Thrombotic Microangiopathy™ after Allogeneic Peripheral Blood Stem Cell Transplantation with Nonmyeloablative Conditioning (NMSCT) Compared with Myeloablative Conditioning (MSCT).

Background: Thrombotic microangiopathy (TM) is a severe complication of allogeneic transplantation. The use of CsA for GvHD prophylaxis and unrelated donor appear to be the most significant risk factors for TM after transplantation with conventional myeloablative conditioning (MSCT). Allogeneic transplantation with reduced-intensity conditioning (RIC) is associated with a similar risk of TM, but TM has never been studied after NMSCT.

Purpose: To determine the risk factors, incidence and outcome of TM in NMSCT compared to MSCT.

Patients: Consecutive patients undergoing NMSCT (group 1, n=103) or MSCT (group 2, n=136) in our center between 1995 and 2004 were retrospectively analysed for TM. Median age was 55 vs 34 yrs in groups 1 and 2 respectively (p<0.0001). Donor was unrelated for 52% of the patients in group 1 and for 38% in group 2 (p=0.0287).

Results: TM was diagnosed in 18 (20%) and in 30 (26%) patients in groups 1 and 2, respectively (NS). Most cases were grade 2 TM (18/18 in group 1 and 24/30 in group 1, NS). Neurological signs were present in 50% of the patients in group 1 and 57% in group 2 (NS). In both groups, TM was significantly associated with unrelated donor (p=0.0476 in group 1, p=0.0005 in group 2) and with CMV disease (p=0.0332 in group 1, p=0.0346 in group 2) but not CMV infection. AGvHD of all grades was correlated with TM in group 1 (p=0.0004) but only severe (grade 3–4) AGvHD in group 2 (p<0.0001). Median time of onset of TM was 39 (range 18–157) days in group 1 and 38 (range 0–428) in group 2. First line treatment consisted in switching GvHD prophylaxis to alternative treatment (including tacrolimus) in 54% of the patients and plasmaphereses (36±10 in group 1 and 21±4 in group 2) in 63%. Vincristine (in 11% and 13% of the patients in groups 1 and 2, respectively) and other treatments were rarely used. Forty-four % of the patients died without achieving resolution of their TM in group 1, and 50% in group 2 (NS). For patients who responded to therapy, median duration of TM was 57 (range 5–165) days in group 1 and 46 (range 5–163) days in group 2 (NS). In group 1, the 100-d and 1-yr survival rates were 64% and 28% for patients who developed TM, and 84% and 69% for those without TM, respectively (p=0.0002). In group 2, survival was also significantly reduced in the case of TM (48% vs 70% at day 100 and 23% vs 53% at 1 yr, respectively, p=0.0126).

Conclusion: TM remains a frequent and severe complication of allografting. Its incidence and severity in NMSCT is not decreased compared to MSCT and the same factors appear to contribute to its development.