We asked , and you answered ! Here are a few responses from this month ’ s “ You Make the Call .”

For the full description of the clinical dilemma , and to see how the expert responded , turn to page 14 .

CLINICAL DILEMMA :

I am treating a 40-year-old female patient with a new diagnosis of aggressive systemic mastocytosis ( ASM ). She had a years-long history of progressive back pain , further exacerbated by a motor vehicle accident in January 2020 .

A CT scan of her chest , abdomen , and pelvis showed subcentimeter left axilla nodes and dense , diffuse , bony sclerosis with small areas of lysis . Her bone scan revealed diffuse increased bony remodeling in the distribution of the adult red marrow ; metastatic or metabolic bony disease was felt to be unlikely based on lack of heterogeneity and peripheral involvement . She has a reported history of blotchy erythema to the thighs when exposed to the cold ( a dermatologist diagnosed telangiectasia macularis eruptiva perstans ( TMEP ) on skin biopsy years ago . Her past medical history included TMEP and chronic back pain , and she has no family history of blood disorders .

Subsequent bone marrow analysis was normocellular for her age , revealing many aggregates / clusters of CD117 + mast cells and areas of densely packed spindle-shaped mast cells that account for 30-40 % of the marrow . There was minimal surrounding fibrosis . Karyotype was normal , molecular testing was positive for KIT D816V although at low variant allele frequency . Her tryptase level was 73.7 ng / mL .

The patient meets the major and three minor criteria for aggressive systemic mastocytosis , with one B finding ( bone marrow mast cells > 30 %) and one C finding ( lytic lesions ). She is starting on midostaurin 100 mg orally twice daily .

Given her young age , would you consider allogeneic hematopoietic cell transplantation ( alloHCT )? If so , what timing would you recommend ? Is there a particular bisphosphonate you would recommend ? We have access to zoledronic acid and pamidronic acid in our medical day unit . Would you suggest cromolyn sodium for her bone pain ?

Since she is young , I ’ d recommend prepping her for alloHCT ( I would not wait more than 5 years ). Zoledronic acid is a good choice for the bone pain .

Adel Al-Marzouki , MBBS Jeddah , Saudi Arabia

I would initially treat the patient with cladribine or midostaurin , depending on her access to these medications . Then I would proceed to alloHCT with myeloablative conditioning , as the data are much more robust regarding long-term remission with myeloablative conditioning .

Suchitra Krishnamurthy , MBBS , MRCP , FRCPath Whangarei , New Zealand in progress . I would definitely complete HLA typing , but I find my patients with ASM are very heterogeneous . It would be helpful to know about her cladribine exposure and whether she ’ s been maxed out on mast cell stabilizers .

Martina Trinkaus , MD , FRCPC Toronto , Ontario , Canada

I would treat the patient with midostaurin until progression , then cladribine until progression , then alloHCT if a good donor is available .

Robert John Ellis , MD Springfield , MO

The role of alloHCT in patients with advanced systemic mastocytosis is based on case series . Transplant may be considered for patients whose disease fails to respond to , or relapses after , a tyrosine kinase inhibitor ( TKI ), who have an underlying hematological neoplasm that does not respond to a TKI , who have a high-risk karyotype including monosomy 7 or a complex karyotype or high-risk mutations including RUNX1 , SRSF2 , and ASXL1 . Ideally , the patient should be young and fit with a matched related donor available , but these factors should not preclude transplant .

Hamza Hashmi , MD , MBBS Charleston , SC

I would treat the patient with avapritinib , which has outstanding results compared to midostaurin . There are trials for both indolent and aggressive systemic mastocytosis

Cromolyn sodium is not necessarily the best agent for controlling this patient ’ s bone pain due to mastocytosis . I would start her on a regimen of H1 and H2 blockers , in combination with a leukotriene inhibitor or mast cell stabilizer ( montelukast , ketotifen , etc .), to see if reducing the activity of the mast cells reduces the pain . If she continues to be symptomatic , I would pursue a clinical trial with avapritinib long before considering alloHCT . I recommend bisphosphonate therapy for all patients with mastocytosis and osteoporosis , but the choice of which bisphosphonate usually depends on insurance coverage .

See previous clinical dilemmas at ashclinicalnews . org / you-make-the-call .

Laura W . Bickel , APRN Salt Lake City , UT

4 ASH Clinical News March 2021