Systemic mastocytosis (SM) is a rare hematological neoplasm characterized by the abnormal proliferation and accumulation of mast cells. Clinical manifestations are heterogeneous depending on the tissue infiltration and mast cell mediators released by their degranulation. The gain-of-function point mutations at codon 816 of KIT gene, high serum tryptase level, and expression of CD25 represent minor diagnostic criteria, however, the unique major one is depicted by bone marrow (BM) biopsy. A subset of SM occurs with other hematological neoplasms, most frequently myeloid malignancies such as myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia and myelodysplasia (MDS). Here we report the case of a 56-year-old female patient affected by SM associated with a hematological neoplasm: she presented with thorax skin rash and a blood test revealed white blood cell count of 12.3 x 109/L, increased basophils (3.08 x 109/L) and platelets 567 x 109/L. Screening of JAK2, CALR, MPL and BCR/ABL1 mutations was negative. Therefore, the patient underwent a BM biopsy, which showed the typical clusters of mast cells associated with an MDS/MPN and a grade 2 reticulin fibrosis. Second-level analyses showed an increased serum tryptase level (148 ng/mL) and peripheral CD34+ cells (172/μL). The abdominal ultrasonography showed a spleen diameter of 19 cm. NGS myeloid panel (Illumina MiSeqTM) detected no mutations in any of the 30 genes analyzed, among them, KIT mutations were negative. Therefore, imatinib 400 mg daily was started, and after 3 months of therapy the patient achieved a significant symptoms improvement. In addition, the BM biopsy showed an outstanding response of SM and an improvement in both MDS/MPN and the grade of fibrosis (MF-1) (Figure 1). Serum tryptase level decreased up to 3 ng/ml and spleen diameter up to 16 cm. The therapy with imatinib was well tolerated, except for grade 3 thrombocytopenia. Platelet count was restored after 2 weeks of imatinib interruption; treatment was resumed at lower dosage with no thrombocytopenia recurrence. To our knowledge, there are no data in the literature concerning effective therapeutic option in this specific setting. Being aware of the limits of the present report, mainly the short follow-up, we can speculate that imatinib may represent a safe and effective option, not only in the context of non-KIT D816V mutated SM, but also leading to a clinical and histological improvement as far as MDS/MPN is concerned.

Successful treatment with Imatinib for systemic mastocytosis associated with MDS/MPN / E. Barozzi, D. Cattaneo, C. Bucelli, U. Gianelli, F.I. Grifoni, A. Iurlo. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 106:10 (Suppl.3)(2021 Oct), pp. D117.158-D117.159. ((Intervento presentato al 48. convegno Congress of the Italian Society of Hematology: October, 27 - 31 tenutosi a Milano nel 2021.

Successful treatment with Imatinib for systemic mastocytosis associated with MDS/MPN

E. Barozzi
Primo
;
D. Cattaneo
Secondo
;
U. Gianelli;
2021-10

Abstract

Systemic mastocytosis (SM) is a rare hematological neoplasm characterized by the abnormal proliferation and accumulation of mast cells. Clinical manifestations are heterogeneous depending on the tissue infiltration and mast cell mediators released by their degranulation. The gain-of-function point mutations at codon 816 of KIT gene, high serum tryptase level, and expression of CD25 represent minor diagnostic criteria, however, the unique major one is depicted by bone marrow (BM) biopsy. A subset of SM occurs with other hematological neoplasms, most frequently myeloid malignancies such as myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia and myelodysplasia (MDS). Here we report the case of a 56-year-old female patient affected by SM associated with a hematological neoplasm: she presented with thorax skin rash and a blood test revealed white blood cell count of 12.3 x 109/L, increased basophils (3.08 x 109/L) and platelets 567 x 109/L. Screening of JAK2, CALR, MPL and BCR/ABL1 mutations was negative. Therefore, the patient underwent a BM biopsy, which showed the typical clusters of mast cells associated with an MDS/MPN and a grade 2 reticulin fibrosis. Second-level analyses showed an increased serum tryptase level (148 ng/mL) and peripheral CD34+ cells (172/μL). The abdominal ultrasonography showed a spleen diameter of 19 cm. NGS myeloid panel (Illumina MiSeqTM) detected no mutations in any of the 30 genes analyzed, among them, KIT mutations were negative. Therefore, imatinib 400 mg daily was started, and after 3 months of therapy the patient achieved a significant symptoms improvement. In addition, the BM biopsy showed an outstanding response of SM and an improvement in both MDS/MPN and the grade of fibrosis (MF-1) (Figure 1). Serum tryptase level decreased up to 3 ng/ml and spleen diameter up to 16 cm. The therapy with imatinib was well tolerated, except for grade 3 thrombocytopenia. Platelet count was restored after 2 weeks of imatinib interruption; treatment was resumed at lower dosage with no thrombocytopenia recurrence. To our knowledge, there are no data in the literature concerning effective therapeutic option in this specific setting. Being aware of the limits of the present report, mainly the short follow-up, we can speculate that imatinib may represent a safe and effective option, not only in the context of non-KIT D816V mutated SM, but also leading to a clinical and histological improvement as far as MDS/MPN is concerned.
Settore MED/15 - Malattie del Sangue
Società Italiana di Ematologia (SIE)
https://haematologica.org/issue/view/392
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/914483
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