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A significant percentage of B-cell lymphomas are characterized by bone marrow involvement (BMI) at diagnosis. In most cases, there is a concordance between the type of lymphoma present in the lymph node and the lymphoma present in the bone marrow. Herein, we presented a sixty-seven years old female patient, who was diagnosed with High-Grade B-cell Lymphoma (HGBL) in the bone marrow, while simultaneously, in the peripheral lymph node, the presence of Follicular Lymphoma (FL) was noted. The patient was presented to the hospital with spontaneous tumor lysis syndrome, a finding compatible with the aggressive course of the HGBL. To our knowledge, this is the first case of the co-existence of HGBL in the bone marrow and FL in a lymph node, which might be attributed to merely a coincidence or to the transformation of the cells in the preferable milieu of the bone marrow.

The present cross-sectional study consists of a comprehensive analysis of epidemiological, laboratory, and clinical characteristics of COVID-19 patients in relation to their immunogenetic profiles. We studied 125 COVID-19 patients comprising different stages of disease severity; non-hospitalized (mild n = 69) and hospitalized (n = 56). Analysis of disease characteristics revealed no major differences between males and females of each group of patients while hospitalized patients were older and presented with comorbidities. A positive allele association was observed for HLA-DRB1*01 in total COVID-19 patients versus healthy controls. Subgrouping of COVID-19 patients in mild and hospitalized further identified a statistically significant increase in HLA-DRB1*01 in mild COVID-19 patients versus controls. The frequency of A*11, A*23, and DRB1*09 alleles was higher, while the frequency of C*12 was lower, in hospitalized patients versus healthy controls albeit with uncorrected statistical significance. The identification of specific allele associations may provide useful future markers for disease susceptibility in order to allow successful clinical management of COVID-19 patients.

Background: Multicentric Castleman Disease (MCD) presents with enlarged lymph nodes in multiple regions and systemic inflammatory symptoms, due to the dysregulation of cytokines, most commonly interleukin-6 (IL-6). Human herpes virus-8 (HHV-8) is strongly related to MCD (HHV-8-associated MCD) and is being implicated in cytokine dysregulation in patients, the majority of whom are HIV positive or immunosuppressed. Preferred treatment of HHV-8- associated MCD depends on the presence or not of concurrent Kaposi sarcoma and on whether the patient has life-threatening organ failure or poor performance status thought to be related to HHV- 8-associated MCD. Case Presentation: Herein, we describe a female patient with HHV-8 positive, HIV negative MCD, who responded well to the administration of rituximab once weekly for four weeks alone for three cycles. Conclusion: HHV-8 positive, HIV negative MCD treatment modalities are only anecdotal due to the rarity of this form of MCD. Administration of rituximab alone seems to be beneficial among patients with good performance status and the absence of life-threatening organ failure in cases of HHV-8 positive, HIV negative MCD.

Feasibility of haploidentical stem cell transplantation (haploSCT) is enhanced by use of post-transplant cyclophosphamide (PTCY). Despite preservation of non-alloreactive T cells, delayed reconstitution of cellular immunity and viral reactivation may compromise the outcome of T cell replete haploSCT. The study included 47 patients, aged 19-70 (median, 53) years, who underwent haploSCT with PTCY for myeloid (n=35) or lymphoid (n=12) malignancies. Myeloablative conditioning was mainly utilized (n=36). Graft source was peripheral blood (n=29) or bone marrow (n=18). Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood in cases with hemorrhagic cystitis (HC). Preemptive therapy was the principal modality for CMV infection in all but 1 patient who received letermovir prophylaxis. Reconstitution of cellular immunity was assessed by flow cytometry. With a median follow-up of 30 months, cumulative incidences (CIN) of relapse and non-relapse mortality were 13.4% (95% CI, 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free and overall survival were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34/45 patients at risk. Recurrent CMV infection occurred in 17/34 with median 1.5 (range, 1-6) episodes per patient. Median duration of anti-CMV therapy was 27 (range, 14-199) days. CMV disease was documented in 2 patients. CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 1 year, and preemptive therapy with rituximab was required in 2 patients. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%). CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy was required in 5/13 and nephrostomy in 1/13 patients. Reconstitution of T cell immunity was considerably delayed, with median CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was associated with the recovery of CD4+ cells at 3 months (Figure, median CD4+ count of 191/uL versus 62/uL in patients with 1 or ³2 episodes of CMV reactivation, respectively; p=0.009). Haplo-SCT with PTCY is associated with substantial rates of viral reactivation resulting in the need for prolonged antiviral therapy and considerable morbidity as well. Strategies to prevent viral infection are strongly warranted. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution.

Lymphoblastic lymphoma, seen primarily in children or young adults, is a type of non-Hodgkin lymphoma that originates from B or T lymphocyte precursors and rarely occurs in the oral cavity. A case of systemic precursor T-cell lymphoblastic lymphoma mimicking periodontitis of a lower second molar in a 20-year-old adult is currently presented. The case was initially misdiagnosed as periodontal disease and treated with tooth extraction by a dentist. Re-evaluation of the patient due to worsening of symptoms lead to cone beam computed tomography scanning that thoroughly revealed an extended osteolytic lesion of the right mandible. Afterward, a biopsy was performed, thus reaching the diagnosis of precursor T-cell lymphoblastic lymphoma. This report discusses differences in epidemiology of T-cell and B-cell lymphoblastic lymphomas, as well as their various intraoral manifestations that are mimicking a large family of oral pathology. It also focuses on conventional imaging findings that imply malignancy, which are often neglected during routine radiology interpretation.

Introduction: The preferred method for haploidentical stem cell transplantation (haploSCT) is currently the use of post-transplantation cyclophosphamide (PTCY) since it obviates the need for depletion of T lymphocytes, which is associated with profound immunosuppression. Despite preservation of non-alloreactive donor T cells, reconstitution of pathogen-specific immunity may be delayed even after T cell replete haploSCT. The incidence and clinical sequelae of viral reactivation may thus compromise the outcomes of the procedure. Patients and Methods: The study included 47 patients, who underwent haploSCT with PTCY from 12/2013 until 05/2019 and achieved stable donor engraftment. Median age at transplant was 53 years (range, 19-70). The indications for transplant were acute myeloid (n=19) or lymphoblastic (n=10) leukemia, myelodysplastic syndrome (n=10), myelofibrosis (n=4), chronic myeloid (n=2) or lymphocytic (n=1) leukemia, and T-prolymphocytic leukemia (n=1). Myeloablative conditioning was mainly utilized (n=36), with the exception of certain patients who received reduced-intensity (n=10) or non-myeloablative (n=1) regimens. The graft source was peripheral blood in 29 and bone marrow in 18 cases. Tacrolimus in combination with mycophenolate mofetil was administered for prevention of graft-versus-host disease. Recipient/donor cytomegalovirus (CMV) serostatus was -/- (n=2), -/+ (n= 5), +/- (n=11), or +/+ (n=29). CMV, Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months post haploSCT. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood specimens in cases with symptoms suggestive of hemorrhagic cystitis (HC). Prophylaxis with letermovir was available in 1 patient only, and preemptive antiviral therapy was the principal modality for the management of CMV infection. Cellular immunity reconstitution was assessed by flow cytometry at 3, 6, and 12 months after transplant. Results: With a median follow-up time of 30 months (range, 2-64), the cumulative incidences (CIN) of relapse and non-relapse mortality (NRM) were 13.4% (95% confidence interval [CI], 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free (DFS) and overall survival (OS) were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. The CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34 out of 45 patients who were at risk, whereas recurrent CMV reactivation was observed in 17 patients with a median number of 1.5 episodes (range, 1-6) per patient. The median total duration of antiviral therapy for CMV infection was 27 days (range, 14-199). CMV disease (pneumonia) was documented in 2 patients. The CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 12 months. No case of EBV-related post-transplant lymphoproliferative disorder was observed, however preemptive therapy with rituximab was required in 2 patients with rapidly increasing EBV viral load. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%), but only one required therapy with foscarnet due to high viral load (>10,000 copies/ml). The CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy for bladder hemostasis was required in 5/13 and nephrostomy in 1/11 patients with HC. Reconstitution of helper T cell immunity was considerably delayed, with median absolute CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was significantly associated with the recovery of CD4+ cells at 3 months (Figure; median CD4+ count of 191/uL versus 62/uL in patients with 1 and 2 or more episodes of CMV reactivation, respectively; p=0.009). Conclusions: HaploSCT with PTCY is associated with substantial rates of viral reactivation (especially CMV and BKV) resulting in the need for prolonged antiviral therapy and considerable morbidity. Strategies to prevent viral infection are strongly warranted in haploidentical stem cell transplantation. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution following haploSCT. Figure Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Gilead: Other: Travel Grant; Aenorasis: Other: Travel Grant; Takeda: Other: Travel Grant; Pfizer: Other: Travel Grant; Innovis: Other: Travel Grant.

BACKGROUND - AIM Ruxolitinib can be effectively used for the treatment of splenomegaly or constitutional symptoms in patients with myelofibrosis. Its main side effect is myelosuppression which leads to dose modifications. Real-life data from the use of ruxolitinib in every-day practice were analysed to assess efficacy, safety, dose modifications or reasons for treatment discontinuation. PATIENTS - METHODS A retrospective observational study was conducted in patients with primary or secondary myelofibrosis, treated in 13 sites. Statistical analysis was done with non-parametric tests using SPSSv17 software. A total of 116 patients, diagnosed between 1993 and 2016 were included in the analysis. The male:female ratio was 2:1, median age at diagnosis was 63 years (range 27 to 82) and median duration of ruxolitinib therapy was 15.3 months. The study expands over 664.2 patient-years of observation, including 176.7 patient-years while on ruxolitinib. RESULTS The diagnosis, revisited according to the WHO 2008 criteria, was primary myelofibrosis in 56%, post-essential thrombocythemia myelofibrosis in 22% and post-polycythemia vera myelofibrosis in 22% of patients. At the beginning of ruxolitinib treatment, the international prognostic scoring system (IPSS) risk category was low (6.2%), intermediate-1 (26.5%), intermediate-2 (39.8%), high (23%). Constitutional symptoms were present in 48% of patients at diagnosis and in 73% of them at the onset of ruxolitinib therapy. Median spleen size was 5cm (centimeters) below costal margin at diagnosis and 12cm at onset of ruxolitinib. Ruxolitinib starting dose was 5mg (16%), 10mg (18%), 15mg (31%), 20mg (35%) twice daily (BID), while the final dose was Ruxolitinib was permanently discontinued in 29% of patients, due to progressive disease in 6.4%, transformation to acute leukemia in 2.7% and death in 8.2% of patients. Side effects (including anemia, thrombocytopenia, investigator decision, patient preference) was the reason for treatment discontinuation in 5.5% and lack of response in 2.7% of patients. Efficacy (reduction in constitutional symptoms and spleen size) and hematological toxicity (values of platelets, white blood cell counts, hemoglobin) of ruxolitinib was assessed after 1, 6 and 12 months of treatment (table 1). Thrombocytopenia (PLT Constitutional symptoms after 1 month were significantly less frequent with increased doses of ruxolitinib, whereas there was no statistically significant difference among the various doses at 6 and 12 months of treatment. Platelet counts were significantly lower in patients taking 5mg BID at 6 months of treatment (p=0.02), and they also tended to be lower in 1 and 12 months (p=0.07, p=0.08 respectively). White blood cells and hemoglobin values did not differ significantly among the various doses of ruxolitinib in either time point. Table 1. Results at 1, 6, 12 months of treatment, according to different doses. CONCLUSIONS Ruxolitinib can effectively improve splenomegaly and alleviate constitutional symptoms in patients with myelofibrosis. The symptoms are relieved slower with the low dosage, whereas the main side effect is thrombocytopenia. It can however be maintained within safety limits (grade < 3), with dose modifications without hampering efficacy. Table Table. Disclosures No relevant conflicts of interest to declare.