16 research outputs found

    Treatment Sequencing and Outcome of Chronic Lymphocytic Leukemia Patients Treated at Fondazione Policlinico Universitario Agostino Gemelli IRCCS: A Thirty-Year Single-Center Experience

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    Background: This monocentric retrospective study describes the treatment patterns and outcomes of chronic lymphocytic leukemia (CLL) patients. Methods: Adult CLL patients treated between 1992 and 2022 were included. The time to next treatment (TTNT) was defined as the time from the treatment’s start to the start of a subsequent therapy or death. The time to next treatment failure or death (TTNTF) was defined as the time from treatment discontinuation to the discontinuation of a subsequent therapy or death. Results: Of 637 registered patients, 318 (49.9%) received treatment. We evaluated 157 cBTKi-exposed, 34 BCL2i-exposed cBTKi-naïve, and 26 double-exposed patients. The five-year TTNT values in the cBTKi-exposed patients were 80% (median NR), 40% (median 40 months), and 21% (median 24 months) months in the first line (1L), second line (2L), and beyond the second line (>2L), respectively (p 2L, respectively (p = 0.185). The median TTNTF was 9 months (range 1–87) after cBTKi and 17 months (range 8–49) after both a cBTKi and BCL2i. Conclusions: This study suggests that, in CLL patients, the earlier we used targeted therapies, the better was the outcome obtained. Nonetheless, the poor outcomes in the advanced lines of therapy highlight the need for more effective treatments

    New and old monoclonal antibodies for the treatment of chronic lymphocytic leukemia

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    Over the last few years, several new agents have been under evaluation in preclinical studies and clinical trials, showing promise in treating chronic lymphocytic leukemia (CLL). Among these agents, monoclonal antibodies (mAbs) such as rituximab and alemtuzumab have changed the natural course of the disease. Nowadays there are several new promising monoclonal antibodies under investigation against the CD20, CD23, CD37 and CD40 molecules. Application of newer monoclonal antibodies represents an area of ongoing clinical research in CLL

    Regulatory T-cell number is increased in chronic lymphocytic leukemia patients and correlates with progressive disease

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    Regulatory T-cells (Treg) actively maintain immunological self-tolerance and play a significant role in the progression of cancer. Treg cell numbers have been evaluated in 80 patients with previously untreated chronic lymphocytic leukemia (CLL) and in 40 normal healthy volunteers. Treg cells are higher in CLL patients than in controls and correlate with disease status (more advanced clinical stage, peripheral blood B-cell lymphocytosis, absolute CD38+ B-cell number, and more elevated LDH levels). No correlation was found with ZAP-70 expression, IgVH mutational status and cytogenetic abnormalities. This data shows that Treg cell number is abnormal in CLL patients

    Comparison between oral and intravenous fludarabine plus cyclophosphamide regime as front-line therapy in patients affected by chronic lymphocytic leukaemia: influence of biological parameters on the clinical outcome

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    The fludarabine plus cyclophosphamide (FC) regimen was reported to be superior to chlorambucil or fludarabine alone in terms of complete response (CR), overall response (OR) and progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukaemia (CLL). In the present study, we compared the efficacy and toxicity of FC administered through oral and intravenous route in 65 untreated patients affected by advanced CLL. No statistical differences were noticed between the two routes of administration in terms of OR, PFS, time to re-treatment (TTR) and overall survival (OS) of analysed patients. We also assessed the influence on the clinical outcome of the mutation status of the immunoglobulin variable region heavy chain (IgVH) gene, of the cytogenetic abnormalities and of the expression of ZAP70 and CD38 in patients' primary samples. Among the 58 evaluable patients, 31 (53%) achieved a CR and 18 (31%) a partial response. The median PFS was 35 months, median TTR was 42 months and median OS was not reached after 45 months (range, 1-161). A significantly lower OR rate was noticed in patients with high-risk cytogenetic abnormalities (del 17p, del 11q). In this study, high-risk cytogenetic abnormalities and unmutated IgVH genes were independent predictors of TTR. These results underline the importance of biological stratifications in front-line treatment of CLL patients. We confirm that FC is an effective regimen with mild toxicities; it could be recommended for patients with low-risk biological parameters who represent, in our experience, about 30% of the total

    Intralesional administration of rituximab for treatment of CD20 positive orbital lymphoma: safety and efficacy evaluation

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    B-cell lymphomas constitute the most frequent malignant neoplasm of the ocular adnexal, often presenting with localized disease. Five patients with primary localized CD20 positive B cell non Hodgkin ocular adnexal lymphomas received intralesional rituximab at the dose of 5mg once a week for one month, followed by 10mg weekly in case of incomplete response. Four of five patients obtained regression of symptoms and 2 of them showed complete response. No patients experienced side effects besides pain on the site of the injection. Local treatment with Rituximab for OAL is a safe and useful first-line therapeutic option

    Low-dose valganciclovir as preemptive therapy for cytomegalovirus infection occurring in allogeneic stem cell transplant recipients

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    Few data are available to date on the dose of oral valganciclovir as cytomegalovirus (CMV) preemptive therapy in stem cell transplantation patients. This study aimed to evaluate the efficacy and safety of low-dose valganciclovir (900 mg/day) as preemptive treatment in allotransplanted recipients. Valganciclovir was used in 34 patients who underwent allogeneic stem cell transplantation for hematological malignancies at the dose of 900 mg oral administration/day (12 patients, group 1) or 1,800 mg oral administration/day (22 patients, group 2). Thirty-two out of 34 patients (94%) obtained negativization of polymerase chain reaction for CMV at a median of 12.5 days from the beginning of valganciclovir administration (10/12 patients of group 1, 22/22 patients of group 2). We conclude that oral administration of valganciclovir can induce clearance of CMV viral load in about 2 weeks; moreover, lower-dose oral valganciclovir (900 mg/day) has a comparable efficacy to the proposed standard dose (1,800 mg/day)

    Light chain deposition in peripheral nerve as a cause of mononeuritis multiplex in Waldenstr\uf6m's macroglobulinaemia.

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    Waldenstr\uf6m's macroglobulinaemia is a form of monoclonal IgM gammopathy associated with a rare B-cell lympho-plasmacytic lymphoma, characterized by the involvement of bone marrow, lymph nodes and spleen. Neurological complications involving peripheral nerves are common and different pathogenic mechanisms have been reported. We describe a patient with severe multineuropathy associated with Waldenstr\uf6m's macroglobulinaemia. Nerve biopsy revealed copious light chain deposition which subverted the normal architecture of the endoneurium and epineurium resulting in massive fascicular hyalinosis and epineural arteries disruption, respectively. This report confirms that massive immunoglobulin deposition is one of the several mechanisms of nerve damage in IgM-related neuropathy. Since their recognition has important therapeutical consequences, nerve biopsy is an essential diagnostic tool in patients with an unusual clinical presentation of IgM-related neuropathies. Copyright \ua9 2010 Elsevier B.V. All rights reserved


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    <span style="mso-ansi-language: EN-US;" lang="EN-US"><span style="font-size: small;"><span style="font-family: Times New Roman;"><p>Even if Chronic lymphocytic leukemia (CLL) often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT) CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.</p><p>Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM) rates of 38-50%:</p><p>A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT) has been the introduction of non-myeloablative or reduced intensity conditioning (RIC) regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL) activity.</p><p>The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD) affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.</p><p>Sensitive minimal residual disease (MRD) quantification has strong prognostic impact after transplant. <strong></strong></p></span></span></span><p> </p&gt

    Neurologic improvement after peripheral blood stem cell transplantation in poems

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    We read with interest the recent article by Kuwabara et al.1 describing the clinical and electrophysiologic findings in 9 patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome and treated with autologous peripheral blood stem cell transplantation (auto-PBSCT). From May 2003 until September 2006, we treated 4 patients with POEMS syndrome with chemotherapy and auto-PBSCT.2 There were 3 men and 1 woman with a median age of 53 years (range 44\u201362). Three patients had severe and rapidly progressive sensory\u2013 motor peripheral neuropathy with predominant involvement of the lower limbs leading to inability to walk, reduced muscle strength of the upper limbs, absent deep tendon reflexes, and distal sensory impairment