Treatment responses to cladribine and dasatinib in rapidly progressing aggressive mastocytosis.
BACKGROUND
Systemic mastocytosis (SM) is a mast cell neoplasm in which neoplastic cells usually display the D816V-mutated variant of KIT. Cladribine (2CdA) and dasatinib are two drugs that counteract the in vitro growth of neoplastic mast cells in SM. However, only little is known about the in vivo effects of these drugs in SM.


METHODS
We report on a patient with highly aggressive interferon-alpha-resistant SM who was treated with 2CdA and dasatinib. In vitro pretesting revealed a response of neoplastic mast cells to both compounds with reasonable IC(50) values.


RESULTS
The patient was treated with six cycles of 2CdA (0.13 mg kg(-1) intravenously daily on 5 consecutive days). Despite a short-lived major clinical response and a decrease in serum tryptase, the patient progressed to mast cell leukaemia after the sixth cycle of 2CdA. The patient then received two further courses of 2CdA followed by treatment with dasatinib (100 mg per os daily). However, no major response was obtained and the patient died from disease progression after 2 months.


CONCLUSIONS
In a patient with rapidly progressing aggressive SM, neither 2CdA nor dasatinib produced a long-lasting response in vivo, despite encouraging in vitro results. For such patients, alternative treatment strategies have to be developed.
Aichberger
K J
KJ
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria.
Sperr
W R
WR
Gleixner
K V
KV
Kretschmer
A
A
Valent
P
P
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017338:Cladribine / Q000627:therapeutic use*; D000069439:Dasatinib; D018450:Disease Progression; D004359:Drug Therapy, Combination; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007946:Leukemia, Mast-Cell / Q000188:drug therapy* / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000097:blood / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D017211:Treatment Failure; D053802:Tryptases / Q000097:blood
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D017338:Cladribine; D053802:Tryptases; D000069439:Dasatinib