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The Histiocyte Society has conducted three consecutive prospective clinical trials (LCH I-III) on front-line treatment of multisystem LCH between 1991 and 2008.

LCH-I (1991-1995):

Patients with histologically confirmed multisystem LCH were randomly assigned to receive 24 weeks treatment of vinblastine (Arm A) or etoposide (Arm B). An initial pulse of high-dose methyl-prednisolone was given in both arms to treat constitutional symptoms. Five hundred and twenty-three patients were registered on LCH-I, of whom 210 had multisystem disease and 143 were randomized. Read more...

LCH-II (1996-2001):

LCH-II was a randomized phase-III trial for patients with multisystem LCH. It investigated the value of the addition of etoposide (Arm B) to the standard combination of prednisolone and vinblastine (Arm A) in patients with MS-LCH. The randomized trial focused on risk patients. “Risk” was defined either by age below 2 years or by involvement of at least one risk organ (RO; e.g. liver, spleen, hematopoietic system, or lung) irrespective of age. The continuation therapy included 6-MP in addition to the prednisolone/ vinblastine pulses for a total treatment duration of 6 months.  Read more...

LCH-III (2001-2008):

LCH-III was a multicenter, prospective, open, phase-III, randomized clinical trial for patients with MS-LCH. Previously untreated patients with MS-LCH were stratified into a “high risk” and a “low risk” group, depending on presence of RO involvement at diagnosis.  Read more...


LCH-I-S (1994-1998):

This salvage therapy trial was opened in 1994, in which the questions asked were whether it was possible to improve survival for MS-LCH patients whose disease progressed on current ‘‘best’’ therapy, and whether it was possible to cure those patients. Read more...

LCH-S-98 (1999-2004):

This salvage approach was designed as a non-randomized phase II study, aiming to evaluate the activity of cladribine (2-chlorodeoxyadenosine;  2-CdA) in patients with risk organ involvement (RO+), whose disease progressed after combination therapy with prednisolone, vinblastine and etoposide and in patients without risk organ involvement (RO-) with multiple disease reactivations (≥ 2 episodes). Read more...

LCH-S-2005 (2005-2010):

This open-label, prospective, non-randomized, phase 2 trial, was based on the promising results of a previous pilot trial of the French LCH Study Group. Read more...


Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis and in 1983 the long-term survival was reported as 4%. Prompted by these poor results, in 1994 the Histiocyte Society developed a treatment strategy (HLH-94) which combined two previously reported regimens, chemotherapy and immunotherapy. HLH-94 is based on etoposide (VP-16), corticosteroids, cyclosporin A (CSA), and, in selected patients, IT MTX, prior to intended stem cell transplantation (SCT). Read more...



The HLH-94 study resulted in a remarkably improved outcome with a 5-year probability of survival (pSu) of 54% (±6%). HLH-2004 was initiated with the aim to improve survival further, and reduce pre-SCT mortality and neurological sequelae.

HLH-2004 was based on HLH-94, with eight weeks initial treatment followed by a continuation phase, both including etoposide and dexamethasone.  Read more...

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Fax: +1 (856) 589-6614

Histiocyte Society
332 N Broadway
Pitman, NJ 08071 USA

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