Hemophagocytic lymphohistiocytosis

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search

Back to Top

Section editor
GauravGoyal.jpg
 Gaurav Goyal, MD
UAB
Birmingham, AL
Social-twitter-icon.png GauravGoyalMD
4 regimens on this page
4 variants on this page


Guidelines

Histiocyte Society

  • 2019: La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N, Birndt S, Gil-Herrera J, Girschikofsky M, Jordan MB, Kumar A, van Laar JA, Lachmann G, Nichols KE, Ramanan AV, Wang Y, Wang Z, Janka G, Henter JI. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019 Jun 6;133(23):2465-2477. Epub 2019 Apr 16. link to original article PubMed

"How I treat"

  • 2015: Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult patient. Blood. 2015 May 7;125(19):2908-14. Epub 2015 Mar 10. link to original article PubMed

Untreated

HLH-94 regimen

Regimen

Study Evidence
Henter et al. 1997 (HLH-94) Non-randomized

Immunosuppressive therapy, initial

  • Dexamethasone (Decadron) in a tapering schedule as follows:
    • Weeks 1 & 2: 10 mg/m2/day (single or split doses not specified)
    • Weeks 3 & 4: 5 mg/m2/day (single or split doses not specified)
    • Weeks 5 & 6: 2.5 mg/m2/day (single or split doses not specified)
    • Week 7: 1.25 mg/m2/day (single or split doses not specified)
    • Taper off during week 8 (exact schedule not specified)
  • Etoposide (Vepesid) as follows:
    • Weeks 1 & 2: 150 mg/m2 IV twice per week
    • Weeks 3 to 8: 150 mg/m2 IV once per week

CNS therapy

  • Methotrexate (MTX) (dose not specified) IT once per week for weeks 3 to 6 in patients with progressive neurological symptoms and/or persisting abnormal cerebrospinal fluid findings.

Supportive therapy

8-week course; patients without familial or persistent disease then stopped. Patients with familial, persistent, or relapsed disease were treated with up to one year of continuation therapy, until an allogeneic HCT could be performed, as follows:

Immunosuppressive therapy, continuation

Up to 52-week course

References

  1. HLH-94: Henter JI, Aricò M, Egeler RM, Elinder G, Favara BE, Filipovich AH, Gadner H, Imashuku S, Janka-Schaub G, Komp D, Ladisch S, Webb D; HLH study Group of the Histiocyte Society. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. Med Pediatr Oncol. 1997 May;28(5):342-7. link to original article does not contain dosing details PubMed
    1. Update: Henter JI, Samuelsson-Horne A, Aricò M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G; Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002 Oct 1;100(7):2367-73. link to original article contains dosing details in manuscript PubMed
    2. Update: Trottestam H, Horne A, Aricò M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI; Histiocyte Society. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood. 2011 Oct 27;118(17):4577-84. Epub 2011 Sep 6. link to original article contains dosing details in manuscript link to PMC article PubMed

HLH-2004 regimen

Regimen

Study Evidence
Henter et al. 2007 (HLH-2004) Non-randomized

Immunosuppressive therapy, initial

  • Start allogeneic stem cell transplant (SCT) donor search
  • Dexamethasone (Decadron) in a tapering schedule as follows:
    • Weeks 1 & 2: 10 mg/m2 (route not specified) once per day
    • Weeks 3 & 4: 5 mg/m2 (route not specified) once per day
    • Weeks 5 & 6: 2.5 mg/m2 (route not specified) once per day
    • Week 7: 1.25 mg/m2 (route not specified) once per day
    • Week 8: "taper then discontinue"
  • Etoposide (Vepesid) as follows:
    • Weeks 1 & 2: 150 mg/m2 IV twice per week
    • Weeks 3 to 8: 150 mg/m2 IV once per week
  • Cyclosporine A 3 mg/kg/dose by mouth twice per day (total dose per day is 6 mg/kg), if normal kidney function. **Titrate doses with goal of levels around 200 mcg/L (monoclonal, trough level). It was not clear from the paper whether this is modified or non-modified cyclosporine.

Intrathecal therapy

To "start only if progressive neurological symptoms or if an abnormal CSF has not improved," maximum of 4 doses, as follows:

    • Weeks 3 to 6: Methotrexate (MTX) (dosed by age as listed below) IT once per week, by the following criteria:
      • less than 1 year old: 6 mg each dose
      • 1 to 2 years old: 8 mg each dose
      • 2 to 3 years old: 10 mg each dose
      • Greater than 3 years old: 12 mg each dose
    • Weeks 3 to 6: Prednisolone IT once per week, by the following criteria:
      • less than 1 year old: 4 mg each dose
      • 1 to 2 years old: 6 mg each dose
      • 2 to 3 years old: 8 mg each dose
      • Greater than 3 years old: 10 mg each dose

Supportive therapy

8-week course; patients with resolved, non-familial, non-genetically verified disease stopped therapy. Patients with familial, genetically verified, persistent, or reactivation/relapsed disease continued to continuation therapy, until an allogeneic HCT could be performed, as follows:

Immunosuppressive therapy, continuation

Starts during week 9.

  • Dexamethasone (Decadron) 10 mg/m2 (route not specified) once per day for three days, every two weeks (on even weeks)
  • Etoposide (Vepesid) 150 mg/m2 IV once every two weeks (on odd weeks)
  • Cyclosporine A by mouth twice per day, aiming for trough blood levels of 200 mcg/L (not clear from the paper whether this is modified or non-modified)
  • Proceed with allogeneic stem cell transplant (SCT) as soon as an acceptable donor is found, such as:
    • HLA-idential record donor
    • Matched unrelated donor
    • Mismatched unrelated donor
    • Family haploidentical donor

Used continuously, with allogeneic stem cell transplant done when possible

Relapsed or refractory

DEP

DEP: Doxil (Pegylated liposomal doxorubicin), Etoposide, MethylPrednisolone

Regimen

Study Evidence Efficacy
Wang et al. 2015a Phase 2 ORR: 76%

Note: Pegylated liposomal doxorubicin could be repeated, although details are scant in the text.

Chemotherapy

Glucocorticoid therapy

  • Methylprednisolone (Solumedrol) as follows:
    • Days 1 to 3: 15 mg/kg/day
    • Days 4 to 6: 2 mg/kg/day
    • Days 7 to 10: 1 mg/kg/day
    • Days 11 to 14: 0.75 mg/kg/day
    • Days 15 to 21: 0.5 mg/kg/day
    • Days 22 to 28: 0.4 mg/kg/day
    • Days 29 to 35: 0.3 mg/kg/day
    • Days 36 to 42: 0.2 mg/kg/day
    • Days 43 to 49: 0.1 mg/kg/day

7-week course

References

  1. Wang Y, Huang W, Hu L, Cen X, Li L, Wang J, Shen J, Wei N, Wang Z. Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood. 2015 Nov 5;126(19):2186-92. Epub 2015 Aug 19. link to original article contains dosing details in manuscript link to PMC article PubMed

Emapalumab & Dexamethasone

Regimen

Study Evidence
Locatelli et al. 2020 (NI-0501-04) Non-randomized Phase 2/3 (RT)
Locatelli et al. 2020 (NI-0501-05) Phase 2/3

Note: some untreated patients were included in the trials; however, the FDA approval is for relapsed/refractory disease.

Immunosuppressive therapy

References

  1. NI-0501-04: Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, De Benedetti F, Grom A, Lapeyre G, Jacqmin P, Ballabio M, de Min C. Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. N Engl J Med. 2020 May 7;382(19):1811-1822. link to original article PubMed NCT01818492
  2. NI-0501-05: Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, De Benedetti F, Grom A, Lapeyre G, Jacqmin P, Ballabio M, de Min C. Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. N Engl J Med. 2020 May 7;382(19):1811-1822. link to original article PubMed NCT02069899
Retrieved from "https://hemonc.org/w/index.php?title=Hemophagocytic_lymphohistiocytosis&oldid=66615"