Symptomatic Response to Imatinib Mesylate in Cutaneous Mastocytosis Associated with Chronic Myelomonocytic Leukemia

Abstract

1 major and 1 minor, or 3 minor World Health Organization diagnostic criteria, which are listed in Table ii 4 . Although cutaneous and systemic involvement can occur together in adults, children rarely experience systemic manifestations and often have self-limiting disease [5][6][7] . The treatment of sm in adults remains a challenge, in part because of its chronicity and heterogeneity. CASE DESCRIPTIONA 67-year-old white woman presented with progressive and debilitating pruritus of 5 years' duration.Her symptoms had begun with intermittent pruritus of her arms, which then progressed to involve unexposed areas. The condition was unresponsive to treatment with histamine antagonists and ultraviolet B phototherapy. Two years later, she was noted to have peripheral blood monocytosis. Bone marrow (bm) examination demonstrated hypercellularity, dysplastic erythroid precursors and megakaryocytes, and increased monocyte precursors (Figure 1), but no increase in blasts. Blood and marrow findings were diagnostic of chronic myelomonocytic leukemia (cmml) 1. Mast cell numbers and morphology were normal.When the patient presented to our tertiary care centre, her pruritus had become constant and involved her entire body. She was unable to sleep unless medicated with sedatives. She was struggling to work and was having suicidal thoughts. Hot showers exacerbated her pruritus, but symptoms persisted even with avoidance of triggers. She noted a chronic truncal rash and erythematous patches on her arms. She denied flushing, wheezing, and diarrhea. Her medical history was otherwise unremarkable.Physical examination revealed a fine maculopapular rash with tan lesions over the patient's anterior trunk, concentrated near the umbilicus and under the breasts, and erythematous plaques on the left arm. She did not have dermatographia.White blood cell count was 6.8×10 3 /μL, with 19% monocytes and 1% eosinophils. Hemoglobin ABSTRACTMastocytosis is an uncommon disorder defined by increased and abnormal mast cells in one or more tissues. Cutaneous mastocytosis (cm) is limited to the skin, with varying degrees of rash, pruritus, and disfigurement. Systemic mastocytosis (sm) typically involves the bone marrow, sometimes in association with other bone marrow disorders, including chronic myelomonocytic leukemia (cmml). Mastocytosis has been associated with somatic mutations in the gene encoding the tyrosine kinase Kit, leading to identification of Kit as a therapeutic target. The Kit inhibitor imatinib mesylate is approved for aggressive sm. We present an unusual patient with disabling pruritus from telangiectasia macularis eruptiva perstans, a subtype of cm, and cmml, but with no evidence of systemic mast cell disease. She was treated with imatinib and experienced marked improvement in her pruritus. Concomitant cm and cmml have not previously been reported, and the present report is the first of successful imatinib therapy in an adult patient with cm.

Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature

“…Overall, 46 patients with mastocytosis lacking the D816V KIT mutation and other extracellular membrane/transmembrane KIT mutations who were treated with imatinib and further evaluated for response to therapy have been reported, with an overall response rate of 80% (37/46 cases) [ 18 , 32 – 35 , 37 , 42 , 45 – 62 ]. However, almost one third of such responding cases corresponded to patients with SM associated with either HES/CEL ( n = 11/37) [ 32 , 34 , 37 , 45 – 47 ] or chronic basophilic leukemia ( n = 1/37) [68] carrying rearrangements of PDGFR α/ PDGFR β; in turn, another 10/37 patients only showed improvement of MC-mediator release-associated symptoms and/or skin lesions [ 32 , 48 , 51 , 52 , 55 , 57 ] Among the remaining 15 cases, 5 fulfilled criteria for CR [ 18 , 49 , 51 , 53 , 54 ] and 10 were reported to have PR [ 32 , 45 , 49 , 50 , 56 ]. It should be noted that unlike CR, which was defined in all reports by the disappearance of all mastocytosis-related signs and symptoms together with decrease of sT levels to < 20 μg/L, criteria used for establishing PR were more heterogeneous, a significant reduction of BM MC infiltrates being documented in only 4/10 PR patients [ 32 , 45 ].…”

Transient improvement of skin symptoms in an adult patient with pediatric‐onset cutaneous mastocytosis treated with interferon‐α

“…2 In the experience of some authors, effective treatment with imatinib in CM has been reported. 24 what's more, with good tolerance of treatment. 26 To summarize, although the disappearance of skin lesions has been reported because of cytoreductive therapies in SM, the use of potentially toxic drugs in CM is not recommended.…”

“…However, complete and permanent resolution of skin lesions is not achieved with mentioned therapies . Interestingly, partial or complete remission of cutaneous symptoms was observed in some patients with SM treated with cytoreductive therapy . Generally, interferon‐ α is not recommended in purely CM because of serious side effects of the therapy .…”

“…In the experience of some authors, effective treatment with imatinib in CM has been reported . Morren et al .…”

“…15,16 Interestingly, partial or complete remission of cutaneous symptoms was observed in some patients with SM treated with cytoreductive therapy. 2,[21][22][23][24][25][26] Generally, interferon-a is not recommended in purely CM because of serious side effects of the therapy. 2,3 IFN-a treatment is frequently (up to 50%) complicated by flu-like symptoms, bone pain, fever, cytopenias, depression, and hypothyroidism.…”