Knowledge on rare diseases and orphan drugs

It is extremely rare (less than 1% of cases of SM).

Mast cell leukemia (MCL) is a hematological disease that may occur at any age and is characterized by a massive infiltration of bone marrow by abnormal mast cells (at least 20% MC on BM smears). In patients suffering from the classical variant of MCL, circulating MC are also found. However, in a substantial number of patients with MCL, the leukemic spread into the peripheral blood is less extensive or is even absent. When MCs comprise less than 10% of all circulating blood leukocytes, the disease is termed aleukemic MCL. In a majority of patients, cutaneous lesions are absent. In most patients with MCL, signs and symptoms of organ damage, so-called C Findings, are present, and qualify the disease as acute MCL (aMCL). Patients with aMCL have a very poor prognosis with a median survival of less than 6 months, due to multiple organ failures caused by massive infiltration by MCs and/or to anaphylactic shock. Presentation is with organ dysfunction related to mast cell invasion (C-findings) and the intense release of mediators resulting in syncope, recurrent flushing, diarrhea, pain and organomegaly. C-findings include bone marrow (BM) dysfunction, palpable hepatomegaly with impairment of liver function, ascites, and/or portal hypertension, skeletal involvement with large osteolytic lesions and/or pathological fractures, palpable splenomegaly with hypersplenism and malabsorption with ascites. However, a subvariant of MCL, termed chronic MCL (cMCL), is defined by at least 20% MCs on BM smears and absence of C-Findings. MC in BM smears of cMCL patients appear more mature than those in BM smears of aMCL patients. Patients with cMCL have longer median survival as compared to those with acute MCL. However, in patients with chronic MCL in whom one or more C-Findings develop, the diagnosis changes from chronic to acute MCL.

In the few cases that have been studied, activating mutations of the gene KIT (D816V, D816Y, G820V), chromosome location 4q12, have been found in malignant mast cells, however, various chromosomal anomalies have also been noted.

Diagnosis is based on the histological and cytological analysis of bone marrow samples. Cytological analysis reveals a proportion of bone marrow mast cells over 20%. In most cases of mast cell leukemia, bone marrow mast cells with an atypical appearance, immature with a bi or multi-lobed core or, sometimes, a blast-like morphological appearance. Abnormal mast cells are present in the blood in most cases, with a proportion greater than 10% of circulating white blood cells. Additional tests include measurement of serum tryptase (above 20 ng/mL, with values sometimes exceeding 1,000 ng/mL), searching for mutations of KIT and phenotyping bone marrow mast cells.

Differential diagnoses include all other acute leukemias and rare cases of basophilic leukemia.

Management includes chemotheraphy, with or without interferon alpha or cladribine. For MCL patients with rapid progression and those who are resistant against 2CdA or midostaurin, poly-chemotherapy (protocols otherwise used for high-risk AML) is usually recommended. In patients who are young and fit and have a suitable donor, stem cell transplantation (SCT) should be considered after successful debulking. The outcome after allogeneic SCT is better for those prepared with ablative conditioning compared with less-intensive (nonmyeloablative) conditioning. In cases with splenomegaly with hypersplenism, splenectomy is indicated. Hydroxyurea is a palliative treatment.

The prognosis in acute MCL is very poor and survival time is several months. In chronic MCL, the clinical course is unpredictable. Some of these patients have an indolent course for several months or even years. Other patients progress to acute MCL within a short time. In most cases reported so far, progression to acute MCL was seen.

Last update: May 2020 - Expert reviewer(s): Pr Michel AROCK