Autologous stem cell transplantation in a lymphoma patient with a long history of ankylosing spondylitis

Sir, Based on animal studies and anecdotal human data, high‐dose chemotherapy supported by stem cell transplantation (SCT) has been recently suggested as an experimental therapy in patients with various autoimmune diseases [1, 2]. While allogeneic SCT performed for another reason may lead to an apparent cure in some patients with concomitant rheumatic diseases [3], experience has been less promising in the case of autologous SCT (ASCT) [4, 5]. ASCT has recently been performed in about 140 patients solely on the grounds of severe or therapy‐resistant autoimmune disease [6]. Although a number of transplants have been performed in patients with systemic sclerosis, systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), there are no reports on the effects of ASCT in patients with ankylosing spondylitis (AS). A man born in 1934 was diagnosed as having AS in the 1960s. He had been previously treated with non‐steroidal anti‐inflammatory drugs, antimalarials, and corticosteroids. In 1996 the activity of the disease increased and the patient showed signs of advanced AS with a stiff spine, prominent thoracic kyphosis, limited chest movements and peripheral arthritis with dactylitis. Sulphasalazine was started and intramuscular methotrexate (12.5 mg/week) and oral prednisolone were added. In October 1996 the erythrocyte sedimentation rate (ESR) was 80 mm/h and C‐reactive protein (CRP) was 116 mg/l. The dose of methotrexate was doubled, which led to clinical improvement. In September 1997 the patient was diagnosed as having large cell B‐cell lymphoma with poor prognostic features. All anti‐rheumatic drugs were stopped. The patient received eight cycles of CHOP (cyclophosphamide 750 mg/m2 day 1, doxorubicin 50 mg/m2 day 1, vincristine 2 mg day 1 and prednisolone 100 mg on days 1–5), which led to a complete remission. Peripheral blood stem cell mobilization was performed with high‐dose cyclophosphamide (4 g/m2) and filgrastim 5 μg/kg/day. In April 1998 the patient was consolidated with BEAM (carmustine 300 mg/m2 day −7, etoposide 200 mg/m2 days −6 to −3, cytosine arabinoside 200 mg/m2 days −6 to −3 and melphalan 140 mg/m2 day −3) followed by infusion of unselected graft (2.6 × 106/kg CD34‐positive cells). The post‐transplant course has been uneventful. The patient has been in remission for lymphoma and without signs of peripheral arthritis or other signs of active AS. In August 1999, the ESR was 8 mm/h and CRP was <10 mg/l. At the most recent follow‐up in October 1999 the patient was well without any medication. Our patient had active AS treated with three anti‐rheumatic drugs before therapy for lymphoma including ASCT. After the initiation of chemotherapy, all anti‐rheumatic drugs were withdrawn and the patient is now well and in remission 20 months after ASCT and 27 months after stopping all anti‐rheumatic drugs. Several patients with RA or SLE and one patient with Sjögren's syndrome (SS) treated with ASCT for lymphoma have been reported in the literature (Table 1). Most of the patients have been conditioned with BEAM supported with unselected autologous peripheral blood stem cells as was also the case in our patient. Some patients have enjoyed prolonged remission of their rheumatic disease after ASCT [8, 9], but there has also been early immunological and clinical relapses [4, 5]. It is currently unknown why some patients with rheumatic diseases have responded well to ASCT while others have not. Several possible explanations for the favourable outcome of AS in our patient exist. The remission may simply reflect a fluctuation in the natural history of AS in this patient. CHOP chemotherapy might have caused remission in the rheumatic process, which has been previously described [10]. Further, the intensive immune ablation followed by immune reconstitution might have led to diminution or even eradication of the putative autoreactive T‐cell clone. And finally, if the recent activation of the rheumatic disease was indeed a paraneoplastic phenomenon, cure of the lymphoma could have led to the remission of AS. This report suggests that complete clinical remission is possible in active AS following chemotherapy for lymphoma including ASCT. Some severe and therapy‐resistant forms of AS exist, and these patients might be considered for experimental intensive therapeutic approaches. This report gives some hints that high‐dose chemotherapy supported by ASCT may work in AS. Summary of outcome of rheumatic diseases after ASCT for lymphoma BU, busulphan; CY, cyclophosphamide; VP, etoposide; BCNU, carmustine; PBSC, peripheral blood stem cells; BM, bone marrow. Summary of outcome of rheumatic diseases after ASCT for lymphoma BU, busulphan; CY, cyclophosphamide; VP, etoposide; BCNU, carmustine; PBSC, peripheral blood stem cells; BM, bone marrow. Correspondence to: E. Jantunen.