Acute mast cell leukemia is a very rare but extremely aggressive form of acute myeloid leukemia , which usually occurs de novo , but can occasionally occur as a malignant transformation of chronic myeloid leukemia into more aggressive acute myeloid leukemia (the so-called "blast transformation" and the following " blast crisis ”). In a small percentage of cases, acute mast cell leukemia occurs from a more rapidly progressive form of systemic mastocytosis . The diagnosis of acute mast cell leukemia according to WHO criteria requires the presence of at least 20% of malignant mast cells in the bone marrow and at least 10% of the total number of “white cells” in the blood. [1] If malignant mast cells make up less than 10% of all nucleated (ie “white”) blood cells, then this form is called “aleukemic” or “subleukemic” acute mast cell leukemia.
| Acute mast cell leukemia | |
|---|---|
 A smear of the peripheral blood of a patient with acute mast cell leukemia | |
| ICD-10 | C 94.3 |
| ICD-10-KM | and |
| ICD-9 | 207.8 |
| ICD-O | M 9742/3 |
| Diseasesdb | 30102 |
| Mesh | D007946 |
Content
- 1 Laboratory findings
- 1.1 Cytochemistry
- 1.2 Tumor markers
- 1.3 Biochemistry
- 2 Clinical course
- 3 Treatment
- 4 Forecast
- 5 notes
Laboratory Findings
Cytochemistry
The cytochemical properties of leukemic cells for the diagnosis of acute mast cell leukemia should correspond and be typical of mast cells (the presence of metachromatic granules positively stained for alpha-naphthyl-chloroacetate esterase, but not for peroxidase). [2] Mast cell tryptase is an enzyme found in mast cell granules. Mast cell counts are most easily calculated using immunohistochemical staining for tryptase, since poorly granulated malignant mast cells may poorly, very poorly, or not stain positively with alpha-naphthyl-chloroacetate esterase. [one]
Tumor Markers
Leukemic mast cells are usually dramatically positive for CD13, CD33 , CD68 and CD117 surface antigens. Characteristically, basophilic (e.g., CD11b , CD123) and monocytic (e.g., CD14 , CD15 ) markers are absent. Cells typically express CD2 and CD25. [3] Malignant mast cells overexpress the anti-apoptotic protein Bcl-2. [4] Most patients have a mutation in the KIT gene. [5]
Biochemistry
The total serum tryptase content in acute mast cell leukemia is increased. The normal level of total (alpha + beta isoform) serum tryptase averages about 6 μg / L (range from 0 to 11 μg / L). Levels of the order of hundreds of μg / L are characteristic for acute mast cell leukemia. [6] Histamine levels in plasma and urine are often elevated in patients with acute mast cell leukemia. The histidine decarboxylase enzyme is an enzyme that catalyzes the conversion of histidine to histamine. Measurement of histidine decarboxylase levels in patients' bone marrow cells is a very sensitive marker for the presence and number of mast cells in the bone marrow. [7]
Clinical course
Acute mast cell leukemia has an aggressive, rapidly progressing course with a large number of leukemic mast cells in the bone marrow and blood. Typical symptoms include fever, headaches, flushing of the face and neck with redness (due to the release of histamine). [8] [9] Typical skin mast cell-cell pigment urticaria infiltrates in patients with acute mast cell leukemia are absent both before, and at the time of diagnosis, and after. [10] Symptoms often include abdominal pain, bone pain, peptic ulcer, which is much more common than other AML subtypes. These symptoms are also associated with the release of large amounts of histamine by tumor cells. [11] An increase in the size of the liver and spleen , or, in other words, hepatomegaly and splenomegaly is also very characteristic. [2] Malignant mast cells also secrete a large number of different anticoagulants , such as heparin , which, coupled with thrombocytopenia , can lead to serious bleeding . Impaired liver and spleen function also contribute to bleeding. [12] The involvement of bones in the tumor process, as well as the leaching of calcium from them under the influence of heparin and other biologically active substances secreted by mast cells, often leads to the development of osteoporosis in these patients. For diagnosis, it is important to perform an ultrasound examination of the abdominal organs and computed tomography of the body, which makes it possible to identify pronounced hepatomegaly, splenomegaly and lymphadenopathy, which are not characteristic of many other types of AML. To assess the presence of osteoporosis, bone radiography and densitometry are necessary. Upper and lower endoscopy and biopsy are indicated due to the frequent involvement of the stomach and intestines in the tumor process and the frequent presence of peptic ulcers in the stomach. [13]
Treatment
Immunoglobulin E ( IgE ) is important for the functioning of mast cells. Experimental immunotherapy with anti-IgE immunoglobulin resulted in a short-term decrease in the number of circulating blast mast cells in one patient with acute mast cell leukemia. [14] Although splenectomy leads to a short-term improvement in the condition of patients with acute mast cell leukemia and a short-term decrease in the number of circulating blast mast cells, there is no way to make a firm conclusion about the effectiveness or indications of such treatment, due to the small number of patients and observations. [10] [15] . Chemotherapy according to protocols designed to treat other forms of AML (for example, 7 + 3 with cytarabine and daunorubicin , or idarubicin , or mitoxantrone , or ADE with the addition of etoposide , or FLAG-like regimens ) may help, however, its effectiveness in this form of AML not studied in detail. Hematopoietic stem cell transplantation is a possible option, but there is no data on the response to this therapy and long-term treatment results (in terms of overall and relapse-free survival). [5]
Forecast
Acute mast cell leukemia is an extremely aggressive form of acute myeloid leukemia and has a very poor prognosis. In the vast majority of cases, multi-organ failure, including bone marrow failure, develops within a few weeks or months from the moment of diagnosis. [16] The median survival after diagnosis is only about 6 months. [10]
Notes
- ↑ 1 2 Lichtman MA, Segel GB Uncommon phenotypes of acute myelogenous leukemia: basophilic, mast cell, eosinophilic, and myeloid dendritic cell subtypes: a review // Blood Cells, Molecules and Diseases : journal. - 2005. - Vol. 35 , no. 3 . - P. 370-383 . - DOI : 10.1016 / j.bcmd.2005.08.006 . - PMID 16203163 .
- ↑ 1 2 Kufe D, et al. . Holland Frei Cancer Medicine. - 5th. - BC Decker, 2000.
- ↑ Valent P. 1995 Mack-Forster Award Lecture. Review Mast cell differentiation antigens: expression in normal and malignant cells and use for diagnostic purposes (English) // European Journal of Clinical Investigation : journal. - 1995 .-- October ( vol. 25 , no. 10 ). - P. 715-720 . - DOI : 10.1111 / j.1365-2362.1995.tb01948.x . - PMID 8557056 .
- ↑ Cerveró C., Escribano L., San Miguel JF, et al. Expression of Bcl-2 by human bone marrow mast cells and its overexpression in mast cell leukemia (English) // American Journal of Hematology : journal. - 1999 .-- March ( vol. 60 , no. 3 ). - P. 191-195 . - DOI : 10.1002 / (SICI) 1096-8652 (199903) 60: 3 <191 :: AID-AJH4> 3.0.CO; 2-Y . - PMID 10072109 .
- ↑ 1 2 Rare Hematological Malignancies / Ansell SM. - Springer, 2008.
- ↑ Sperr WR, Jordan JH, Fiegl M., et al. Serum tryptase levels in patients with mastocytosis: correlation with mast cell burden and implication for defining the category of disease (English) // Int. Arch. Allergy Immunol. : journal. - 2002 .-- June ( vol. 128 , no. 2 ). - P. 136-141 . - DOI : 10.1159 / 000059404 . - PMID 12065914 .
- ↑ Krauth MT, Agis H., Aichberger KJ, et al. Abstracts of the American Society of Hematology 46th Annual Meeting. December 4-7, 2004, San Diego, California, USA (English) // Blood : journal. - American Society of Hematology 2004 .-- November ( vol. 104 , no. 11 Pt 2 ). - P. 272b . - PMID 15562525 .
- ↑ Daniel MT, Flandrin G., Bernard J. [Acute mast-cell leukemia. Cytochemical and ultrastructural study, about a particular case (author's transl)] (Fr.) // Nouv Rev Fr Hematol. - 1975. - T. 15 , No. 3 . - S. 319-332 . - PMID 54900 .
- ↑ Le Cam MT, Wolkenstein P., Cosnes A., et al. [Acute mast cell leukemia disclosed by vasomotor flushing ] (Fr.) // Ann Dermatol Venereol. - 1997. - T. 124 , No. 9 . - S. 621-622 . - PMID 9739925 .
- ↑ 1 2 3 Travis WD, Li CY, Hoagland HC, Travis LB, Banks PM Mast cell leukemia: report of a case and review of the literature (Eng.) // Mayo Clinic Proceedings : journal. - 1986. - December ( vol. 61 , no. 12 ). - P. 957-966 . - DOI : 10.1016 / s0025-6196 (12) 62636-6 . - PMID 3095598 .
- ↑ Valent P., Sperr WR, Samorapoompichit P., et al. Myelomastocytic overlap syndromes: biology, criteria, and relationship to mastocytosis (English) // Leukemia Research : journal. - 2001 .-- July ( vol. 25 , no. 7 ). - P. 595-602 . - DOI : 10.1016 / S0145-2126 (01) 00040-6 . - PMID 11377685 .
- ↑ Cather JC, Menter MA Red-brown skin lesions and pruritus (neopr.) // Proc (Bayl Univ Med Cent). - 2000. - July ( vol. 13 , No. 3 ). - S. 297-299 . - PMID 16389403 .
- ↑ Hoffbrand AV, Catovsky D, Tuddenham E. Postgraduate Haematology. - 5th. - Blackwell, 2005.
- ↑ Ribeiro I., Carvalho IR, Fontes M., et al. Eosinophilic leukaemia with trisomy 8 and double gammopathy (English) // Journal of Clinical Pathology : journal. - 1993 .-- July ( vol. 46 , no. 7 ). - P. 672–673 . - DOI : 10.1136 / jcp.46.7.672 . - PMID 8157759 .
- ↑ Dalton R., Chan L., Batten E., Eridani S. Mast cell leukaemia: evidence for bone marrow origin of the pathological clone (Eng.) // British Journal of Haematology : journal. - 1986 - October ( vol. 64 , no. 2 ). - P. 397-406 . - DOI : 10.1111 / j.1365-2141.1986.tb04133.x . - PMID 3096368 .
- ↑ Hoffman R, Benz E, Shattil S, Furie B, Cohen H. Hematology: Basic Principles and Practice. - 4th. - Churchill Livingstone, 2004.