A matched case-control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication.

Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

[Allergic thrombocytopenia to heparin]. / Thrombocytopénie par allergie à l'héparine.

Various heparin preparations can induce an allergic reaction in certain patients. This results in a fall in platelet count and, paradoxically, thrombosis. This phenomenon is called heparin induced thrombocytopenia type 2 (HIT-2), and should be distinguished from the mild and usually asymptomatic non-immunologic thrombocytopenia, that often occurs during therapy with heparin (HIT-1). In HIT-2, platelets counts fall by at least fifty per cent between the fifth and the fourteenth day of therapy. Immediate interruption of heparin administration is required. It is due to intense platelet activation by circulating immune complexes containing antibodies to the heparin-platelet factor 4 complex. These complexes cause damage to endothelial cells, which increases the risk of thrombosis. This risk persists over the subsequent weeks after cessation of heparin and the correction of platelet count. Anticoagulation must be maintained, often using recombinant hirudin, which is progressively replaced by oral anti-vitamin K agents.

[Venous and arterial thromboembolism in a patient with factor V R506Q Leiden mutation and heparin-induced immuno-allergic reaction]. / Accidents thrombo-emboliques veineux et artériels chez un patient porteur d'une mutation du facteur V R506Q Leiden et ayant développé une réaction immuno-allergique à l'héparine.

A forty-six-year old in-patient was treated with heparin for massive pulmonary embolism. During the hospitalization, the clinical evolution was unusual and characterised as follows: a) the extent of pulmonary embolism justified a thrombolysis by streptokinase; b) an acute thrombocytopenia occurred a few days later, preceded by a slower, but significant decrease of platelet count; c) a non-occlusive aortic thrombosis developed, distal to renal arteries, causing distal embolisation, successfully treated by local fibrinolysis. The prompt correction of platelet count after interruption of heparin therapy confirmed the diagnosis, before the detection of antibodies against heparin-PF4 complexes. Heparin was immediately replaced by another direct anticoagulant, recombinant hirudin (lépirudine-Refludan), initially given alone and progressively replaced by an antivitamin K (Sintrom). The occurrence of distal embolism from aortic thrombosis, developed during the critical period, characterizes this syndrome, which appears rare but whose incidence is probably underestimated. A subsequent investigation for risk factors for venous thromboembolism in this patient revealed a heterozygous mutation of the Leiden type factor V in our patient, and also in others family members.