High prevalence of myeloid neoplasms in adults with non-Langerhans cell histiocytosis

作者：Papo Matthias; Diamond Eli L; Cohen Aubart Fleur; Emile Jean Francois; Roos Weil Damien; Gupta Nishant; Durham Benjamin H; Ozkaya Neval; Dogan Ahmet; Ulaner Gary A; Rampal Raajit; Kahn Jean Emmanuel; Sene Thomas; Charlotte Frederic; Hervier Baptiste; Besnard Caroline; Bernard Olivier A; Settegrana Catherine; Droin Nathalie; Helias Rodzewicz Zofia; Amoura Zahir; Abdel Wahab Omar^*; Haroche Julien^*

来源：Blood, 2017, 130(8): 1007-1013.

DOI：10.1182/blood-2017-01-761718

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAFV600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. Insomecases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm.

• 出版日期2017-8-24