Mast cell leukemia medical therapy: Difference between revisions

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Latest revision as of 15:58, 9 November 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Nawal Muazam M.D.[2]

Overview

The mainstay of therapy for symptomatic mast cell leukemia patients is immunochemotherapy.

Medical Therapy

Therapeutic approaches are limited and consist of reducing the tumor burden and conservation of organ functions.^[1]

Corticosteroids

Corticosteroids have been recommended as a short term use in combination with cytotoxic drugs.^[2]^[1]
It could also be beneficial in some situations such as:

Interferon-α

Interferon-α reduces the frequency of:^[2]^[1]

Histamine related attacks
Decrease bone marrow infiltration by mast cells
Decrease liver infiltration by mast cells
Decrease skin manifestations
Improve osteoporosis

2-Chloro-deoxy-adenosine

2-Chloro-deoxy-adenosine has a potential value in the treatment of mast cell leukemia with symptomatic responses and improvement in mast cell variables.^[2]^[1]

Cladribine

Cladribine has been used in rare cases of mast cell leukemia with relatively small or no efficacy.^[2]^[1]

Imatinib

Imatinib does not have direct effect on the D816V KIT mutation, but it may affect other sporadic mutations.^[2]^[1]

Dasatinib

Dasatinib demonstrates significant inhibitory activity against WT KIT as well as juxtamembrane domain mutant KIT. This activity has been proven in patients negative for D816V KIT.^[2]^[1]

Nilotinib

Nilotinib displays also equipotent activity to imatinib in D816V c-KIT negative patients.^[2]^[1]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 Georgin-Lavialle, S.; Lhermitte, L.; Dubreuil, P.; Chandesris, M.-O.; Hermine, O.; Damaj, G. (2012). "Mast cell leukemia". Blood. 121 (8): 1285–1295. doi:10.1182/blood-2012-07-442400. ISSN 0006-4971.
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 Joris, Magalie; Georgin-Lavialle, Sophie; Chandesris, Marie-Olivia; Lhermitte, Ludovic; Claisse, Jean-François; Canioni, Danielle; Hanssens, Katia; Damaj, Gandhi; Hermine, Olivier; Hamidou, Mohammed (2012). "Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive". Case Reports in Hematology. 2012: 1–6. doi:10.1155/2012/517546. ISSN 2090-6560.

[Georgin-LavialleLhermitte2012-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 Georgin-Lavialle, S.; Lhermitte, L.; Dubreuil, P.; Chandesris, M.-O.; Hermine, O.; Damaj, G. (2012). "Mast cell leukemia". Blood. 121 (8): 1285–1295. doi:10.1182/blood-2012-07-442400. ISSN 0006-4971.

[JorisGeorgin-Lavialle2012-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 Joris, Magalie; Georgin-Lavialle, Sophie; Chandesris, Marie-Olivia; Lhermitte, Ludovic; Claisse, Jean-François; Canioni, Danielle; Hanssens, Katia; Damaj, Gandhi; Hermine, Olivier; Hamidou, Mohammed (2012). "Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive". Case Reports in Hematology. 2012: 1–6. doi:10.1155/2012/517546. ISSN 2090-6560.

[1]

[2]

@@ Line 3: / Line 3: @@
 {{CMG}};{{AE}}{{NM}}
 ==Overview==
+The mainstay of therapy for symptomatic mast cell leukemia patients is immunochemotherapy.
 ==Medical Therapy==
-Therapeutic approaches are limited and consist of reducing the tumor burden and conservation of organ functions. To date, there is no approved standard therapy to treat systemic mastocytosis with the exception of imatinib in D816V c-KIT negative patients.
+Therapeutic approaches are limited and consist of reducing the tumor burden and conservation of organ functions.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
+===Corticosteroids===
-Corticosteroids have been recommended as a short term use in combination with cytotoxic drugs.
+*Corticosteroids have been recommended as a short term use in combination with cytotoxic drugs.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
-It could also be beneficial in some situations such as malabsorption, ascites, or anaphylaxis.
+*It could also be beneficial in some situations such as:
-Besides its role in alleviating MCMRS, corticosteroids decrease tissue mast cell burden by decreasing tissue stem cell factor and this has been obviously demonstrated in our patient’s case with a dramatic tumor response and improvement of symptoms.
+:*[[Malabsorption]]
-Thus, corticosteroids could be used as an emergency treatment for ASM and MCL.
+:*[[Ascites]]
+:*[[Anaphylaxis]]
-Preliminary studies suggested that Interferon-α reduces the frequency of histamine related attacks, decrease bone marrow infiltration by Mast cells, hepatomegaly, skin manifestations, and improve osteoporosis.
+===Interferon-α===
-However, no major responses were obtained and overall survival was not improved.
+Interferon-α reduces the frequency of:<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
-Relapses occurred frequently at the end of therapy and side effects were frequent.
+*[[Histamine]] related attacks
-As a consequence the dropout rate is very high 25%.
+*Decrease bone marrow infiltration by mast cells
-Its efficacy in mast cell leukemia patients is very low or inexistent.
+*Decrease liver infiltration by mast cells
--Chloro-deoxy-adenosine has a potential value in the treatment of ASM with symptomatic responses and improvement in mast cell variables.
+*Decrease skin manifestations
-Complete responses are very rare.
+*Improve osteoporosis
-Cladribine has been used in rare cases of mast cell leukemia with relatively small or no efficacy.
+===2-Chloro-deoxy-adenosine===
-It is now well established that Imatinib does not have direct effect on the D816V KIT mutation, but it may affect other sporadic mutations.
+-Chloro-deoxy-adenosine has a potential value in the treatment of mast cell leukemia with symptomatic responses and improvement in mast cell variables.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
-Dasatinib demonstrates significant inhibitory activity against WT KIT as well as juxtamembrane domain mutant KIT.
+===Cladribine===
-This activity has been proven in patients negative for D816V KIT.
+Cladribine has been used in rare cases of mast cell leukemia with relatively small or no efficacy.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
-Nilotinib displays also equipotent activity to Imatinib in D816V c-KIT negative patients and WT Kit cell line.
+===Imatinib===
-Masatinib is a protein-tyrosine kinase inhibitor which, in vitro, potently and selectively inhibits the mutated form, in the juxtamembrane region, of the c-KIT receptor and the c-KIT wild-type receptor.
+Imatinib does not have direct effect on the D816V ''KIT'' mutation, but it may affect other sporadic mutations.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
-It also inhibits the PDGF receptor and the mutated fibroblast growth factor receptor.
+===Dasatinib===
-Masatinib has been shown to be effective in patients with ISM or CM, not bearing the activating point mutations in the phospho transferase domain of c-KIT with an acceptable toxicity.
+Dasatinib demonstrates significant inhibitory activity against WT ''KIT'' as well as juxtamembrane domain mutant ''KIT''. This activity has been proven in patients negative for D816V ''KIT''.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
-Recently, Georgin-Lavialle et al. reported on a case of MCL with an exon 9 c-KIT mutation that was successfully treated by masatinib.
+===Nilotinib===
-Thus, this drug should be included in the therapeutic arsenal of mastocytosis patients especially D816V negative.
+Nilotinib displays also equipotent activity to imatinib in D816V c-''KIT'' negative patients.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>
-An international randomized phase III in patients with CM and ISM independent of the c-KIT mutation status is ongoing.
-Finally, PKC412 (midostaurin) is a small molecule inhibitor of multiple type III receptor tyrosine kinases involved in hematopoiesis and leukemia, an inhibitor of all major isoforms of protein kinase C, the tyrosine kinase associated with the vascular endothelial growth factor receptor.
-It can also exert inhibitory activity on other mutated tyrosine kinases implicated in a variety of diseases, like KIT (systemic mast cell disease, gastrointestinal stromal tumors) PDGFR, or FGFR1.
-Midostaurin has shown strong inhibitory activity on neoplastic human MCs carrying the D816V c-KIT mutation in preclinical and clinical settings. Preliminary data of an ongoing phase II trial in patients with advanced systemic mastocytosis treated with 100mg bid.
-Midostaurin revealed high overall response rates of 73%.
-An international phase II study in ASM and MCL is ongoing.
 ==References==
 {{reflist|2}}