Abstract 4482

Introduction:

Allogeneic hematopoietic cell transplantation (HCT) following reduced-intensity conditioning (RIC) including radioimmunotherapy (RIT) with yttrium-90 ibritumomab tiuxetan is a potential salvage treatment for patients with advanced high-risk B-cell lymphoma. The influence of RIT combined with RIC on immune reconstitution after allogeneic HCT has not been evaluated.

Methods:

We compared data on immune reconstitution of 14 patients receiving allogeneic HCT after RIT-RIC at our institution from 2006 to 2008. Yttrium-90 ibritumomab tiuxetan as RIT and RIC with either fludarabine (30 mg/m2, day −8 to −4)/melphalan (140 mg/m2, day −3)/alemtuzumab (20 mg for related donors and 30 mg for unrelated donors, day −3 and −2) (n=7, FLU/MEL/AL-RIT group) or fludarabine (30 mg/m2, day −4 to −2)/2 Gy total body irradiation (day 0) (n=7, FLU/TBI-RIT group) were used. Immunosuppression consisted of cyclosporine A alone (FLU/MEL/AL-RIT group) or cyclosporine A combined with mycophenolate mofetil (FLU/TBI-RIT group). The results were compared to 14 patients in a concurrent control group with similar conditioning regimens without RIT (n=7, FLU/MEL (without alemtuzumab); n=7, FLU/TBI). Differences in engraftment and immune reconstitution were evaluated.

Results:

Diagnoses in the RIT groups were high-grade NHL (n=6), low-grade NHL (n=6) and CLL (n=2). In the control groups diagnoses were high-grade NHL (n=4), acute leukemia (n=6), MDS (n=1), multiple myeloma (n=1), Hodgkin's lymphoma (n=1) and CLL (n=1). Neutrophil engraftment (>500/μl) was observed after a median of 20 days (range 13–26) in the FLU/MEL/AL-RIT-group compared to 15 days (range 11–21) in the control group (p=0.11). After a median of 13 days (range 7–17) and 12 days (range 8–27) neutrophil engraftment was noted in the FLU/TBI-RIT group and control group, respectively (p=0.40). Median time to thrombocyte engraftment (>20,000/μl) was 11 days (range 8–42) in the FLU/MEL/AL-RIT-group and 21 days (range 5–29) in the control group (p=0.81). After a median of 10 days (range 7–16) and 11 days (range 10–35) thrombocyte engraftment was noted in the FLU/TBI-RIT group and control group, respectively (p=0.23). Immune reconstitution in the four groups is shown in Table 1:

FLU/MEL/AL-RITFLU/MELFLU/TBI-RITFLU/TBI
daycells/μl median (range)p=cells/μl median (range)p=
CD3+ T-cells +100 65 (38–201) 239 (92–353) 0.06 405 (247–7452) 483 (301–909) 0.27 
 +500 820 (117–994) 1409 (422–2532) 0.13 465 (261–4481) 536 (10–2553) 0.49 
CD3+4+ T-cells +100 57 (22–81) 73 (35–99) 0.36 189 (85–1105) 251 (27–337) 0.32 
 +500 90 (27–151) 184 (72–366) 0.22 102 (42–951) 186 (3–257) 0.26 
CD3+8+ T-cells +100 13 (4–126) 139 (33–218) 0.08 214 (84–6181) 251 (137–539) 0.27 
 +500 240 (13–271) 732 (72–1469) 0.09 100 (35–2917) 215 (2–2062) 0.67 
CD19+ B-cells +100 0 (0–1) 9 (0–190) 0.20 2 (0–46) 45 (4–155) 0.07 
 +500 56 (3–891) 174 (1–520) 0.65 140 (8–440) 83 (5–851) 0.60 
CD16+56+ NK-cells +100 60 (39–1170) 176 (112–1199) 0.80 153 (59–631) 209 (39–435) 1.00 
 +500 303 (77–837) 275 (46–676) 0.79 269 (58–2102) 81 (2–214) 0.25 
FLU/MEL/AL-RITFLU/MELFLU/TBI-RITFLU/TBI
daycells/μl median (range)p=cells/μl median (range)p=
CD3+ T-cells +100 65 (38–201) 239 (92–353) 0.06 405 (247–7452) 483 (301–909) 0.27 
 +500 820 (117–994) 1409 (422–2532) 0.13 465 (261–4481) 536 (10–2553) 0.49 
CD3+4+ T-cells +100 57 (22–81) 73 (35–99) 0.36 189 (85–1105) 251 (27–337) 0.32 
 +500 90 (27–151) 184 (72–366) 0.22 102 (42–951) 186 (3–257) 0.26 
CD3+8+ T-cells +100 13 (4–126) 139 (33–218) 0.08 214 (84–6181) 251 (137–539) 0.27 
 +500 240 (13–271) 732 (72–1469) 0.09 100 (35–2917) 215 (2–2062) 0.67 
CD19+ B-cells +100 0 (0–1) 9 (0–190) 0.20 2 (0–46) 45 (4–155) 0.07 
 +500 56 (3–891) 174 (1–520) 0.65 140 (8–440) 83 (5–851) 0.60 
CD16+56+ NK-cells +100 60 (39–1170) 176 (112–1199) 0.80 153 (59–631) 209 (39–435) 1.00 
 +500 303 (77–837) 275 (46–676) 0.79 269 (58–2102) 81 (2–214) 0.25 
View Large

Regeneration of CD3+8+ T-cells on day +100 and day +500 was significantly (p<0.10) reduced in the FLU/MEL/AL-RIT group compared to the FLU/MEL control group (p=0.08 and p=0.09) while no difference was observed between the FLU/TBI-RIT and the FLU/TBI group. No significant long-term difference in recovery of the CD19+ B-cells was observed although early B-cell levels on day +100 were reduced in the RIT groups.

Conclusion:

Not the use of yttrium-90 ibritumomab tiuxetan alone but its combination with alemtuzumab leads to a significantly slower immune reconstitution after allogeneic HCT.

Disclosures:

Off Label Use: Off-label conditioning regimen.

Topics:
conditioning (psychology), hematopoietic stem cell transplantation, ibritumomab tiuxetan, immune reconstitution, yttrium, alemtuzumab, allogeneic hematopoietic stem cell transplant, yttrium-90-ibritumomab tiuxetan, cyclosporine, fludarabine

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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