autologous blood and marrow transplantation - Blog Science ...

466 Chapter 8: Autoimmune Disease
into infected disease-susceptible recipient strains results in an equally high
mortality from neurologic disease. Allogeneic transplantation using healthy but
previously infected disease-resistant donors into infected disease-susceptible
recipient strains results in a significantly lower mortality. Therefore, in a viralmediated
autoimmune disease, the immune system is a double-edged sword.
Temporary ablation of the immune system may unleash viral cytopathic effects.
However, in those animals that survive transplant, immune-mediated demyelination
is diminished. Further advances in HSCT of viral-associated autoimmune
diseases should recognize the importance of controlling viral cytotoxicity after
transplantation with either peritransplant antiviral drugs and/or viral specific
adoptive immunotherapy at the time of graft infusion. HSCT in animal models of
viral-induced autoimmunity may help understand the interrelationships between
viral immunity, autoimmunity, and tolerance.
SYSTEMIC LUPUS ERYTHEMATOSUS
The mortality from SLE improved with the introduction of better antihypertensive
medications and after general acceptance of more aggressive immunosuppressive
therapy with National Institutes of Health (NIH) short-course
cyclophosphamide (500-1000 mg/m 2
monthly X 6 months, then quarterly as
necessary). 30
However, as a rule of thumb, for all patients with SLE, the mortality
is still 1% per year. 31-35
High-risk patients for early mortality are those with
visceral organ involvement who have active disease despite corticosteroids and at
least six cycles of cyclophosphamide (500-1000 mg/m 2
). We consider these
patients to be candidates for autologous HSCT.
Since SLE is responsive to cyclophosphamide, we choose a cyclophosphamide
(200 mg/kg) and antithymocyte (90 mg/kg) conditioning regimen that is commonly
used for allogeneic transplantation of aplastic anemia. This regimen also avoids the
pulmonary and late carcinogenic side effects of total-body irradiation. Since
patients are generally referred with active and refractory disease, we mobilize stem
cells with cyclophosphamide (2 g/m 2
) and granulocyte colony-stimulating factor
(G-CSF) (10 pg/kg). The cyclophosphamide mobilization ameliorates disease
activity, may help prevent a potential G-CSF flair of disease, and theoretically
provides a partial in vivo purge of lymphocytes. Lymphocytes are further purged
ex vivo by immunoadsorption for CD34 +
progenitor cells using the CellPro
CEPRATE device.
For patients with SLE, end organ dysfunction is not necessarily a contraindication
for transplantation provided a biopsy demonstrates reversible active disease,
not just chronic fibrosis. This is exemplified by activity and chronicity indices on
renal biopsy. For example, a patient with a creatinine of 5.0 mg/dL may still have
significant improvement if the activity indices are high and chronicity score low.