Development of an Artificial-Intelligence-Based Tool for Automated Assessment of Cellularity in Bone Marrow Biopsies in Ph-Negative Myeloproliferative Neoplasms.

The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University "Luigi Vanvitelli" in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as .tiff images and .png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists' evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners.

Safety of Subcutaneous Daratumumab in Anti-CD38 Monoclonal Antibody-Naïve Patients with Plasma Cell Disorders: A Multicenter Real-Life Experience.

BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, is used for treatment of multiple myeloma (MM) and light chain amyloidosis at an intravenous dosage of 16 mg/kg or at a subcutaneous fixed dose of 1800 mg. However, the subcutaneous formulation has only recently been approved in Europe, and real-life data on its safety are still few. OBJECTIVE: In this multicenter retrospective real-life experience, we provided evidence for the safety of subcutaneous daratumumab in plasma cell disorders. PATIENTS AND METHODS: A total of 189 patients diagnosed with MM or light chain amyloidosis were included in this retrospective study, and all subjects were daratumumab-naïve. Primary endpoint was safety of subcutaneous daratumumab, especially for infusion-related reaction (IRR) incidence and severity. All patients received premedication with dexamethasone, paracetamol, and antihistamine, with montelukast usage in 85% of cases. RESULTS: Eight patients (4%) experienced IRRs, mainly of grade I-II, and other frequent toxicities were: hematological (thrombocytopenia, 4%; neutropenia, 5%; lymphopenia, 6%) and non-hematological (pneumonia, 4%; diarrhea, 2%; and cytomegalovirus reactivation, 0.5%). In our multicenter retrospective real-life experience, subcutaneous daratumumab was well-tolerated with an excellent safety profile with a very low (4%) IRR incidence, even in frailer MM patients with severe renal impairment or increased body weight. CONCLUSIONS: Subcutaneous daratumumab was safe in a real-life setting including patients with severe renal failure and advanced disease. However, further studies on larger and prospective cohorts are required to confirm our real-life observations.

How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas ALK+ Therapy: A Case Report.

BACKGROUND: The t (2; 5) chromosomal rearrangement of the ALK gene with nucleophosmin 1 gene (NPM1), resulting in an NPM1-ALK fusion, was first demonstrated in 1994 in anaplastic large cell lymphoma, (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and the monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. RESULTS: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK+, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of brentuximab, still pending allo-SCT after two failed donor selections. Facing a new therapeutic failure, we requested and obtained authorization from the Italian drug regulatory agency to administer 250 mg of crizotinib twice a day, a drug incomprehensibly not registered for ALCL ALK +. CONCLUSIONS: The response to crizotinib was optimal since no adverse event occurred, and CT-PET scans persisted negative; this drug has proved to be a valid bridge to allo-SCT.

Use of Rituximab in NHL Malt Type Pregnant in I° Trimester for Two Times.

Administration of rituximab, one of the basic drugs for the therapy of B-cell lymphoproliferative diseases, during pregnancy has been suspected to cause developmental fetal events, particularly if given during the first trimester of pregnancy. Therefore, use in pregnancy is not permitted. Howe ver, several cases of pregnant women being treated with rituximab are reported herein; an exception is often made in cases with grave illness. We describe an exceptional case of a woman with non-Hodgkin lymphoma of the mucosa-associated lymphoid tissue type where rituximab was given as a single agent without interruption during two consecutive pregnancies. This case can certainly supply important indications on the safety of rituximab.

Long-term follow-up study on the role of serum CA-125 as a prognostic factor in 221 newly diagnosed patients with Hodgkin's lymphoma.

The present study has explored the possible value of sCA-125 as a prognostic factor in Hodgkin's lymphoma (HL). From August 1992 to June 2005 sCA-125 was measured at presentation and at the end of the treatments in 221 newly diagnosed adult patients with HL. In this study 90/221 (41%) patients showed a value greater than the standard upper limit of 35 U/ml, and 79/90 (88%) with an abnormal sCA-125 were at an advanced stage of the disease. Patients with elevated sCA-125 showed a significant reduction in complete remission (CR) rate (76%vs. 98%; p < 0.0001). Failure of normalization of sCA-125 during the treatment revealed that CR had not been reached. Furthermore, no traces of the glycoprotein sCA-125 were found in a series of paraffin-embedded samples coming from 15 patients of this study. In addition, soluble CA-125 was not detected in supernatants coming from four different Hodgkin-derived cell lines. The long-term follow-up revealed that the group of patients with sCA-125 lower than 35 U/ml, at diagnosis, had an estimated 92% event free survival (EFS) rate and a 94% overall survival (OS) rate, while the group of patients with sCA-125 greater than 35 U/ml had only a 60% EFS rate (log-rank 33.43, p < 0.0001) and a 70% OS rate (log-rank 23.52, p < 0.0001). Extranodal disease, severe lymphocytopenia and age proved to be the only standard factors that could represent a poor chance to survive. At multivariate analysis, high sCA-125, E sites >1 and age were the only independent factors producing poor outcomes in terms of CR, EFS and OS. Therefore, we believe that sCA-125 is a simple, reliable and reproducible tool, which may improve existing prognostic systems.