Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia

Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial to investigate two hypotheses: i) higher doses of venetoclax are tolerable and more effective, and ii) azacitidine can be discontinued after deep remissions. Forty-two newly diagnosed AML patients were enrolled in the investigator-initiated High Dose Discontinuation Azacitidine+Venetoclax (HiDDAV) Study (clinicaltrials gov. Identifier: NCT03466294). Patients received one to three “induction” cycles of venetoclax 600 mg daily with azacitidine. Responders received MRD-positive or MRDnegative “maintenance” arms: azacitidine with 400 mg venetoclax or 400 mg venetoclax alone, respectively. The toxicity profile of HiDDAV was similar to 400 mg venetoclax. The overall response rate was 66.7%; the duration of response (DOR), event-free survival (EFS) and overall survival were 12.9, 7.8 and 9.8 months, respectively. The MRD negativity rate was 64.3% by flow cytometry and 25.0% when also measured by droplet digital polymerase chain recation. MRD-negative patients by flow cytometry had improved DOR and EFS; more stringent measures of MRD negativity were not associated with improved OS, DOR or EFS. Using MRD to guide azacitidine discontinuation did not lead to improved DOR, EFS or OS compared to patients who discontinued azacitidine without MRD guidance. Within the context of this study design, venetoclax doses >400 mg with azacitidine were well tolerated but not associated with discernible clinical improvement, and MRD may not assist in recommendations to discontinue azacitidine. Other strategies to optimize, and for some patients, de-intensify, venetoclax+azacitidine regimens are needed

High grade sarcoma presenting as multifocal recurrent seromas after inguinal hernia repair: A case report

In this report, we describe a 54-year-old male with cystic retroperitoneal sarcoma extending through the inguinal canal. Patient initially underwent inguinal hernia repair with mesh placement for suspected cord lipoma, after which he developed recurrent loculated retroperitoneal fluid collections refractory to multiple attempts at drain placement and laparotomy. Twenty-nine months after initial surgery, patient was referred to our institution on suspicion of malignancy. Pathology of resections taken during subsequent laparotomy showed foci of malignant cells interspersed throughout reactive proliferations. Follow-up immunohistochemistry confirmed high-grade sarcoma, likely atypical liposarcoma, but was unable to definitively establish subtype. Despite en bloc resection and gemcitabine/docetaxel chemotherapy, local progression continued, and patient was enrolled in clinical trials of doxorubicin with dual immune checkpoint blockade. This case suggests that sarcoma should be considered as a differential diagnosis of retroperitoneal or inguinal mass unresponsive to treatment; and highlights the difficulty of subtyping and managing cystic retroperitoneal sarcoma

Autoreactive Antibodies Associated with Castleman Disease Triad

The Castleman triad has been described in a select few patients presenting with a retroperitoneal mass, mucocutaneous pemphigus vulgaris, and bronchiolitis obliterans. Here, we describe the Castleman triad in a 19-year-old male with unicentric hyaline vascular type Castleman disease (HV-CD). This patient presented with an array of positive antibodies, including anti-cyclic citrullinated peptide, anti-double-stranded DNA, and Sjogren’s IgG. Interestingly, the patient’s rheumatologic symptoms resolved after tumor resection, while his antibody profile remained relatively unchanged. HV-CD, with a triad presentation, was thought to be from a paraneoplastic syndrome secondary to an underlying lymphoproliferative disorder. The findings presented here identify multiple autoantibodies potentially contributing to this patient’s presentation with HV-CD

Evaluating bone biopsy quality by technique in an animal model

Rationale and Objectives: Powered bone biopsy technique is popular due to its ease of use. However, there is conflicting evidence regarding the diagnostic quality of the samples. The purpose of this study is to evaluate the diagnostic adequacy of different bone biopsy devices and techniques as it relates to the frequency of sample artifacts. Materials and Methods: Bone biopsy was performed on same-day processed lamb femora using the following techniques: manual, pulsed powered and full powered. Ten samples were collected using each method by a single musculoskeletal-trained radiologist and were reviewed by 3 blinded pathologists. Samples were compared across multiple categories: length, bone dust, thermal/crush artifact, cellular morphology, fragmentation, and diagnostic acceptability. Bayesian Multilevel Nonlinear Regression models were performed assessing the association between the techniques across the categories. Results: Statistical analysis revealed that the manual technique outperformed any powered technique across all categories: decreased thermal/crush artifact (P = 0.014), decreased bone dust (p<0.001), better cellular morphology (P = 0.005), less fragmentation (P < 0.0001) and better diagnostic acceptability (P < 0.0001). Conclusion: Manually obtained bone biopsy samples generally produce a more diagnostic sample as compared to powered techniques in an animal model. Given these results, manual bone biopsy methods should be encouraged after consideration for lesion composition, difficulty of access and the patient's overall condition