Systemic Mastocytosis
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Systemic mastocytosis, often termed systemic mast cell disease (SMCD), is a myeloproliferative neoplasm characterized by infiltration of clonally derived mast cells in different tissues, including bone marrow (see the image below), skin, the gastrointestinal tract, the liver, and the spleen. [1, 2, 3, 4] Median survival ranges from 198 months in patients with indolent systemic mastocytosis to 41 months in aggressive systemic mastocytosis and 2 months in mast cell leukemia.
Manifestations of systemic mastocytosis may include the following:
Anemia and coagulopathy
Abdominal pain is the most common GI symptom, followed, by diarrhea, nausea, and vomiting
Symptoms and signs of gastroesophageal reflux disease (GERD)
Pruritus and flushing
Anaphylactoid reaction (eg, to Hymenoptera stings, general anesthetics, intravenous contrast media, other drugs, foods) [5, 6]
Findings on physical examination may include the following:
Signs of anemia (eg, pallor)
Hepatomegaly (27%)
Splenomegaly (37%)
Lymphadenopathy (21%)
Urticaria (41%)
Osteolysis and pathological fractures (rare)
See Presentation for more detail.
Findings on blood studies may include the following:
Anemia (45% of patients)
Thrombocytopenia
Leukocytosis
Some patients have eosinophilia, basophilia, thrombocytosis, and monocytosis
The combination of anemia, thrombocytopenia, hypoalbuminemia, and excess bone marrow blasts (>5%) portends a poor prognosis [7]
Measurement of serum tryptase may reveal the following:
Total serum tryptase levels of 20 ng/mL or higher in a baseline serum sample with a total–to–beta-tryptase ratio greater than 20:1 [8]
Serum tryptase levels of 11.5 ng/mL or higher (the cut-off value used in more recent studies) are found in more than 50% of patients
The following imaging studies may be necessary to identify the extent and stage of the disease:
GI radiography, ultrasonography, and liver-spleen computed tomography scanning in patients with abdominal pain
Skeletal surveys and bone CT scanning in patients with suspected bone involvement
Diagnostic procedures are as follows:
Bone marrow aspiration and biopsy are essential
GI procedures (eg, barium studies, endoscopy) are indicated for patients with GI symptoms
Liver biopsy can show mast cell infiltration in patients with hepatomegaly
Skin biopsy may be warranted in patients with cutaneous manifestations
The major diagnostic criterion for systemic mastocytosis is the presence of dense infiltrates of mast cells in bone marrow or other extracutaneous tissues. Mast cells should be seen in aggregates of 15 or more.
Major criteria may be absent in early disease. In this situation, the minor criteria are used to make the pathologic diagnosis. Three of the following four minor criteria are required to make the diagnosis:
Atypical mast cell morphology in 25% or more of the mast cells
Expression of CD2 and/or CD25 in addition to normal mast cell markers
Serum/plasma tryptase levels greater than 20 ng/mL
A codon-816 c-kit mutation in peripheral blood, bone marrow, or involved tissue
Types of systemic mastocytosis (World Health Organization criteria) are as follows:
Indolent systemic mastocytosis
Smoldering systemic mastocytosis
Systemic mastocytosis with an associated hematological neoplasm
Aggressive systemic mastocytosis
Mast cell leukemia
Mast cell sarcoma
See Workup for more detail.
Therapy for systemic mastocytosis is primarily symptomatic; no therapy is curative. Treatment modalities include the management of the following:
Anaphylaxis and related symptoms
Pruritus and flushing
Intestinal malabsorption
Agents for symptomatic relief include the following:
Epinephrine is used in acute anaphylaxis
H1 and H2 receptor blockers are used to control anaphylactic symptoms
Corticosteroids have been used to control malabsorption, ascites, and bone pain and to prevent anaphylaxis
Cromolyn is helpful for decreasing bone pain and headaches and for improving skin symptoms
Patients with osteopenia that does not respond to therapy may receive a trial of interferon alfa-2b
First-generation histamine H1 antagonists (eg, diphenhydramine, hydroxyzine) have been used to treat pruritus and flushing
Histamine H2 antagonists and proton pump inhibitors have been used to treat gastric hypersecretion and peptic ulcer disease
Aspirin can be used when H1 and H2 receptor blockers do not prevent vascular collapse
Mast cell stabilizers (eg, ketotifen) have been used to treat pruritus and whealing
Leukotriene antagonists (eg, zafirlukast, montelukast) have been used
Cromolyn is helpful for decreasing bone pain and headaches and for improving skin symptoms
Psoralen ultraviolet A therapy may provide transient relief of pruritus and may cause fading of skin lesions
Anticholinergics have been used in the treatment of diarrhea
Disodium cromolyn has been used in the treatment of abdominal cramping and diarrhea
Chemotherapy has not been particularly successful in the management of systemic mastocytosis, but the following regimens have been tried [9] :
Interferon-alfa may be beneficial, especially in patients with aggressive systemic mastocytosis
2-Chlorodeoxyadenosine (cladribine [Leustatin])
Thalidomide in advanced disease
Imatinib mesylate (Gleevec) in patients who do not have mutations of the codon 816 on the c-kit gene and carry the wild-type kit, or who carry the FIP1L1-PDGFRA rearrangement [10]
Midostaurin (Rydapt) is approved by the FDA for aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL), collectively referred to as advanced systemic mastocytosis [11]
See Treatment and Medication for more detail.
Systemic mastocytosis, often termed systemic mast cell disease (SMCD), is a heterogeneous clonal disorder of the mast cell and its precursor cells. The clinical symptoms and signs of systemic mastocytosis result from the accumulation of these clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal (GI) tract, the liver, and the spleen. [1, 2, 12, 3, 4]
Systemic mastocytosis is characterized by mast cell infiltration of extracutaneous organs, which is in contrast to cutaneous mast cell disorders, which involve only the skin. Ehrlich first described mast cells in 1877 when he found cells that stained metachromatically with aniline dyes. [13] He called these cells “mast Zellen” because the cells were distended with granules (ie, the botanical definition of mast, which refers to an accumulation of nuts on the forest floor).
Cutaneous mastocytosis was identified in the late 19th century. Sangster first described urticaria pigmentosa, which is one of the cutaneous mast cell disorders, in 1878. In 1933, Touraine suggested that this disease could involve internal organs. In 1949, Ellis first established at autopsy that cutaneous mastocytosis can also involve internal organs. An autopsy of a 1-year-old infant revealed mast cell infiltration of the bone marrow, lymph nodes, spleen, kidneys, and pancreas.
For patient education information, see the Allergies Center, as well as Allergic Reaction and Severe Allergic Reaction (Anaphylactic Shock).
Systemic mastocytosis (systemic mast cell disease) is characterized by mast cell infiltration of extracutaneous organs. Mast cells typically infiltrate the bone marrow and consequently affect the peripheral blood and coagulation system. [14] Mast cells are derived from CD34+/ KIT+ pluripotent hematopoietic cells in the bone marrow. [15] The neoplastic clone of mast cells express abnormal cell surface markers CD25 and/or CD2.
Mueller et al reported that the adhesion molecule CD44 is expressed in systemic mastocytosis cell lines and correlates with the aggressiveness of the disorder. They found that serum levels of soluble CD44 were higher in advanced systemic mastocytosis compared with indolent systemic mastocytosis or cutaneous mastocytosis, and correlated with overall and progression-free survival. [16]
The marrow cellularity ranges from normocellular to markedly hypercellular changes. Erythropoiesis is usually normoblastic without any significant abnormalities. Eosinophilia is a common bone marrow histology finding (see Workup, Histologic Findings). Hypocellular bone marrow and myelofibrosis can be observed in late stages of systemic mastocytosis (systemic mast cell disease).
Ho et al evaluated the plasma level of pro–major basic protein (proMBP), a precursor of major basic protein that is contained in eosinophil cytoplasmic granules, in eosinophilic and chronic myeloproliferative disorders. [17] They found that the plasma proMBP level was significantly higher in patients with systemic mastocytosis with eosinophilia, idiopathic eosinophilia, and myeloproliferative disorders with eosinophilia than in healthy controls. In addition, the median proMBP level of patients with postpolycythemic myeloid metaplasia and those with postthrombocythemic myeloid metaplasia was significantly higher than in those with polycythemia vera and essential thrombocythemia. [17]
Ho et al also reported that the presence and size of splenomegaly was correlated with proMBP levels in certain conditions. In patients with idiopathic eosinophilia, the presence of splenomegaly was significantly associated with elevated proMBP. [17] In 76 patients with de novo myelofibrosis, the proMBP level was correlated with spleen size and the presence of hypercatabolic symptoms. All of these find ings led the investigators to conclude that “significantly elevated levels of proMBP in myelofibrosis patients implies that proMBP could be an important stromal cytokine in bone marrow fibrosis.” [17]
Focal mast cell lesions in the bone marrow are found in approximately 90% of adult patients with systemic mastocytosis. A typical mast cell has a spindle-shaped nucleus and fine eosinophilic granules, which can be visualized at high magnification. These cells are likely to return positive findings upon Giemsa staining. Peripheral blood can show anemia, leukopenia, thrombocytopenia, and lymphopenia. The most common abnormality found in the peripheral blood is anemia. In some patients, eosinophilia, leukocytosis, basophilia, thrombocytosis, and monocytosis can be observed.
Spleen and lymphoid tissue involvement is a significant manifestation of systemic mastocytosis. Mast cell infiltrates in the spleen can cause nodular areas that could be confused with lymphomas. A biopsy specimen from the spleen can reveal findings similar to a myeloproliferative disorder or hairy cell leukemia. Histopathology studies of the spleen can reveal two types of involvement: (1) diffuse infiltration of the red pulp and sinuses and (2) focal infiltration of the white pulp. Lymph node biopsy can show mast cell infiltrates, particularly in the paracortex. Follicles and medullary involvement can be observed in some cases.
The immune system is affected as a consequence of the previously mentioned pathology. Mast cell products, such as interleukin 4 (IL-4) and interleukin 3 (IL-3), may induce immunoglobulin E (IgE) synthesis and augment T-cell differentiation toward an allergic phenotype. Mast cells also release histamine, which results in inhibition of interleukin 2 (IL-2).
GI involvement includes microscopic infiltration of the liver, pancreas, and intestines by mast cells. [18, 19] Abdominal pain has been attributed to peptic ulcer disease, involvement of the GI tract by mast cells, mediators released by mast cells, and motility disorders. GI involvement includes esophageal involvement (eg, esophagitis, stricture, varices), gastric involvement (eg, peptic ulcer disease, mucosal lesions), small intestine involvement (eg, dilatated small bowel, malabsorption), colon and rectal involvement (eg, multiple polyposis, diverticulitis), and liver involvement (eg, hepatomegaly and portal hypertension, ascites, sclerosing cholangitis, Budd-Chiari syndrome).
Osteoporosis is a common manifestations of systemic mastocytosis, particularly in adults, and can result in vertebral fractures. The mechanism of bone loss is not yet fully elucidated, but stimulation of osteoclast activity through RANK-RANKL signaling appears to be most important. Histamine and other cytokines also play significant roles. [20]
Systemic mastocytosis has many features common to myeloproliferative disorders. However, the 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia no longer lists mastocytosis under the broad heading of myeloproliferative neoplasms (MPNs), and instead assigns it to a separate category. [21]
Systemic mastocytosis is almost always associated with the KIT D816V mutation. This gain of function KIT receptor mutation is detected by polymerase chain reaction (PCR) techniques in 68% of bone marrow specimens in patients with systemic mastocytosis. [7] Additional molecular markers being tested include mutations of JAK2, MPL, and TET2. The association between JAK2 V617F and systemic mastocytosis is weak and was noted in just 4% of patients with systemic mastocytosis (all had associated non–mast cell hematological disease). [7] The incidence of TET2 mutations (reportedly as high as 29% in KIT+ systemic mastocytosis) seems to influence the phenotype without affecting the prognosis. [22]
United States
Systemic mastocytosis is an extremely rare disorder; the specific incidence has not been reported.
International
Epidemiologic data on the incidence of systemic mastocytosis are lacking. Some studies in Great Britain showed two cases per year from a study population of 300,000.
Systemic mastocytosis is a progressive neoplastic disorder that has no known curative therapy. Survival in patients with indolent systemic mastocytosis (ISM), with a median survival of 198 months, is not significantly different from the general population. However, median survival with aggressive systemic mastocytosis (ASM) is 41 months and that with SM-AHNMD (associated hematological non– mast cell disorder) is 24 months. Mast cell leukemia (MCL) has the poorest prognosis with a median survival of 2 months.
Early evolution into acute leukemia may occur in as many as 32% of patients with aggressive mastocytosis. [12] Leukemic transformation is rare with indolent systemic mastocytosis. [7]
A slight male preponderance in the incidence of mastocytosis is noted. [7] Mastocytosis is more common in children than in adults, and it is usually transient and self-limited in children compared with the adult version. Onset in those younger than 2 years is noted in 55% of patients, and, in an additional 10% of patients, the onset is between the ages of 2 and 15 years.
Progression of pediatric cutaneous mastocytosis is uncommon, but not so in adults, where it frequently progresses to systemic disease. [3]
The median age at diagnosis of systemic mastocytosis in adults is 55 years. Patients with indolent systemic mastocytosis were younger and symptomatic for a longer duration of time as compared with patients with aggressive systemic mastocytosis or SM-AHNMD (with other hematological disorders). [7]
Akin C, Metcalfe DD. Systemic mastocytosis. Annu Rev Med. 2004. 55:419-32. [Medline].
Bain BJ. Systemic mastocytosis and other mast cell neoplasms. Br J Haematol. 1999 Jul. 106(1):9-17. [Medline].
Bunimovich O, Grassi M, Baer MR. Systemic mastocytosis: classification, pathogenesis, diagnosis, and treatment. Cutis. 2009 Jan. 83(1):29-36. [Medline].
Pettigrew HD, Teuber SS, Kong JS, Gershwin ME. Contemporary challenges in mastocytosis. Clin Rev Allergy Immunol. 2010 Apr. 38(2-3):125-34. [Medline].
Bonadonna P, Zanotti R, Pagani M, Caruso B, Perbellini O, Colarossi S. How much specific is the association between hymenoptera venom allergy and mastocytosis?. Allergy. 2009 Sep. 64(9):1379-82. [Medline].
Weingarten TN, Volcheck GW, Sprung J. Anaphylactoid reaction to intravenous contrast in patient with systemic mastocytosis. Anaesth Intensive Care. 2009 Jul. 37(4):646-9. [Medline].
Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009 Jun 4. 113(23):5727-36. [Medline].
Schwartz LB, Irani AM. Serum tryptase and the laboratory diagnosis of systemic mastocytosis. Hematol Oncol Clin North Am. 2000 Jun. 14(3):641-57. [Medline].
Ustun C, Corless CL, Savage N, et al. Chemotherapy and dasatinib induce long-term hematologic and molecular remission in systemic mastocytosis with acute myeloid leukemia with KIT D816V. Leuk Res. 2009 May. 33(5):735-41. [Medline].
Pardanani A, Ketterling RP, Brockman SR, et al. CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood. 2003 Nov 1. 102(9):3093-6. [Medline]. [Full Text].
Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, et al. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30. 374 (26):2530-41. [Medline]. [Full Text].
Pieri L, Bonadonna P, Elena C, Papayannidis C, Grifoni FI, et al. Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients. Am J Hematol. 2016 Apr 7. [Medline].
Ehrlich P. Beitrage zur Kenntnis der Anilinfarbungen und ihrer Verwendung in der mikroskopischen Technik. Arch mikr Anat. 1877. 13:263-7.
Parker RI. Hematologic aspects of systemic mastocytosis. Hematol Oncol Clin North Am. 2000 Jun. 14(3):557-68. [Medline].
Kirshenbaum AS, Goff JP, Semere T, Foster B, Scott LM, Metcalfe DD. Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13). Blood. 1999 Oct 1. 94(7):2333-42. [Medline].
Mueller N, Wicklein D, Eisenwort G, Jawhar M, Berger D, Stefanzl G, et al. CD44 is a RAS/STAT5-regulated invasion receptor that triggers disease expansion in advanced mastocytosis. Blood. 2018 Jul 17. [Medline].
Ho CL, Kito H, Squillace DL, Lasho TL, Tefferi A. Clinical correlates of serum pro-major basic protein in a spectrum of eosinophilic disorders and myelofibrosis. Acta Haematol. 2008. 120(3):158-64. [Medline].
Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000 Jun. 14(3):579-623. [Medline].
Kirsch R, Geboes K, Shepherd NA, et al. Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases. Mod Pathol. 2008 Dec. 21(12):1508-16. [Medline].
Rossini M, Zanotti R, Orsolini G, Tripi G, Viapiana O, Idolazzi L, et al. Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis. Osteoporos Int. 2016 Feb 18. [Medline].
[Guideline] Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19. 127 (20):2391-405. [Medline]. [Full Text].
Tefferi A, Levine RL, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia. 2009 May. 23(5):900-4. [Medline].
Butterfield JH. Survey of aspirin administration in systemic mastocytosis. Prostaglandins Other Lipid Mediat. 2009 Apr. 88(3-4):122-4. [Medline].
Mital A, Prejzner W, Hellmann A. Acquired von Willebrand syndrome during the course of systemic mastocytosis – analysis of 21 cases. Pol Arch Intern Med. 2018 Jul 11. [Medline]. [Full Text].
Ma Y, Zeng S, Metcalfe DD, et al. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Blood. 2002 Mar 1. 99(5):1741-4. [Medline]. [Full Text].
Pardanani A, Elliott M, Reeder T, et al. Imatinib for systemic mast-cell disease. Lancet. 2003 Aug 16. 362(9383):535-6. [Medline].
Garcia-Montero AC, Jara-Acevedo M, Teodosio C, Sanchez ML, Nunez R, Prados A, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006 Oct 1. 108(7):2366-72. [Medline].
Jawhar M, Schwaab J, Horny HP, Sotlar K, Naumann N, Fabarius A, et al. Impact of Centralized Evaluation of Bone Marrow Histology in Systemic Mastocytosis. Eur J Clin Invest. 2016 Feb 23. [Medline].
Lueke AJ, Meeusen JW, Donato LJ, Gray AV, Butterfield JH, Saenger AK. Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: A marker of systemic mastocytosis. Clin Biochem. 2016 Feb 18. 264 (1):217-22. [Medline].
Horny HP. Mastocytosis: an unusual clonal disorder of bone marrow-derived hematopoietic progenitor cells. Am J Clin Pathol. 2009 Sep. 132(3):438-47. [Medline].
Metcalfe DD. Classification and diagnosis of mastocytosis: current status. J Invest Dermatol. 1991 Mar. 96(3 suppl):2S-4S; discussion 4S, 60S-65S. [Medline]. [Full Text].
Jawhar M, Schwaab J, Horny HP, Sotlar K, Naumann N, Fabarius A, et al. Impact of Centralized Evaluation of Bone Marrow Histology in Systemic Mastocytosis. Eur J Clin Invest. 2016 Feb 23. [Medline].
Worobec AS. Treatment of systemic mast cell disorders. Hematol Oncol Clin North Am. 2000 Jun. 14(3):659-87, vii. [Medline].
van der Veer E, van der Goot W, de Monchy JG, Kluin-Nelemans HC, van Doormaal JJ. High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy. 2012 Mar. 67(3):431-8. [Medline].
Aichberger KJ, Sperr WR, Gleixner KV, Kretschmer A, Valent P. Treatment responses to cladribine and dasatinib in rapidly progressing aggressive mastocytosis. Eur J Clin Invest. 2008 Nov. 38(11):869-73. [Medline].
Dowse R, Ibrahim M, McLornan DP, Moonim MT, Harrison CN, Radia DH. Beneficial effects of JAK inhibitor therapy in Systemic Mastocytosis. Br J Haematol. 2016 Feb 5. [Medline]. [Full Text].
Chaar CI, Bell RL, Duffy TP, Duffy AJ. Guidelines for safe surgery in patients with systemic mastocytosis. Am Surg. 2009 Jan. 75(1):74-80. [Medline].
Vega-Ruiz A, Cortes JE, Sever M, et al. Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis. Leuk Res. 2009 Nov. 33(11):1481-4. [Medline].
Yacoub A, Prochaska L. Ruxolitinib improves symptoms and quality of life in a patient with systemic mastocytosis. Biomark Res. 2016. 4:2. [Medline]. [Full Text].
Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009 Jun 4. 113(23):5727-36. [Medline].
Pardanani A, Lim KH, Lasho TL, et al. Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies. Blood. 2009 Oct 29. 114(18):3769-72. [Medline].
Akin C, Schwartz LB, Kitoh T, et al. Soluble stem cell factor receptor (CD117) and IL-2 receptor alpha chain (CD25) levels in the plasma of patients with mastocytosis: relationships to disease severity and bone marrow pathology. Blood. 2000 Aug 15. 96(4):1267-73. [Medline]. [Full Text].
Kumar S, Moody P. Mastocytosis. Pediatr Rev. 2001 Jan. 22(1):33-4. [Medline].
Longley BJ, Metcalfe DD. A proposed classification of mastocytosis incorporating molecular genetics. Hematol Oncol Clin North Am. 2000 Jun. 14(3):697-701, viii. [Medline].
Pauls JD, Brems J, Pockros PJ, et al. Mastocytosis: diverse presentations and outcomes. Arch Intern Med. 1999 Feb 22. 159(4):401-5. [Medline].
Seitz S, Barvencik F, Koehne T, Priemel M, Pogoda P, Semler J, et al. Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis. Osteoporos Int. 2013 Feb 23. [Medline].
Soter NA. Mastocytosis and the skin. Hematol Oncol Clin North Am. 2000 Jun. 14(3):537-55, vi. [Medline].
Sperr WR, El-Samahi A, Kundi M, Girschikofsky M, Winkler S, Lutz D. Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology. Eur J Clin Invest. 2009 Oct. 39(10):914-23. [Medline].
Swolin B, Rodjer S, Roupe G. Cytogenetic studies in patients with mastocytosis. Cancer Genet Cytogenet. 2000 Jul 15. 120(2):131-5. [Medline].
Tefferi A, Li CY, Butterfield JH, Hoagland HC. Treatment of systemic mast-cell disease with cladribine. N Engl J Med. 2001 Jan 25. 344(4):307-9. [Medline].
van Daele PL, Beukenkamp BS, Geertsma-Kleinekoort WM, et al. Immunophenotyping of mast cells: a sensitive and specific diagnostic tool for systemic mastocytosis. Neth J Med. 2009 Apr. 67(4):142-6. [Medline].
Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, Royal College of Physicians
Disclosure: Nothing to disclose.
Devapiran Jaishankar, MBBS Associate Professor, Division of Oncology, East Tennessee State University, James H Quillen College of Medicine
Devapiran Jaishankar, MBBS is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Hematology, American Society of Clinical Oncology
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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
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Ronald A Sacher, MBBCh, FRCPC, DTM&H Professor of Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MBBCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada
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Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences
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Thomas H Davis, MD, FACP Associate Professor, Fellowship Program Director, Department of Internal Medicine, Section of Hematology/Oncology, Geisel School of Medicine at Dartmouth
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The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Stephen J Smith, MD, Harsha G Vardhana, MD, and Guha Krishnaswamy, MD, to the development and writing of this article.
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