Paraproteinaemia after allo-SCT, association with alemtuzumab-based conditioning and CMV reactivation

Abstract

Paraproteinaemia following allo-SCT is common. We analysed 91 consecutive patients undergoing allo-SCT; conditioning included alemtuzumab in 42% of the patients. Paraproteinaemia incidence at 2 years was 32%. In univariate analysis paraproteinaemia was associated with unrelated donor, age, recipient seropositivity for CMV and alemtuzumab conditioning (hazard ratio (HR) 3.93, P ¼ 0.0006). Paraproteinaemia was not associated with haematological diagnosis; disease status at transplant; varicella zoster, herpes simplex or EBV serology; reduced-intensity vs myeloablative conditioning or GVHD. CMV reactivation-more frequent in alemtuzumab recipients-was associated with paraproteinaemia (HR 7.52, Po0.0001). In multivariate analysis, only increasing age (HR 1.04 per year, P ¼ 0.048) and CMV reactivation (HR 5.74, P ¼ 0.001) were significantly associated with paraproteinaemia. Alemtuzumab without CMV reactivation, however, resulted in significantly more paraproteinaemia, suggesting an effect that is independent of CMV reactivation. OS was poorer in patients with paraproteinaemia (HR 2.54, P ¼ 0.04) and relapse increased (HR 2.38, P ¼ 0.087). Paraproteinaemia was not significantly independently associated with decreased survival on multivariate analysis. Post transplant paraproteinaemia is associated with CMV reactivation, is more frequent in alemtuzumab-conditioned transplants and is not associated with improved OS.

Correlation between paraproteinaemia and viral reactivation after allo-SCT

“…We propose that EBV reactivation evaluation should be carried out in patients submitted to allogeneic SCT as recommended by European Conference of Infections in Leukemia, 10 particularly when recognized risk factors are present. Medd et al 1 did not perform an EBV load monitoring in patients after HSCT, and they reported that there is no evidence of progression to lymphoproliferative disorder in patients with paraproteinaemia after HSCT. In our cohort, 5/6 patients with posttransplant lymphoproliferative disease showed a paraproteinaemia and in 2 cases it persisted also after EBV clearance after Rituximab therapy.…”

“…CMV reactivation was co-present in 17/49 patients, 13 of them with abnormalities in g-region at SPE and 9/13 with also a paraproteinaemia. Considering that alemtuzumab, adopted by Medd et al 1 as GVHD prophylaxis in the series of patients with paraproteinemia, is considered as a risk factor for EBV reactivation after allogenic SCT, the role of CMV reactivation per se as a risk factor for the subsequent development of paraproteinemia should be kept with caution in the absence of EBV viral load monitoring. 8,9 In our series, pre-emptive therapy for EBV reactivation was able to modify the extent of paraproteinemia leading to complete disappearance of gammopathy in a significant number of patients and it calls for a causative effect.…”

“…Medd et al, 1 retrospectively studied the occurrence of paraproteinaemia after allo-SCT in a cohort of 91 patients. They detected a paraproteinaemia incidence of 32%, multiple in the majority of cases, with a predominance of an IgG isotype and with equal kappa/lambda restriction.…”

Response to ‘Correlation between paraproteinaemia and viral reactivation after allo-SCT’

“…Although CMV reactivation was the strongest factor associated with paraproteinaemia in our study, a significantly increased incidence of paraproteinaemia also occurred in alemtuzumab recipients who did not reactivate CMV. 1 We raised the possibility that this may be due to EBV reactivation, which is also more frequent in alemtuzumab recipients. In the profoundly lymphopenic environment that exists after in vivo T-cell depleted allo-SCT, viruses provides a powerful antigenic stimulus to oligoclonal lymphoid expansion phenomena.…”

“…This finding was significantly associated with CMV reactivation in multivariate analysis. 1 We did not routinely monitor EBV reactivation in our series, as this was not our practice at that time. The last allo-SCT in that series was performed in 2007, 2 years prior to the publication of the European Conference on Infections in Leukemia guidelines recommending routine EBV viral load monitoring following allo-SCT.…”