Journal of Hematology - Supplements - Haematologica

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Table 2. Neurologic disorders.
Table 4. Gastrointestinal disorders.
Disease Age/ Disease Conditioning Follow-up Last
sex duration regimen 3 mos 6 mos Follow-up/mos
(yrs) (yrs)
MS 22 M 1 Cy/Ara-C/DXM/ALG PR PR PR/24
MS 46 F 23 FLU/DXM/ALG NR
MS 40 M 10 FLU/DXM/ALG PR
MYASTHENIA 47 F 28 Cy/ALG PR PR PR/12
CR: complete remission; PR: response >50%; REL: relapse; NR: no response.
Disease Age/ Disease Conditioning Follow-up Last
sex duration regimen 3 mos 6 mos Follow-up/mos
(yrs) (yrs)
Auto-Entero. 14 F 13 Cy/ALG PR PR REL/ 12
Crohn’s disease 3 F 2 FLU/ALG PR PR
Auto-Entero: Autoimmune enteropathy; CR: complete remission; PR: response
>50%; REL: relapse.
Table 3. Hematologic disorders.
Disease Age/ Disease Conditioning Follow-up Last
sex duration regimen 3 mos 6 mos follow-up
(yrs) (yrs) (mos)
PRCA 44 M 3 Cy/ALG CR CR REL/ 8
PRCA 7 F 2 FLU/ALG NR
AITP 4 F 3 FLU/ALG CR CR CR/ 25
CR: complete remission; PR: response >50%; REL: relapse; NR: no response.
able to move normally and had a markedly
improved electromyogram. She is still in partial
remission after 12 months (Table 2).
PRCA. Two patients with very severe disease
not responsive to steroids, cyclophosphamide,
ALG and cyclosporine, requiring blood transfusions
every 15-20 days. The first patient became
transfusion-free for 6 months with an increased
reticulocyte count but relapsed after 6 months.
The second patient showed no response to the
procedure (see Table 3).
AITP. A patient with a life-threatening condition
with a fixed platelet level of 100x10 9 /L. Prednisone was gradually
tapered down and stopped after 5 months. At
the last follow-up, 25 months after HSCT, the
patient had a platelet count of 250x10 9 /L having
maintained a level above 200x10 9 /L at the
times (Table 3).
IBD. The patient had been affected by severe
Crohn’s disease, involving the entire gastrointestinal
tract, since the age of one year. The disease
was steroid-dependent and not responsive
to azathioprine, cyclosporine, thalidomide,
enteral nutrition, or etanercept. The patient had
severe side-effects due to long-term steroid treatment.
Six months after HSCT the disease was
limited to the large bowel and required small
doses of steroids (see Table 4).
Autoimmune enteropathy. This patient had
received total parenteral nutrition since her first
years of life. After the procedure her parameters
of intestinal absorption improved (ratio mannitol/lactulose,
xylose test) without any modification
of intestinal biopsy or any clinical advantage.
MEAD. After the procedure the patient’s respiratory
function improved (increased Sa02
without needing oxygen supplementation). The
hemolytic autoimmune anemia disappeared
and the patient had a negative Coombs’ test.
Cortisone was gradually tapered down with
resumption of growth but, after 22 months, it
was not possible to interrupt all therapy. No
improvement in the IDDM was noted.
Discussion
The first objective of this study was to assess
the feasibility and toxicity of a non-myeloablative
conditioning regimen followed by infusion
of autologous ex vivo treated hematopoietic stem
cells in a cohort of patients, mostly in pediatric
age, with severe autoimmune diseases. The procedure
was well tolerated; the patients did not
suffer any major complications either during the
conditioning or after the transplant and spent a
short timein hospital. There was no treatmentrelated
mortality; this compares with the 8% of
TRM of the EBMT/EULAR database and the
unacceptable 20% in a subgroup of children
affected by juvenile chronic arthritis. 23,24 In terms
of effectiveness all but two patients achieved a
partial or complete remission but the high rate
of early relapse (after a median of 12 months) in
the first group treated with low-dose cyclophosphamide
led to the cytoxan being replaced by a
more immunosuppressive fludarabine-based
conditioning regimen. Fludarabine, a nucleotide
analog which targets both resting and proliferating
lymphocytes, proved to be very effective in
the treatment of autoimmune diseases. 25 In the
second group of eleven patients 60% are in complete
or partial remission after a median followup
of 14 months (range 3-25 months).
In comparison to other published experiences
the number of relapses seems higher but counterbalanced
by a lower incidence of undesirable
effects. For pediatric patients, who would otherwise
suffer persistent handicap by continuous
progression of disease, even a short-lived remission
can be considered an advantage, especial-
haematologica vol. 85(supplement to n. 11):November 2000