Difference between revisions of "Langerhans cell histiocytosis"

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m (Text replacement - "'''Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.'''" to "'''Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer. If this is your first time visiting, we suggest you read the tutorial.'''")
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''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=
 +
==Euro-Histio-Net==
 +
*'''2013:''' [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:''' [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]
  
−
=All lines of therapy=
+
=Untreated=
  
−
==Cladribine monotherapy {{#subobject:da32fb|Regimen=1}}==
+
==Etoposide & Prednisone {{#subobject:566a87|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 18: Line 23:
 
|}
 
|}
  
−
===Regimen {{#subobject:1ef1c0|Variant=1}}===
+
===Regimen {{#subobject:#3c6b84|Variant=1}}===
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|-
 
|-
−
|[http://onlinelibrary.wiley.com/doi/10.1002/pbc.22229/abstract Weitzman et al. 2009 (LCH-S-98)]
+
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
−
|style="background-color:#EEEE00"|Phase II
+
|style="background-color:#00CD00"|Phase III
 +
|[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 +
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
 
To be completed
 
To be completed
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cladribine (Leustatin)]]
+
*[[Etoposide (Vepesid)]]
 +
*[[Prednisone (Sterapred)]]
  
 
===References===
 
===References===
−
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/pbc.22229/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19731321 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. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
  
−
==Cladribine & Cytarabine {{#subobject:4c5b41|Regimen=1}}==
+
==Etoposide, Vinblastine, Prednisone {{#subobject:5145a8|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 40: Line 50:
 
|}
 
|}
  
−
===Regimen {{#subobject:7b85e8|Variant=1}}===
+
===Regimen {{#subobject:#7ace0e|Variant=1}}===
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015]
+
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
−
|style="background-color:#EEEE00"|Phase II
+
|style="background-color:#00CD00"|Phase III
 +
|[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 +
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy, induction====
+
''Total duration of therapy is 24 weeks.''
−
*[[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'''
+
====Chemotherapy, initial====
−
**Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
+
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once per week
−
*[[Cytarabine (Cytosar)]] 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'''
+
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
  
−
'''35-day cycle for 2 or more cycles'''
+
'''6-week course, followed by:'''
  
−
''Patients with a "good response" proceeded to consolidation therapy:''
+
====Chemotherapy, continuation====
 +
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once on day 1
 +
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
  
−
====Chemotherapy, consolidation====
+
'''21-day cycle for 6 cycles'''
−
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
 
 
−
'''21-day cycle for 2 cycles, followed by:'''
 
−
 
 
−
====Chemotherapy, maintenance====
 
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once every 2 weeks for 6 months
 
−
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 of every 2nd week for 6 months
 
−
*[[Mercaptopurine (Purinethol)]] 50 mg/m<sup>2</sup> PO once per day for 18 months
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once per week for 18 months
 
−
 
 
−
'''Total of 18 months of maintenance'''
 
  
 
===References===
 
===References===
−
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
+
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
−
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26194764 PubMed]
 
  
−
==Etoposide & Prednisone {{#subobject:566a87|Regimen=1}}==
+
==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 81: Line 87:
 
|}
 
|}
  
−
===Regimen {{#subobject:#3c6b84|Variant=1}}===
+
===Regimen {{#subobject:#f569ce|Variant=1}}===
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
Line 88: Line 94:
 
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|-
 
|-
−
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
+
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
−
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
+
|[[#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
Line 96: Line 102:
 
To be completed
 
To be completed
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Etoposide (Vepesid)]]
+
*[[Methotrexate (MTX)]]
 +
*[[Vinblastine (Velban)]]
 
*[[Prednisone (Sterapred)]]
 
*[[Prednisone (Sterapred)]]
  
 
===References===
 
===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. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
+
# 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://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]
  
−
==Etoposide, Vinblastine, Prednisone {{#subobject:5145a8|Regimen=1}}==
+
==Vinblastine & Prednisone {{#subobject:378322|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 108: Line 115:
 
|}
 
|}
  
−
===Regimen {{#subobject:#7ace0e|Variant=1}}===
+
===Regimen {{#subobject:#bf6a74|Variant=1}}===
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
Line 114: Line 121:
 
|'''Comparator'''
 
|'''Comparator'''
 
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 +
|-
 +
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
 +
|style="background-color:#00CD00"|Phase III
 +
|[[#Etoposide_.26_Prednisone|Etoposide & Prednisone]]
 +
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
 
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
−
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
+
|[[#Etoposide.2C_Vinblastine.2C_Prednisone|Etoposide, Vinblastine, Prednisone]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 +
|style="background-color:#00CD00"|Phase III
 +
|[[#Methotrexate.2C_Vinblastine.2C_Prednisone|Methotrexate, Vinblastine, Prednisone]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''Total duration of therapy is 24 weeks.''
+
''Total duration of therapy is 24 weeks, in LCH-II.''
 
====Chemotherapy, initial====
 
====Chemotherapy, initial====
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once per week
 
 
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
 
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
 
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
 
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
Line 130: Line 146:
  
 
====Chemotherapy, continuation====
 
====Chemotherapy, continuation====
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once on day 1
 
 
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
 
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
Line 137: Line 152:
  
 
===References===
 
===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. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
 
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
 
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
 +
# 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://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]
 +
 +
=Relapsed or refractory=
  
−
==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}==
+
==Cladribine monotherapy {{#subobject:da32fb|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 145: Line 164:
 
|}
 
|}
  
−
===Regimen {{#subobject:#f569ce|Variant=1}}===
+
===Regimen {{#subobject:1ef1c0|Variant=1}}===
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
+
|[http://onlinelibrary.wiley.com/doi/10.1002/pbc.22229/abstract Weitzman et al. 2009 (LCH-S-98)]
−
|style="background-color:#00CD00"|Phase III
+
|style="background-color:#EEEE00"|Phase II
−
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 
To be completed
 
To be completed
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Methotrexate (MTX)]]
+
*[[Cladribine (Leustatin)]]
−
*[[Vinblastine (Velban)]]
+
 
−
*[[Prednisone (Sterapred)]]
+
===References===
 +
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/pbc.22229/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19731321 PubMed]
 +
 
 +
==Cladribine & Cytarabine {{#subobject:4c5b41|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
===Regimen {{#subobject:7b85e8|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015]
 +
|style="background-color:#EEEE00"|Phase II
 +
|-
 +
|}
 +
====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'''
 +
**Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
 +
*[[Cytarabine (Cytosar)]] 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'''
 +
 
 +
''Patients with a "good response" proceeded to [[#Cladribine_monotherapy_2|cladribine consolidation]].''
  
 
===References===
 
===References===
−
# 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://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]
+
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
 +
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26194764 PubMed]
  
 
==Vemurafenib monotherapy {{#subobject:953978|Regimen=1}}==
 
==Vemurafenib monotherapy {{#subobject:953978|Regimen=1}}==
Line 182: Line 222:
 
|-
 
|-
 
|}
 
|}
−
''This was part of a basket trial, all patients had BRAF V600E mutations.''
+
''This was part of a basket trial, all patients had BRAF p.V600E mutations. A minority (7/18, 39%) of participants were untreated.''
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
 
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
Line 189: Line 229:
  
 
===References===
 
===References===
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26287849 PubMed]
+
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26287849 PubMed]
  
−
==Vinblastine & Prednisone {{#subobject:378322|Regimen=1}}==
+
=Relapsed or refractory, consolidation=
 +
==Cladribine monotherapy {{#subobject:7db44f|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
 
+
===Regimen {{#subobject:77d734|Variant=1}}===
−
===Regimen {{#subobject:#bf6a74|Variant=1}}===
 
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
−
|'''Comparator'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
 
|-
 
|-
−
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015]
−
|style="background-color:#00CD00"|Phase III
+
|style="background-color:#EEEE00"|Phase II
−
|[[Histiocytoses#Etoposide_.26_Prednisone|Etoposide & Prednisone]]
+
|-
−
|style="background-color:#ffffbf"|Seems not superior
+
|}
 +
====Preceding treatment====
 +
*[[#Cladribine_.26_Cytarabine|Cladribine & Cytarabine]]
 +
====Chemotherapy====
 +
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
 
 +
'''21-day cycle for 2 cycles'''
 +
 
 +
''Treatment followed by [[#Mercaptopurine.2C_Methotrexate.2C_Vinblastine.2C_Prednisolone|4-drug maintenance]].''
 +
 
 +
===References===
 +
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
 +
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26194764 PubMed]
 +
 
 +
=Relapsed or refractory, maintenance=
 +
==Mercaptopurine, Methotrexate, Vinblastine, Prednisolone {{#subobject:b3e901|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
+
|[[#top|back to top]]
−
|style="background-color:#00CD00"|Phase III
+
|}
−
|[[Histiocytoses#Etoposide.2C_Vinblastine.2C_Prednisone|Etoposide, Vinblastine, Prednisone]]
+
===Regimen {{#subobject:231bee|Variant=1}}===
−
|style="background-color:#ffffbf"|Seems not superior
+
{| border="1" style="text-align:center;" !align="left"  
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015]
−
|style="background-color:#00CD00"|Phase III
+
|style="background-color:#EEEE00"|Phase II
−
|[[Histiocytoses#Methotrexate.2C_Vinblastine.2C_Prednisone|Methotrexate, Vinblastine, Prednisone]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
−
''Total duration of therapy is 24 weeks, in LCH-II.''
+
====Preceding treatment====
−
====Chemotherapy, initial====
+
*[[#Cladribine_monotherapy_2|Cladribine]] x 2
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
+
====Chemotherapy====
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
+
*[[Mercaptopurine (Purinethol)]] 50 mg/m<sup>2</sup> PO once per day for 18 months
 +
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once per week for 18 months
 +
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once every 2 weeks for '''first''' 6 months
 +
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 of every 2nd week for '''first''' 6 months
  
−
'''6-week course, followed by:'''
+
'''Total of 18 months of maintenance'''
−
 
 
−
====Chemotherapy, continuation====
 
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
  
 
===References===
 
===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. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
+
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. -->
−
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
+
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26194764 PubMed]
−
# 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://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]
 
  
 
[[Category:Langerhans cell histiocytosis regimens]]
 
[[Category:Langerhans cell histiocytosis regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Histiocytoses]]
 
[[Category:Histiocytoses]]

Revision as of 04:07, 16 December 2017

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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.

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

Euro-Histio-Net

Untreated

Etoposide & Prednisone

back to top

Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2001 (LCH-I) Phase III Vinblastine & Prednisone Seems not superior

To be completed

Chemotherapy

References

  1. 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

Etoposide, Vinblastine, Prednisone

back to top

Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2007 (LCH-II) Phase III Vinblastine & Prednisone Seems not superior

Total duration of therapy is 24 weeks.

Chemotherapy, initial

6-week course, followed by:

Chemotherapy, continuation

21-day cycle for 6 cycles

References

  1. 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 verified protocol PubMed

Methotrexate, Vinblastine, Prednisone

back to top

Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2013 (LCH-III) Phase III Vinblastine & Prednisone Seems not superior

To be completed

Chemotherapy

References

  1. 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

Vinblastine & Prednisone

back to top

Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2001 (LCH-I) Phase III Etoposide & Prednisone Seems not superior
Gadner et al. 2007 (LCH-II) Phase III Etoposide, Vinblastine, Prednisone Seems not superior
Gadner et al. 2013 (LCH-III) Phase III Methotrexate, Vinblastine, Prednisone Seems not superior

Total duration of therapy is 24 weeks, in LCH-II.

Chemotherapy, initial

6-week course, followed by:

Chemotherapy, continuation

21-day cycle for 6 cycles

References

  1. 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
  2. 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 verified protocol PubMed
  3. 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

Relapsed or refractory

Cladribine monotherapy

back to top

Regimen

Study Evidence
Weitzman et al. 2009 (LCH-S-98) Phase II

To be completed

Chemotherapy

References

  1. 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 PubMed

Cladribine & Cytarabine

back to top

Regimen

Study Evidence
Donadieu et al. 2015 Phase II

Chemotherapy

  • Cladribine (Leustatin) 9 mg/m2 IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
    • Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
  • Cytarabine (Cytosar) 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

Patients with a "good response" proceeded to cladribine consolidation.

References

  1. 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 verified protocol link to PMC article PubMed

Vemurafenib monotherapy

back to top

Regimen

Study Evidence
Hyman et al. 2015 Phase II, <20 pts in this arm

This was part of a basket trial, all patients had BRAF p.V600E mutations. A minority (7/18, 39%) of participants were untreated.

Chemotherapy

Duration of treatment not specified

References

  1. 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 verified protocol link to PMC article PubMed

Relapsed or refractory, consolidation

Cladribine monotherapy

back to top

Regimen

Study Evidence
Donadieu et al. 2015 Phase II

Preceding treatment

Chemotherapy

21-day cycle for 2 cycles

Treatment followed by 4-drug maintenance.

References

  1. 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 verified protocol link to PMC article PubMed

Relapsed or refractory, maintenance

Mercaptopurine, Methotrexate, Vinblastine, Prednisolone

back to top

Regimen

Study Evidence
Donadieu et al. 2015 Phase II

Preceding treatment

Chemotherapy

Total of 18 months of maintenance

References

  1. 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 verified protocol link to PMC article PubMed
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