Stem cell source: Peripheral blood versus bone mar row

N o difference was observed in the rate o f reconstitution o f memory and effector T -cells in recipients o f peripheral blood or bone marrow at any time point post-transplant. As described previously, there was no difference in the rate o f reconstitution o f naïve T -cells or levels o f thymic output in patients who received peripheral blood or bone marrow derived stem cells. Therefore, the reconstitution o f all T-cell subsets was similar regardless o f whether patients received peripheral blood or bone marrow derived stem cells. There are numerous other issues surrounding the use o f either peripheral blood or bone marrow as the preferred source o f haematopoietic stem cells. However, the previous observations suggest that at least in terms o f T-cell recovery, peripheral blood and bone marrow are equally viable sources o f haematopoietic stem cells.

Ch a p t e r 4

C a m p a t h - I H

A significant effect of administration o f pre-transplant Campath-IH on naïve T-cell recovery at 3 months post-transplant was described previously. Therefore this analysis was extended to look at the effects o f Campath-IH administration on the recovery o f mem ory and effector T-cells.

I analysed the effects o f pre-transplant infusions of Campath-IH on the recovery o f memory CD4^ ( 4 .12A) and CD8^ (4.12B) T-cells at 3 months post-HCT. Median mem ory CD4* T-cell counts at 3 months post-transplant were 137 cells per pi (range: 45 to 568) in patients who did not receive Campath-IH compared to a median memory CD4^ T-cell count o f 49 cells per pi (range: 10 to 539) in patients who received Campath-IH as part o f their pre-transplant conditioning. This reduction in memory CD4^ T-cell numbers was statistically significant at 3 months post-transplant (P = 0.001) but there was no difference in memory CD4^ T-cell numbers at 6, 9 or 12 months post-transplant. A reduction in the number o f non-naïve CD8^ T-cells was also apparent with a median non-naïve CD8* T-cell count o f 324 cells per pi (range 92 to 1800) in patients who did not receive Campath-IH compared to 73 cells per pi in patients who received Campath-IH (range 10 to 3 6 9 9 ). Again, there was no difference in non-naïve CD8^ T-cell numbers at 6, 9 or 12 months post-transplant regardless o f whether patients received pre-transplant Campath-IH or not.

ii*

-C a m p a th + C a m p a th

B

-C a m p a th -(-Cam path

Figure 4.12: Ejfect o f Campath-IH administration on memory CD4* and non-naïve CD8^ T-cell recovery at 3 months post-HCT

A b s o l u t e n u m b e r s o f m e m o r y C D T T - c e l l s (A) a n d n o n - n a ï v e C D 8 ^ T - c e l l s (B ) w e r e c a l c u l a t e d fo r p a t i e n t s

w h o r e c e i v e d ( b l u e t r ia n g le s ) o r d i d no t r e c e i v e ( p u r p l e s q u a r e s ) i n f u s i o n s o f C a m p a t h - I H a s pa rt o f t h e i r p r e ­

t r a n s p l a n t c o n d i t i o n i n g . T h e b l a c k b a r s in e a c h p lo t r e p r e s e n t m e d i a n v a l u e s f o r e a c h p a t i e n t g r o u p .

Ch a i t i;i< 4

In contrast, there was no difference in the recovery of the more differentiated effector- type T-cell subsets (CD4TD45RO"^CD27 and CD8^CD57"^CD28 ) at any time points p ost­ transplant whether the patients received pre-transplant C am path-IH or not.

-C am path -t-Campath

B

Figure 4.13: Ejfect o f Campath-1H administration on reconstitution o f total CD3*, CD4"

and CDS* T-cells at 3 months post-HCT

A b s o l u t e n u m b e r s o f CD 3* T -c e l l s (A ), CD 4* T -c e l l s (B) a n d C D 8 " T -c e lls (C) w er e c a l c u l a t e d for p a t i e n t s w h o

e i t h e r r e c e i v e d ( b lu e tr ia n g le s) or did not re c e i v e ( p u rp l e s q u a re s ) i n f u sio n s o f C a m p a t h - I H as part o f th e ir p r e ­

t r a n s p l a n t c o n d i t i o n i n g . T h e b l a c k b a r s in e a c h plot r e p re s e n t m e d i a n v a l u e s fo r e a c h p a tie n t g ro u p .

The recovery of total C D 3 \ CD4"^ and CD8^ T-cell numbers was also analysed in patients who received or did not receive Cam path-IH as part of their pre-transplant conditioning regimen. There were significantly lower numbers of C D 3 \ CD4^ and CD8'' T-cells at 3 months post-transplant in patients who received pre-transplant C am p ath -IH compared to those who did not (Figure 4.13). However, similar to the naïve, memory and effector T- cell subsets, there was no difference in total C D 3 \ CD4^ or CD8"^ T-cell numbers in patients who received pre-transplant C am path-IH compared to those who did not at 6, 9 or 12 months post-transplant.

These results demonstrate that of all the parameters that have been analysed separately, administration of C am path-IH as part of the pre-transplant conditioning regimen is the only parameter that consistently predicts low T-cell numbers at 3 months post-transplant.

Ch a p t e r 4