheumatology, University Hospital, Otfried-Müller-Str 10, 72076 Tübingen, Germany; ina.koettermed.uni-tuebingen.de

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Transplantation of peripheral blood stem cells (PBSCT) is currently explored in patients with refractory autoimmune diseases,1,2 and results so far show that about two thirds of patients who receive a transplant benefit from this procedure.3 Transplant related mortality in patients with autoimmune disease is similar to that seen in patients with non-Hodgkin’s lymphoma.4

CASE REPORT

We report on a 34 year old male patient with a 16 year history of psoriatic arthropathy with mutilating bilateral lesions of the wrists, metacarpal, proximal and distal interphalangeal and metatarsal, and lower extremity interphalangeal joints, who was refractory to treatment with multiple disease modifying, immunosuppressive substances, including gold, methotrexate (MTX), MTX plus sulfasalazine, cyclosporin A (CSA), mycophenolate mofetil (MMF) alone or in combination with CSA, steroids, and a combination of CSA, MTX, and MMF. IgA κ monoclonal gammopathy of unknown significance developed later in the course of the disease without evidence for either multiple myeloma or systemic amyloidosis. Treatment of arthritis with a non-steroidal anti-inflammatory drug (NSAID) was complicated by a duodenal ulcer. There were only modest psoriatic skin lesions affecting the extensor surfaces of both knees and elbows.

PBSCT was considered in this patient, because tumour necrosis factor α antagonists had not yet been licensed for use in psoriatic arthropathy at that time. We were particularly concerned about the presence of the IgA κ paraprotein, so therapeutic strategies to control symptoms of arthritis also aimed at eliminating the potentially hazardous plasma cell clone. Haematopoietic stem cells were mobilised with cyclophosphamide (Cy) 4000 mg/m2 and granulocyte-colony stimulating factor (G-CSF) 5 μg/kg. Stem cell apheresis was performed following standard procedures, and T cell depletion of the graft was achieved by CD 34+ selection using the CliniMACS device. CD 34+ cells (11.38×106 cells/kg) were harvested. Myeloablative immunosuppression consisted of Cy 200 mg/kg (50 mg/kg/day, days −5 to −2), and in vivo T cell depletion was achieved with antithymocyte globulin (ATG) (Fresenius) 80 mg/kg (20 mg/kg/day, days −4 to −1). CD 34+ cells (5.21×106 cells/kg) were retransfused on day 0. An acute flare of arthritis occurred while the patient was receiving G-CSF for stem cell mobilisation, and this was symptomatically treated with an NSAID. Pancytopenia after myeloablative treatment was complicated by neutropenic fever (39.1°C) on day 11, subsiding under standard antibiotic treatment. Mucositis and diarrhoea WHO grade I occurred, lasting for 3 days. Within 3 days after the start of high dose Cy the symptoms of arthritis completely disappeared, as did the psoriatic lesions. As granulocytes did not recover by day 15, G-CSF was started, and no new flare of arthritis was observed. Granulocytes were >109/l by day 19, platelets >20×109/l by day 21, and the erythrocyte sedimentation rate and C reactive protein subsequently normalised.

Clinical findings were confirmed by negative bone scintigraphy on day 21. Within 6 months after PBSCT the IgA κ paraprotein disappeared.

However, 16 months after PBSCT, polyarthritis recurred, although without laboratory evidence of systemic inflammation (erythrocyte sedimentation rate and C reactive protein were within normal limits), apparently now following a more benign course. At present, the patient is receiving low dose MTX (10 mg/week) and a COX-2 selective NSAID (celecoxib) and has only mild signs of arthritis of the right wrist. Monoclonal gammopathy has not reappeared.

DISCUSSION

To our knowledge this is the first report of PBSCT in a patient with psoriatic arthropathy. In rheumatoid arthritis, disease activity decreased markedly in 8 of 12 patients, with patients free from disease modifying antirheumatic drug treatment for a period of 130 days during a 7–21 month follow up after PBSCT.5 Remission of arthritis in patients with rheumatoid arthritis after PBSCT usually lasts for 6–9 months.5–7 In our patient relapse of arthritis, with a now more benign course, did not occur until 16 months after PBSCT, possibly owing to a more aggressive immunosuppressive regimen, including in vivo T cell depletion with ATG and graft manipulation. Three patients with remission of psoriasis (without arthropathy) after PBSCT due to a haematological disease relapsed within 6–14 months as described in a previously published report.8 However, skin involvement was not of major concern in our patient.

We conclude that it may be worth exploring PBSCT further in young patients with mutilating psoriatic arthropathy who are resistant to disease modifying antirheumatic drugs and for whom tumour necrosis factor α antagonist treatment has failed.

REFERENCES

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