an article recently published demonstrated the efficacy of eculizumab in the treatment of children with severe hematopoietic stem cell transplantation - associated thrombotic micro - angiopathy ( hsct - tma ) .
we report the case of an adult with hsct - tma successfully treated with eculizumab .
hsct - tma is a rare but very serious complication of allogeneic hematopoietic progenitor stem cell transplantation .
several factors have been implicated in the endothelial damage which leads to hsct - tma : calcineurin inhibitors , acute graft versus host disease ( gvhd ) and cytomegalovirus ( cmv ) infection ; however , in recent years another mechanism has been described in which complement deregulation plays an important role . therefore complement - modulating therapies are beginning to gain ground in the treatment of this complication .
we report the case of a 30-year - old man , diagnosed with very serious acquired bone marrow aplasia in july 2014 .
he underwent progenitor stem cell transplantation of bone marrow from his hla - identical sister in july 2014 .
the conditioning regimen consisted of cyclophosphamide ( 30 mg / kg / day , 7 to 4 ) , fludarabine ( 30 mg / m2/day , 5 to 2 ) and antithymocyte globulin ( 2.5 mg / kg / day , 3 to 1 ) .
, the patient developed acute cutaneous and liver gvhd ( grade ii ) which initially responded to treatment with corticosteroids and etanercept .
the patient was readmitted on post - transplant day 116 with diarrhea and hyperbilirubinemia ( 1.7 mg / dl , normal values 0.3 - 1.1 mg / dl ) and colonoscopy confirmed the existence of acute intestinal gvhd .
after the diagnosis of acute grade iii gvhd , which was refractory to steroids , he sequentially received various lines of treatment ( corticosteroids , mesenchymal stromal cells and sirolimus ) without any response . on post - transplant day 189 ,
the patient developed severe bloody diarrhea ( up to 3000 ml / day ) followed by persistent rectal bleeding that required intense transfusional support and treatment with activated factor vii ( 5 mg/2 h  6 doses ) .
a new colonoscopy was performed and the colonic mucosa biopsy confirmed worsening of the intestinal gvhd without histological evidence of hsct - tma ( figure 1 ) .
iu / l ) , total bilirubin 0.7 mg / dl ( normal values 0.3 - 1.1 mg / dl ) , hemoglobin 8.5 g / dl , platelets 4210/l and normal coagulation tests .
treatment was then initiated with one dose of pentostatin ( 4 mg / m2 iv ) and alemtuzumab ( 20 mg sc 3 times / week for 2 weeks ) .
one week after the administration of pentostatin , and with persistent gastrointestinal bleeding , biochemistry showed hyperbilirubinemia ( total bilirubin 6.4 mg / dl , direct bilirubin 5.5 mg / dl , normal values 0.0 - 0.5 mg / dl ) and elevated ldh ( 2700
the blood count revealed profound anemia ( up to 6.8 g hb / dl ) , reticulocytosis ( 0.310/l ) , thrombocytopenia 3910/l and the presence of numerous schistocytes in blood smear ( 6% ) .
other laboratory findings were : negative direct coombs test , undetectable haptoglobin , proteinuria ( 30 mg / dl ) , normal adamst13 activity ( 94% ) and normal complement proteins ( c3 and c4 ) .
that the patient was diagnosed with hsct - tma , treatment was initiated with eculizumab 900 mg iv weekly for 4 doses followed by a single maintenance dose of 1200 mg 2 weeks later .
after the first dose of eculizumab , the patient ceased to require transfusions and a progressive improvement in analytical parameters for microangiopathy was observed until their complete normalization after 7 weeks ( hb 11.4 g / dl , platelets 16410/l , no schistocytes , bilirubin 0.8 mg / dl and 450 ldh iu / l ) .
ch50 determinations showed complement activity inhibition after each dose had been administered . coinciding with the improved of hsct - tma ,
the patient presented a clear response to his acute gvhd with disappearance of the diarrhea and bilirubin normalization ( figure 2 ) , although it has not been documented histologically .
he was discharged eight weeks after the start of treatment ( post - transplant day 257 ) .
unfortunately , one month later , the patient was readmitted by diarrhea ; a new colonoscopy showed intestinal gvhd relapse .
the patient died two weeks after admission because of acute respiratory distress syndrome of unknown cause , with diffuse bilateral infiltrates , cardiomegaly and right pleural effusion in chest ct .
plasma exchange , defibrotide , rituximab and basiliximab have been used with variable response rates .
we started eculizumab instead of plasma exchange for the poor results of this treatment in hsct - tma cases associated with acute gvhd . in our case , the rapid clinical and analytical response to early treatment with eculizumab ( a humanized monoclonal antibody against complement fraction 5 ) supports the implication of the complement in its pathophysiology .
the rapid response of a severe , refractory gvhd is noteworthy and suggests that the drug has a beneficial effect when used as coadjuvant therapy in this situation .
 a 30-year - old man with acquired aplastic anemia underwent an hla - identical bone marrow transplant . 
 he developed a grade iii acute graft versus host disease ( gvhd ) refractory to various lines of treatment . 
 on post - transplant day 196 , he was diagnosed with stem cell transplantation - associated thrombotic micro - angiopathy ( hsct - tma ) and he received treatment with eculizumab 900 mg iv weekly for 4 doses followed by a single dose of 1200 mg 2 weeks later . 
 after the first dose of eculizumab , the patient ceased to require transfusions and a progressive improvement in analytical parameters for microangiopathy was observed until their complete normalization . coinciding with the improved of hsct - tma , 
 the patient presented a clear response to his acute gvhd with disappearance of the diarrhea and bilirubin normalization . 
 he was discharged eight weeks after the start of treatment . 
 unfortunately , one month later , the patient was readmitted for a gvhd relapse and he died two weeks later by an acute respiratory distress syndrome . in our case , 
 the rapid clinical and analytical response to early treatment with eculizumab supports the implication of the complement in hsct - tma and suggests that the drug has a beneficial effect when used as coadjuvant therapy in acute gvhd . 
Introduction
Case Report
Discussion and Conclusions