Page 1336 - Hematology_ Basic Principles and Practice ( PDFDrive )

1182 Part VII Hematologic Malignancies

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multilineage involvement of the KIT D816V mutation in more than measures. These medications include H1-histamine blockers for
just MCs (e.g., other myeloid lineages, and sometimes lymphoid flushing and pruritis, and H2-histamine blockers for SM-related
cells) is a poor prognostic factor and leads to an increased risk of gastrointestinal (GI) symptomatology such as diarrhea, abdominal
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progression to advanced SM. Many of these patients may suffer discomfort/cramping, and peptic ulcer disease. Leukotriene antago-
from overt SSM. In patients with SM, eosinophilia was also associ- nists such as Montelukast are commonly added to H1-histamine
ated with inferior outcomes in one study, and was prognostically blockers for persistent flushing and pruritis. In rare cases, aspirin can
neutral in another series. SM patients with eosinophilia tend to suffer be a alternative therapy for refractory flushing, but needs to be used
from SSM, ASM, or MCL, but even in ISM, eosinophilia may be with caution because of its ability to precipitate MC activation,
detected. bleeding tendency, and GI tract ulcerative disease. In general, however,
aspirin is not recommended for use in SM. Although the MC stabi-
lizer sodium cromoglycate (Gastrocrom) is geared to persistent GI
TREATMENT symptoms such as diarrhea, proton pump inhibitors may be specifi-
cally useful for patients with refractory GERD/peptic ulcer disease.
Therapy of mastocytosis centers on addressing symptoms related to Alternative treatments that have been used for refractory mediator
MC activation (in all categories), and using cytoreductive agents to symptoms include the off-label antihistamine/MC stabilizer ketoti-
reverse organ damage caused by neoplastic MC infiltrates in advanced fen, and the anti-IgE antibody omalizumab, which has also been used
SM. Fig. 72.8 provides a treatment algorithm for indolent versus for anaphylaxis, as well as asthma. Although bisphosphonates (alen-
advanced stages of SM and the broad therapeutic strategies that are dronate 70 mg q week; risedronate 35 mg q week; pamidronic acid
available based on the presence of mediator symptoms, organ damage, 90 mg intravenously (IV) q 4 weeks; and zoledronic acid 4 mg IV q
and a concomitant AHN. 4 weeks) are recommended for bony disease, reports of their use in
SM primarily consists of single cases or small cases series. A generally
accepted rule is to start with a bisphosphonate when the T-score drops
Mast Cell Activation Symptoms/Anaphylaxis to below −2. IFN-α has been employed with bisphosphonates and/
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or as single agent therapy, especially for patients with refractory bony
All adult mastocytosis patients, regardless of prior anaphylactic pain and/or MC-related osteoporosis and pathologic fractures.
events, should carry two doses of an adrenaline autoinjector (and Concerns regarding the cosmetic appearance of cutaneous lesions or
should be instructed in its safe use, e.g., by an allergist) to treat skin-related mediator symptoms refractory to the aforementioned
potential future episodes of anaphylaxis. In addition, emergency therapies can be helped for a limited period of time with phototherapy
medicines such as diphenhydramine or oral prednisolone should be (UVA 1 , narrow-band UVB, and UVA plus psoralen). In addition,
considered, although their utility for mitigating acute symptoms is occlusion dressings embedded with topical steroids with or without
less well-established. Because anaphylaxis can also be a feature of phototherapy, and both topical and oral forms of sodium cromogly-
MCAS, these patients are candidates for similar therapy even if no cate, have been used with some benefit.
overt SM was diagnosed. The treatment of choice for life-threatening
Hymenoptera allergy/anaphylaxis is venom immunotherapy that
should be undertaken with caution using a multidisciplinary approach Cytoreductive Agents
led by allergists. Similarly, perioperative management of anesthetics,
which can precipitate immediate and delayed MC activation, requires IFN-α and cladribine (2-chlorodeoxyadenosine) have typically been
consultation with the surgical, anesthesiology, and allergy teams to used for patients with progressive SSM and for cytoreduction in
minimize the occurrence and severity of anaphylaxis. General guide- advanced SM patients (ASM, MCL, and SM-AHN) to reduce or
lines regarding anesthesia and analgesic management in patients with reverse organ damage. In most instances, cladribine is favored over
mastocytosis have been published. IFN-α to induce debulking of neoplastic MCs in advanced SM
The treatment of MC activation symptoms follows a stepwise patients. The use of both drugs is recommended to treat patients with
approach using antimediator drugs and other supportive care less rapidly progressive disease (PD). In addition, cladribine and

Midostaurin; 2-CdA or IFN-α ;
clinical trial; multi-agent
ASM/MCL chemotherapy for MCL;
allogeneic HSCT

Organ damage? AHN-directed Midostaurin;
SM-AHN treatment 2-CdA or IFN-α ;
Which disease or clinical trial
Diagnosis of requires treatment?
SM
ISM or SSM Drugs for Refractory? 2-CdA or IFN-α
Symptomatic mediator symptoms or clinical trial

ISM
Asymptomatic Observe
Fig. 72.8 TREATMENT OPTIONS BASED ON SUBTYPE OF SYSTEMIC MASTOCYTOSIS. Treat-
ment options are listed based on subvariant of SM (indolent vs. advanced forms of disease), whether organ
damage is considered related to SM or the associated myeloid neoplasm in patients with SM-AHN, and
whether cytoreductive therapy may need to be considered in patients with ISM and refractory mediator
symptoms. 2-CdA, 2-Chlorodeoxyadenosine; ASM, aggressive systemic mastocytosis; HSCT, hematopoietic
stem cell transplantation; ISM, indolent systemic mastocytosis; IFN-α, interferon-α; MCL, mast cell leukemia;
SM, systemic mastocytosis; SM-AHN, systemic mastocytosis with an associated hematologic neoplasm;
SSM, smoldering systemic mastocytosis.