1,721,057 research outputs found
Diffuse large B-cell lymphoma.
No full textDiffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults accounting for 31% of all NHL in Western Countries. Following, morphological, biological and clinical studies have allowed the subdivision of DLBCLs into morphological variants, molecular and immunophenotypic subgroups and distinct disease entities. However, a large number of cases still remain biologically and clinically heterogeneous, for which there are no clear and accepted criteria for subclassification; these are collectively termed DLBCL, not otherwise specified (NOS). DLBCL-NOS occurs in adult patients, with a median age in the seventh decade, but the age range is broad, and it may also occur in children. Clinical presentation, behaviour and prognosis are variable, depending mainly of the extranodal site when they arise. These malignancies present in localized manner in approximately 20% of patients. Disseminated extranodal disease is less frequent, and one third of patients have systemic symptoms. Overall, DLBCLs are aggressive but potentially curable malignancies. Cure rate is particularly high in patients with limited disease with a 5-year PFS ranging from 80% to 85%; patients with advanced disease have a 5-year PFS≈50%. The International Prognostic Index (IPI) and age adjusted IPI (aaIPI) are the benchmarks of DLBCL prognosis. First-line treatment for patients with DLBCL is based on the individual IPI score and age, and three major subgroups should be considered: elderly patients (>60years, aaIPI=0-3); young patients with low risk (<60years, aaIPI=0-1); young patients with high risk (<60years, aaIPI=2-3). The combination of the anti-CD20 monoclonal antibody rituximab and CHOP chemotherapy, every 14 or 21days, is the standard treatment for DLBCL patients. Recent randomized trials suggest that high-dose chemotherapy supported by autologous stem cell transplant (HDC/ASCT) should not be used as upfront treatment for young high-risk patients outside prospective clinical trials. HDC/ASCT is actually recommended in young patients who did not achieve CR after first-line chemotherapy. Consolidation radiotherapy should be reserved to patients with bulky disease who did not achieve CR after immunochemotherapy. Patients with high IPI score, which indicates increased LDH serum level and the involvement of more than one extranodal site, and patients with involvement of certain extranodal sites (a.e., testes and orbit) should receive CNS prophylaxis as part of first-line treatment. HDC/ASCT should be considered the standard therapy for DLBCL patients with chemotherapy-sensitive relapse. Overall results in patients who cannot be managed with HDC/ASCT due to age or comorbidity are disappointing. New effective and less toxic chemotherapy drugs or biological agents are also worth considering for this specific and broad group of patients. Several novel agents are undergoing evaluation in DLBCL; among other, immunomodulating agents (lenalidomide), m-TOR inhibitors (temsirolimus and everolimus), proteasome inhibitors (bortezomib), histone deacetylase inhibitors (vorinostat), and anti-angiogenetic agents (bevacizumab) are being investigated in prospective trials.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved
New salvage treatment options for relapsing-refractory patients with diffuse large B-cell lymphoma previously treated with chemo-immunotherapy
No full text[No abstract available
Therapeutic advances in neoplastic hematology: target therapy anti-CD33
No full textAntibodies capable to recognize antigen expressed on cancer cells represents the ideal approach for targeted anti neoplastic therapies. The CD33 antigen is present on 90% of acute myeloid leukemia blasts and is shared on normal hemopoietic cells only on the non stem dillerentiating fraction. Gemtuzumab Ozogamicin (GO) is an engineered humanized antibody anti-CD33 conjugated with a potent intercalating agent, named calicheamicin, which is release only at intracellular level (lower pH), following a selective binding to CD33-positive cells, thus representing a promising approach for target anti-leukemia therapy. GO was approved conditionally by the Federal Drug Administration in May 2000 as a single therapy for first recurrence of Acute Myeloid Leukemia (AML) in a subset of older patients. Since 2000, treatment trials and pilot studies have revealed potential expanded applications along with potential limitations. Phase II trials have confirmed the activity and the efficacy of GO as single agent in the treatment of relapsed AML. More recently, clinical trials on induction and post-remission treatment of adult AML have shown efficacy of GO in combination chemotherapy. The strong and homogeneous CD33 expression in Acute Promyelocytic Leukemia (APL), have resulted in an effective treatment of this disease with GO used as salvage treatment, as well as innovative approach for molecular relapsed patients. However, the incidence of veno-occlusive disease, better defined as sinusoidal occlusive syndrome (SOS), must be taken into account as potential complication associated with the GO administration, especially in patients treated with ablative regimens. In conclusion, the extension of the approval in Italy to AML CD33+ in relapsed, regardless age limitation, along with the ongoing evaluation by the European EMEA, represent the basis for a large clinical application of GO in myeloid malignancies potentially extended to paediatric patients with AML and to ALL CD33+
Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy
No full textIntroduction Chimeric antigen receptor T (CAR-T) therapy has revolutionized the treatment of relapsed/refractory large B-cell lymphoma (LBCL). However, patients who are excluded or have no access to CAR-T represent a challenge for clinicians and have generally a dismal outcome. The landscape for this category of patients is constantly evolving: new agents have been approved in the last 2-3 years, alone or in combination, and novel treatment modalities are under investigation. Areas Covered Thereafter, we reviewed the currently available therapeutic strategies: conventional chemotherapy, antibody-drug conjugate ADC (mainly polatuzumab and loncastuxumab), bispecific antibodies (CD19/CD3 and focus on novel CD20/CD3 Abs), immunomodulatory drugs (covering tafasitamab and lenalidomide, checkpoint inhibitors mainly in PMBL), small molecules (selinexor, BTK, and PI3K inhibitors), and the role of radiotherapy. Expert Opinion Navigating this scenario will uncover new challenges, including identifying an ideal sequence for these therapies, the most effective combinations, and search for consistent predictive factors to help selecting the appropriate population of LBCL patients. At present, supporting clinical research for CAR-T ineligible patients, a new and challenging group, must remain a major focus that is complementary to advances in CAR T-cell therapy
Primary mediastinal lymphoma: diagnosis and treatment options.
Full text linkPrimary mediastinal large B-cell lymphoma (PMBCL) is a unique B-cell lymphoma variant that arises from a putative thymic medulla B cell. It constitutes 2-4% of non-Hodgkin lymphomas and occurs most frequently in young females. PMBCL is characterized by a diffuse proliferation of medium-to-large B cells associated with sclerosis. Molecular analysis shows that PMBCL is a distinct entity compared to other types of diffuse large B-cell lymphomas. PMBCL is characterized by a locally invasive anterior mediastinal bulky mass. The combination of rituximab with CHOP/CHOP-like regimens followed by mediastinal radiation therapy (RT) is associated with a 5-year progression-free survival of 75-85%. However, the role of consolidation RT still remains uncertain. More intensive regimens, such as DA-EPOCH-R without mediastinal RT, have shown very promising results. The conclusive role of PET-CT scan requires prospective studies and there is hope that this may allow to de-escalate RT and accordingly yield reliable prognostic information
Primary mediastinal large B-cell lymphoma
Full text linkPrimary mediastinal large B-cell lymphoma (PMLBCL) is a distinct clinical and biological disease from other types of DLBCL. It is more frequent in young female and constitutes 6%-10% of all DLBCL. PMLBCL is characterized by a diffuse proliferation of medium to large B-cells associated with sclerosis. Molecular analysis shows it to be a distinct entity from other DLBCL. Rituximab CHOP/MACOP-B-like regimens followed by mediastinal radiotherapy (RT) were associated with a 5-years PFS of 75%-85%. More intensive regimens, as DA-EPOCH-R without mediastinal RT, have shown very promising results, but this therapeutic advance needs to be confirmed in further prospective trials. The role of consolidative mediastinal RT should be still better assess in prospective comparative studies. PET-CT scan is a powerful tool to define the real quality of response and it is hoped that future prospective trials may allow its role in the de-escalation of mediastinal RT.</p
INTENSIFIED THERAPY PROGRAM FOLLOWED BY HIGH-DOSE THERAPY AND AUTOLOGOUS STEM CELL TRANSPLANTATION AS FIRST-LINE TREATMENT FOR PERIPHERAL T-CELL LYMPHOMA: PRELIMINARY RESULTS OF A PROSPECTIVE STUDY
No full textPREDICTIVE FACTORS FOR INFECTIOUS ADVERSE EVENTS IN PATIENTS WITH B-CELL NON-HODGKIN LYMPHOMA TREATED WITH BENDAMUSTINE-RITUXIMAB (R)+/- R MAINTENANCE. RESULTS OF A RETROSPECTIVE ANALYSIS
No full textBackground
The combination of bendamustine (B) and rituximab (R) is an effective and well tolerated treatment for B-cell malignancies. However, previous reports have shown a higher incidence of lymphopenia and secondary infectious complications in patients treated with BR than in patients treated with other chemoimmunotherapy regimens.
Aims
We performed a retrospective analysis at our institution in patients treated with BR with or without R maintenance, with the aim of determining the incidence of the infectious adverse events (AEs) and of identifying potential predictors factors.
Methods
We collected data from 65 patients with B-cell non-Hodgkin lymphoma (NHL) who received at least two cycles of BR ± R maintenance between 2010 and 2016 at our institution. The AEs – including neutropenia (N), neutropenic fever (NF), lymphopenia, infections episodes and the occurrence of second tumors - were recorded according to the CTCAE v4.0 grade score. We compared the risk factors of patients who developed infections and those who did not. Univariate analysis with Fisher's exact test was used to evaluate the potential risk factors.
Results
The median age at the first treatment cycle was 66 years (range 36-89), 33 patients (50%) were ≥65 years, 27 (41%) were male, 53 (82%) had advanced disease and 37 (60%) had bone marrow involvement. Thirty (46%) patients had follicular lymphoma, 17 (26%) mantle cell lymphoma, 11 (17%) marginal lymphoma, 5 (7%) diffuse large B-cell lymphoma and 4% other indolent lymphomas. Thirty two patients (49%) received BR as first line treatment, 51% as second line and above. Bendamustine was administered either at the dosage of 70 or 90 mg/sqm iv on days 1, 2 and R was administered at a dose of 375 mg/sqm iv or sc, on day 1. Therapy was administered every 4 weeks up to 6 courses. Twenty nine patients (46%) received R maintenance every 8-12 weeks for two years. The mean number of cycles administered was 5 (range 2-6), 13 patients (20%) discontinued treatment due to toxicity: 8/13 for non-hematologic toxicity. Primary or secondary G-CSF prophylaxis was administered to 25 patients (38%), while the prophylaxis with trimetropin-sulfametoxazole against Pneumocystis jiroveci pneumonia was given to all patients. Twenty two patients (34%) had at least one infection. Bacterial pneumonia was identified in 6/22 patients, varicella zoster virus infection in 4/22, cytomegalovirus reactivation in 2/22 and other infections in 10 patients. At univariate analysis, the infectious AEs were associated only with lymphopenia during the second cycle (p=0.043) and with neutropenia during the second, third and fourth cycle (p=0.026; p=0.003, p=0.018, respectively). No correlation with age, line of treatment and G-CSF administration was documented. Other AEs were: grade 3/4 neutropenia (49%), neutropenic fever (3%), grade 3/4 lymphopenia (80%). We reported also a 5% incidence of second tumors after treatment (lung cancer in 2 patients and prostate cancer in 1).
Conclusion
In our analysis, BR ± R maintenance confirms a toxicity profile similar to that reported in previous experiences. According to our results, an early lymphopenia and neutropenia (after two cycles) are predictive factors for infections AEs and for premature treatment discontinuation. Twenty % of patients discontinued treatment mostly because of the early withdrawal due to infectious complications. These data raise the question on the role of antibacterial, antiviral and primary G-CSF prophylaxis in all patients treated with BR
MACOP-B +/- RITUXIMAB FOLLOWED BY INVOLVED MEDIASTINAL RADIOTHERAPY IS A SAFE AND HIGH EFFECTIVE THERAPY FOR PRIMARY MEDIASTINAL LARGE B CELL LYMPHOMA (PMBL): LONG TERM RESULTS AND LATE TOXICITY FROM A SINGLE ITALIAN CENTER
No full textBackground: Primary Mediastinal B cell lymphoma is a distinct subtype of diffuse large B
cell lymphoma that is more common in younger female age. Combined regimen of
chemotherapy (CT) with involved field radiotherapy (IFRT) is considered the mainstay of
treatment. In the pre-Rituximab era third generation regimens as MACOP-B has improved
survival in PMBL patients (pts) over CHOP, but the current combination of Rituximab
with CHOP regimen equalize this difference. The real need of consolidation mediastinal
IFRT is still debated for the risk of secondary cancer and cardiac disease. We report the long
term results on a large series of PMBL treated at our institute.
Method: 107 pts with PMBL were treated between June 1991 and September 2006; 80
pts had stage II and 27 stage IIE-IV, 75% had elevated LDH, bulky disease was in 95 pts
including 58 (55%) with clinical evidence of superior vena cava obstruction. Median
age was 34 yrs (15-61), 71% were females. The IPI score was 0-1 in 60 pts and 2-3 in 47.
Ninety-two pts were treated with standard MACOP-B regimen and 15 received a Rchemotherapy since March 2004. Overall 94% received IFRT at dose of 30-36 Gy. The
response was evaluated at the end of CT and of IFRT.
Results: At the end of the program, the CR/CRu was obtained in 76 pts (71%), PR in
23(21%), NR 1(1%), 7 pts were not evaluable: 6 pts received an early intensification for
progressive disease and 1 died for toxicity by CT. At the end of the program: 14 of PR
pts obtained a CR/CRu after IFRT with an overall CR/CRu rate of 89%; 9 pts relapsed
within 10 months and 4 of them died of progressive disease.
At a median follow-up of 111 months (1-238) the 10-yrs OS, PFS and EFS were 88%,
85% and 83% respectively. No statistically significant difference was recorded with
MACOP-B +/- Rituximab in order to survival end-points. Pts with IPI 0-1 have
significant better PFS p=0.020. In our experience 1/107 pt developed a secondary
cancer (acute myeloid leukemia) after 164 months from the end of therapy and no
breast cancer occurred. Four/107 (4%) presented late severe cardiotoxicity: 3
congestive heart failure and 1 sudden arrhythmic death.
Conclusions: This is the largest reported series of PMBL treated at single center.
MACOP-B +/- Rituximab plus IFRT is highly effective and devoid of a severe long term
toxicity. Future randomized trials should evaluate the real need of a mediastinal IFRT
in pts who obtained a PET negative CR after a R-chemotherapy regimen
CENTRAL NERVOUS SYSTEM (CNS) INVOLVEMENT IN DIFFUSE LARGE B-CELL LYMPHOMA. A SINGLE CENTER ANALYSIS OF THE RISK FACTORS AND THE IMPACT OF CNS PROPHYLAXIS IN THE RITUXIMAB ERA
No full textBackground: Central nervous system (CNS) relapse is a serious and generally fatal complication of diffuse large B-cell lymphoma (DLBCL) occurring in almost 5-7% of patients in the pre-rituximab era. The median time from diagnosis to detection of CNS disease is less than 1 year, suggesting that seeding in the CNS occurs early in the course of disease, with the exception of primary testis lymphoma in which it can occur up to 10 years after diagnosis. Up to date, there is no general consensus on how to define high-risk patients and what is the optimal CNS prophylaxis. The addition of rituximab to CHOP chemotherapy (RCHOP) has improved the clinical outcome of DLBCL. Nevertheless, the impact of rituximab on the incidence of CNS complications is still unclear. Aims: This retrospective study aimed to analyze the predictive factors of CNS relapse and the impact of CNS prophylaxis in DLBCL patients treated at our Institute over a 12-years period. and 2014. The patients with all stage of disease, regardless of the IPI score, were eligible and all received RCHOP every 14 or 21 days for at least 4/6 cycles. Patients with HIV or CNS involvement at diagnosis were excluded. Prophylaxis with intrathecal methotrexate (IT-MTX) was administered in patients with a high risk of CNS relapse according to the Italian Society of Hematology’s guidelines. The diagnosis of CNS relapse was based on CT/MRI assessment and/or cerebrospinal fluid cytology. Results: The median age was 58 years (IQR 47-68), 54% were males; 212/393 patients (54%) had stage III-IV, a bone marrow (BM) involvement was found in 51/393 patients (13%), while 49 (12%) had an involvement of more than 1 extranodal site, testis involvement was in 20/393 patients (5%). B symptoms were experienced by 100/393 patients (25%) and an elevated LDH was present in 115/393 patients (29%). According to the IPI score, 197/393 patients (50%) had a IPI2. Twelve/393 patients (3%) experienced a CNS relapse: 7 of them had a brain mass, 2 had a leptomeningeal involvement and 3 had both. CNS prophylaxis was carried out in 81/393 patients (21%): 27 with a IPI2 (p=0.009), presence of B symptoms (p=0.000), elevated LDH (p=0.006), involvement of >1 extranodal sites (p=0.000), BM involvement plus elevated LDH (p=0.003), testis localization (p=0.019) and IPI>=2 (p=0.000) were associated with an increased risk of CNS relapse. At multivariate analysis, only PS>2 (p=0.031, 95%CI: 0.009-0.189), testis involvement (p=0.001, 95%CI: 0.048-0.2) and BM involvement plus elevated LDH (p=0.016, 95%CI: 0.021- 0.2) were predictive factors of high risk of CNS relapse. The 2-year overall survival of the CNS relapsed patients was 9%, with a median follow-up of 8 months from diagnosis (IQR 4-28). Summary/Conclusions: CNS relapse remains a fatal event for patients with DLBCL even in the rituximab era. Poor PS, testis and BM involvement combined relapse. In our experience, single IT-MTX prophylaxis did not reduced CNS
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