Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
Journal website https://jh.elmerpub.com

Review

Volume 14, Number 4, August 2025, pages 174-192

Mast Cell Leukemia: Comprehensive Review of Literature With Current Insights and Updates on Management

Figures

↓  Figure 1. High power view of bone marrow biopsy showing > 20% atypical mast cells (black arrows).
Figure 1.
↓  Figure 2. A clot section of bone marrow biopsy showing dense infiltration and clustering of atypical mast cells with diffuse and increased CD117 expression.
Figure 2.
↓  Figure 3. A clot section of bone marrow biopsy with dense infiltration and clustering of atypical mast cells with diffuse tryptase staining.
Figure 3.
↓  Figure 4. A high-power view of an iliac bone biopsy showing an increased number of atypical mast cells (black arrows).
Figure 4.
↓  Figure 5. A clot section of the iliac bone biopsy showing cells with diffuse CD117 expression.
Figure 5.
↓  Figure 6. A clot section of the iliac bone biopsy showing an increased number of cells with diffuse tryptase staining.
Figure 6.
↓  Figure 7. Computed tomography of lumbar spine with contrast showing the osteolytic lesions and pathological fractures in multiple lumbar vertebrae (black arrows).
Figure 7.
↓  Figure 8. Computed tomography of lumbar spine with contrast showing the osteolytic lesion with fracture in the L5 lumbar vertebra (black arrow).
Figure 8.
↓  Figure 9. Computed tomography of chest with contrast showing the osteoblastic lesions in multiple ribs (black arrows).
Figure 9.
↓  Figure 10. Computed tomography of spine with contrast showing the osteoblastic lesions in the sternum and multiple thoracic and lumbar vertebrae (black arrows).
Figure 10.
↓  Figure 11. Computed tomography of abdomen and pelvis with contrast showing osteoblastic lesions in the pelvis (appendicular skeleton) (black arrows).
Figure 11.
↓  Figure 12. Computed tomography of abdomen and pelvis with contrast showing hepatosplenomegaly and portal vein dilatation (white arrows).
Figure 12.
↓  Figure 13. Basic treatment algorithm recommended for mast cell leukemia.
Figure 13.

Tables

↓  Table 1. Classification of Mastocytosis (WHO/ICC)
 
Type Key features Diagnostic criteria Subtypes Prognosis
CM: cutaneous mastocytosis; ICC: International Consensus Classification; KIT: receptor tyrosine kinase type III; MC: mast cell; MCL: mast cell leukemia; MCS: mast cell sarcoma; SM: systemic mastocytosis; SM-AHN: SM with associated hematologic neoplasm; WHO: World Health Organization.
CM Confined to skin; no systemic organ involvement on biopsy or imaging Clinical and dermatological findings: flushing, itching, urticaria, anaphylaxis; positive Darier’s sign Maculopapular CM; urticaria pigmentosa; diffuse CM; cutaneous mastocytoma Excellent; typically normal life expectancy
SM Involves bone marrow or extracutaneous organs; may cause systemic symptoms and/or organ dysfunction Requires 1 major + 1 minor OR ≥ 3 minor criteria: major: dense MC aggregates (> 15%); minor: atypical MCs, KIT mutation, CD25/CD2/CD30 expression, serum tryptase > 20 µg/L Indolent SM; smoldering SM; aggressive SM; SM-AHN; MCL Varies: indolent types have a good prognosis; aggressive/MCL subtypes have a poor prognosis
MCS Rare, localized malignant tumor in soft tissue or visceral organ Histology: highly atypical mast cells in an aggressive and destructive tumor. Typically KIT-mutated None (distinct from systemic forms; may progress to MCL) Very poor; rapid progression, often fatal

 

↓  Table 2. Brief Overview of Systemic Mastocytosis Subtypes
 
Subtype Clinical features Histopathology Prognosis
ASM: aggressive systemic mastocytosis; BM: bone marrow; BMM: bone marrow mastocytosis; CMML: chronic myelomonocytic leukemia; ISM: indolent systemic mastocytosis; MC: mast cell; MCL: mast cell leukemia; MDS: myelodysplastic neoplasm; MPN: myeloproliferative neoplasm; SM-AHN: systemic mastocytosis-associated hematologic neoplasm; SSM: smoldering systemic mastocytosis.
ISM Skin lesions, flushing, itching, abdominal pain, diarrhea, and anaphylaxis. No B-findings or C-findings. Multifocal aggregates of mast cells in BM biopsy. Normal life expectancy
BMM All findings of ISM without skin lesions. Serum tryptase < 125 µg/L. No dense MC infiltrates in an extramedullary organ. Normal life expectancy
SSM Higher MC burden than ISM. More severe symptoms than ISM with organ involvement but without organ damage. Increased MC burden in BM. Intermediate prognosis
SM-AHN Associated with another hematologic disorder, such as MDS/MPN, or AML. CMML is the most common MDS/MPN. Symptoms of MC activation and cytopenias. BM involvement with both MCs and an associated hematologic neoplasm. Variable prognosis
ASM Organ damage or dysfunction due to MC infiltration (C-findings): hepatomegaly, splenomegaly, lymphadenopathy, skeletal lesions, cytopenias, and malabsorption. MC infiltration and organ damage in various tissues. Poor prognosis
MCL ASM+ rapid progression with > 20% MCs in BM aspirate. BM infiltrated with > 20% MCs. Poor prognosis

 

↓  Table 3. Clinical Features and Organ Dysfunctions in MCL
 
System/feature Clinical findings Notes
CNS: central nervous system; DIC: disseminated intravascular coagulation; GI: gastrointestinal; MCAS: mast cell activation syndrome; MCL: mast cell leukemia.
Skin Blistering lesions Common in secondary MCL
GI tract Abdominal pain, diarrhea, peptic ulcers, GI bleeding, malabsorption Also part of MCAS symptoms
Musculoskeletal system Bone pain, osteolytic and osteoblastic lesions, pathological fractures, osteoporosis Osteoblastic lesions less common; non-vertebral metastases rare
Bone marrow Pancytopenia (anemia, thrombocytopenia, leukopenia), immunosuppression, infections, sepsis Due to marrow infiltration by mast cells
CNS Headache, dizziness, cognitive impairment, neuropsychiatric symptoms CNS involvement is less frequent but clinically significant.
Liver (hepatomegaly) Transaminitis, hypoalbuminemia, coagulopathy, DIC, ascites, portal hypertension Liver dysfunction indicates advanced disease.
Spleen (splenomegaly) Left upper quadrant pain/fullness, early satiety, hypersplenism with cytopenias May accompany hepatomegaly
Lymph nodes Diffuse lymphadenopathy; painful in some cases Due to mast cell infiltration
Constitutional symptoms Fever, fatigue, anorexia, malaise, weight loss, night sweats, decreased exercise tolerance Common in chronic MCL
MCAS (systemic) Anaphylaxis-like symptoms involving cardiovascular (hypotension, tachycardia, syncope), cutaneous (flushing, urticaria, pruritus), respiratory (wheezing, dyspnea, stridor), and GI (nausea, vomiting, diarrhea, abdominal pain) It can occur at any stage/type of MCL. The best marker is elevated serum tryptase level.

 

↓  Table 4. Summary of Common Drugs Used to Manage MCL and Their Notable Adverse Effects
 
Treatment category/drug Role in management Adverse/side effects
AdvSM: advanced systemic mastocytosis; AHN: associated hematological neoplasm; AIHA: autoimmune hemolytic anemia; ARDS: acute respiratory distress syndrome; CHF: congestive heart failure; FDA: Food and Drug Administration; GI: gastrointestinal; HSCT: hematopoietic stem cell transplantation; IFN-α: interferon-alpha; ILD: interstitial lung disease; ITP: immune thrombocytopenic purpura; MC: mast cell; MCAS: mast cell activation syndrome; MCL: mast cell leukemia; PUD: peptic ulcer disease; SM: systemic mastocytosis.
Targeted therapy: tyrosine kinase inhibitors
Mainstay of treatment currently.
Midostaurin and avapritinib are the two agents approved by the FDA for MCL.		 Midostaurin Improved prognosis in all types of MCL irrespective of the stage of the disease. Hyperglycemia; GI symptoms; myelosuppression (manageable); rare: arrhythmias, pneumonitis, hepatotoxicity
Avapritinib (only used if platelets are > 50,000) Good response rate even in the most aggressive forms of MCL. Favorable risk profile with fewer adverse effects when compared. Pancytopenia; risk of intracranial bleeding (rare); peripheral and periorbital edema; GI issues; cognitive impairment
Imatinib Mainly effective in patients without the KIT D816V mutation, some patients even achieving complete response. In patients with D816V mutation, only a partial response is noted. Pancytopenia; fatigue, myalgias; GI symptoms; rare but serious: CHF, arrhythmias, hepatotoxicity, severe myelosuppression
Dasatinib Only theoretical benefit noted in KIT D816V positive cases.
Even in D816V negative cases, response rates and adverse effects were undesirable.		 All the above adverse effects of imatinib +; rare: pulmonary arterial hypertension, pancreatitis, pleural effusion
Bezuclastinib Drug in clinical trials with promising improvement in the disease markers and no serious adverse effects. Pancytopenia; GI issues and taste disorders; rare and serious: hepatotoxicity, hypersensitivity reaction
Chemotherapy:
Out of favor with the invention of targeted therapy.
Tumor debulking to decrease MC burden and related symptoms.
Pre- and post-HSCT to prolong remission and improve survival.
Main treatment for aggressive AHN.		 Cladribine Potential value in other forms of AdvSM, but very little, and transient response seen in MCL. Used as a monotherapy or as a part of multidrug therapy for tumor debulking and before HSCT. Adverse effects that are common to all chemo drugs: rash and pruritic; flu-like symptoms; GI symptoms; bone marrow suppression with increased risk of infections; hepatotoxicity (transaminitis); fatigue and malaise; tumor lysis syndrome Arrhythmias; increased risk of AHN
Cytarabine Used in combination with cladribine for tumor debulking and with fludarabine before HSCT. Cerebellar toxicity; peripheral neuropathy; rare: cytarabine syndrome, ARDS, pancreatitis
Fludarabine Used as a part of polychemotherapy with either cladribine or cytarabine, mainly before HSCT. Encephalopathy/coma and seizures; AIHA and ITP; heart failure; ILD and pulmonary fibrosis
IFN-α Limited role in MCL. Studied in combination with steroids. Psychiatric issues; thyroid dysfunction, alopecia; peripheral neuropathy; ILD and pulmonary fibrosis (rare)
Immuno-modulators:
No disease-modifying effect.
Used to manage MC-related symptoms alongside chemotherapy or targeted therapies.
Commonly employed in the treatment of MCAS.		 Thalidomide Can be used as a single therapy for benign forms of SM. Not well studied in AdvSM/MCL; can be used to control MC symptoms. Drowsiness and sedation; peripheral neuropathy; pancytopenia
Cromolyn Control symptoms and improve quality of life in all forms of SM. Important role in MCAS. Rash and pruritus; dizziness; GI symptoms (nausea, vomiting, diarrhea); paradoxical bronchospasm; fatigue and malaise
Cortico-steroids Main role in refractory and severe (anaphylaxis) cases of MCAS. Control of musculoskeletal pain associated with bone metastases. Used in organ damage from MC infiltration, particularly GI issues. Typically, not used long enough to cause adverse effects: muscle weakness; Cushingoid features; PUD and GI bleeding; increased risk of infections; vision changes, headache, and psychosis