Abstract

TTP is one of the complications of allogeneic hematopoietic stem cell transplantation (HSCT). In contrast to idiopathic cases, post-transplantation TTP may not be associated with severe von Willebrand factor-cleaving protease deficiency but rather a diffuse endothelial injury. Our aim was to define incidence, risk factors and mortality of TTP following allogeneic HSCT. 1312 patients with lymphoid malignancies (n=605), myeloid malignancies (n=688) or aplastic anemia (AA, n=18) who were treated with ablative preparative regimens (n=614) or reduced intensity regimens (n=697) followed by HSCT from an HLA matched related (MRD, n=694) or unrelated donor (MUD; n=461) and 1–3 antigen mismatched related (MMR, n=99) or unrelated donor (MMUD, n=57) between December 1997 and December 2004 were studied. Patients with prior allogeneic HSCT or graft failure were excluded. GVHD prophylaxis was tacrolimus-based in 1276 (97.3%) and cyclosporine based in 15 (1.1%) patients. Twenty patients did not receive GVHD prophylaxis per protocol. Anti-thymocyte-globulin (ATG) was added in 350 patients. Stem cell sources were bone marrow (n=626), peripheral blood (n=635) or cord blood (n=50).

The following variables were evaluated: age, gender, primary diagnosis, disease status before HSCT, intensity of preparative regimen, stem cell source and acute GVHD(aGVHD) grade ≥2 (time dependent variable).

Of the 1312 patients with a median follow-up from transplantation of 11.4 months (range, 5 days-7.2 years), 77 developed TTP (6%). The actuarial risk of developing TTP was 6.5% at 1 year. The median time of the onset of TTP was 67 days post HSCT (range, 11–1812) with 27 cases (35%) presenting after day 100. Female gender, lymphoid malignancies, unrelated or antigen mismatched related donor and aGVHD grade ≥2 were found to be independent risk factors. (Table1). Among the patients who had aGVHD grade≥2, the median time of interval between the onsets of two events was 25 days (range, 2–335 days). All patients were treated with therapeutic plasma exchange (PE). Of the 77 patients only 1 died of TTP (intracranial hemorrhage). The overall one-year survival after TTP was 29% and the most common cause of death were acute or chronic GVHD (n=35, 55%) and primary disease progression (n=10, 16%).

Stem cell donors other than MRD, lymphoid malignancies and aGVHD≥2 have been established as risk factors associated with development of TTP and therapeutic PE has been shown to decrease TTP related mortality.

Risk factors for TTP after allogeneic HSCT

Variables sample size events HR 95% CI 
Male 793 33 1.0   
Female 518 44 2.2 1.3–3.6 0.002 
Myleoid malignancy 688 33 1.0   
Lymphoid malignancy 605 42 1.9 1.1–3.3 0.03 
AA 18 1.3 0.2–8.0 0.75 
MRD 694 28 1.0   
MUD 461 40 2.9 1.6–5.1 <0.001 
MMR 99 2.4 0.9–6.0 0.06 
MMUD 57 1.7 0.4–7.6 0.5 
aGVHD ≥2 370 39 3.3 2.0–5.5 <0.001 
Variables sample size events HR 95% CI 
Male 793 33 1.0   
Female 518 44 2.2 1.3–3.6 0.002 
Myleoid malignancy 688 33 1.0   
Lymphoid malignancy 605 42 1.9 1.1–3.3 0.03 
AA 18 1.3 0.2–8.0 0.75 
MRD 694 28 1.0   
MUD 461 40 2.9 1.6–5.1 <0.001 
MMR 99 2.4 0.9–6.0 0.06 
MMUD 57 1.7 0.4–7.6 0.5 
aGVHD ≥2 370 39 3.3 2.0–5.5 <0.001 

Author notes

Corresponding author