The role of pentraxin 3 and oxidative status in the prognosis of multiple myeloma.

Multiple myeloma (MM) is a bone marrow malignancy characterized by plasma cell proliferation. It was aimed to investigate pentraxin 3 (PTX3) levels, oxidative/antioxidative status, and their correlation in MM. In the study, four groups were established, including newly diagnosed MM (NDMM), MM in remission (Rem-MM), relapsed/refractory MM (RRMM) patients, and a healthy control group. PTX3 levels were measured using enzyme-linked immunosorbent assay, and the total antioxidant status (TAS) and total oxidant status (TOS) were assessed with an autoanalyzer. The oxidative stress index (OSI) was calculated using the formula: OSI (arbitrary unit) = TOS (µmol H2O2 Eq/L)/TAS (mmol Trolox Eq/L) × 100. The study involved comparing PTX3, TAS, TOS, and OSI levels among these four groups. PTX3 levels were significantly elevated in NDMM and RRMM groups compared to controls and the Rem-MM group (NDMM vs control; p < 0.001, NDMM vs Rem-MM; p < 0.001, RRMM vs control; p < 0.001, and RRMM vs Rem-MM; p = 0.006). TAS was higher in NDMM and RRMM groups versus controls (p = 0.009 and p < 0.001, respectively), and TOS was higher in rem-MM group versus NDMM and control groups (p < 0.001 and p = 0.016, respectively). OSI was higher in the Rem-MM group than in NDMM and RRMM groups (p < 0.001 and p = 0.009, respectively). Multivariate analysis confirmed associations between MM groups and PTX3 levels. Receiver operating characteristic analysis revealed high specificity (90%) and sensitivity (79%) for PTX3 in NDMM at a >0.56 ng/mL cut-off value. This study suggests that PTX3 levels may have diagnostic and prognostic potential in MM and its relationship with oxidative stress requires further exploration.

Differentiation Between Disseminated Carcinomatosis of the Bone Marrow From Urothelial Cancer and Intravascular Large B-cell Lymphoma: A Case Report.

This case report describes a rare case of intravascular large B-cell lymphoma (IVLBCL), initially presenting with nonspecific symptoms of fever and fatigue, and tentatively diagnosed as disseminated carcinomatosis of the bone marrow originating from urothelial cancer in an 80-year-old woman. The patient's journey began with symptoms treated as common ailments and progressed through multiple differential diagnoses, including giant cell arteritis, TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) syndrome, and disseminated carcinomatosis of the bone marrow originating from urothelial cancer due to the presence of systemic inflammation, anasarca, and elevated soluble interleukin 2 receptor levels, indicative of an intense immunological response. Despite initial treatments, her condition deteriorated, leading to further investigations that ultimately revealed the presence of malignant cells in the urine and bone marrow, confirming the diagnosis of IVLBCL. This case underscores the diagnostic challenges faced when elderly patients present with systemic inflammation and the critical need for thorough investigation beyond initial impressions. It highlights the importance of considering differentiation between disseminated carcinomatosis of the bone marrow and IVLBCL in the differential diagnosis of persistent inflammation, especially in cases where common causes have been excluded and the primary malignancy is not immediately apparent.

Evaluation of an open-source machine-learning tool to quantify bone marrow plasma cells.

AIMS: The objective of this study was to develop and validate an open-source digital pathology tool, QuPath, to automatically quantify CD138-positive bone marrow plasma cells (BMPCs). METHODS: We analysed CD138-scanned slides in QuPath. In the initial training phase, manual positive and negative cell counts were performed in representative areas of 10 bone marrow biopsies. Values from the manual counts were used to fine-tune parameters to detect BMPCs, using the positive cell detection and neural network (NN) classifier functions. In the testing phase, whole-slide images in an additional 40 cases were analysed. Output from the NN classifier was compared with two pathologist's estimates of BMPC percentage. RESULTS: The training set included manual counts ranging from 2403 to 17 287 cells per slide, with a median BMPC percentage of 13% (range: 3.1%-80.7%). In the testing phase, the quantification of plasma cells by image analysis correlated well with manual counting, particularly when restricted to BMPC percentages of <30% (Pearson's r=0.96, p<0.001). Concordance between the NN classifier and the pathologist whole-slide estimates was similarly good, with an intraclass correlation of 0.83 and a weighted kappa for the NN classifier of 0.80 with the first rater and 0.90 with the second rater. This was similar to the weighted kappa between the two human raters (0.81). CONCLUSIONS: This represents a validated digital pathology tool to assist in automatically and reliably counting BMPC percentage on CD138-stained slides with an acceptable error rate.

Diagnostic Accuracy of Quantitative Imaging Biomarkers in the Differentiation of Benign and Malignant Vertebral Lesions : Combination of Diffusion-Weighted and Proton Density Fat Fraction Spine MRI.

PURPOSE: To compare and combine the diagnostic performance of the apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) and proton density fat fraction (PDFF) derived from chemical-shift encoding (CSE)-based water-fat magnetic resonance imaging (MRI) for distinguishing benign and malignant vertebral bone marrow lesions (VBML). METHODS: A total of 55 consecutive patients with 53 benign (traumatic, inflammatory and primary) and 36 malignant (metastatic and hematologic) previously untreated VBMLs were prospectively enrolled in this IRB-approved study and underwent sagittal DWI (single-shot spin-echo echo-planar with multi-slice short TI inversion recovery fat suppression) and CSE-based MRI (gradient-echo 6­point modified Dixon) in addition to routine clinical spine MRI at 1.5 T or 3.0 T. Diagnostic reference standard was established according to histopathology or imaging follow-up. The ADC = ADC (0, 800) and PDFF = fat / (water + fat) were calculated voxel-wise and examined for differences between benign and malignant lesions. RESULTS: The ADC and PDFF values of malignant lesions were significantly lower compared to benign lesions (mean ADC 861â€¯× 10-6 mm2/s vs. 1323â€¯× 10-6 mm2/s, p < 0.001; mean PDFF 3.1% vs. 28.2%, p < 0.001). The areas under the curve (AUC) and diagnostic accuracies were 0.847 (p < 0.001) and 85.4% (cut-off at 1084.4â€¯× 10-6 mm2/s) for ADC and 0.940 (p < 0.001) and 89.9% for PDFF (cut-off at 7.8%), respectively. The combined use of ADC and PDFF improved the diagnostic accuracy to 96.6% (malignancy if ADC ≤ 1118.2â€¯× 10-6 mm2/s and PDFF ≤ 20.0%, otherwise benign). CONCLUSION: Quantitative evaluation of both ADC and PDFF was useful in differentiating benign VBMLs from malignancy. The combination of ADC and PDFF improved the diagnostic performance and yielded high diagnostic accuracy for the differentiation of benign and malignant VBMLs.

Access to Palliative Care Services and Clinical Outcomes of Patients With Solid Malignancy-Associated Myelophthisis in a Resource-Limited Setting.

BACKGROUND: Myelophthisis (MPT) has been associated with a dreadful prognosis. Patients' access to palliative care (PC) and factors influencing its clinical outcomes are poorly described. Our aim was to analyze the impact of patient- and disease-specific characteristics on survival of patients with MPT and describe their use of PC in a resource-limited setting. METHODS: Retrospective study including patients with solid tumor MPT, diagnosed between 1996 and 2018. RESULTS: Seventy patients (median 58 years) were included. 58% were synchronously diagnosed with MPT at time of primary tumor diagnosis. Most common oncologic diagnoses were prostate (25.7%), gastrointestinal (20%), and breast (18.6%) neoplasms. Median overall survival (OS) was 1.9 months. Primaries other than prostate, breast, and lung (HR 1.37, 95% CI 1.15 - 1.8; p = 0.02) and transfusion requirements (HR 2.8, 95% CI 1.01 - 7.9; p = 0.04) were independently associated with decreased OS. Administration of multiple systemic therapeutic interventions (HR 0.15, 95% CI 0.06 - 0.39; p = 0.01) was the sole factor improving OS. Assessment by PC was pursued in 51.4% of patients. The median number of consults per patient was two, with no difference in assessment rate or consult number across different primaries (P = 0.96). Four cases of palliative sedation were reported, all performed by the primary care team. CONCLUSION: MPT is highly heterogeneous and risk stratification to optimize the use of therapeutic interventions in unison with palliative interventions is needed to maximize efforts toward improving patient quality of life. There is an alarming need of PC services in the multidisciplinary management of patients within developing regions.

Large B-cell lymphoma presenting primarily in bone marrow is frequently associated with haemophagocytic lymphohistiocytosis and has distinct cytogenetic features.

The criteria for primary bone marrow large B-cell lymphoma (PBMLBCL) have not yet been clearly established. We aimed to investigate the clinicopathological features of PBMLBCLs (27 cases) and large B-cell lymphomas (LBCLs) with secondary marrow involvement (55 cases). PBMLBCL was defined as LBCLs presenting initially in bone marrow without lymphadenopathy, extramedullary tumour or localised bone tumour, and no evidence of transformation from low grade B-cell lymphoma. Compared with the patients in the secondary group, more patients in the primary group had haemophagocytic lymphohistiocytosis, cytogenetic aberrations, cytopenias, and atypical lymphocytes in peripheral blood. The most common chromosome abnormality in both groups was 6q deletion. The primary group had additional chromosome 10, 2, and 3 abnormalities. The acquired chromosome 10 aberration was associated with the risk of haemophagocytic lymphohistiocytosis. The 1-year survival rate was lower in the primary group than in the secondary group; however, the difference was not significant when the cases without chemotherapy plus rituximab were excluded. Moreover, multivariate analysis revealed that relatively high white blood cell count, not receiving chemotherapy plus rituximab, and cytogenetic aberrations were poor prognostic factors in the secondary group, but only not receiving chemotherapy plus rituximab was retained in the primary group. In conclusion, PBMLBCL is genetically and clinically distinct. Although patients with PBMLBCL generally have a poor outcome, the disease is treatable and some patients become long-term survivors.

[Pediatric myeloid neoplasms associated with eosinophilia and platelet-derived growth factor receptor beta gene rearrangement: a case report and literature review].

Objective: To investigate the clinical features and therapeutic strategies of childhood myeloid neoplasms associated with eosinophilia and platelet-derived growth factor receptor beta (PDGFRB) gene rearrangement. Methods: Clinical data of myeloid neoplasms associated with eosinophilia and t (1;5) (q21;q33) chromosomal translocation of PDGFRB gene rearrangement in a child hospitalized in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences on May 2015 was collected and analyzed. Using'eosinophilia child'and'PDGFRB'as keywords, the relevant reports in literature were searched from China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and Biomedical Literature Database (PubMed) until April 2017. Results: The patient was a boy, 19 months old, who began to get sick at six months after birth, with the main clinical manifestations of high fever, diarrhea, epistaxis and hepatosplenomegaly. Peripheral blood smear showed a significant elevation in white blood cells (127×10(9)/L) and eosinophils(20.32×10(9)/L). Bone marrow examination showed hyperplastic marrow, increased proportion of granulocytes, apparent visible eosinophils and decreased megakaryocytes. Chromosome karyotype detection revealed t (1; 5) (q21; q33) translocation. Fluorescence in situ hybridization (FISH) examination uncovered that PDGFRB gene rearrangement was positive. The final diagnosis was myeloid neoplasms with eosinophilia and PDGFRB gene rearrangement. After treatment with oral imatinib 100 mg, once a day for 2 months, complete hematologic remission, complete cytogenetic and molecular remission were all achieved. The relevant literature was reviewed, no Chinese cases had been reported, 6 reports in English literature have complete clinical data. Four cases had t (1; 5) translocation. Four pediatric patients treated with imatinib achieved complete remission. Conclusion: Myeloid neoplasms associated with eosinophilia and PDGFRB gene rearrangement is extremely rare in children. Imatinib treatment can make these patients quickly achieve complete hematologic remission, complete cytogenetic and molecular remission. Imatinib should be recommended as the first line treatment of these patients.

Circulating Levels of Urokinase-Type Plasminogen Activator Receptor and D-Dimer in Patients With Hematological Malignancies.

BACKGROUND: Patients with cancer exhibit changes in their hemostatic mechanisms. The D-dimer (D-D) is the most important subproduct of fibrinolysis, and urokinase plasminogen activator receptor (uPAR) is related to invasiveness and metastases, and is overexpressed in neoplastic cells. The objective of this study was to identify in patients with hematological neoplasia, the serum levels of uPAR and D-D, and to determine their effects on outcome. PATIENTS AND METHODS: A cross-sectional study was performed. Clinical and demographic data were obtained from the clinical chart. Determination of uPAR in serum (pg/L) was performed using an enzyme-linked immunosorbent assay, and D-D (µg/dL) using nephelometry. RESULTS: We included 42 patients (35 with lymphomas). Statistically significant differences were found in D-D (P < .001) and uPAR (P < .01) between patients and control participants. Response was an accumulated clinical outcome. We observed statistical differences between groups (P < .001). D-D was positive in 70% of cases. CONCLUSION: We found differences in D-D serum levels and soluble uPAR between control participants and patients with lymphoma. These results indicate that D-D serum levels and soluble uPAR should be considered biomarkers of response and survival in patients with lymphoma.

Blastic plasmacytoid dendritic cell neoplasm: skin and bone marrow infiltration of three cases and the review of the literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a distinct and rare neoplastic entity and was classified as a subgroup of acute myeloblastic leukemia by the WHO in 2008. The median survival of patients was 15.2 months in a large case series. Allogeneic or autologous bone marrow transplantation has been recommended by some reports because of the disease's poor prognosis. We present three patients who presented with both skin and bone marrow infiltration. A 57-year-old man, a 62-year-old woman, a 64-year-old man were admitted to our outpatient clinic because of skin lesions. All of the patient's had bone marrow infiltration with positivity of the CD4, CD56, and CD123 staining. Survival of the patient's were 42, 6 and 12 months, respectively. Two of the patients who presented as blastic form didn't respond to any chemotherapy. BPDCN is a difficult disease to diagnosis and manage. CD4, CD56, CD123, CD303, and T cell leukemia/lymphoma 1. Cutaneous lesions can present as isolated nodules, macules, and disseminated macules and nodules. Positivities are crucial to the diagnosis of the disease in histological examination. Bone marrow infiltration or disease relapse at presentation were related to poor prognosis. Complete immunocytochemical staining must be performed for all patients who have cutaneous lesions with or without blood count abnormalities. Bone marrow (allogeneic or autologous) transplantation should be considered at the first remission.

Rectal cancer with disseminated carcinomatosis of the bone marrow: report of a case.

We report a rare case of disseminated carcinomatosis of the bone marrow from rectal cancer with disseminated intravascular coagulation (DIC). A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. Histologic examination showed disseminated carcinomatosis of the bone marrow. The DIC was considered to be caused by disseminated carcinomatosis of the bone marrow from rectal cancer, and we immediately started treatment with anti-DIC therapy and anticancer chemotherapy with the modified FOLFOX6 regimen (mFOLFOX6). After some response to therapy, the patient's general condition deteriorated, and he died 128 days after admission. This is the first English report showing disseminated carcinomatosis of the bone marrow from colorectal cancer treated with mFOLFOX6.

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center / Resultados do transplante alogênico de células-tronco em doentes com leucemia mieloide aguda com doença ativa: experiência de um único Centro Oncológico Europeu

Summary Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) representes a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. Results: The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months (95CI 3.266-12.734) and median PFS, 3 months (95CI 1.835-4.165). Conclusion: In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.

Resumo Introdução: o transplante alogênico de células-tronco hematopoiéticas (TCTH-alo) representa uma abordagem potencialmente curativa para pacientes com leucemia mieloide aguda (LMA) recorrente ou refratária. Nosso trabalho apresenta o resultado de pacientes com recaída ou doença refratária tratados com TCTH-alo. Método: coorte retrospectiva incluindo 61 pacientes de 1994 a 2013 com diagnóstico de recidiva/LMA refratária. Os desfechos de interesse foram mortalidade relacionada ao transplante (MRT), incidência da doença aguda e crônica do enxerto contra hospedeiro (DECH), incidência de recaídas, sobrevida livre de progressão (PFS - progression-free survival) e sobrevida global (SG). A significância estatística foi considerada para p<0,05. Resultados: a média de idade foi de 61 anos (variação de 1 a 65). A incidência cumulativa de 90 dias, 1 ano e 3 anos de MRT foram de 60%, 26,7% e 13,3%, respectivamente (p<0,001). A incidência de recaída foi de 21,7% em 1 ano, 13% em 3 anos e 8,7% em 5 anos. A SG mediana foi estimada em 8 meses (IC 95% 3,266-12,734) e a mediana de PFS, em 3 meses (IC 95% 1,835-4,165). Conclusão: em nossa coorte, MRT no primeiro ano após o transplante permanece considerável, mas TCTH-alo nesse cenário parece ser uma boa opção para pacientes com LMA ativa. No entanto, novas abordagens são necessárias para reduzir MRT e recaída nesse conjunto de pacientes.