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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Multisystem Langerhans cell histiocytosis is the severe form of this rare histiocytosis, in which the abnormal cells involve several organs at once, most dangerously the liver, spleen and bone marrow of infants. It is treated with a year of vinblastine and prednisone, with stronger drugs or BRAF-targeted tablets for children who do not respond quickly; survival is now high but late effects remain.
Multisystem Langerhans cell histiocytosis involves two or more organ systems, typically skin, bone, lymph nodes, pituitary, lungs and, in the highest-risk children, the liver, spleen and haematopoietic system. Risk-organ involvement, defined by hepatomegaly with liver dysfunction, splenomegaly or cytopenias, and a poor response to the first six weeks of therapy are the two strongest predictors of death; the mortality of risk-organ-positive disease has fallen from more than half in the 1980s to a small minority in the era of standardised protocols and salvage therapy. BRAF V600E is present in most multisystem cases, and the mutant clone can be traced to haematopoietic progenitors in the marrow, which explains why high-risk disease behaves like a systemic myeloid neoplasm; circulating BRAF V600E DNA tracks disease burden and predicts relapse.
The Histiocyte Society trials built the standard. LCH-I and LCH-II established vinblastine and prednisone as the backbone; LCH-III (Blood 2013), which randomised 376 patients, showed that adding methotrexate did not help but that extending treatment from six to twelve months roughly halved reactivation, and that children who respond by week six do well. For children with risk-organ disease who do not respond, cytarabine and cladribine (LCH-S-2005) or, in the most refractory, the intensive cladribine-cytarabine regimen followed by reduced-intensity allogeneic transplantation are salvage options, and the ongoing LCH-IV trial tests longer and intensified therapy. BRAF inhibitors changed refractory disease: vemurafenib and dabrafenib produce rapid responses in BRAF V600E-mutant children, including infants with risk-organ disease, though the disease returns when they stop, and cobimetinib is approved for adults with histiocytic neoplasms; combining targeted agents with chemotherapy to achieve durable remissions is the current trial question. Survivors face diabetes insipidus and anterior pituitary deficiency in a substantial minority, neurodegenerative disease years later, sclerosing cholangitis, hearing loss and orthopaedic problems, so structured long-term follow-up is standard.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis and staging | Biopsy with BRAF testing; blood count, liver tests, coagulation, abdominal ultrasound, skeletal survey or whole-body MRI, pituitary assessment. | not mapped |
| First line | Vinblastine and prednisone induction for six to twelve weeks, then continuation to twelve months in total (LCH-III); mercaptopurine added for risk-organ disease in some protocols. | not mapped |
| Non-response at week six or risk-organ progression | Switch to cytarabine or cladribine; intensive cladribine-cytarabine for refractory risk-organ disease; BRAF inhibitor (vemurafenib, dabrafenib) for BRAF V600E-mutant disease; reduced-intensity allogeneic transplantation in selected cases. | not mapped |
| Reactivation | Repeat vinblastine-prednisone or cytarabine; targeted therapy for repeated reactivation; enrolment in LCH-IV. | not mapped |
| Long-term follow-up | Endocrine, neurological, hearing, hepatic and orthopaedic surveillance for late effects through a survivorship programme. | not mapped |