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Section editor
	Gaurav Goyal, MD UAB Birmingham, AL, USA LinkedIn

11 regimens on this page 11 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 PubMed
2013: Haupt et al. Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years PubMed

International Expert Consensus

2022: Goyal et al. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults PubMed

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 contains dosing details in manuscript PubMed NCT02389400

Etoposide & Prednisone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gadner et al. 2001 (LCH-I)	1991-1995	Phase 3 (E-switch-ic)	Vinblastine & Prednisone	Did not meet efficacy endpoints

Chemotherapy

Etoposide (Vepesid) 150 mg/mg² IV once per day on days 1 to 3

Glucocorticoid therapy

Prednisone (Sterapred) as follows:
- Cycles 1: (dose/route not specified) once

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 contains dosing details in abstract PubMed

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 split three times per day for 4 weeks, then tapering off over 2 weeks
- Cycles 2 to 7: 40 mg/m²/day 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 contains dosing details in manuscript PubMed 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 contains dosing details in manuscript PubMed NCT00276757

Vinblastine & Prednisone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gadner et al. 2001 (LCH-I)	1991-1995	Phase 3 (E-switch-ic)	Etoposide & Prednisone	Did not meet efficacy endpoints
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 split three times per day for 4 weeks, then tapering off over 2 weeks
- Cycles 2 to 7: 40 mg/m²/day split three times per day on days 1 to 5

6-week course, then 21-day cycle for 6 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 PubMed
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 contains dosing details in manuscript PubMed 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 PubMed NCT00276757

Relapsed or refractory

Cladribine monotherapy

Regimen

Study	Dates of enrollment	Evidence
Weitzman et al. 2009 (LCH-S-98)	1999-04 to NR	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 contains dosing details in manuscript PubMed

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 contains dosing details in manuscript link to PMC article PubMed

Cobimetinib monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Diamond et al. 2019 (MSK 15-216)	2016-NR	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 contains dosing details in manuscript link to PMC article PubMed 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 contains dosing details in manuscript link to PMC article PubMed

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 contains dosing details in manuscript link to PMC article PubMed

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 contains dosing details in manuscript link to PMC article PubMed

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{| class="wikitable" style="text-align:center; width:50%;"
+{{#lst:Editorial board transclusions|hist}}
-!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
-|-
-|style="background-color:#F0F0F0"|[[File:GauravGoyal.jpg|frameless|upright=0.3|center]]
-|<big>Gaurav Goyal, MD<br>UAB<br>Birmingham, AL</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/GauravGoyalMD GauravGoyalMD]
-|-
-|}
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 18: / Line 12: @@
 ''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.'''
 ==[https://www.eurohistio.net/index_eng.html Euro-Histio-Net]==
-===Older===
-*'''2013:''' Girschikofsky et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667012/ Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-Net]
+*'''2013:''' Girschikofsky et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667012/ Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-Net] [https://pubmed.ncbi.nlm.nih.gov/23672541/ PubMed]
-*'''2013:''' Haupt et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557042/ Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years]
+*'''2013:''' Haupt et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557042/ Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years] [https://www.ncbi.nlm.nih.gov/pubmed/23109216 PubMed]
 ==International Expert Consensus==
-*'''2022:''' Goyal et al. [https://doi.org/10.1182/blood.2021014343 International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults]
+*'''2022:''' Goyal et al. [https://doi.org/10.1182/blood.2021014343 International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults] [https://www.ncbi.nlm.nih.gov/pubmed/35271698 PubMed]
 ==[https://www.nccn.org NCCN]==
-*[https://www.nccn.org/professionals/physician_gls/pdf/histiocytic_neoplasms.pdf NCCN Guidelines - Histiocytic Neoplasms]
+*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1502 NCCN Guidelines - Histiocytic Neoplasms].''
 =Untreated=
 ==Cytarabine & Methotrexate (CYM) {{#subobject:b24b28|Regimen=1}}==
@@ Line 48: / Line 46: @@
 </div></div>
 ===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. [https://doi.org/10.1002/ajh.25864 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32395858/ PubMed] NCT02389400
+#'''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. [https://doi.org/10.1002/ajh.25864 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32395858/ PubMed] [https://clinicaltrials.gov/study/NCT02389400 NCT02389400]
 ==Etoposide & Prednisone {{#subobject:566a87|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 68: / Line 66: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Etoposide (Vepesid)]]
+*[[Etoposide (Vepesid)]] 150 mg/mg<sup>2</sup> IV once per day on days 1 to 3
 ====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
+*[[Prednisone (Sterapred)]] as follows:
+**Cycles 1: (dose/route not specified) once
+'''21-day cycle for 8 cycles'''
 </div></div>
 ===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. [https://doi.org/10.1067/mpd.2001.111331 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11343051/ PubMed]
+# 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. [https://doi.org/10.1067/mpd.2001.111331 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11343051/ PubMed]
 ==Etoposide, Vinblastine, Prednisone {{#subobject:5145a8|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 84: / Line 85: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
+|[https://doi.org/10.1182/blood-2007-08-106211 Gadner et al. 2007 (LCH-II)]
 |1996-2001
 |style="background-color:#1a9851"|Phase 3 (E-esc)
@@ Line 103: / Line 104: @@
 **Cycle 1: 40 mg/m<sup>2</sup>/day split three times per day for 4 weeks, then tapering off over 2 weeks
 **Cycles 2 to 7: 40 mg/m<sup>2</sup>/day split three times per day on days 1 to 5
+'''6-week course, then 21-day cycle for 6 cycles'''
 </div></div>
 ===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. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18089850/ PubMed] ISRCTN57679341
+# '''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. [https://doi.org/10.1182/blood-2007-08-106211 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18089850/ PubMed] ISRCTN57679341
 ==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 116: / Line 118: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
+|[https://doi.org/10.1182/blood-2012-09-455774 Gadner et al. 2013 (LCH-III)]
 |2001-2008
 |style="background-color:#1a9851"|Phase 3 (E-esc)
@@ Line 125: / Line 127: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Methotrexate (MTX)]]
+*[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
-*[[Vinblastine (Velban)]]
+*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36
 ====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
+*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 28, then tapered off by day 42
+'''6-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*See paper for details of treatment beyond induction.
 </div></div>
 ===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. [http://www.bloodjournal.org/content/121/25/5006.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/23589673/ PubMed] NCT00276757
+# '''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. [https://doi.org/10.1182/blood-2012-09-455774 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23589673/ PubMed] [https://clinicaltrials.gov/study/NCT00276757 NCT00276757]
 ==Vinblastine & Prednisone {{#subobject:378322|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 148: / Line 156: @@
 |style="background-color:#ffffbf"|Did not meet efficacy endpoints
 |-
-|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
+|[https://doi.org/10.1182/blood-2007-08-106211 Gadner et al. 2007 (LCH-II)]
 |1996-2001
 |style="background-color:#1a9851"|Phase 3 (C)
@@ Line 154: / Line 162: @@
 |style="background-color:#ffffbf"|Did not meet primary endpoint of rapid response
 |-
-|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
+|[https://doi.org/10.1182/blood-2012-09-455774 Gadner et al. 2013 (LCH-III)]
 |2001-2008
 |style="background-color:#1a9851"|Phase 3 (C)
@@ Line 170: / Line 178: @@
 **Cycle 1: 40 mg/m<sup>2</sup>/day split three times per day for 4 weeks, then tapering off over 2 weeks
 **Cycles 2 to 7: 40 mg/m<sup>2</sup>/day split three times per day on days 1 to 5
+'''6-week course, then 21-day cycle for 6 cycles'''
 </div></div>
 ===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. [https://doi.org/10.1067/mpd.2001.111331 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11343051/ PubMed]
-# '''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. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18089850/ PubMed] ISRCTN57679341
+# '''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. [https://doi.org/10.1182/blood-2007-08-106211 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18089850/ PubMed] 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. [http://www.bloodjournal.org/content/121/25/5006.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/23589673/ PubMed] NCT00276757
+# '''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. [https://doi.org/10.1182/blood-2012-09-455774 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23589673/ PubMed] [https://clinicaltrials.gov/study/NCT00276757 NCT00276757]
 =Relapsed or refractory=
 ==Cladribine monotherapy {{#subobject:da32fb|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:1ef1c0|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://doi.org/10.1002/pbc.22229 Weitzman et al. 2009 (LCH-S-98)]
+|1999-04 to NR
 |style="background-color:#91cf61"|Phase 2
 |-
@@ Line 189: / Line 200: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cladribine (Leustatin)]]
+*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
+'''21-day cycle for up to 6 cycles'''
 </div></div>
 ===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. [https://doi.org/10.1002/pbc.22229 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19731321/ PubMed]
+# '''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. [https://doi.org/10.1002/pbc.22229 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19731321/ PubMed]
 ==Cladribine & Cytarabine {{#subobject:4c5b41|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 208: / Line 221: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cladribine (Leustatin)]] 9 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''should not be administered simultaneously with cytarabine'''
+*[[Cladribine (Leustatin)]] by the following weight-based criteria:
-**Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
+**10 kg or more: 9 mg/m<sup>2</sup> 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/m<sup>2</sup> 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'''
 </div>
 <div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *LCH-S-2005, patients with a good response: [[#Cladribine_monotherapy_2|Cladribine]] consolidation
@@ Line 219: / Line 234: @@
 ===References===
 <!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
-# '''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. [http://www.bloodjournal.org/content/126/12/1415.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed]
+# '''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. [https://doi.org/10.1182/blood-2015-03-635151 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed]
 ==Cobimetinib monotherapy {{#subobject:a6f6dd|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 234: / Line 249: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ Diamond et al. 2019 (MSK 15-216)]
 |2016-NR
-|style="background-color:#ffffbe"|Phase 2, <20 pts in this arm (RT)
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this arm (RT)
 |-
 |}
@@ Line 244: / Line 259: @@
 </div></div>
 ===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. [https://doi.org/10.1038/s41586-019-1012-y link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30867592/ PubMed] NCT02649972
+# '''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. [https://doi.org/10.1038/s41586-019-1012-y link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30867592/ PubMed] [https://clinicaltrials.gov/study/NCT02649972 NCT02649972]
 ==Vemurafenib monotherapy {{#subobject:953978|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 255: / Line 270: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ Hyman et al. 2015 (VE-BASKET)]
 |2012-2014
-|style="background-color:#ffffbe"|Phase 2, <20 pts in this arm
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this arm
 |-
 |}
@@ Line 282: / Line 297: @@
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Cladribine_.26_Cytarabine|Cladribine & Cytarabine]]
+*Salvage [[#Cladribine_.26_Cytarabine|Cladribine & Cytarabine]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
@@ Line 295: / Line 310: @@
 ===References===
 <!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
-# '''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. [http://www.bloodjournal.org/content/126/12/1415.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed]
+# '''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. [https://doi.org/10.1182/blood-2015-03-635151 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed]
 =Relapsed or refractory, maintenance=
 ==Mercaptopurine, Methotrexate, Vinblastine, Prednisolone {{#subobject:b3e901|Regimen=1}}==
@@ Line 312: / Line 327: @@
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Cladribine_monotherapy_2|Cladribine]] x 2
+*Salvage [[#Cladribine_monotherapy_2|Cladribine]] x 2
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day
+*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 14
 *[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once per day on days 1 & 8
 *[[Vinblastine (Velban)]] as follows:
@@ Line 323: / Line 338: @@
 *[[Prednisolone (Millipred)]] as follows:
 **Cycles 1 to 13: 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
-'''14-day cycles for 39 cycles (18 months)'''
+'''14-day cycle for 39 cycles (18 months)'''
 </div></div>
 ===References===
 <!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
-# '''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. [http://www.bloodjournal.org/content/126/12/1415.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed]
+# '''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. [https://doi.org/10.1182/blood-2015-03-635151 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed]
 [[Category:Langerhans cell histiocytosis regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Histiocytoses]]

Difference between revisions of "Langerhans cell histiocytosis"

Latest revision as of 23:36, 24 June 2024

Guidelines

Euro-Histio-Net

International Expert Consensus

NCCN

Untreated

Cytarabine & Methotrexate (CYM)

Regimen

Chemotherapy

References

Etoposide & Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Etoposide, Vinblastine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Methotrexate, Vinblastine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

References

Vinblastine & Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Relapsed or refractory

Cladribine monotherapy

Regimen

Chemotherapy

References

Cladribine & Cytarabine

Regimen

Chemotherapy

Subsequent treatment

References

Cobimetinib monotherapy

Regimen

Targeted therapy

References

Vemurafenib monotherapy

Regimen

Targeted therapy

References

Relapsed or refractory, consolidation

Cladribine monotherapy

Regimen

Preceding treatment

Chemotherapy

Subsequent treatment

References

Relapsed or refractory, maintenance

Mercaptopurine, Methotrexate, Vinblastine, Prednisolone

Regimen

Preceding treatment

Chemotherapy

Glucocorticoid therapy

References

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