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| Name | Class |
|---|---|
| Meyer Children's Hospital IRCCS | OTHER |
| Leiden University Medical Center | OTHER |
| Children's Hospital Medical Center, Cincinnati | OTHER |
| Ehime University Graduate School of Medicine |
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Without therapy HLH is often fatal, and often rapidly fatal. The treatment protocol HLH-94 has improved survival markedly as compared to the survival earlier. We now aim to improve survival further.
The most dangerous period after HLH diagnosis is the first 2 months. In HLH-2004 we provide additional therapy during this period as compared to in HLH-94.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Etoposide, Dexamethasone, Cyclosporin A plus IT MTX & Steroids | Experimental | As compared to the HLH-94 treatment, the main changes are that
Drugs, dosage, frequency and duration are described in the paragraph "Interventions" below. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexamethasone | Drug | 10 mg/m2 daily wk 1-2 5 mg/m2 daily wk 3-4 2.5 mg/m2 daily wk 5-6 1.25 mg/m2 daily wk 7 Steroids tapered wk 8 If continuation: Pulses every 2nd wk, 10 mg/m2 for 3 days |
| Measure | Description | Time Frame |
|---|---|---|
| Survival | 1-year after diagnosis |
| Measure | Description | Time Frame |
|---|---|---|
| Late effects | 5-years after diagnosis |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jan-Inge Henter, MD, PhD | Karolinska Institutet | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childhood Cancer Research Unit, Karolinska Hospital | Stockholm | S-171 76 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16937360 | Background | Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039. | |
| 28935695 | Result | Bergsten E, Horne A, Arico M, Astigarraga I, Egeler RM, Filipovich AH, Ishii E, Janka G, Ladisch S, Lehmberg K, McClain KL, Minkov M, Montgomery S, Nanduri V, Rosso D, Henter JI. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017 Dec 21;130(25):2728-2738. doi: 10.1182/blood-2017-06-788349. Epub 2017 Sep 21. |
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| ID | Term |
|---|---|
| D051359 | Lymphohistiocytosis, Hemophagocytic |
| ID | Term |
|---|---|
| D015616 | Histiocytosis, Non-Langerhans-Cell |
| D015614 | Histiocytosis |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D003907 | Dexamethasone |
| D005047 | Etoposide |
| D016572 | Cyclosporine |
| D033581 | Stem Cell Transplantation |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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| OTHER |
| Universitätsklinikum Hamburg-Eppendorf | OTHER |
| Baylor College of Medicine | OTHER |
| Great Ormond Street Hospital for Children NHS Foundation Trust | OTHER |
| St. Anna Kinderkrebsforschung | OTHER |
| Hospital de Cruces | OTHER |
| Hospital JP Garrahan | OTHER_GOV |
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| Etoposide | Drug | 150 mg/m2 iv twice/wk (wk 1-2) 150 mg/m2 iv once/wk (wk 3-8) If continuation: 150 mg/m2 iv, every 2nd wk |
|
| Cyclosporin | Drug | WK 1-8: - Aim at around 200 microgram/L (trough value). Start: 6 mg/kg daily (divided in 2 daily doses) wk 1, if kidney function is normal. If continuation: - Aim for around 200 microgram/L. Monitor GFR. |
|
| Intrathecal therapy | Procedure | If at 2 wks there are progressive neurological symptoms or if an abnormal CSF (cell count and protein) has not improved, then give 4 wkly intrathecal inj. Be aware that some pat may have increased intracranial pressure. Methotrexate: <1 yr 6 mg, 1-2 yrs 8 mg, 2-3 yrs 10 mg, >3 yrs 12 mg. Prednisolone: <1 yr 4 mg, 1-2 yrs 6 mg, 2-3 yrs 8 mg, >3 yrs 10 mg. |
|
| Stem cell transplant | Procedure | The SCT procedure is up to the treating physician. However, a suggested regimen is provided. |
|
| 32780845 | Derived | Bergsten E, Horne A, Hed Myrberg I, Arico M, Astigarraga I, Ishii E, Janka G, Ladisch S, Lehmberg K, McClain KL, Minkov M, Nanduri V, Rosso DA, Sieni E, Winiarski J, Henter JI. Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study. Blood Adv. 2020 Aug 11;4(15):3754-3766. doi: 10.1182/bloodadvances.2020002101. |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |