Absence of BCL-2 expression identifies a subgroup of AML with distinct phenotypic, molecular, and clinical characteristics

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the rapid and uncontrolled clonal growth of myeloid lineage cells in the bone marrow. The advent of oral, selective inhibitors of the B-cell leukemia/lymphoma-2 (BCL-2) apoptosis pathway, such as venetoclax, will likely induce a paradigm shift in the treatment of AML. However, the high cost of this treatment and the risk of additive toxicity when used in combination with standard chemotherapy represent limitations to its use and underscore the need to identify which patients are most-and least-likely to benefit from incorporation of venetoclax into the treatment regimen. Bone marrow specimens from 93 newly diagnosed AML patients were collected in this study and evaluated for BCL-2 protein expression by immunohistochemistry. Using this low-cost, easily, and readily applicable analysis method, we found that 1 in 5 AML patients can be considered as BCL-2(-). In addition to a lower bone marrow blast percentage, this group exhibited a favorable molecular profile characterized by lower WT1 expression and underrepresentation of FLT3 mutations. As compared to their BCL-2(+) counterparts, the absence of BCL-2 expression was associated with a favorable response to standard chemotherapy and overall survival, thus potentially precluding the necessity for venetoclax add-on

Pulmonary mass: never judge a book by its cover

Abstract: This case shows that a tumor can present in an uncommon way. When dealing with pulmonary masses, tissue remains the most important issue. We present the case of a 71-year-old woman with a mass of more than 10 cm in the left lung. Pulmonary CT scan and PET scan confirmed this with also revealing mediastinal, thoracic and paravertebral invasion, without extrathoracic metastatic lesions. Bronchoscopic evaluation and ultrasound guided transbronchial needle aspiration could not yield a diagnosis. Because of rapid clinical deterioration, new imaging was performed, showing a cavitary lesion with air-fluid level in the tumor. Extensive microbiological work-up remained negative. To yield a pathological diagnosis, we performed a thoracotomy, revealing a polymorphic lymphoid infiltrate with scattered large atypical B-cells infected with Epstein-Barr virus, vasculitis and granulomatosis leading to a diagnosis of Lymphomatoid Granulomatosis. The patient received 6 cycles of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Methylprednisolone), 2 doses of Rituximab monotherapy, 4 doses of intrathecal Methotrexate and consolidation radiotherapy with a complete response. Lymphomatoid granulomatosis (LYG) is a rare pulmonary disease, which should be included in the differential diagnosis of 'a pulmonary mass'. This case emphasizes the need for tissue acquisition

Herpes zoster is associated with herpes simplex and other infections in under 60 year-olds

OBJECTIVES: We assessed the association between herpes zoster (HZ) and herpes simplex (HS) occurrence whilst controlling for risk factors of HZ. METHODS: Using a Belgian general practitioner network, a retrospective cohort study with 3736 HZ patients and 14,076 age-gender-practice matched controls was performed, covering over 1.5 million patient-years. Multiple logistic regression was used with HZ as outcome and several diagnoses (malignancy, depression, diabetes mellitus, auto-immune diseases, asthma, multiple sclerosis, HIV, fractures), medications (systemic corticosteroids, biologicals, vaccination), HS and other infections as variables. RESULTS: HS was significantly associated with HZ for all analysed time intervals (up to five years) post HZ (OR of 3.51 [2.09 5.88] 95%CI one year post HZ) and to a lesser extent for time ranges pre HZ. Registration of other infections was significantly associated with HZ in all time intervals pre and post HZ (OR up to 1.37). Malignancy up to five years pre HZ, depression up to one year pre or post HZ, fractures up to two years pre HZ, asthma, auto-immune diseases, and immunosuppressive medication one year pre or post HZ were also associated with HZ. CONCLUSIONS: HZ and HS occurrences are significantly associated and potentially share a common susceptibility beyond the known risk factors

Absence of BCL-2 expression identifies a subgroup of AML with distinct phenotypic, molecular, and clinical characteristics

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the rapid and uncontrolled clonal growth of myeloid lineage cells in the bone marrow. The advent of oral, selective inhibitors of the B-cell leukemia/lymphoma-2 (BCL-2) apoptosis pathway, such as venetoclax, will likely induce a paradigm shift in the treatment of AML. However, the high cost of this treatment and the risk of additive toxicity when used in combination with standard chemotherapy represent limitations to its use and underscore the need to identify which patients are most-and least-likely to benefit from incorporation of venetoclax into the treatment regimen. Bone marrow specimens from 93 newly diagnosed AML patients were collected in this study and evaluated for BCL-2 protein expression by immunohistochemistry. Using this low-cost, easily, and readily applicable analysis method, we found that 1 in 5 AML patients can be considered as BCL-2(-). In addition to a lower bone marrow blast percentage, this group exhibited a favorable molecular profile characterized by lower WT1 expression and underrepresentation of FLT3 mutations. As compared to their BCL-2(+) counterparts, the absence of BCL-2 expression was associated with a favorable response to standard chemotherapy and overall survival, thus potentially precluding the necessity for venetoclax add-on