Journal of Hematology - Supplements - Haematologica

83
Table 1. Rheumatologic disorders.
Disease Age/ Disease Conditioning Follow-up Last
sex duration regimen 3 mos 6 mos Follow-up/mos
(yrs) (yrs)
JCA 9 F 3 Cy/ALG CR CR REL / 8
JCA 15 F 12 Cy/ALG PR REL
JCA 15 F 6 Cy/ALG CR REL
JCA 20 M 5 FLU/ALG CR CR REL / 18
JCA 14 F 3 FLU/ALG CR CR REL / 12
VASCULITIS 17 F 11 Cy/ALG PR PR REL/ 13
RA 45 F 19 FLU/ALG CR CR REL/ 12
SJÖGREN 46 F 4 FLU/ALG CR CR CR/ 12
BEHÇET’S 33 F 3 FLU/ALG CR CR CR/ 15
CR: complete remission; PR: response >50%; REL: relapse.
cells were infused 4 hours after ALG therapy had
been completed.
All patients received cyclosporine (3 mg/kg/day)
intravenous from day –1 until the seventh day
when it was given orally.
Approval for the procedure was given by the
institutional Ethics Committee and written consent
was obtained from the patients or their families.
Results
To date 19 patients (5 M, 14 F) have been treated
for severe autoimmune diseases. Their median
age was 23.4 years (range 3-47), 10 were children.
The source of cells was peripheral blood in 13 cases
and marrow in 6. Nine patients were suffering
from a rheumatologic disorder (5 JCA, 1 RA, 1
vasculitis, 1 Behçet’s disease, 1 Sjögren’s syndrome),
4 suffered from a neurologic disorder (3
MS, 1 myasthenia gravis), 3 from a hematologic
disease (2 PRCA, 1 AITP), 2 from a gastrointestinal
disorder (1 IBD, 1 autoimmune enteropathy)
and 1 multiple expression autoimmune disease.
Toxicity
Non-hematologic toxicity was limited to grade
1 severity in the gastrointestinal system (nausea,
vomiting) according to WHO toxicity criteria. One
patient with MS presented a transient elevation of
bilirubin (grade 3); 7 patients experienced neutropenia
(neutrophil count < 0.5x10 9 /L) lasting a
few days (median 3 days, range 2-5); during the
period of neutropenia 1 patient had a positive
blood culture for Staphylococcus epidermidis. The
patient with systemic vasculitis had a flare up of
symptoms during ALG infusion and required three
blood-derivative transfusions.
After the procedure no post-transplant opportunistic
infections occurred. The median time of
hospitalization, including conditioning, was 12
days (range 8-20).
Clinical outcome
JCA. One patient had a systemic form while the
other 4 had a systemic and polyarticular form.
All had severe disease resistant to any treatment.
The disease evolution was followed by the factors
described by Giannini, including jointswelling
scores, pain scores and erithrocyte sedimentation
rate (ESR). 21 All drug administration
was stopped before the transplant and prednisone
was tapered down and stopped within
two months after HSCT. Four patients achieved
complete remission and one a partial remission
lasting at least 6 months. All patients relapsed
between 6 and 18 months after HSCT (Table 1).
Systemic vasculitis. The patient had a severe lifethreatening
systemic leukocytoclastic vasculitis
for 11 years with cutaneous, intestinal and cerebral
involvement. The disease evolution was followed
clinically and with serial measurements of
ESR and fibrin degradation products. All drugs
were stopped before the procedure. After the procedure
prednisone was tapered down and
stopped within two months; in addition monthly
plasmaphereses were performed. The girl
achieved a partial remission for 13 months then
relapsed (see Table 1).
RA. This patient was a 45-year old woman diagnosed
as having RA 19 years before the procedure.
Assessment parameters were joint-swelling
scores, patient’s assessment of pain and acutephase
reactant values. 22 After HSCT prednisone
was tapered down and stopped within 2 months.
Complete remission was achieved and maintained
for 12 months before the patient relapsed
(see Table 1).
Sjögren’s syndrome. The patient had severe pulmonary
involvement with a low forced vital
capacity (FVC) (2.2 L); after the procedure FVC
increased markedly (3.2 L) and, for the first time
since disease onset, ANA were normal and RF
absent. Twelve months after the HSCT the
patient is still in complete remission, being treated
only with cyclosporine (Table 1).
Behçet’s disease. The patient presented all the
major diagnosis criteria and a severe polyarthritis.
After the procedure she had a complete remission
of all symptoms that continued at the last followup
15 months after the procedure (Table 1).
MS. All 3 patients had rapidly progressive disease
despite immunosuppressive therapy during
the year before transplant. After HSCT two of
them had subjective and objective neurologic
improvement defined as a decrease in the Kurtzke
EDSS by at least 1 point after a follow-up of 3
and 24 months. The third patient showed no
response and died 3 months after the procedure
due to disease progression (see Table 2).
Myasthenia gravis. This patient was completely
paralyzed and, because the involvement of respiratory
muscles, underwent a tracheostomy.
One month after HSCT the tracheostomy was
closed. By the end of the second month she was
haematologica vol. 85(supplement to n. 11):November 2000