Thrombotic Thrombocytopenic Purpura after Allogeneic Hematopoietic Stem Cell Transplantation: A Complication Still Frequent and Responsible of Severe Outcome.

Introduction

Thrombotic thrombocytopenic purpura (TTP) might costitute a severe complication after hematopoietic stem cell transplantation (HSCT) with a variable incidence depending on different diagnostic criteria adopted in the past.

Patients and Methods

The current study enrolled 551 consecutive patients (pts) (314 males, median age 29 years) undergoing HSCT from January 2000 to April 2005 from HLA match (m) or mismatch (mm) family donor (350/551) and unrelated donor (201/551) for malignant (501/551) or non malignant diseases (50/551). The diagnosis of TTP was performed on the basis of homogeneous five clinical and seven laboratory criteria. Univariate (by chi square test and Fisher’s exact test) or multivariate (by logistic regression method) analyses were performed to evaluate the effect of some candidate risk factors on both TTP occurrence and outcome.

Results

Sixty four of 551 pts presented TTP (11,6%) at a median time of 47 days post-HSCT; 59/64 were affected by malignant and 5/64 by non malignant diseases. Multivariate analysis showed GVHD >II° (p=0,0001), stem cell donors (m/mm unrelated or mm related) (p=0,024), female gender (p=0,0186),TBI-based conditioning regimen (p=0,03) and status of hematological remission (p=0,03) as factors influencing the occurrence of TTP. Only three predicting factors for TTP outcome have been demonstrated statistically significative by multivariate analysis: age (p=0,0186), stem cell donors (m/mm unrelated or mm related) (p=0,01) and TTP index (p=0,018). The TTP mortality rate was 40% while the outcome after TTP diagnosis was partially influenced by TTP treatment. In particular, Defibrotide seemed to be a promising drug in univariate analysis compared with alternative therapies for 34 alive and good responders pts out of 64 TTP pts.

Conclusions

The study underlines the possibility to identify those patients who are more prone to develop post-HSCT TTP, complication still frequent (11,6%) when homogeneous diagnostic criteria are adopted. TTP outcome seems to be conditioned by some peculiar risk factors as adult age, m/mm unrelated or mm related donors HSCTs. Prospective randomized therapeutic trials, focusing on the possible advantage of Defibrotide versus other treatments, should be encouraged.