Delayed Immune Reconstitution After Allogeneic Hematopoietic Cell Transplantation with Yttrium-90 Ibritumomab Tiuxetan-Based Reduced-Intensity Conditioning

Abstract

AbstractAbstract 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/TBIdaycells/μl median (range)p=cells/μl median (range)p=CD3+ T-cells+10065 (38–201)239 (92–353)0.06405 (247–7452)483 (301–909)0.27+500820 (117–994)1409 (422–2532)0.13465 (261–4481)536 (10–2553)0.49CD3+4+ T-cells+10057 (22–81)73 (35–99)0.36189 (85–1105)251 (27–337)0.32+50090 (27–151)184 (72–366)0.22102 (42–951)186 (3–257)0.26CD3+8+ T-cells+10013 (4–126)139 (33–218)0.08214 (84–6181)251 (137–539)0.27+500240 (13–271)732 (72–1469)0.09100 (35–2917)215 (2–2062)0.67CD19+ B-cells+1000 (0–1)9 (0–190)0.202 (0–46)45 (4–155)0.07+50056 (3–891)174 (1–520)0.65140 (8–440)83 (5–851)0.60CD16+56+ NK-cells+10060 (39–1170)176 (112–1199)0.80153 (59–631)209 (39–435)1.00+500303 (77–837)275 (46–676)0.79269 (58–2102)81 (2–214)0.25Regeneration 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.