From Istituto di Ematologia, Università Cattolica S. Cuore, Rome, Italy (GP, LP, MTV); Department of Hematology, Hadassah University Hospital, Jerusalem, Israel (DB-Y)
Correspondence: Giuseppe Leone, ...Istituto di Ematologia, Universita Cattolica S. Cuore, L. go A. Gemelli, 1, 00168 Rome, Italy. E-mail: gleone{at}rm.unicatt.it
Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is an increasingly recognized treatment complication in patients treated with radiotherapy or chemotherapy for previous hematologic malignancies or solid tumors. Distinct clinical entities have been described according to the primary treatment, corresponding to defined genetic lesions. Chromosome 7 and/or 5 losses or deletions are typical of alkylating agent-induced AML, while development of t-AML with balanced translocations involving chromosome bands 11q23 and 21q22 has been related to previous therapy with drugs targeting DNA-topoisomerase II. In addition, antimetabolites, and in particular the immunosuppressant azathioprine, have been shown to induce defective DNA-mismatch repair. This could promote survival of misrepaired cells giving rise to the leukemic clone. Individual predisposing factors, including polymorphisms in detoxification and DNA repair enzymes have been identified. Their combination may significantly increase the risk of t-MDS/AML. Among patients with hematologic malignancies, long-term survivors of Hodgkins lymphoma are exposed to an increased risk of t-MDS/AML, particularly when receiving MOPP-based, and escalated BEACOPP regimens, and when alkylators are combined with radiotherapy. Patients with Hodgkins and non-Hodgkins lymphoma are at highest risk when total body irradiation followed by autologous stem cell transplantation is used as rescue or consolidation therapy. The addition of granulocyte-colony-stimulating factor and radiotherapy plays a significant role in t-AML following treatment of children with acute lymphoblastic leukemia. In non-hematologic malignancies, treatment for breast cancer and germ-cell tumors has been associated with a 1–5% lifetime risk of both lymphoid as well as myeloid leukemia. In all cases the risk of t-MDS/AML drops sharply by 10 years after treatment.
Key words: susceptibility, therapy-related, AML, MDS.
The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by ...a heterogeneous clinical behavior.
We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data.
We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis.
Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.
The aim of this study was to evaluate prognostic factors, treatments and outcome of invasive aspergillosis in patients with acute myeloid leukemia based on data collected in a registry.
The registry, ...which was activated in 2004 and closed in 2007, collected data on patients with acute myeloid leukemia, admitted to 21 hematologic divisions in tertiary care centers or university hospitals in Italy, who developed proven or probable invasive aspergillosis.
One hundred and forty cases of invasive aspergillosis were collected, with most cases occurring during the period of post-induction aplasia, the highest risk phase in acute myeloid leukemia. The mortality rate attributable to invasive aspergillosis was 27%, confirming previous reports of a downward trend in this rate. Univariate and multivariate analyses revealed that the stage of acute myeloid leukemia and the duration of, and recovery from, neutropenia were independent prognostic factors. We analyzed outcomes after treatment with the three most frequently used drugs (liposomal amphotericin B, caspofungin, voriconazole). No differences emerged in survival at day 120 or in the overall response rate which was 71%, ranging from 61% with caspofungin to 84% with voriconazole.
Our series confirms the downward trend in mortality rates reported in previous series, with all new drugs providing similar survival and response rates. Recovery from neutropenia and disease stage are crucial prognostic factors. Efficacious antifungal drugs bridge the period of maximum risk due to poor hematologic and immunological reconstitution.
Highlights • We report the long-term results (2–4 years) with Flow Diverter Devices (FDD) from a single-center. • We recommend the use of FDD for large-neck aneurysms of the ICA syphon. • We think ...that more sophisticate FDD will reduce the incidence of technical adverse events.
Two novel cobalt diphenylphosphine complexes were synthesized by reacting cobalt(II) chloride with
-butyl(diphenyl)phosphine (P
BuPh
) and (
)-(+)neomenthyldiphenylphosphine (
)-NMDPP. The crystal ...structure of the former was determined by single-crystal X-ray diffraction studies. The two complexes were then used in combination with methylaluminoxane (MAO) for the polymerization of 1,3-butadiene: crystalline highly syndiotactic 1,2 poly(1,3-butadiene)s were obtained, with a 1,2 content and a syndiotactic index (percentage of syndiotactic triads
) up to 95% and 85%, respectively. The results obtained further support and confirm what was already observed in the polymerization of 1,3-butadiene with CoCl
(PRPh
)
-MAO (R = methyl, ethyl,
-propyl,
-propyl, and cyclohexyl): the nature of the phosphine ligand strongly affects the polymerization stereoselectivity, the polymer syndiotacticity increasing with increasing phosphine ligand steric hindrance.
The study of monoclonal serum proteins has led to the generation of two major theories: one proposing that individuals who had monoclonal proteins without any symptoms or evidence of end-organ damage ...have a benign condition; the other one suggesting that some individuals with asymptomatic monoclonal proteins may progress to multiple myeloma and thus are affected by a monoclonal gammopathy of undetermined significance (MGUS). Longitudinal studies of subjects with MGUS have supported the second theory. Subsequent studies have characterized and defined the existence of another precursor of multiple myeloma, smoldering multiple myeloma (SMM), intermediate between MGUS and multiple myeloma. Primary molecular events, chromosome translocations, and chromosome number alterations resulting in hyperploidy, required for multiple myeloma development, are already observed in myeloma precursors. MGUS and SMM are heterogeneous conditions with the presence of tumors with distinct pathogenic phenotypes and clinical outcomes. The identification of MGUS and SMM patients with a molecularly defined high risk of progression to MM offers the unique opportunity of early intervention with a therapeutic approach on a low tumor burden.
CAR-T Cell Therapy in Large B Cell Lymphoma Testa, Ugo; Leone, Giuseppe; Pelosi, Elvira ...
Mediterranean journal of hematology and infectious diseases,
2023, Letnik:
15, Številka:
1
Journal Article
Odprti dostop
Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin's lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with ...first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies. CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. CAR-T cell therapy has also been explored for treating high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement. Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T; therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials evaluate bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and reduce the number of refractory/relapsing patients.
CAR-T Cell Therapy for Follicular Lymphomas Testa, Ugo; D'Alò, Francesco; Pelosi, Elvira ...
Mediterranean Journal of Hematology and Infectious Diseases,
2024, Letnik:
16, Številka:
1
Journal Article
Odprti dostop
Follicular lymphoma is the second most diagnosed lymphoma in Western Europe. Significant advancements have considerably improved the survival of FL patients. However, 10-20% of these patients are ...refractory to standard treatments, and most of them will relapse. The treatment of follicular lymphoma patients with multiply relapsed or refractory disease represents an area of high-unmet needing new treatments with stronger efficacy. Chimeric antigen receptor (CAR)-T cell therapy targeting B-cell antigens, such as CD19 or CD20, is emerging as an efficacious treatment for R/R follicular lymphoma patients, particularly for those with early relapse and refractory to alkylating agents and to anti-CD20 monoclonal antibodies, resulting in a high rate of durable responses in a high proportion of patients.
This paper describes how Unmanned Aerial Vehicles (UAVs) may support the long-term monitoring of crack patterns in the context of architectural heritage preservation. In detail, this work includes: ...(i) a state of the art about the most used techniques in ancient structural monitoring; (ii) the description of the implemented methods, taking into account the requirements and constraints of the case study; (iii) the results of the experimentation carried out in the lab; and (iv) conclusions and future works.
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