HLH Treatment

1
HLHTreatment

• Thomas G. Gross, MD, PhD
• Columbus Childrens Hospital
• The Ohio State University

2
HLH Treatment

• Rapid institution of potent anti-inflammatory
  therapy
• Steroids, cyclosporine, ATG, or chemotherapy
• Antibiotics
• Supportive care
• Transfusions
• Parental nutrition
• Control seizures
• Make every attempt to determine etiology

3
HLH 94/2004 Therapy Principles

• Induce remission (resolve clinical symptoms and
  minimize organ damage do to disease)
• Provide definitive immunologic correction with
  allogeneic hematopoietic stem cell transplant
  (HSCT/BMT) from best available donor
• Genetic/familial disease
• Progressive disease
• Recurrent disease

4
HLH 94
Henter JI, et al. (Histiocyte Society) Blood.
2002100(7)2367-73.
5
Outcome in HLH94
Henter JI, et al. (Histiocyte Society) Blood.
2002100(7)2367-73.
6
Factors that Affect Outcome withHLH94

• Factors that had No Effect on outcome
• Gender, age, familial vs non-familial, CNS
  disease at diagnosis
• Biggest factor that did affect outcome
• Presence of active disease after 2 months of
  therapy had much poorer outcome
• Other factors that are associated with poorer
  outcome
• Active disease at time of BMT
• Donor source for HSCT/BMT

7
Effect of Donor sources for HSCT/BMT in HLH94
Horne A, et al (Histiocyte Society) Br J
Haematol. 2005129(5)622-30.
8
Reasons HSCT/BMT failed in HLH94

• 31/86 (36) died following HSCT/BMT
• 2 died following relapse of HLH
• 1 died of secondary leukemia
• 1 died of surgical complications
• 27 (87) died of transplant-related complications
  (organ damage mainly lung and liver,
  infections,GvHD, etc.)
• 23 died within 100 days following BMT

9
Reduced intensity HSCT/BMT for HLH

• Twelve patients, mixed etiologies
• Eight in CR of HLH at HSCT/BMT (HLH 94)
• Majority matched unrelated donors
• Fludarabine, Melphalan, In Vivo T depletion
• Nine survive (three mixed chimeras)

Cooper N et al, Blood. 2006107(3)1233-6.