Systemic Mastocytosis Guidelines

Updated: May 30, 2023
  • Author: Devapiran Jaishankar, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
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Guidelines Summary

The National Comprehensive Cancer Network (NCCN) has published guidelines for the diagnosis and management of systemic mastocytosis. [57]


For diagnosis, the NCCN guidelines recommend the following testing [57] :

  • Bone marrow aspirate and biopsy 
  • Immunophenotyping using flow cytometry and/or immunohistochemistry (IHC) of mast cells
  • Molecular testing for KIT D816V, additional KIT genetic sequencing as needed; if  KIT D816V negative and eosinophilia is present, screen for  FIP1L1::PDGFRA
  • Multigene next-generation sequencing (NGS) panel that includes genes such as SRSF2, ASXL1, and RUNX

Diagnosis is based on 2022 World Health Organization (WHO) or International Consensus Classification (ICC) criteria. Once the diagnosis of systemic mastocytosis is confirmed, further workup to determine subtype and organ involvement includes [57] :

  • CT/MRI or ultrasound of the abdomen/pelvis
  • Dual x-ray absorptiometry (DEXA) scan to evaluate for osteopenia/osteoporosis
  • Metastatic skeletal survey to evaluate for osteolytic lesions
  • Organ-directed biopsy (eg, endoscopy, liver biopsy) as needed with immunohistochemistry (CD117, CD25, tryptase, and CD3 as a control T-cell marker)

Treatment for indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM)

Treatment considerations for ISM and SSM are as follows [57] :

  • Referral to specialized centers with expertise in mastocytosis
  • Patients should carry injectable epinephrine to manage anaphylaxis
  • Assessment of symptom burden and quality of life (QOL) using the Mastocytosis Symptom Assessment Form (MSAF) and the Mastocytosis Quality of Life Questionnaire (MQLQ)

Asymptomatic patients can be monitored for signs and symptoms of disease; symptomatic patients are managed with anti-mediator drug therapy.  Both asymptomatic and symptomatic patients should be offered enrollment in clinical trials. [57]

Treatment for aggressive systemic mastocytosis (ASM)

The treatment recommendations for ASM are as follows [57] :

  • Enrollment in clinical trial or
  • Avapritinib (if platelets ≥50 × 10 9/L) or midostaurin

Cladribine or peginterferon alfa-2a with or without prednisone are other recommended regimens. Imatinib is useful for KIT D816V mutation negative or unknown; well-differentiated SM or if eosinophilia is present with FIP1L1::PDGFRA gene fusion. [57]

Patients with an adequate response to treatment may be considered for allogeneic hematopoietic cell transplant (HCT); patients with an inadequate or loss of response to treatment should be restaged. [57]

Treatment for systemic mastocytosis with an associated hematologic neoplasm (SM-AHN)

If the associated hematologic neoplasm (AHN) requires more immediate treatment, the guidelines recommend AHN-directed therapy following the guidelines relevant to the AHN.  Management of SM is determined by the number of C-findings. If no C-findings are present, monitor the patient for development of new C-findings and/or severe/ refractory symptoms of mast cell activation. [57]

If there are one or more C-findings, the guidelines recommend the following treatment of the SM:

  • Enrollment in clinical trial or
  • Avapritinib (if platelets ≥50 × 10 9 /L) or
  • Midostaurin
  • Cladribine is particularly useful when rapid debulking of disease is required
  • Peginterferon alfa-2a ± prednisone may be more suitable for patients with slowly progressive disease without the need for rapid cytoreduction

Treatment for mast cell leukemia (MCL)

Key treatment recommendations for MCL include the following [57] :

  • Enrollment in clinical trial or
  • Avapritinib (if platelets ≥50 x 10 9/L) or
  • Midostaurin
  • Cladribine is also recommended