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Haematopoietic stem cell transplantation (HSCT) has been used in an attempt to control autoimmune diseases that respond poorly to conventional treatment, or as a way of readjusting the immunological balance.1 As far as we know, only one case of primary Sjögren's (SS) has been reported,2 with an unfavourable outcome. Another patient received an allogeneic bone marrow transplant and also had an unfavourable outcome.3 We describe here a further patient with primary SS who underwent HSCT for a non-Hodgkin's lymphoma affecting the lung (large cell, mucosa associated lymphoid tissue (MALT) lymphoma) and review the literature on the effects of HSCT on the autoimmune features and histopathological changes in primary SS.
A white woman, aged 42, developed recurrent parotid swelling and symptomatic sicca syndrome, with a Schirmer's test I of 5 mm in the right eye and 4 mm in the left eye. Break up time was 6 s and sialometry was <1 ml.
She had periodic relapses of her parotid swelling. In August 1994 (aged 57) lung x rays and computed tomography disclosed a parenchymal nodule of 3 cm in diameter in the basal left lobe. She underwent a lobectomy that disclosed a MALT, of the large cell B lymphoma histotype, stage IE. In December 1994 two more nodules in the right lobe, with hilar bilateral adenomegaly, led to the diagnosis of a relapse of her lymphoma, which had progressed to stage IV. She then received six courses of F-MACHOP (vincristine 0.5 mg/m2 at hours 0 and 12; cyclophosphamide 800 mg/ m2 intravenous (IV) bolus at hour 36, 5-fluorouracil 15 mg/kg IV for six hours at hour 36, cytosine-arabinoside 1000 mg/m2 IV for six hours at hour 42, doxorubicin 60 mg/m2 IV bolus at hour 48, methotrexate 500 mg/m2 IV for six hours at hour 60, prednisone 60 mg/m2 from day 1 to 14), and folinic rescue (20 mg/m2, IV bolus at hours 84, 96, 108, 120), with a prompt reduction of hilar adenopathies and a net decrease of pulmonary nodule size. However, no complete remission was recorded. She was then offered the possible chance of an HSCT. Table 1 (patient 1) reports the myeloablation, conditioning, recovery, and reinfusion of stem cells. After three years of follow up no relapse of the lymphoma has occurred. Sicca syndrome after transplantation was unmodified, however, with a persistently poor function of the salivary glands, an unchanged serology (antinuclear antibody titre 1/2560), and an unchanged histopathology (Chisholm-Mason grading = 4) despite having mild fibrosis of the salivary glands.
In table 1 we give the characteristics of the other patient with primary SS (No 2), previously reported. It can be seen that the conditioning regimen, myeloablation, previous treatment, stem cell rescue, and bone marrow reconstitution were different. However, in this case, also, SS was not cured and there was no remission. An immunological reassessment showed persistence of the immunological imbalance and poor function of the salivary apparatus.
Table 2 shows the results for patients with three more common autoimmune rheumatic diseases (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma (SSc)) treated with HSCT and who received an adequate follow up.4 A total of 270 such patients are registered so far in the European Bone Marrow Transplant/EULAR database, but the number who have received adequate follow up is much smaller.
Current data suggest that best results have been obtained in RA, the worst in SSc, suggesting that T helper 2 oriented diseases have a poorer response.
Results for SS seem to confirm this because HSCT cured lymphoma but did not improve the autoimmune disease. No changes were recorded in the function of salivary glands, or in the synthesis of ANA, or the histopathology. The other case reported did show some early improvement in the function of the glands, but no improvement afterwards and an infection leading to death. Early recurrence of autoimmune features and of autoantibodies was seen in patients with SLE and CREST.5 We do not know whether various conditioning regimens or myeloablation approaches (with or without T cell depletion) might result in different outcomes. It seems unlikely that T cell depletion would offer a better prospect, especially in view of the increased risk of long term immunosuppression, lymphoproliferative diseases, and infections. On the other hand, allogeneic bone marrow transplantation, even though clearly appealing given the chance of eradicating the intrinsic stem cell defect,6 does not represent a definite cure either and the related morbidity-mortality still remains too high to be accepted as a possible alternative. As benefits have been seen in around two thirds of the cases treated so far, controlled trials in the three major rheumatic diseases are eagerly waited.
We gratefully acknowledge the invaluable help we received from Professor A Tyndall, who provided us with the latest data available of the EBMT/EULAR registry on haematopoietic stem cell transplantation in autoimmune diseases.
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