1. Case Western Reserve University and University Hospitals of Cleveland
Poster 427: Enterococcus AS an Infectious trigger for HEmophagocytic Lymphohistiocytosis in AML patients post Allogeneic Hematopeitic stem cell transplant
Lubna Mehyar MD, Hasan Hashem MD, Irina Pateva MD, Peter De Blank MD, Jignesh Dalal MD Pediatric Hematology Oncology
Case Western Reserve University and University Hospitals of Cleveland
CONCLUSIONS
HLH is a rare entity and its occurrence in patients post HSCT is frequently associated with infectious complications. We describe the first two cases to our knowledge with enterococcus associated HLH post HSCT.
HLH is difficult to recognize and is likely under-diagnosed. We advocate for high level of suspicion in patients post HSCT who develop multiorgan failure and early initiation of appropriate therapy.
OBJECTIVE
To describe two AML patients who developed IA-HLH post HSCT. Both patients had Enterococcus bacteremia at the time when HLH occurred, which has not been described in the medical literature previously.
BACKGROUND
Hemophagocytic Lymphohistiocytosis is a rare, potentially fatal syndrome. It is classified as primary (genetic) or secondary. The latter is related to infections, malignancies, rheumatologic and metabolic diseases. Infection associated HLH post HSCT has been described to occur with a variety of pathogens including bacteria, viruses, fungi and protozoa. Association between enterococcus and HLH post transplant
is not well characterized like EBV or fungal associated HLH. Inflammasome or nod2/ card15 pathways stimulation have been suggested in macrophage activation syndrome in the setting of enterococcus sepsis in one reported case of cryopyrin-associated periodic syndrome (CAPS) which could have a similar pathway in the development of HLH.
RESULTS
As shown in tables below.
Cases
Diagnosis in 2014
AML Treatment
HSCT Donors
and outcomes
Preparative regimen
GVHD prophylaxis
Complications during transplant
HLH Treatment
6y/o F
AML with chloroma of the jaw
COG treatment protocol
Three HSCTs;
third transplant was 6/10 haploidentical bone marrow
Graft failure X3
RIC
Tacrolimus
MMF
BK viruria/viremia
Disseminated mucormycosis
VRE bacteremia/pneumonia
HHV-6 viremia.
Encephalopathy
Multiorgan failure
HLH at T+15 of third transplant
Expired T+21 post third transplant
Dexamethasone
IVIG
Antimicrobials Antifungals
23 y/o F
Relapsed AML, 8 years off treatment
2006, COG clinical trial;
2014, re-induction with FLAG therapy followed by Cytarabine with Asparaginase
4/6 HLA matched double UCBT
Engrafted on T+21
Tacrolimus MMF
BK viremia/viruria
Transplant Associated Microangiopathy
Vancomycin sensitive Enterococcus faecium sepsis
HLH at T+40
Expired T+56
Plasmapheresis
Table 1: Cases summary. UCBT: Unrelated Cord Blood Transplant, RIC: Reduced Intensity Conditioning, COG: Children’s Oncology Group.
HLH criteria
Fever ᵒC
Cytopenias
Ferritin ug/L
Fibrinogen
mg/dL
Triglycerides
Soluble IL-2 U/ml
Coagulation profile
Direct bilirubin
Bone Marrow
Case 1
40.7
WBC<0.1x10E9/L, Hb 9.3g/dL, platelets 42x10E9/L
>40,000
865
1185
7780
Normal
6.3
Hypocellular
Case 2 39
WBC 32x10E9/L, Hb 8.6g/dL, platelets 20x10E9/L 88
275
1073
Schistocytes,
↑ D-dimer, PT, LDH
8.2
Not performed
Table 2: HLH helpful criteria in our cases.