Mast cell leukemia

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Acute mast cell leukemia
Mast cell leukemia.jpg
Peripheral blood showing mast cell leukemia.
Specialty Hematology and oncology

Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. [1] If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.

Contents

Signs and symptoms

Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing of face and trunk. [2] [3] The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. [4] Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of acute myeloid leukemia. These former symptoms are due to release of a substance called histamine from neoplastic mast cells. [5] Enlargement of the liver and spleen, or hepatosplenomegaly is characteristic. [6] The mast cells release also many anticoagulants like heparin which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. [7] Involvement of the bone can lead to osteoporosis. Abdominal ultrasound or computerized tomography (CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected. [8]

Diagnosis

Cytochemistry

Cytochemical properties of the leukemic cells must be typical of mast cell derivation (presence of metachromatic granules staining with alpha-naphthyl chloroacetate esterase, but not with peroxidase). [6] Mast cell tryptase is an enzyme contained in mast cell granules. Mast cell numbers are best estimated by tryptase immunostaining because very poorly granulated cells may stain very weakly if at all for alpha-naphthol chloroacetate esterase. [1]

Tumor markers

The leukemic cells usually are strongly positive for CD13, CD33, CD68, and CD117. Characteristically, basophil (e.g. CD11b, CD123) and monocyte markers (CD14, CD15) are absent. The cells usually express CD2 and CD25. [9] Malignant mast cells overexpress the anti-apoptosis gene, bcl-2. [10] A mutation called KIT mutation is detected in most patients. [11]

Biochemistry

Total serum tryptase is elevated in mast cell leukemia. Normal total (alpha + beta) serum tryptase is approximately 6 micro g/L (range 0 to 11 micro g/L). Values of several hundred micro g/L are characteristic of mast cell leukemia. [12] Plasma and urinary histamine levels are frequently elevated in mast cell leukemia. Histidine decarboxylase (HDC) is the enzyme that catalyzes the reaction which produces histamine from histidine. Measurement of histidine carboxylase in the marrow cells of patients with mast cell leukemia is a very sensitive marker of mast cells. [13]

Treatment

Immunoglobulin E (IgE) is important in mast cell function. Immunotherapy with anti-IgE immunoglobulin raised in sheep resulted in a transient decrease in the numbers of circulating mast cells in one patient with mast cell leukemia. [14] Although splenectomy has led to brief responses in patients with mast cell leukemia, [4] [15] no firm conclusions as to the efficacy of this treatment are possible. Chemotherapy with combination of cytosine arabinoside and either idarubicin, daunomycin, or mitoxantrone as for acute myeloid leukemia has been used. Stem cell transplantation is an option, although no experience exists concerning responses and outcome. [11]

Prognosis

Acute mast cell leukemia is extremely aggressive and has a grave prognosis. In most cases, multi-organ failure including bone marrow failure develops over weeks to months. [16] Median survival after diagnosis is only about 6 months. [4]

Related Research Articles

Mastocytosis Medical condition

Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells and CD34+ mast cell precursors.

Myelodysplastic syndrome Diverse collection of blood-related cancers that involve ineffective production of certain blood cells

A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, so do not become healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include feeling tired, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.

Mast cell

A mast cell is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumours.

Tumors of the hematopoietic and lymphoid tissues Medical condition

Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid malignancies are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation closely related and often overlapping problems.

Acute lymphoblastic leukemia Blood cancer characterised by overproduction of lymphoblasts

Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.

Myeloid sarcoma Medical condition

A myeloid sarcoma, is a solid tumor composed of immature white blood cells called myeloblasts. A chloroma is an extramedullary manifestation of acute myeloid leukemia; in other words, it is a solid collection of leukemic cells occurring outside of the bone marrow.

Myeloproliferative neoplasm Medical condition

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.

Acute myeloid leukemia Cancer of the myeloid line of blood cells

Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.

Splenic marginal zone lymphoma (SMZL) is a type of cancer made up of B-cells that replace the normal architecture of the white pulp of the spleen. The neoplastic cells are both small lymphocytes and larger, transformed lymphoblasts, and they invade the mantle zone of splenic follicles and erode the marginal zone, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar lymph nodes are involved along with the peripheral blood. The neoplastic cells circulating in the peripheral blood are termed villous lymphocytes due to their characteristic appearance.

Acute monocytic leukemia is a type of acute myeloid leukemia. In AML-M5 >80% of the leukemic cells are of monocytic lineage. This cancer is characterized by a dominance of monocytes in the bone marrow. There is an overproduction of monocytes that the body does not need in the periphery. These overproduced monocytes interfere with normal immune cell production which causes many health complications for the infected individual.

Chronic myelomonocytic leukemia Medical condition

Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell.

Acute myeloblastic leukemia with maturation Medical condition

Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.

Aggressive NK-cell leukemia Medical condition

Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells and a rapidly declining clinical course.

FIP1L1

Factor interacting with PAPOLA and CPSF1 is a protein that in humans is encoded by the FIP1L1 gene. A medically important aspect of the FIP1L1 gene is its fusion with other genes to form fusion genes which cause clonal hypereosinophilia and leukemic diseases in humans.

Acute myelomonocytic leukemia (AMML) is a form of acute myeloid leukemia that involves a proliferation of CFU-GM myeloblasts and monoblasts. AMML occurs with a rapid increase amount in white blood cell count and is defined by more than 20% of myeloblast in the bone marrow. It is classified under "M4" in the French-American-British classification (FAB). It is classified under "AML, not otherwise classified" in the WHO classification.

Acute eosinophilic leukemia (AEL) is a rare subtype of acute myeloid leukemia with 50 to 80 percent of eosinophilic cells in the blood and marrow. It can arise de novo or may develop in patients having the chronic form of a hypereosinophilic syndrome. Patients with acute eosinophilic leukemia have a propensity for developing bronchospasm as well as symptoms of the acute coronary syndrome and/or heart failure due to eosinophilic myocarditis and eosinophil-based endomyocardial fibrosis. Hepatomegaly and splenomegaly are more common than in other variants of AML.

Acute panmyelosis with myelofibrosis (APMF) it is a poorly defined disorder that arises as either a clonal disorder, or following toxic exposure to the bone marrow.

Midostaurin

Midostaurin, sold under the brand name Rydapt, is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus.

Mast cell activation syndrome (MCAS) is one type of mast cell activation disorder (MCAD), and is an immunological condition in which mast cells inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including anaphylaxis or near-anaphylaxis attacks. Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological and respiratory problems.

References

  1. 1 2 Lichtman MA, Segel GB (2005). "Uncommon phenotypes of acute myelogenous leukemia: basophilic, mast cell, eosinophilic, and myeloid dendritic cell subtypes: a review". Blood Cells Mol. Dis. 35 (3): 370–83. doi:10.1016/j.bcmd.2005.08.006. PMID   16203163.
  2. ↑ Daniel MT, Flandrin G, Bernard J (1975). "[Acute mast-cell leukemia. Cytochemical and ultrastructural study, about a particular case (author's transl)]". Nouv Rev Fr Hematol (in French). 15 (3): 319–32. PMID   54900.
  3. ↑ Le Cam MT, Wolkenstein P, Cosnes A, et al. (1997). "[Acute mast cell leukemia disclosed by vasomotor flushing]". Ann Dermatol Venereol (in French). 124 (9): 621–2. PMID   9739925.
  4. 1 2 3 Travis WD, Li CY, Hoagland HC, Travis LB, Banks PM (December 1986). "Mast cell leukemia: report of a case and review of the literature". Mayo Clin. Proc. 61 (12): 957–66. doi:10.1016/s0025-6196(12)62636-6. PMID   3095598.
  5. ↑ Valent P, Sperr WR, Samorapoompichit P, et al. (July 2001). "Myelomastocytic overlap syndromes: biology, criteria, and relationship to mastocytosis". Leuk. Res. 25 (7): 595–602. doi:10.1016/S0145-2126(01)00040-6. PMID   11377685.
  6. 1 2 Kufe D, et al. (2000). Holland Frei Cancer Medicine (5th ed.). BC Decker.
  7. ↑ Cather JC, Menter MA (July 2000). "Red-brown skin lesions and pruritus". Proc (Bayl Univ Med Cent). 13 (3): 297–9. doi:10.1080/08998280.2000.11927693. PMC   1317061 . PMID   16389403.
  8. ↑ Hoffbrand AV, Catovsky D, Tuddenham E (2005). Postgraduate Haematology (5th ed.). Blackwell.
  9. ↑ Valent P (October 1995). "1995 Mack-Forster Award Lecture. Review. Mast cell differentiation antigens: expression in normal and malignant cells and use for diagnostic purposes". Eur. J. Clin. Invest. 25 (10): 715–20. doi:10.1111/j.1365-2362.1995.tb01948.x. PMID   8557056.
  10. ↑ Cerveró C, Escribano L, San Miguel JF, et al. (March 1999). "Expression of Bcl-2 by human bone marrow mast cells and its overexpression in mast cell leukemia". Am. J. Hematol. 60 (3): 191–5. doi: 10.1002/(SICI)1096-8652(199903)60:3<191::AID-AJH4>3.0.CO;2-Y . PMID   10072109.
  11. 1 2 Ansell SM, ed. (2008). Rare Hematological Malignancies. Cancer Treatment & Research. Springer.
  12. ↑ Sperr WR, Jordan JH, Fiegl M, et al. (June 2002). "Serum tryptase levels in patients with mastocytosis: correlation with mast cell burden and implication for defining the category of disease". Int. Arch. Allergy Immunol. 128 (2): 136–41. doi:10.1159/000059404. PMID   12065914.
  13. ↑ Krauth MT, Agis H, Aichberger KJ, et al. (November 2004), "Histidine carboxylase (HDC) as novel marker of immature neoplastic mast cells in systemic mastocytosis", Blood, Abstracts of the American Society of Hematology 46th Annual Meeting. December 4–7, 2004, San Diego, California, USA, 104 (11 Pt 2): 272b, doi:10.1182/blood.V104.11.4755.4755, PMID   15562525
  14. ↑ Ribeiro I, Carvalho IR, Fontes M, et al. (July 1993). "Eosinophilic leukaemia with trisomy 8 and double gammopathy". J. Clin. Pathol. 46 (7): 672–3. doi:10.1136/jcp.46.7.672. PMC   501401 . PMID   8157759.
  15. ↑ Dalton R, Chan L, Batten E, Eridani S (October 1986). "Mast cell leukaemia: evidence for bone marrow origin of the pathological clone". Br. J. Haematol. 64 (2): 397–406. doi:10.1111/j.1365-2141.1986.tb04133.x. PMID   3096368.
  16. ↑ Hoffman R, Benz E, Shattil S, Furie B, Cohen H (2004). Hematology: Basic Principles and Practice (4th ed.). Churchill Livingstone.
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