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López-Pereira, P.1; Figuera, Á.1; Ormazábal, I.1; Cornago, J.2; Sola, E.1; Quesada, M.1; Savchuk, A.1; Lizandro, V.1; de la Fuente, A.3; Ayala, R.4; A′lvarez-Twose, I.5; Steegmann, J. L.1

doi: 10.1097/01.HS9.0000567396.87038.9a
Publication Only: Myeloproliferative neoplasms - Clinical

1Hematology, Hospital La Princesa

2Hematology, Hospital Fundacio′n Jime′nez Di′az

3Hematology, M.D. Anderson Cancer Center

4Hematology, Hospital Universitario 12 de Octubre, Madrid

5Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain

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Mast cell leukemia (MCL) is an extremely rare subtype of systemic mastocytosis (SM), with only 50 cases described so far. It confers an extremely bad prognosis, with an overall survival of few months.

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To describe an extremely rare case of MCL and AML treated with Gemtuzumab-Ozogamicin (GO).

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A 69-year old lady started in November 2016 with diarrhea, weight loss and eosinophilia, in the range of 2 × 109/L, with slight elevation of serum tryptase (40 ug/L) and no cytopenias. In April 2017, the patient developed severe fatigue, increasing eosinophilia, and cytopenias. Bone marrow (BM) exam was consistent with SM-with associated hematologic neoplasm (SM-AHN), in this case, an eosinophilic leukemia. A CT scan showed involvement of colon, liver, and bone. Molecular exams were negative, including D816 V assessment. On May 31st Midostaurin and prednisone were started, with clinical and eosinophil response. Two months later, clinical deterioration, progressive eosinophilia (max: 4.6 × 109/L) and transfusion-dependent cytopenias developed. BM exam disclosed the D816 V mutation. Four cycles of Azacitidine were added, with no response.

In March 2018, a BM exam disclosed a diffuse (>90%) infiltration of atypical immature CD 25+ CD33High mastocytes. Cladribine was added on March 2018 and a noteworthy clinical and hematologic response ensued. A compassionate use of GO was requested.

On July 2018, the clinical status deteriorated, with severe cytopenia, and 76% blasts in blood (CD34+CD117+Cd33+CD25-). BM showed a mixed population of dysplastic mastocytes (80%) CD25+cKIT+ with intercalated myeloblasts. Decitabine was started, with no benefit. On August 2018, the patient was very ill, with fever, diarrhea, cachexia, anasarca, and marked liver and spleen enlargement. Blood exam showed severe anemia and thrombocytopenia with 43% myeloblasts. Serum tryptase rose again. The BM exam disclosed 2 populations. 80% of the cells were atypical fusiform mastocytes, CD117+CD25+ CD33high and 10% were myeloblasts (CD34+ CD33+w). D816 V was detected by PCR. NGS studies disclosed: c-KIT mutation D816 V (p.Asp816Val) with an allelic frequence of 8.2%. 2.RUNX1 mutation p.Arg162Lys: 85.4%, AXL1 mutation p.Glu635fs: 48,.8%, and AXL1 mutation p.Gly966del: 47.6%. No other mutations were detected.

GO was given at a dose of 6 mg/m2, on August 30th, and was repeated after 20 days at dose of 3 mg/m2. Thereafter doses of 6 mg/m2 and 3 mg/m2, with an interval of 10 days. Between GO doses, Decitabine was given in 5 days cycle, two cycles. The only response seen was the great diminution of splenomegaly and lowering of tryptase. The clinical status did not improve, and cytopenias and PB blasts remained unchanged. BM yielded a dry tap. The patient condition worsened, and she died shortly thereafter.



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This case illustrates several findings of interest. Despite the dismal prognosis of MCL and SM-AHN, two cases of successful use of GO have been reported in CD33+ cases, one in a child with SM-AML, and another, reported previously by one of us, in a 69-year-old woman with CD33+ refractory MCL who, similar to our case, had received several lines of treatment. Whereas in our first case a complete response was obtained, in the case here presented the only effect was seen at the spleen level, probably reflecting a mast cell response. These different outcomes probably could be explained by two facts. The first one is the weak expression of CD33 in the accompanying AML population, and the second one, the mutations of RUNX1 and AXL1, which confer a bad prognosis not only in AML, but in advanced SM.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.