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Engraftment syndrome (ES) is an increasingly recognized complication of AHCT. The clinical features consist of peri-engraftment non-infectious fever, skin rash, diarrhea, hepato-renal dysfunction or capillary leak. In severe cases, ES is more analogous to autologous graft-versus host disease (AGVHD).
In this study, we analyze a cohort of 584 consecutive AHCT recipients for multiple myeloma (MM) or lymphoma at our center between 2002 and 2010 to determine risk factors associated with ES/AGVHD. Median follow-up was 49 months. To our knowledge, this is the largest series to report on this topic.
The median age was 57 yrs with 355 males. The underlying disease was MM in 71% (n=415); non-Hodgkin lymphoma (NHL) in 20% (n=116); and Hodgkin lymphoma (HL) in 9% (n=54).
Patients were identified with ES according to Maiolino and Spitzer criteria. A total of 131 patients (22%) developed ES (n=104) or biopsy proven AGVHD (n=27). Onset of clinical ES/AGVHD was between 3 days prior and up to 10 days after neutrophil engraftment; at a median of 12 days after AHCT. Clinical features were fever (90%), skin rash (50%), diarrhea (68%) and LFT abnormalities (23%). The majority (93%) were treated with corticosteroids, achieving a complete response. The median duration of steroids was 12 (2-151) days. Seven patients required additional immunosuppressive treatment. Six deaths were attributable to ES/AGVHD. Patients with ES had longer hospital stays with a median admission of 15 days in those without ES/AGVHD (7-58) and 17 days (12-157) in those with ES/AGVHD (p<0.001).
By univariate analysis, ES/AGVHD was more associated with MM and increasing patient age. Multivariate analyses were performed stratified by disease type MM or lymphoma. ES was significantly more common after 2005 in the era of novel anti-myeloma agents with ES/AGVHD only occurring in 7.5% before 2005 and in 22.6% during and after 2005 (p=<0.001).
In multivariate models, NHL/HL was associated with lower risk of developing ES/AGVHD (HR=0.36, p = 0.0003) while age >60 yrs was associated with higher risk (HR = 1.94; p=0.001). Considering MM patients only, pre-AHCT exposure to Lenalidomide (HR=1.89; p=0.005) or Bortezomib (HR=2.6; p<0.0001) and age >60 yrs (HR= 2; p=0.001) were strongly associated with ES/AGVHD. There was no difference in TRM, relapse, PFS or OS between the two groups suggesting a lack of graft-versus-myeloma effect with ES/AGVHD.
In conclusion, these data demonstrate that the increasing incidence of ES/AGVHD in recent years maybe associated with novel agent induction in MM. Novel agent induction may affect T cell subpopulations in the infused graft capable of mediating ES/AGVHD.
