Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group.

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

The effect of body position on intraocular and CSF pressures in the lateral ventricle, and in cortical and lumbar subarachnoid spaces in cats.

BACKGROUND: Correlation between cerebrospinal fluid (CSF) and intraocular pressure (IOP) is still unclear. We compared CSF pressure from different parts of the CSF system and IOP measured by the same invasive technique in a new experimental model in cats during changes of body position. METHODS: Pressure changes were recorded on anesthetized cats (n = 7) in the lateral ventricle (LV), in the cortical (CSS) and lumbar (LSS) subarachnoid spaces, and in the anterior ocular chamber. Animals and measuring instruments were both fixed on a board at an adequate hydrostatic level. RESULTS: In a horizontal position, IOP (18.5 ± 0.6 cm H(2)O) and CSF pressures (LV = 17.4 ± 0.9; CSS = 17.2 ± 0.7; LSS = 17.8 ± 1.2 cm H(2)O) were similar. In a vertical position, pressure in the LSS increased (33.5 ± 2.3 cm H(2)O), pressures inside the cranial cavity dropped (LV = -4.1 ± 0.9 cm H(2)O; CSS = -4.8 ± 0.5 cm H(2)O), while IOP slightly decreased (14.3 ± 0.1 cm H(2)O). CONCLUSION: Change in body position from horizontal to upright causes drastic changes in CSF pressure and relatively small changes in IOP, which indicates that the IOP does not reflect CSF pressure. In an upright position, CSF pressures were equal at the same hydrostatic level in LV and CSS, which suggests that CSF pressure inside the cranium depends on its anatomical and biophysical features, and not on CSF secretion and absorption.

Septic arthritis due to Streptococcus sanguis.

Septic arthritis may represent a direct invasion of joint space by various microorganisms, including bacteria, viruses and fungi. Although any infectious agent may cause bacterial arthritis, bacterial pathogens are the most significant because of their rapidly destructive nature. We present a case of septic arthritis in a 56-year old male patient due to Streptococcus viridans which is member of the viridans group streptococci. Patient was admitted to Our Hospital presented as fever of unknown origin, losing more than 30 kg of body weight during couple of months, and anemia of chronic disease as paraneoplastic process. He had long history of arterial hypertension and stroke. There was swelling and pain of the right sternoclavicular joint and precordial systolic murmur in physical status. A large diagnostic panel has been made, computerized tomography (CT) of right sternoclavicular joint showed widening of periarticular soft tissue and loss of clavicular corticalis. Cytologic analysis of synovial fluid showed more than 90% of polymorphonuclear leukocytes. There were no crystals on microscopic examination and Gram stain of fluid was negative. Blood cultures were positive for S. sanguis and there was a consideration about possible periodontal disease. Stomatologic examination verified periapical ostitis and extraction of potential cause of infection has been done. Therapy with benzilpenicilline was followed by the gradual improvement of clinical and laboratory parameters. Although viridans group streptococci and Streptococcus sanguis in particular are rare causes of septic arthritis in native joints, they should be considered in the differential diagnosis of periodontal disease.

T-lymphoblastic lymphoma with an unusual t(8;14)(q24;q11)--case report.

Cytogenetic abnormalities seen at presentation of acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/ LBL) are associated with distinct clinical and hematologic disease entities. T-ALL/LBL are morphologically indistinguishable from those of B-ALL/LBL. An abnormal kariotype is found in 50-70% of cases of T-ALL/LBL. We present a 35-year old male patient with T-ALL/LBL and t(8;14)(q24;q11.2). Our patient presented with B-symptoms, bulky mediastinal disease and CNS infiltration. Bone marrow was morphologically normal and cytogenetically without clonal aberrations. Cytological findings of the supraclavicular lymph node showed numerous CD3 positive (100%) and CD2 positive (88%) lymphoblasts, negative for CD34 and CD10. Flow cytometry of lymph node revealed T cell phenotype of immature cells: CD45+CD2+CD5+CD7+CD4+CD8+CD3cyt +CD3TdT+CD10-CD34-HLAD/DR-. Cytogenetic analysis of lymph node showed translocation t(1;4)(p32;p12), t(8;14)(q24;q11.2). Southern blot analysis of extracted DNA from the supraclavicular lymph node demonstrated clonal rearrangement of the T cell antigen receptor (TCR/J) gene (region Vb+Jb2). Based on these findings, diagnosis of T lymphoblastic non Hodgkin lymphoma was established. Cerebrospinal fluid analysis showed CNS infiltration with 49% lymphoblasts positive for CD4 and CD8. The disease progressed rapidly with poor response to therapy. T-ALL/LBL with an unusual t(8;14)(q24;q11.2) is a very rare hematologic disorder with rapid disease progression and poor response to conventional therapy because of frequent central nervous system involvement and early relapses.

Lenalidomide induced good clinical response in a patient with multiple relapsed and refractory Hodgkin's lymphoma.

BACKGROUND: A 24-year-old female patient was diagnosed with classic Hodgkin's lymphoma in clinical stage II, and combination chemotherapy followed by radiotherapy was initiated. During the following 5 years, the disease progressed despite several standard therapeutic approaches, including autologous and allogeneic stem cell transplantation. METHODS: Lenalidomide (25 mg daily) treatment was then initiated in a continuous dosing schedule. Positron emission tomography scans were performed before and during lenalidomide treatment. Hematologic and laboratory values, as well as physical condition were also assessed before and during lenalidomide treatment. RESULTS: Four months after continuous lenalidomide treatment, tumor load was significantly reduced, B symptoms had resolved, and the patient's physical condition had improved, allowing her to resume normal daily-living activities. Evaluations after 15 months of lenalidomide treatment indicated limited disease progression. Nevertheless, the patient was feeling well and maintaining a normal active life. Treatment was well tolerated, allowing the patient to remain on continuous dosing, which has now been maintained for 18 months. CONCLUSION: Daily, long-term lenalidomide treatment provided clinical benefit and was well tolerated in a patient with relapsed, advanced classic Hodgkin's lymphoma.