acute myeloblastic leukemia was diagnosed in a 51-year - old man in germany in september 2012 . according to international standards , cytogenetic and molecular examination determined that this form of leukemia was  poor risk  at the time of diagnosis .
because of the patient s risk status , the physicians intended to perform allogeneic stem cell transplantation after induction and consolidation chemotherapy , which was scheduled to end in january 2013 , and a conditioning chemotherapy regimen , which was planned to be given in march . because of lack of a related hla - matched donor , an international donor search
was performed ; 1 fully matched unrelated female donor was identified in the german national registry .
the 24-year - old woman , who was registered as a volunteer donor in the german bone marrow donor registry , was selected .
the donor had scheduled a trip to sri lanka , and was to return 3 days before the scheduled start of granulocyte - colony - stimulating factor ( g - csf ) application . according to german ( http://www.zrkd.de/de/_pdf/zrkd_standards-v9_deutsch.pdf ) and international ( http://www.worldmarrow.org/fileadmin/committees/stdc/20140101-stdc-wmda_standards.pdf ) guidelines , such travel should have led to the postponement of donation because many infectious diseases are endemic to sri lanka .
however , the donor was unable to postpone her trip , and the recipient was in urgent need of the transplant .
the transplant physicians agreed to keep the dates as scheduled and confirmed the exception as declaration of urgent medical need of the transplant .
five days before the scheduled transplant ( day 5 ) , the recipient tested positive for klebsiella pneumoniae infection of the central venous catheter .
the donor had returned from her trip 3 days before the start of g - csf - injections without any signs of infection . on the day of apheresis ( day 0 ) ,
the donor showed signs of a respiratory infection with axillary temperature of < 39c , bone pain , and headache .
oral azithromycin ( 2  250 mg / d ) and ibuprofen 400 mg were given .
the stem cell mobilization result was poor : 11 cd34 + cells/l peripheral blood ( 0.04% of leukocytes ) were measured at the beginning of apheresis . before apheresis ,
the donor s blood count showed mild thrombocytopenia ( 134,000 cells/l ) after g - csf mobilization .
standard leukopheresis processing of 14 l of blood from the donor was performed without problems .
approximately 90  10 cd34 + cells , corresponding to 10 cd34 + progenitor cells per kg bodyweight of the recipient , could be collected .  
a second apheresis or a bone marrow collection was considered , but neither was performed because the clinical condition of the donor worsened .
her temperature increased to 41c , the platelet count dropped from 84,000 cells/l on day 0 to 74,000/l the day after . in the morning of the second day after apheresis ( + 2 ) ,
the platelet count dropped to 47,000/l , procalcitonine level was elevated at 1.10 g / l , c - reactive protein level was elevated at 10.5 mg / l , and a slight skin rash developed . because of the clinical course , on day + 1 , physicians suspected a possible denv infection .
a serum sample test showed a weak positive result for denv by using igm and igg antibody tests ( in - house indirect immunofluorescence assay ) , as used by tappe et al .
( 5 ) , and a strong positive result for denv nonstructural protein-1 ( ns1 ) antigen , demonstrating acute denv infection .
quantitative real - time reverse transcription pcr for denv rna ( 6 ) was positive and showed a denv rna load of 2.6  10 copies / ml . testing of the sample containing the progenitor cells showed a denv rna load of 4.8  10 copies / ml . after being informed about possible infection of the donor , the transplant physicians administered immunoglobulin to the recipient intravenously ( 0.5 g / kg / y for 4 days ) . at posttransplantation day + 3 , antibiotic drug therapy was switched from piperacillin / tazobactam to meropenem .
on the same day , physical examination revealed painful hepatomegaly and increased total bilirubin , diagnosed as hepatic veno - occlusive disease ( table ) .
therefore , defibrotide prophylaxis , which had been initiated on day 8 , was increased to treatment dose . on day + 7 , empiric antifungal therapy was added . on the same day
, staphylococcus epidermidis was detected in blood cultures and vancomycin was given . on day + 8 ,
the recipient experienced severe abdominal pain accompanied by hematochezia , hypoxia , and metabolic acidosis .
bacteriologic culture of a tracheal aspirate grew acinetobacter baumannii , which was only susceptible to colomycin and tigecyclin .
the recipient was transferred to the intensive care unit and died from cardiopulmonary arrest 9 days posttransplant .
a blood sample from the recipient on day + 3 was retrospectively analyzed and tested negative for denv igm and igg but positive for denv ns1 antigen and denv rna with a denv rna load of 8.6 10 copies / ml .
sequencing of the denv amplicons from all samples demonstrated a denv serotype 1 ( denv 1 ) genotype 1 infection of the donor and recipient .
phylogenetic analysis of the complete envelope protein coding gene of denv 1 strains revealed that the denv 1 genotype 1 strains detected in the donor were closely related to currently circulating denv 1 genotype 1 strains in sri lanka ( figure ) .
bayesian phylogenetic tree based on complete envelope protein coding gene of dengue virus 1 ( denv-1 ) serotype .
the tree was constructed by using the bayesian markov chain monte carlo sampling method and beast software ( http://beast.bio.ed.ac.uk ) .
the general time reversible model of sequence evolution with gamma - distributed rate variation among sites and a proportion of invariable sites and a relaxed ( uncorrelated log - normal ) molecular clock model were used .
bayesian posterior probabilities and percentages of replicate trees in which the associated taxa clustered in the bootstrap test ( 1,000 replicates ) obtained by using a maximum - likelihood analysis are shown at the branches .
strains are denoted by genbank accession number , name , year of isolation , and country of origin .
however , although the transmission of denv was demonstrated , the patient s death was probably caused by hepatic veno - occlusive disease and toxic enterocolitis related to the conditioning regimen .   to avoid transmission of tropical viruses such as denv , under german federal ministry of health rules , blood and stem cell donors
are excluded from donation 4 weeks after returning from areas to which such disease agents are endemic ( 7 ) .
denv has an incubation period of 314 days , and the risk for transmission of such viruses under this exclusion is very low .
few cases of denv transmission by blood transfusion or organ transplantation have been published or reported ( 811 ) .
this case represents a difficult situation : a patient in urgent need of a lifesaving transplant that must be performed without delay , and the only matched donor scheduled for travel to a region to which denv is endemic .
the physician decided to proceed with the scheduled transplantation date because of the urgent need of his patient , although he was aware of the risk for transmission of tropical diseases .   in such situations
it is difficult to estimate the risk / benefit ratio , so it will require a case - by - case decision between donor interests and recipient needs .
all diagnostic tools should be used to minimize the risk for viral transmission before transplantation .
this could have been easily accomplished in this case , because preprocedure samples from the donor tested positive for denv ns1 antigen .
thus , we recommend highly sensitive and specific testing for denv ns1 antigen ( 12 ) of every donor returning from regions to which denv is endemic for denv ns1 antigen if transplantation can not be postponed because of urgent medical need .
 three days after donation of peripheral blood stem cells to a recipient with acute myeloblastic leukemia , dengue virus was detected in the donor , who had recently traveled to sri lanka . 
 transmission to the recipient , who died 9 days after transplant , was confirmed . 
The Study
Conclusions