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1.
Clin Case Rep ; 9(2): 978-982, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33598282

ABSTRACT

Management of systemic mastocytosis is an emerging challenge which requires a multidisciplinary diagnostic approach and personalized treatment strategy. Midostaurin can rapidly reduce the disease burden, also in cladribine refractory cases.

3.
Front Oncol ; 10: 506, 2020.
Article in English | MEDLINE | ID: mdl-32457824

ABSTRACT

Epstein-Barr virus (EBV) infection is correlated with several lymphoproliferative disorders, including Hodgkin disease, Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and post-transplant lymphoproliferative disorder (PTLD). The oncogenic EBV is present in 80% of PTLD. EBV infection influences immune response and has a causative role in the oncogenic transformation of lymphocytes. The development of PTLD is the consequence of an imbalance between immunosurveillance and immunosuppression. Different approaches have been proposed to treat this disorder, including suppression of the EBV viral load, reduction of immune suppression, and malignant clone destruction. In some cases, upfront chemotherapy offers better and durable clinical responses. In this work, we elucidate the clinicopathological and molecular-genetic characteristics of PTLD to clarify the biological differences of EBV(+) and EBV(-) PTLD. Gene expression profiling, next-generation sequencing, and microRNA profiles have recently provided many data that explore PTLD pathogenic mechanisms and identify potential therapeutic targets. This article aims to explore new insights into clinical behavior and pathogenesis of EBV(-)/(+) PTLD with the hope to support future therapeutic studies.

4.
PLoS One ; 14(5): e0216715, 2019.
Article in English | MEDLINE | ID: mdl-31071175

ABSTRACT

Invasive fungal infections (IFIs) are a leading cause of morbidity and attributable mortality in oncohematologic patients. Timely diagnosis is essential but challenging. Herein we retrospectively describe 221 cases of antifungal treatments (AFT) administered in a monocentric real-life cohort of hematological malignancies. Between January 2010 and July 2017, 196 oncohematologic patients were treated with AFT at our Hematology Department. Diagnosis of IFIs was carried out according to EORTC/MSG-2008 guidelines.The most represented disease was acute myeloid leukemia (104 patients). Median age was 61 years; at fever onset 177 (80%) patients had a neutrophil count<0.5x109/L. Twenty-nine (13%) patients were receiving antifungal prophylaxis (26 posaconazole, 2 fluconazole, 1 itraconazole). The incidence of AFT was 13%. Serum galactomannan antigen (GM) was positive in 20% of the tested cases, while 85% of the patients had a CT scan suggestive for IFI. Twenty-one percent of these cases had a GM positive. Sixty-five out of 196 patients (33%) showed positive culture results, in particular Candida spp. were identified in 45 isolates, while Aspergillus spp. in 16 cases. Fourteen patients presented multiple positivity. Twenty-two (10%) cases were classified as proven IFIs, 61 (28%) as probable and 81 (37%) as possible, but 57 (26%) cases could not be classified. Fifty-nine percent of the patients received single agent AFT, 37% sequential AFT, 8% a combination regimen. Liposomal-amphotericin-B was the most used AFT. IFIs attributable mortality was 20%. This epidemiologic survey underlined a persistent significant use of AFT and a high mortality rate of IFIs. We suggest that further powerful diagnostic approaches should be investigated to improve the diagnostic accuracy and potential therapeutic implication.


Subject(s)
Hematologic Neoplasms/complications , Invasive Fungal Infections/complications , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Candidiasis, Invasive/complications , Candidiasis, Invasive/drug therapy , Candidiasis, Invasive/epidemiology , Female , Humans , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/epidemiology , Invasive Pulmonary Aspergillosis/complications , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/epidemiology , Leukemia, Myeloid, Acute/complications , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
5.
Oncologist ; 24(9): 1246-1252, 2019 09.
Article in English | MEDLINE | ID: mdl-30940746

ABSTRACT

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype, and approximately 50% of the patients are >60 years of age. Patients with relapsed/refractory (rr) disease have a poor prognosis with currently available treatments. Lenalidomide is available in Italy for patients with rrDLBCL based on a local disposition of the Italian Drug Agency. SUBJECTS, MATERIALS, AND METHODS: An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on effectiveness and safety of lenalidomide use for rrDLBCL in real practice. RESULTS: One hundred fifty-three patients received lenalidomide for 21/28 days with a median of four cycles. At the end of therapy, there were 36 complete responses (23.5%) and 9 partial responses with an overall response rate (ORR) of 29.4%. In the elderly (>65 years) subset, the ORR was 33.6%. With a median follow-up of 36 months, median overall survival was reached at 12 months and median disease-free survival was not reached at 62 months. At the latest available follow-up, 29 patients are still in response out of therapy. Median progression-free survivals differ significantly according to age (2.5 months vs. 9.5 in the younger vs. elderly group, respectively) and to disease status at the latest previous therapy (15 months for relapsed patients vs. 3.5 for refractory subjects). Toxicities were manageable, even if 30 of them led to an early drug discontinuation. CONCLUSION: Lenalidomide therapy for patients with rrDLBCL is effective and tolerable even in a real-life context, especially for elderly patients. IMPLICATIONS FOR PRACTICE: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and approximately 50% of the patients are >60 years of age. Patients with relapsed/refractory (rr) disease have a poor prognosis, reflected by the remarkably short life expectancy of 12 months with currently available treatments. The rrDLBCL therapeutic algorithm is not so well established because data in the everyday clinical practice are still poor. Lenalidomide for patients with rrDLBCL is effective and tolerable even in a real-life context, especially for elderly patients.


Subject(s)
Lenalidomide/administration & dosage , Lymphoma, Large B-Cell, Diffuse/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Italy/epidemiology , Lenalidomide/adverse effects , Lymphoma, Large B-Cell, Diffuse/epidemiology , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Remission Induction , Rituximab/administration & dosage , Rituximab/adverse effects , Treatment Outcome
6.
Oncotarget ; 8(53): 91703-91710, 2017 Oct 31.
Article in English | MEDLINE | ID: mdl-29207679

ABSTRACT

A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. Duration of response did not differ for who achieved at least PR and then either did or did not undergo consolidative transplant. Overall, the treatment was well tolerated and no death has been linked to BV-induced toxicity. Our report confirms activity in elderly patients, duration of response unrelated to the consolidation with transplant procedure, the relevance of the CR status at first restaging, and the role of BV as a bridge to transplant for chemorefractory patients.

7.
Haematologica ; 102(11): 1931-1935, 2017 11.
Article in English | MEDLINE | ID: mdl-28775121

ABSTRACT

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.


Subject(s)
Antineoplastic Agents/therapeutic use , Immunoconjugates/therapeutic use , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Brentuximab Vedotin , Combined Modality Therapy , Drug Resistance, Neoplasm , Female , Humans , Immunoconjugates/administration & dosage , Immunoconjugates/adverse effects , Lymphoma, Large-Cell, Anaplastic/mortality , Male , Middle Aged , Neoplasm Staging , Recurrence , Retreatment , Treatment Outcome , Young Adult
9.
Leuk Lymphoma ; 56(9): 2637-42, 2015.
Article in English | MEDLINE | ID: mdl-25651423

ABSTRACT

According to the European Society for Medical Oncology and National Comprehensive Cancer Network guidelines on Waldenström macroglobulinemia, bendamustine (B) may be considered a suitable therapeutic option. To address the role of B in combination with rituximab (BR), we analyzed the outcome of 71 patients with relapsed/refractory disease, median age 72 years, treated with R 375 mg/m(2) day 1 and B days 1 and 2 (dosage ranging from 50 to 90 mg/m(2)). Patients had previously received a median number of 2 lines of treatment (range 1-5). Overall and major response rates were 80.2% and 74.6%. Major toxicity was grade 3/4 neutropenia occurring in 13% of courses. There was no significant association between baseline features or patients' characteristics and response achievement. Median progression-free survival was not reached after a median follow-up of 19 months (range 3-54). None of the patients developed aggressive lymphoma or secondary myelodysplastic syndrome/acute myeloid leukemia. BR was found to be an active and well-tolerated salvage regimen leading to rapid disease control.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Waldenstrom Macroglobulinemia/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bendamustine Hydrochloride/administration & dosage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Retreatment , Retrospective Studies , Rituximab/administration & dosage , Salvage Therapy , Treatment Outcome , Waldenstrom Macroglobulinemia/diagnosis , Waldenstrom Macroglobulinemia/mortality
10.
Clin Lymphoma Myeloma Leuk ; 13(2): 231-4, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23490992

ABSTRACT

The combination FCR (fludarabine, cyclophosphamide, and rituximab) proved to be active in Waldenström's macroglobulinemia in a mixed population of untreated and previously treated patients. Prolonged myelosuppression and concerns about purine analogue treatment led to the conclusion that this regimen should be avoided in younger patients in first-line treatment. In this retrospective study on 40 patients we observed a response rate of 80% (32) after FCR salvage treatment with 32.5% (13) of patients reaching at least a very good partial remission. None of the prognostic variables had a significant effect on response or good quality of response achievement. Median event-free survival was reached at 77 months; median progression-free survival was not reached after a median follow-up of 51 months with any difference when categorizing patients according to quality of response. The results of this study suggest that the FCR regimen might overcome poor prognostic features and should be taken into account as salvage treatment. Tardive immunosuppression and myelosuppression warrant accurate patient follow-up.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Waldenstrom Macroglobulinemia/drug therapy , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Female , Humans , Male , Middle Aged , Retrospective Studies , Rituximab , Salvage Therapy , Treatment Outcome , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Waldenstrom Macroglobulinemia/mortality
11.
Ann Hematol ; 90(3): 323-30, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20848104

ABSTRACT

Indolent non-follicular non-Hodgkin lymphomas (INFL) are a heterogeneous subset whose treatment has been poorly investigated. In this context we have evaluated the efficacy and safety of combined fludarabine and cyclophosphamide (FC) upfront therapy. Sixty-three patients with advanced INFL were enrolled in the study. Therapy consisted in FC combination (25 and 250 mg/m(2), i.v., respectively, for three consecutive days) every 28 days for six courses. After histological review, 61 patients (36 men, median age 64 years, range 40-70 years) were evaluated (22 small lymphocytic, 11 lymphoplasmacytic, 25 marginal zone and 3 CD5-negative non-Hodgkin lymphomas not otherwise specified). Further two patients were excluded for lack of essential data; six patients were withdrawn before the third cycle because of WHO grade III and IV toxicity. At the final evaluation, the overall response rate was 83% with 40.7% of complete remission. Intention-to-treat analysis showed that at the median follow-up of 36 months, overall survival, progression-free survival and failure-free survival were respectively 78%, 60% and 46%; remission duration among the 49 patients achieving complete remission/partial remission at the end of treatment was 65% (44-78) without significant differences between the main histotypes. The most frequent grade III and IV toxic events were haematological (neutropaenia 34%, anaemia 18% and thrombocytopaenia 11%) and infectious (10%). FC is effective for advanced untreated INFL. Early deaths and haematological toxicity suggest careful patient selection and monitoring.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, B-Cell/drug therapy , Adolescent , Adult , Aged , Anemia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Disease-Free Survival , Female , Humans , Italy , Lymphoma, B-Cell/mortality , Lymphoma, B-Cell/pathology , Male , Middle Aged , Neutropenia/chemically induced , Remission Induction , Thrombocytopenia/chemically induced , Vidarabine/administration & dosage , Vidarabine/adverse effects , Vidarabine/analogs & derivatives , Young Adult
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