Langerhans cell histiocytosis medical therapy: Difference between revisions
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===Low-risk Disease (Single-system Unifocal Disease)=== | ===Low-risk Disease (Single-system Unifocal Disease)=== | ||
====Isolated Skin Involvement==== | ====Isolated Skin Involvement==== | ||
* Observation is recommended for all pediatric patients with isolated [[skin]] involvement of Langerhans cell histiocytosis.<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref> | * Observation is recommended for all [[pediatric]] patients with isolated [[skin]] involvement of Langerhans cell histiocytosis.<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref> | ||
* Medical therapy is suggested only for symptomatic [[cutaneous]] disease that presents with either extensive [[rash]], sever pain, skin [[ulcer|ulceration]], or [[bleeding]]. | * Medical therapy is suggested only for symptomatic [[cutaneous]] disease that presents with either extensive [[rash]], sever pain, skin [[ulcer|ulceration]], or [[bleeding]]. | ||
* Medical therapies used for the treatment of isolated skin lesions of Langerhans cell histiocytosis include: | * Medical therapies used for the treatment of isolated skin lesions of Langerhans cell histiocytosis include: | ||
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:* Oral [[methotrexate]] (20 mg/m2) weekly for 6 months<ref name="pmid7603403">{{cite journal |vauthors=Womer RB, Anunciato KR, Chehrenama M |title=Oral methotrexate and alternate-day prednisone for low-risk Langerhans cell histiocytosis |journal=Med. Pediatr. Oncol. |volume=25 |issue=2 |pages=70–3 |date=August 1995 |pmid=7603403 |doi= |url=}}</ref> | :* Oral [[methotrexate]] (20 mg/m2) weekly for 6 months<ref name="pmid7603403">{{cite journal |vauthors=Womer RB, Anunciato KR, Chehrenama M |title=Oral methotrexate and alternate-day prednisone for low-risk Langerhans cell histiocytosis |journal=Med. Pediatr. Oncol. |volume=25 |issue=2 |pages=70–3 |date=August 1995 |pmid=7603403 |doi= |url=}}</ref> | ||
:* Oral [[thalidomide]] 50 mg to 200 mg each night<ref name="pmid16333818">{{cite journal |vauthors=McClain KL, Kozinetz CA |title=A phase II trial using thalidomide for Langerhans cell histiocytosis |journal=Pediatr Blood Cancer |volume=48 |issue=1 |pages=44–9 |date=January 2007 |pmid=16333818 |doi=10.1002/pbc.20578 |url=}}</ref><ref name="pmid15057007">{{cite journal |vauthors=Sander CS, Kaatz M, Elsner P |title=Successful treatment of cutaneous langerhans cell histiocytosis with thalidomide |journal=Dermatology (Basel) |volume=208 |issue=2 |pages=149–52 |date=2004 |pmid=15057007 |doi=10.1159/000076491 |url=}}</ref> | :* Oral [[thalidomide]] 50 mg to 200 mg each night<ref name="pmid16333818">{{cite journal |vauthors=McClain KL, Kozinetz CA |title=A phase II trial using thalidomide for Langerhans cell histiocytosis |journal=Pediatr Blood Cancer |volume=48 |issue=1 |pages=44–9 |date=January 2007 |pmid=16333818 |doi=10.1002/pbc.20578 |url=}}</ref><ref name="pmid15057007">{{cite journal |vauthors=Sander CS, Kaatz M, Elsner P |title=Successful treatment of cutaneous langerhans cell histiocytosis with thalidomide |journal=Dermatology (Basel) |volume=208 |issue=2 |pages=149–52 |date=2004 |pmid=15057007 |doi=10.1159/000076491 |url=}}</ref> | ||
:* Topical application of [[nitrogen mustard]] can be effective for cutaneous Langerhans cell histiocytosis that is resistant to oral therapies, but not for disease involving large areas of skin.<ref name="pmid21967132">{{cite journal |vauthors=Lindahl LM, Fenger-Grøn M, Iversen L |title=Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis |journal=Br. J. Dermatol. |volume=166 |issue=3 |pages=642–5 |date=March 2012 |pmid=21967132 |doi=10.1111/j.1365-2133.2011.10673.x |url=}}</ref> | :* Topical application of [[nitrogen mustard]] can be effective for [[cutaneous]] Langerhans cell histiocytosis that is resistant to oral therapies, but not for disease involving large areas of skin.<ref name="pmid21967132">{{cite journal |vauthors=Lindahl LM, Fenger-Grøn M, Iversen L |title=Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis |journal=Br. J. Dermatol. |volume=166 |issue=3 |pages=642–5 |date=March 2012 |pmid=21967132 |doi=10.1111/j.1365-2133.2011.10673.x |url=}}</ref> | ||
:* [[Psoralen]] and long-wave [[ultraviolet]] A radiation (PUVA) and UVB can be effective in skin Langerhans cell histiocytosis but its use is limited by the potential for late [[skin cancer]]s.<ref name="pmid18490592">{{cite journal |vauthors=von Stebut E, Schadmand-Fischer S, Bräuninger W, Kreft A, Doberauer C, Steinbrink K |title=Successful treatment of adult multisystemic Langerhans cell histiocytosis with psoralen-UV-A, prednisolone, mercaptopurine, and vinblastine |journal=Arch Dermatol |volume=144 |issue=5 |pages=649–53 |date=May 2008 |pmid=18490592 |doi=10.1001/archderm.144.5.649 |url=}}</ref> | :* [[Psoralen]] and long-wave [[ultraviolet]] A radiation (PUVA) and UVB can be effective in skin Langerhans cell histiocytosis but its use is limited by the potential for late [[skin cancer]]s.<ref name="pmid18490592">{{cite journal |vauthors=von Stebut E, Schadmand-Fischer S, Bräuninger W, Kreft A, Doberauer C, Steinbrink K |title=Successful treatment of adult multisystemic Langerhans cell histiocytosis with psoralen-UV-A, prednisolone, mercaptopurine, and vinblastine |journal=Arch Dermatol |volume=144 |issue=5 |pages=649–53 |date=May 2008 |pmid=18490592 |doi=10.1001/archderm.144.5.649 |url=}}</ref> | ||
====Skull Involvement==== | ====Skull Involvement==== | ||
* [[Curettage]] is the mainstay treatment for single [[skull]] lesions that involve the [[frontal]], [[parietal]], or [[occipital]] bones. | * [[Curettage]] is the mainstay treatment for single [[skull]] lesions that involve the [[frontal]], [[parietal]], or [[occipital]] bones.<ref name="pmid22028518">{{cite journal |vauthors=Aruna DR, Pushpalatha G, Galgali S, Prashanthy |title=Langerhans cell histiocytosis |journal=J Indian Soc Periodontol |volume=15 |issue=3 |pages=276–9 |date=July 2011 |pmid=22028518 |pmc=3200027 |doi=10.4103/0972-124X.85675 |url=}}</ref> | ||
* In certain cases, curettage plus an injection of [[methylprednisolone]] may be used | * In certain cases, curettage plus an injection of [[methylprednisolone]] may be used | ||
* The use of low-dose [[radiation therapy]] is limited among pediatric patients due to severe side effects.<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref> | * The use of low-dose [[radiation therapy]] is limited among pediatric patients due to severe side effects.<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref><ref name="pmid23466581">{{cite journal |vauthors=Kotecha R, Venkatramani R, Jubran RF, Arkader A, Olch AJ, Wong K |title=Clinical outcomes of radiation therapy in the management of Langerhans cell histiocytosis |journal=Am. J. Clin. Oncol. |volume=37 |issue=6 |pages=592–6 |date=December 2014 |pmid=23466581 |doi=10.1097/COC.0b013e318281d6ce |url=}}</ref> | ||
* Patients with isolated lesions to the [[mastoid]], [[temporal]], or [[orbital]] [bone]s are treated with systemic therapy, as to prevent the development of [[diabetes insipidu]]s among such patients. | * Patients with isolated lesions to the [[mastoid]], [[temporal]], or [[orbital]] [bone]s are treated with systemic therapy, as to prevent the development of [[diabetes insipidu]]s among such patients. | ||
* Comparison of diabetes insipidus incidence with no systemic therapy (40%) versus 6 months of [[vinblastine]] {{and }} [[prednisone]] (20%) strongly supports systemic treatment of of such bony lesions. | * Comparison of diabetes insipidus incidence with no systemic therapy (40%) versus 6 months of [[vinblastine]] {{and }} [[prednisone]] (20%) strongly supports systemic treatment of of such bony lesions.<ref name="pmid28532436">{{cite journal |vauthors=Tazi A, Lorillon G, Haroche J, Neel A, Dominique S, Aouba A, Bouaziz JD, de Margerie-Melon C, Bugnet E, Cottin V, Comont T, Lavigne C, Kahn JE, Donadieu J, Chevret S |title=Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study |journal=Orphanet J Rare Dis |volume=12 |issue=1 |pages=95 |date=May 2017 |pmid=28532436 |pmc=5441059 |doi=10.1186/s13023-017-0651-z |url=}}</ref> | ||
====Vertebral or Femoral Bone Lesions at Risk for Collapse==== | ====Vertebral or Femoral Bone Lesions at Risk for Collapse==== | ||
* Observation is recommended for the management of a single [[vertebral body]] lesion that has no soft tissue extension into the extradural space.<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref> | * Observation is recommended for the management of a single [[vertebral body]] lesion that has no soft tissue extension into the extradural space.<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref> | ||
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===Multiple Bone Lesions (Single-system Multifocal Bone Disease)=== | ===Multiple Bone Lesions (Single-system Multifocal Bone Disease)=== | ||
* The most commonly used systemic chemotherapy regimen for the management of multiple [[bone]] lesions is a combination of [[vinblastine]] and [[prednisone]].<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref> | * The most commonly used systemic chemotherapy regimen for the management of multiple [[bone]] lesions is a combination of [[vinblastine]] and [[prednisone]].<ref name="cancer">Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016</ref> | ||
* [[Vinblastine]] treatment is | * [[Vinblastine]] treatment is recommended for 12 months. Weekly doses for the first 7 weeks, which is followed by a dose every 3 weeks for the rest of the management period. | ||
* [[Prednisone]] (40 mg/m2) is given daily for 4 weeks then tapered over 2 weeks. | * [[Prednisone]] (40 mg/m2) is given daily for 4 weeks then tapered over 2 weeks. Afterward, prednisone is given for 5 days at 40 mg/m2 every 3 weeks with the vinblastine injections.<ref name="pmid22916233">{{cite journal |vauthors=Cantu MA, Lupo PJ, Bilgi M, Hicks MJ, Allen CE, McClain KL |title=Optimal therapy for adults with Langerhans cell histiocytosis bone lesions |journal=PLoS ONE |volume=7 |issue=8 |pages=e43257 |date=2012 |pmid=22916233 |pmc=3419729 |doi=10.1371/journal.pone.0043257 |url=}}</ref> | ||
===Multiple Bone Lesions in Combination with Skin, Lymph Node, or Diabetes Insipidus (High-risk Multisystem Disease)=== | ===Multiple Bone Lesions in Combination with Skin, Lymph Node, or Diabetes Insipidus (High-risk Multisystem Disease)=== | ||
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* The same chemotherapy regimen of vinblastine and prednisone as described above is used for 12 months. | * The same chemotherapy regimen of vinblastine and prednisone as described above is used for 12 months. | ||
* Other chemotherapeutic agents used for the treatment of low-risk multisystem Langerhans cell histiocytosis include: | * Other chemotherapeutic agents used for the treatment of low-risk multisystem Langerhans cell histiocytosis include: | ||
:* [[Vincristine]] {{and}} [[cytosine arabinoside]] {{and}} [[prednisone]] | :* [[Vincristine]] {{and}} [[cytosine arabinoside]] {{and}} [[prednisone]]<ref name="pmid22916233">{{cite journal |vauthors=Cantu MA, Lupo PJ, Bilgi M, Hicks MJ, Allen CE, McClain KL |title=Optimal therapy for adults with Langerhans cell histiocytosis bone lesions |journal=PLoS ONE |volume=7 |issue=8 |pages=e43257 |date=2012 |pmid=22916233 |pmc=3419729 |doi=10.1371/journal.pone.0043257 |url=}}</ref> | ||
:* [[Cladribine]] | :* [[Cladribine]]<ref name="pmid10361109">{{cite journal |vauthors=Saven A, Burian C |title=Cladribine activity in adult langerhans-cell histiocytosis |journal=Blood |volume=93 |issue=12 |pages=4125–30 |date=June 1999 |pmid=10361109 |doi= |url=}}</ref> | ||
:* [[Pamidronate]] | :* [[Pamidronate]]<ref name="pmid11196272">{{cite journal |vauthors=Farran RP, Zaretski E, Egeler RM |title=Treatment of Langerhans cell histiocytosis with pamidronate |journal=J. Pediatr. Hematol. Oncol. |volume=23 |issue=1 |pages=54–6 |date=January 2001 |pmid=11196272 |doi= |url=}}</ref> | ||
:* [[Zoledronate]] | :* [[Zoledronate]]<ref name="pmid21519845">{{cite journal |vauthors=Sivendran S, Harvey H, Lipton A, Drabick J |title=Treatment of Langerhans cell histiocytosis bone lesions with zoledronic acid: a case series |journal=Int. J. Hematol. |volume=93 |issue=6 |pages=782–786 |date=June 2011 |pmid=21519845 |doi=10.1007/s12185-011-0839-2 |url=}}</ref> | ||
:* [[Alendronate]] | :* [[Alendronate]]<ref name="pmid27413525">{{cite journal |vauthors=Chellapandian D, Makras P, Kaltsas G, van den Bos C, Naccache L, Rampal R, Carret AS, Weitzman S, Egeler RM, Abla O |title=Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series |journal=Mediterr J Hematol Infect Dis |volume=8 |issue=1 |pages=e2016033 |date=2016 |pmid=27413525 |pmc=4928520 |doi=10.4084/MJHID.2016.033 |url=}}</ref> | ||
===Treatment of High-risk Multisystem Disease=== | ===Treatment of High-risk Multisystem Disease=== | ||
Latest revision as of 06:49, 1 April 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Observation is recommended for all pediatric patients with an isolated Langerhans cell histiocytosis skin involvement. Medical therapy is suggested only for symptomatic cutaneous disease that presents with either extensive rash, sever pain, skin ulceration, or bleeding. Medical therapies used for the treatment of isolated skin lesions of Langerhans cell histiocytosis include topical steroids, nitrogen mustard, and oral thalidomide. Curettage is the mainstay treatment for single skull lesions that involve the frontal, parietal, or occipital bones. The most commonly used systemic chemotherapy regimen for the management of multiple bone lesions is a combination of vinblastine AND prednisone. The standard therapy recommended for Langerhans cell histiocytosis involving the spleen, liver, or bone marrow (high-risk organs) consists of vinblastine AND prednisone AND 6-mercaptopurine for a 12 month period.
Treatment
Low-risk Disease (Single-system Unifocal Disease)
Isolated Skin Involvement
- Observation is recommended for all pediatric patients with isolated skin involvement of Langerhans cell histiocytosis.[1]
- Medical therapy is suggested only for symptomatic cutaneous disease that presents with either extensive rash, sever pain, skin ulceration, or bleeding.
- Medical therapies used for the treatment of isolated skin lesions of Langerhans cell histiocytosis include:
- Topical steroids
- Oral methotrexate (20 mg/m2) weekly for 6 months[2]
- Oral thalidomide 50 mg to 200 mg each night[3][4]
- Topical application of nitrogen mustard can be effective for cutaneous Langerhans cell histiocytosis that is resistant to oral therapies, but not for disease involving large areas of skin.[5]
- Psoralen and long-wave ultraviolet A radiation (PUVA) and UVB can be effective in skin Langerhans cell histiocytosis but its use is limited by the potential for late skin cancers.[6]
Skull Involvement
- Curettage is the mainstay treatment for single skull lesions that involve the frontal, parietal, or occipital bones.[7]
- In certain cases, curettage plus an injection of methylprednisolone may be used
- The use of low-dose radiation therapy is limited among pediatric patients due to severe side effects.[1][8]
- Patients with isolated lesions to the mastoid, temporal, or orbital [bone]s are treated with systemic therapy, as to prevent the development of diabetes insipidus among such patients.
- Comparison of diabetes insipidus incidence with no systemic therapy (40%) versus 6 months of vinblastine AND prednisone (20%) strongly supports systemic treatment of of such bony lesions.[9]
Vertebral or Femoral Bone Lesions at Risk for Collapse
- Observation is recommended for the management of a single vertebral body lesion that has no soft tissue extension into the extradural space.[1]
- Low-dose radiation therapy may be used to try to promote resolution in an isolated vertebral body lesion or a large femoral neck lesion at risk of fracture
- Despite the low dose required (700–1,000 cGy), radiation therapy should be used with caution in the area of the thyroid gland, brain, or any growth plates.
- Patients with soft tissue extension from vertebral lesions are often treated successfully with chemotherapy.
Multiple Bone Lesions (Single-system Multifocal Bone Disease)
- The most commonly used systemic chemotherapy regimen for the management of multiple bone lesions is a combination of vinblastine and prednisone.[1]
- Vinblastine treatment is recommended for 12 months. Weekly doses for the first 7 weeks, which is followed by a dose every 3 weeks for the rest of the management period.
- Prednisone (40 mg/m2) is given daily for 4 weeks then tapered over 2 weeks. Afterward, prednisone is given for 5 days at 40 mg/m2 every 3 weeks with the vinblastine injections.[10]
Multiple Bone Lesions in Combination with Skin, Lymph Node, or Diabetes Insipidus (High-risk Multisystem Disease)
- Vinblastine AND prednisone combination therapy is the mainstay treatment for low-risk multisystem Langerhans cell histiocytosis.[1]
- The same chemotherapy regimen of vinblastine and prednisone as described above is used for 12 months.
- Other chemotherapeutic agents used for the treatment of low-risk multisystem Langerhans cell histiocytosis include:
Treatment of High-risk Multisystem Disease
- The standard therapy length recommended for Langerhans cell histiocytosis involving the spleen, liver, or bone marrow (high-risk organs) consists of vinblastine AND prednisone AND 6-mercaptopurine for a 12 month period.[1]
Treatment of CNS Langerhans cell histiocytosis
- There are three types of Langerhans cell histiocytosis CNS lesions:
- Mass lesions or tumors in the cerebrum, cerebellum, or choroid plexus
- Mass lesions of the hypothalamic-pituitary axis that are always associated with diabetes insipidus
- Neurodegenerative syndrome
- Drugs that cross the blood-brain barrier, such as cladribine, or other nucleoside analogs, such as cytarabine, are used for active CNS Langerhans cell histiocytosislesions.
- Immunochemotherapeutic agents used for the treatment of Langerhans cell histiocytosis neurodegenerative syndrome include:
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Langerhans Cell Histiocytosis Treatment–for health professionals (PDQ®). National Cancer Institute (2015) http://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_91 Accessed on February, 8 2016
- ↑ Womer RB, Anunciato KR, Chehrenama M (August 1995). "Oral methotrexate and alternate-day prednisone for low-risk Langerhans cell histiocytosis". Med. Pediatr. Oncol. 25 (2): 70–3. PMID 7603403.
- ↑ McClain KL, Kozinetz CA (January 2007). "A phase II trial using thalidomide for Langerhans cell histiocytosis". Pediatr Blood Cancer. 48 (1): 44–9. doi:10.1002/pbc.20578. PMID 16333818.
- ↑ Sander CS, Kaatz M, Elsner P (2004). "Successful treatment of cutaneous langerhans cell histiocytosis with thalidomide". Dermatology (Basel). 208 (2): 149–52. doi:10.1159/000076491. PMID 15057007.
- ↑ Lindahl LM, Fenger-Grøn M, Iversen L (March 2012). "Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis". Br. J. Dermatol. 166 (3): 642–5. doi:10.1111/j.1365-2133.2011.10673.x. PMID 21967132.
- ↑ von Stebut E, Schadmand-Fischer S, Bräuninger W, Kreft A, Doberauer C, Steinbrink K (May 2008). "Successful treatment of adult multisystemic Langerhans cell histiocytosis with psoralen-UV-A, prednisolone, mercaptopurine, and vinblastine". Arch Dermatol. 144 (5): 649–53. doi:10.1001/archderm.144.5.649. PMID 18490592.
- ↑ Aruna DR, Pushpalatha G, Galgali S, Prashanthy (July 2011). "Langerhans cell histiocytosis". J Indian Soc Periodontol. 15 (3): 276–9. doi:10.4103/0972-124X.85675. PMC 3200027. PMID 22028518.
- ↑ Kotecha R, Venkatramani R, Jubran RF, Arkader A, Olch AJ, Wong K (December 2014). "Clinical outcomes of radiation therapy in the management of Langerhans cell histiocytosis". Am. J. Clin. Oncol. 37 (6): 592–6. doi:10.1097/COC.0b013e318281d6ce. PMID 23466581.
- ↑ Tazi A, Lorillon G, Haroche J, Neel A, Dominique S, Aouba A, Bouaziz JD, de Margerie-Melon C, Bugnet E, Cottin V, Comont T, Lavigne C, Kahn JE, Donadieu J, Chevret S (May 2017). "Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study". Orphanet J Rare Dis. 12 (1): 95. doi:10.1186/s13023-017-0651-z. PMC 5441059. PMID 28532436.
- ↑ 10.0 10.1 Cantu MA, Lupo PJ, Bilgi M, Hicks MJ, Allen CE, McClain KL (2012). "Optimal therapy for adults with Langerhans cell histiocytosis bone lesions". PLoS ONE. 7 (8): e43257. doi:10.1371/journal.pone.0043257. PMC 3419729. PMID 22916233.
- ↑ Saven A, Burian C (June 1999). "Cladribine activity in adult langerhans-cell histiocytosis". Blood. 93 (12): 4125–30. PMID 10361109.
- ↑ Farran RP, Zaretski E, Egeler RM (January 2001). "Treatment of Langerhans cell histiocytosis with pamidronate". J. Pediatr. Hematol. Oncol. 23 (1): 54–6. PMID 11196272.
- ↑ Sivendran S, Harvey H, Lipton A, Drabick J (June 2011). "Treatment of Langerhans cell histiocytosis bone lesions with zoledronic acid: a case series". Int. J. Hematol. 93 (6): 782–786. doi:10.1007/s12185-011-0839-2. PMID 21519845.
- ↑ Chellapandian D, Makras P, Kaltsas G, van den Bos C, Naccache L, Rampal R, Carret AS, Weitzman S, Egeler RM, Abla O (2016). "Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series". Mediterr J Hematol Infect Dis. 8 (1): e2016033. doi:10.4084/MJHID.2016.033. PMC 4928520. PMID 27413525.