Mast cell leukemia

Mast cell leukemia (MCL) is a form of aggressive systemic mastocytosis.  It is very rare, and accounts for less than 1% of all mastocytosis cases.  It can occur either in patients who previously had mastocytosis or in patients with no history of mast cell disease (de novo.)  Patients with MCL meet the criteria for SM but have infiltration of bone marrow by at least 20% mast cells.  Infiltration of extracutaneous organs is also present, with frequent involvement of liver, spleen and bones.  Diagnosis can be also be made if at least 10% of cells in circulating blood are mast cells.  CKIT mutation may not always be present.  Median survival is 6 months.

Common symptoms include flushing, fever, exhaustion, diarrhea and rapid heartbeat.  Frequent urination, neuropsychiatric symptoms and osteoporosis were rare.  Patients were weak and often had severe weight loss with accompanying anorexia.  Swelling of the spleen and liver were frequently present.  Skin involvement was present in only 1/3 of patients.  Lymph node enlargement was present 37% of the time, while GI symptoms were present 29%.  Gastric ulcers were present, sometimes with bleeding, but only in patients who developed MCL de novo.

Mast cells in MCL patients do not always have the D816V mutation.  They often have other mutations.  They may express both CD25 and CD2 receptors, but in 25% of cases, CD25 is not expressed; in 48% of cases, CD2 is not expressed; in 33% of cases, neither are expressed.  The neoplastic markers typically associated with mast cells in SM are often not found in MCL.

In patients with adult-onset SM, there is a risk of developing leukemia.  The overall risk of this occurring is about 6%.  Of that 6%, 86% of those patients transformed to acute myeloid leukemia (AML) and 13% transformed to MCL.  SM-AHNMD and ASM patients were at the most risk, but SM-AHNMD evolved into MCL accounted for only 8% of cases.  In these patients, the other hematologic disease was typically MDS or CMML.  Markers correlated with transformation include advanced age, history of weight loss, anemia, low platelets, low serum albumin and excessive blasts in BM. 

The average age of diagnosis with MCL is 52 years.  Females are affected more frequently than males.  There have been no familial cases recorded.  27% of MCL patients had a history of mastocytosis, while 73% developed it de novo.  There have been four cases of children with mastocytosis evolving into MCL.  In one case, the patient had diffuse cutaneous mastocytosis and died in childhood from MCL.  In two cases, the patients had a history of urticaria pigmentosa and developed MCL 25 and 53 years later.  In one case, MCL evolved from a mastocytoma.

There are no defined treatment protocols for mast cell leukemia due to its rarity.  Steroids, interferon-a and cladribine are sometimes used.    Nine MCL patients treated by imatinib (Gleevec) have been reported.  Four of these patients had a partial response.  One patient was CKIT+ (D816V mutation) and was alive after 48 months with imatinib as the sole therapy.  Preliminary data from a phase II study showed that of seven patients with MCL (three also had an AHNMD), four had major responses to midostaurin.  Of these four, three had ongoing incomplete remissions (19+ months in two patients, 32+ months in 1 patient.)  Overall survival for MCL patients in this study was 22.6 months.  These data are encouraging.

Seven patients with MCL have received allogenic stem cell transplants.  Only one of them achieved a response, and died 23 months after transplantation in complete remission.

A lot of the figures and statistics we have on MCL are derived from pooling data on all recorded patients, stretching back to the 1950’s.   While MCL is still a grave diagnosis, some patients have lived for up to 8 years.    

References:

LimKH, TefferiA, LashoTL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009;113(23):5727-5736.

NoackF, SotlarK, NotterM, ThielE, ValentP, HornyHP. Aleukemic mast cell leukemia with abnormal immunophenotype and c-kit mutation D816V. Leuk Lymphoma 2004;45(11):2295-2302.

MitalA, PiskorzA, LewandowskiK, WasagB, LimonJ, HellmannA. A case of mast cell leukaemia with exon 9 KIT mutation and good response to imatinib. Eur J Haematol 2011;86(6):531-535.

 

Georgin-Lavialle, Sophie, et al.  Mast cell leukemia.  Blood 2013;10(11).