Chronic mast cell leukemia: A new variant of systemic mastocytosis

Mast cell leukemia (MCL) is a variant of systemic mastocytosis (SM) marked by a significantly shortened lifespan.  In MCL, patients experience massive and devastating proliferation of immature mast cells.  The bone marrow is always affected and the huge amount of mast cells means there is no room for other types of blood cells. Usually, the bone marrow smear reveals over 20% of nucleated cells in bone marrow are atypical mast cells, as well as large quantities present in the blood.  In the aleukemic variant, less than 10% of all white cells in the blood are mast cells.

In most patients with MCL, C-findings (markers of organ infiltration and damage progressing to organ failure) are present.  These include such features as hypersplenism, liver damage, very low blood cell counts, and others.  However, in the last several years, a number of MCL patients described who do not have C findings.  These patients have over 20% mast cells in the nucleated cells of the bone marrow, but the mast cells are mostly mature, and most do not circulate in the blood stream.  This population often demonstrates stability rather than rapid progression toward death, as was previously seen in most MCL patients.  The term “chronic MCL” has been suggested to describe this group.

The more classic MCL presentation (now called acute MCL) has a number of differences from chronic MCL.  In acute MCL, most of the mast cells are not mature, with metachromatic blast cells.  In acute MCL, CD25 receptor is always present on the cells, while this only sometimes occurs in the chronic course.  Chronic MCL never expresses Ki-67 on the outside of the cells, while this is sometimes seen in acute MCL.  Both acute and chronic sometimes have CD2 and D816V mutation, but not always.  Spindle shaped mast cells are almost never present in acute MCL.  Swelling of the spleen is always seen in acute MCL, but only sometimes in the chronic form.  Chronic MCL patients have no C findings.  If they develop a C finding, they are reclassified as acute MCL.

Acute MCL has long been associated with very short survival times following diagnosis, most often less than a year.  This can be extended in some patients with the use of newer medications.  Remarkably, patients with chronic MCL demonstrate a largely stable clinical course comparable to smouldering SM.  In both of these conditions, tryptase levels are high but stable; the spleen is most often swollen; and mast cell burden is high.  Patients with chronic MCL usually have no mast cell skin lesions.

Chronic MCL patients can be stable for years, but can progress to acute MCL or MCL-AHNMD at any time.  Mediator release symptoms more often seen in indolent mast cell diseases are also common in chronic MCL, while less so in acute MCL.

Reference:

P. Valent et al. Chronic mast cell leukemia: A novel leukemia-variant with distinct morphological and clinical features. 23eukemia Research 39 (2015) 1-5.

2 Responses

  1. Nancie Daniel October 17, 2015 / 3:43 pm

    Thank you Lisa for the “Chronic mast cell leukemia: A new variant of systemic mastocytosis,” which I am currently fighting. I have not see an article that differentiates between chronic and acute. Not even Dr. Jason Gotlib (Stanford Medical) pointed this out to me. He diagnosed me with systemic again (as the NIH did in 2005) when I have all the acute symptoms.

    • Lisa Klimas October 17, 2015 / 11:08 pm

      The symptoms can be the same across the forms of systemic mastocytosis. Do you have the pathologic findings for chronic MCL? (I’m in no way asserting that you don’t have chronic MCL, I am just very curious about this diagnosis.) I am keeping this on my radar and will update if I find anything new.

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