Langerhans cell histiocytosis

Back to Top
Last updated on 2024-09-06:12 regimens on this page
12 variants on this page
Note: the majority of the regimens on this page are intended for multi-system Langerhans cell histiocytosis (MS-LCH); many patients with other forms of LCH, such as pulmonary (PLCH) do not necessarily need antineoplastic treatment.
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==Euro-Histio-Net==
*2013: Girschikofsky et al. Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-Net EuroPMC
*2013: Haupt et al. Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years EuroPMC
==International Expert Consensus==
*2022: Goyal et al. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults link to PMC article EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Histiocytic Neoplasms.
=Untreated=
==Cytarabine & Methotrexate (CYM)==
CYM: CYtarabine, Methotrexate
===Regimen===
Study 	Dates of enrollment	Evidence
Cao et al. 2020 (MAALCH)	2014-2018 	Phase 2
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m2)
*Methotrexate (MTX) 1000 mg/m2 IV continuous infusion over 24 hours, started on day 1 
35-day cycle for 6 cycles
===References===
#MAALCH: Cao XX, Li J, Zhao AL, He TH, Gao XM, Cai HC, Zhang L, Zhang Y, Feng J, Zhu TN, Niu N, Sun J, Liang ZY, Duan MH, Zhou DB. Methotrexate and cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis: A single arm, single center, prospective phase 2 study. Am J Hematol. 2020 Sep;95(9):E235-E238. Epub 2020 Jun 20. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02389400
==Etoposide & Methylprednisolone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gadner et al. 2001 (LCH-I)	1991-1995 	Phase 3 (E-switch-ic)	Vinblastine & HDMP	Did not meet efficacy endpoints
====Chemotherapy====
*Etoposide (Vepesid) 150 mg/mg2 IV over 60 minutes once per day on days 1 to 3
====Glucocorticoid therapy====
*Methylprednisolone (Solumedrol) as follows:
**Cycle 1: 30 mg/kg IV bolus once per day on days 1 to 3
21-day cycle for 8 cycles
===References===
# Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Etoposide, Vinblastine, Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gadner et al. 2007 (LCH-II)	1996-2001 	Phase 3 (E-esc)	Vinblastine & Prednisone	Did not meet primary endpoint of rapid response
====Chemotherapy====
*Etoposide (Vepesid) as follows:
**Cycle 1: 150 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
**Cycles 2 to 7: 150 mg/m2 IV over 60 minutes once on day 1
*Vinblastine (Velban) as follows:
**Cycle 1: 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
**Cycles 2 to 7: 6 mg/m2 IV bolus once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows: 
**Cycle 1: 40 mg/m2/day PO split three times per day for 4 weeks, then tapering off over 2 weeks
**Cycles 2 to 7: 40 mg/m2/day PO split three times per day on days 1 to 5
6-week course, then 21-day cycle for 6 cycles
===References===
# LCH-II: Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN57679341
==Methotrexate, Vinblastine, Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gadner et al. 2013 (LCH-III)	2001-2008 	Phase 3 (E-esc)	Vinblastine & Prednisone	Did not meet primary endpoint of early progression at week 6 and response at week 12
====Chemotherapy====
*Methotrexate (MTX) 500 mg/m2 IV once per day on days 1, 15, 29
*Vinblastine (Velban) 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2/day PO on days 1 to 28, then tapered off by day 42
6-week course
====Subsequent treatment====
*See paper for details of treatment beyond induction.
===References===
# LCH-III: Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00276757
==Vinblastine & Methylprednisolone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gadner et al. 2001 (LCH-I)	1991-1995 	Phase 3 (E-switch-ic)	Etoposide & HDMP	Did not meet efficacy endpoints
====Chemotherapy====
*Vinblastine (Velban) 6 mg/m2 IV bolus once on day 1
====Glucocorticoid therapy====
*Methylprednisolone (Solumedrol) as follows:
**Cycle 1: 30 mg/kg IV bolus once per day on days 1 to 3
7-day cycle for 24 cycles
===References===
# LCH-I: Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Vinblastine & Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gadner et al. 2007 (LCH-II) 	1996-2001 	Phase 3 (C)	Etoposide, Vinblastine, Prednisone 	Did not meet primary endpoint of rapid response
Gadner et al. 2013 (LCH-III)	2001-2008 	Phase 3 (C)	Methotrexate, Vinblastine, Prednisone	Did not meet primary endpoint of early progression at week 6 and response at week 12
====Chemotherapy====
*Vinblastine (Velban) as follows:
**Cycle 1: 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
**Cycles 2 to 7: 6 mg/m2 IV bolus once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycle 1: 40 mg/m2/day PO split three times per day for 4 weeks, then tapering off over 2 weeks
**Cycles 2 to 7: 40 mg/m2/day PO split three times per day on days 1 to 5
6-week course, then 21-day cycle for 6 cycles
===References===
# LCH-II: Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN57679341
# LCH-III: Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article EuroPMC NCT00276757
=Relapsed or refractory=
==Cladribine monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Weitzman et al. 2009 (LCH-S-98)	1999-04 to not reported	Phase 2
====Chemotherapy====
*Cladribine (Leustatin) 5 mg/m2 IV over 2 hours once per day on days 1 to 5
21-day cycle for up to 6 cycles
===References===
# LCH-S-98: Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH): results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cladribine & Cytarabine==
===Regimen===
Study 	Dates of enrollment	Evidence
Donadieu et al. 2015 (LCH-S-2005)	2005-04 to 2010-11 	Phase 2
====Chemotherapy====
*Cladribine (Leustatin) by the following weight-based criteria:
**10 kg or more: 9 mg/m2 IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
**Less than 10 kg: 0.3 mg/kg IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
*Cytarabine (Ara-C) 500 mg/m2 IV over 2 hours twice per day on days 1 to 5, should not be administered simultaneously with cladribine
35-day cycle for 2 or more cycles
====Subsequent treatment====
*LCH-S-2005, patients with a good response: Cladribine consolidation
===References===
# LCH-S-2005: Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Cobimetinib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence
Diamond et al. 2019 (MSK 15-216)	2016 to not reported	Phase 2, fewer than 20 pts in this arm (RT)
Note: there were N=2 patients with LCH; it was unclear if they were untreated or previously treated.
====Targeted therapy====
*Cobimetinib (Cotellic) 60 mg PO once per day on days 1 to 21
28-day cycles
===References===
# MSK 15-216: Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019 Mar;567(7749):521-524. Epub 2019 Mar 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02649972
==Vemurafenib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Hyman et al. 2015 (VE-BASKET)	2012-2014 	Phase 2, fewer than 20 pts in this arm
Note: This was part of a basket trial, all patients had BRAF p.V600E mutations. A minority (7/18, 39%) of participants were untreated.
====Targeted therapy====
*Vemurafenib (Zelboraf) 960 mg PO twice per day
Duration of treatment not specified
===References===
# VE-BASKET: Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
=Relapsed or refractory, consolidation=
==Cladribine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Donadieu et al. 2015 (LCH-S-2005)	2005-04 to 2010-11 	Phase 2
====Preceding treatment====
*Salvage Cladribine & Cytarabine
====Chemotherapy====
*Cladribine (Leustatin) 5 mg/m2 IV once per day on days 1 to 3
21-day cycle for 2 cycles
====Subsequent treatment====
*4-drug maintenance
===References===
# LCH-S-2005: Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
=Relapsed or refractory, maintenance=
==Mercaptopurine, Methotrexate, Vinblastine, Prednisolone==
===Regimen===
Study 	Dates of enrollment	Evidence
Donadieu et al. 2015 (LCH-S-2005)	2005-04 to 2010-11 	Phase 2
====Preceding treatment====
*Salvage Cladribine x 2
====Chemotherapy====
*Mercaptopurine (6-MP) 50 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 20 mg/m2 PO once per day on days 1 & 8
*Vinblastine (Velban) as follows:
**Cycles 1 to 13: 6 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) as follows:
**Cycles 1 to 13: 40 mg/m2 PO once per day on days 1 to 5
14-day cycle for 39 cycles (18 months)
===References===
# LCH-S-2005: Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
Category:Langerhans cell histiocytosis regimens
Category:Disease-specific pages
Category:Histiocytoses