Background: Mast cell leukemia (MCL) is a highly life-threatening and extremely rare subtype of systemic mastocytosis (SM). MCL often genetically contains one or more somatic mutations, particularly activating mutations of KIT. This study reported on an acute MCL patient who had a rare phenotype and genetic mutants with a history of primary malignant mediastinal germ cell tumor (GCT). Case Presentation: A 30-year-old Asian male patient who underwent two rounds of surgery and chemotherapy with a history of primary mediastinal GCT (PM-GCTs) was admitted to our hospital due to persistent chest pain and severe fatigue. The diagnosis of acute MCL was confirmed via morphology analysis and chemical staining of marrow aspirate, as well as via marrow biopsy, with the addition of C-findings that included splenomegaly and cytopenia. The atypical MCs were phenotypically positive for CD117 and CD9 but weakly positive for CD2 and negative for CD25. Next-generation sequencing of the marrow aspirate identified heterozygous mutations in TP53 P301Qfs*44, FLT3 R973X, SETBP1 N272D, and JAK3 I688F, whereas mutations in KIT were not found. Although the initial therapy of corticosteroids, ruxolitinib, and dasatinib-based regimens was effective, he died of acute respiratory distress syndrome after the first cycle of chemotherapy with cladribine and cytarabine. The patient’s survival time was 2.4 months after the initial presentation of MCL. Conclusion: In this case, MCL preceded by PM-GCTs had similar clinical symptoms and morphological manifestations but distinctly different genetic profiles than primary MCL. The characteristic morphology of MCL provides the most pivotal evidence that led our diagnosis in the correct direction. A competing hypothesis is that there is a common embryonal cancer stem cell between PM-GCTs and secondary MCL, and the latter is gradually developed in the context of additional “driver mutations”.

Common variable immunodeficiency (CVID) was a kind of primary immunodeficiency disorders with heterogeneous phenotype and genotype. Lipopolysaccharide-responsive and beige-like anchor (LRBA) mutation was identified as disease associated in CVID, advanced genetic method will help to detect atypical cases. We report a case of adult patient manifested as hemophagocytic lymphohistiocytosis (HLH), bone marrow examination suggested prosperity to MDS, manifested as increased immature myeloid cells and dysplastic hematopoiesis. Whole exome sequencing (WES) identified a novel heterogeneous c.1876T > C (p.W626R) mutation in LRBA and four somatic mutations: ASXL1 (c.1967dupA); PTPN11 (c.226G > A), U2AF1 (c.101C > T and c.470A > G), among which ASXL1 was a high-risk marker of clonal hematopoiesis. Combined with her recurrent severe infections and immune abnormalities such as hypoimmunoglobulinemia, the patient was diagnosed with CVID. Subsequent hematopoietic stem cell transplantation saved her from severe cytopenia and immune deficiency. This case report highlights the great promise of utilization of WES for diagnosing rare disease with atypical manifestations and guiding further treatment.

Summary: Chronic myelomonocytic leukemia (CMML) is a rare and aggressive myeloid malignancy with overlapped features of myelodysplastic syndromes/myeloproliferative neoplasms. Azacitidine (AZA), a hypomethylating agent, has been approved for the treatment of CMML in China, but real-world data are limited. Medical records of CMML patients who had received subcutaneously injected AZA were reviewed from January 2018 at five participating sites in China. Response was assessed according to the modified International Working Group (IWG 2006) criteria. Between January 2018 and November 2020, a total of 24 patients with CMML were included with a median age of 63 years. Patients received a median of 3 cycles of AZA treatment (range, 1–8). Overall response rate (ORR) was 37.5% (9 of 24); CR rate, PR rate, and mCR/HI rate were 8.3% (n = 2), 8.3% (n = 2), and 20.8% (n = 5), respectively. At a median duration of follow-up of 14.0 months (range 0.0–22.0 months), the median overall survival (OS) was 23.0 months. Univariate analysis revealed that ≥ 3 cycles of treatment was significantly associated with a higher 1-year OS rate compared with < 3 cycles of AZA treatment. Treatment was generally well-tolerated. The most common (> 10%) AEs were thrombocytopenia (n = 7, 29.2%), pneumonitis (n = 4, 16.7%) and fever (n = 3, 12.5%). This study provides valuable real-life data in China on the treatment schedules, efficacy and safety of AZA in the treatment of CMML.