Abstract
Abstract 4482
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.
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.
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-RIT . | FLU/MEL . | . | FLU/TBI-RIT . | FLU/TBI . | . |
|---|---|---|---|---|---|---|---|
| . | day . | cells/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-RIT . | FLU/MEL . | . | FLU/TBI-RIT . | FLU/TBI . | . |
|---|---|---|---|---|---|---|---|
| . | day . | cells/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 | |
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.
Not the use of yttrium-90 ibritumomab tiuxetan alone but its combination with alemtuzumab leads to a significantly slower immune reconstitution after allogeneic HCT.
Off Label Use: Off-label conditioning regimen.
Author notes
Asterisk with author names denotes non-ASH members.
