autologous blood and marrow transplantation - Blog Science ...

Kuis, Wulffraat, and Sanders 477
started a program for the treatment of refractory JCA with autologous
hematopoietic stem cell transplantation. We here report the 6 to 18 months follow-
up in the first four children with longstanding, severe JCA and polyarticular JCA
treated with autoHSCT.
Patients
Inclusion criteria. Children with systemic chronic arthritis and polyarticular
chronic arthritis refractory to combinations of NSAIDs and immunosuppressive
drugs such as methotrexate, CsA, and corticosteroids, and with a disease course
longer'than 6 months, were included in this study.
Bone marrow harvest and T cell depletion. Hematopoietic stem cells were
obtained by conventional bone marrow aspiration under general anesthesia without
priming. The graft was purged by two cycles of T cell depletion with CD2 and CD3
antibodies. 4
Finally, a suspension of 0.5-6.5 X10 6
CD34 positive cells/kg and less
than 0.5 X10 5
CD3 cells/kg was stored in liquid nitrogen.
Conditioning. The conditioning regimen included 4 days of ATG (IMTIX,
Pasteur Merieux, France) in a dosage of 5 mg/kg daily from day -9 to -6,
cyclophosphamide (Cy) in a dose of 50 mg/kg daily from day -5 to -2, and low-
dose (4 Gy) single-fraction TBI on day -1.
RESULTS
The clinical characteristics of the four patients are depicted in Table 1. They
were characterized by a refractory chronic arthritis with the occurrence of erosions
and growth disturbances of the joints. Laboratory investigations showed increased
ESR and a moderate to severe anemia in all patients. Methotrexate and CsA were
stopped before autoHSCT, and corticosteroids were tapered and stopped 2 months
after autoHSCT. NSAIDs were continued, but in two patients medication could be
stopped completely within 6 months.
The recovery of the bone marrow took 20 to 30 days for neutrophils
(>0.5X 10 9
/L) and 16 to 35 days for the platelets (>20X 10 9
/L). The number of T
cells and mitogen responses normalized within 3-6 months.
Within 2 weeks of autoHSCT, all patients showed a marked improvement as
measured by a decrease in joint swelling, pain, and morning stiffness. ESR, CRP,
and Hb normalized within 8 weeks. As measured by child health assessment
questionnaires (CHAQ), EPM-ROM, juvenile arthritis functional scores (JAFAS),
there was a marked improvement of the functional activities of all children.
Because of the longer follow-up in the first two patients, a favorable effect of
autoHSCT on their growth could already be seen (Table 1). In general, the
autoHSCT was well tolerated, and there were few complications (Table 2).