High efficacy of BGD (bendamustine, gemcitabine, and dexamethasone) in relapsed/refractory Hodgkin Lymphoma.

The optimal salvage therapy in relapsed/refractory Hodgkin lymphoma (R/R HL) has not been defined so far. The goal of this multicenter retrospective study was to evaluate efficacy and safety of BGD (bendamustine, gemcitabine, dexamethasone) as a second or subsequent line of therapy in classical R/R HL. We have evaluated 92 consecutive R/R HL patients treated with BGD. Median age was 34.5 (19-82) years. Fifty-eight patients (63%) had received 2 or more lines of chemotherapy, 32 patients (34.8%) radiotherapy, and 21 patients (22.8%) an autologous hematopoietic stem cell transplantation (autoHCT). Forty-four patients (47.8%) were resistant to first line of chemotherapy. BGD therapy consisted of bendamustine 90 mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1-4. Median number of BGD cycles was 4 (2-7). The following adverse events ≥ 3 grade were noted: neutropenia (22.8%), thrombocytopenia (20.7%), anemia (15.2%), infections (10.9%), AST/ALT increase (2.2%), and skin rush (1.1%). After BGD therapy, 51 (55.4%) patients achieved complete remission, 23 (25%)-partial response, 7 (7.6%)-stable disease, and 11 (12%) patients experienced progression disease. AutoHCT was conducted in 42 (45.7%) patients after BGD therapy, and allogeneic HCT (alloHCT) in 16 (17.4%) patients. Median progression-free survival was 21 months. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL, providing an excellent bridge to auto- or alloHCT.

First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4.

R-CVP (cyclophosphamide, vincristine, prednisone) and R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non-Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression-free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R-CVP to R-CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R-CVP or R-CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m2 q 2 months for 12 cycles. Primary endpoint was event-free survival (EFS). Two-hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenström Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R-CHOP: 127, R-CVP: 123). Median age was 56 years (21-85), 44% were male, 90% were in stage III-IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33·4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43·6/50·9% and 36·3/60·8% in the R-CHOP and R-CVP groups (P = 0·218) respectively. After a median follow-up of 67, 66, and 70 months, five-year EFS was 61% vs. 56% (not significant), progression-free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R-CHOP vs. the R-CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33·1%) and 18 (15·3%) patients, P = 0·001; neutropenia in 16 (11·6%) and 4 (3·4%) patients, P = 0·017; infection in 14 (10·7%) and 3 (2·5%) patients,; P = 0·011; and a second neoplasm in three versus seven patients., in the R-CHOP and the R-CVP groups respectively. This multicentre randomized study with >five-year follow-up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R-CVP or R-CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R-CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second-line therapy.

Outcomes of treatment with dose-adjusted EPOCH-R or R-CHOP in primary mediastinal large B-cell lymphoma.

BACKGROUND: The standard first-line treatment for primary mediastinal B-cell lymphoma (PMBCL) patients is rituximab-based immunochemotherapy; however, this is not due to the result of randomized clinical trials. AIMS: We retrospectively investigated 53 PMBCL patient outcomes treated either with R-CHOP-21 or DA-EPOCH-R-28. The primary endpoint was overall survival (OS). Secondary endpoints were complete remission (CR), overall response rate (ORR), progression-free survival (PFS), and treatment-related complications. RESULTS: Treatment with R-CHOP-21 resulted in a 92.0% ORR (60% CR), while DA-EPOCH-R yielded a 92.6% ORR (70.4% CR). There were no differences in the occurrence of grade 3-4 hematological adverse events, but grade 1-2 cardiologic complications (P = .003) were observed more frequently in the DA-EPOCH-R arm. Median PFS and OS were not achieved. The differences in estimated 12-month PFS in R-CHOP and DA-EPOCH-R group (87% vs 73.9%) and OS (100% vs 92%) were insignificant. Patients treated with R-CHOP-21 and autologous hematopoietic stem cell transplantation (auto-HSCT) had an improved OS (P = .03) but not PFS (P = .43) compared to those treated solely with R-CHOP-21. No differences in PFS or OS were observed between patients treated with R-CHOP-21/auto-HSCT and DA-EPOCH-R. CONCLUSION: The results of this study suggest that R-CHOP-21 may be an alternative to DA-EPOCH-R treatment for PMBCL patients.

Radiological Response and Neutrophil-to-Lymphocyte Ratio as Predictive Factors for Progression-Free and Overall Survival in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib.

Renal cell carcinoma (RCC) represents 2-3% of all malignancies. Most RCC-related deaths are caused by metastases of the disease. Studies suggest that inflammation-related parameters are of prognostic significance in metastatic renal cell carcinoma (mRCC) patients. Neutrophilia and thrombocytosis are markers of systemic inflammation that accompanies cancer, while lymphopenia is related to dysfunctions of the immune system. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) thus seem particularly interesting from a clinical perspective. The goal of this study was to determine if the response to therapy, consisting of reductions in radiologically assessed tumor burden and in inflammation-related parameters after 12 weeks of treatment with sunitinib, has a predictive value for outcome. One hundred thirty-one mRCC patients treated with the first-line sunitinib were evaluated. Inflammation-related parameters and radiologic response were correlated with treatment outcomes, progression-free, and overall survival. We found that the longest median progression-free survival of 37 months (Q1; Q3-15; not reached) and overall survival of 40 months (Q1; Q3-26; not reached) were achieved by patients who had either partial or complete response according to RECIST 1.1 and NLR lower than 1.64. In conclusion, the study confirmed that both objective response and lower grade of inflammation during treatment are predictive of better outcomes in mRCC patients treated with sunitinib.

Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial.

BACKGROUND: Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigator's choice of single-agent therapy in relapsed or refractory mantle cell lymphoma. METHODS: The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0-2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1-21 every 28 days) until progressive disease or intolerability, or single-agent investigator's choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigator's choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigator's choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention-to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667. FINDINGS: Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigator's choice monotherapy). Patients had a median age of 68·5 years and received a median of two previous regimens. With a median follow-up of 15·9 months (IQR 7·6-31·7), lenalidomide significantly improved progression-free survival compared with investigator's choice (median 8·7 months [95% CI 5·5-12·1] vs 5·2 months [95% CI 3·7-6·9]) with a hazard ratio of 0·61 (95% CI 0·44-0·84; p=0·004). In the 167 patients in the lenalidomide group and 83 patients in the investigator's choice group who received at least one dose of treatment the most common grade 3-4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]). INTERPRETATION: Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profile when treated with lenalidomide compared with monotherapy investigator's choice options. FUNDING: Celgene Corporation.

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma.

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.

Primary mediastinal B-cell lymphoma - metabolic and anatomical features in 18FDG-PET/CT and response to therapy.

AIM OF THE STUDY: Determining the role of PET/CT imaging in the evaluation of treatment efficacy in primary mediastinal B-cell lymphoma (PMBCL). MATERIAL AND METHODS: Retrospective analysis of seven PMBCL patients, treated at the University Hospital in Krakow, with interim PET/CT after the third course of chemo-immunotherapy.The analysis was based on the calculation of exact tumour volume and metabolic activity, compared with initial values (directly after diagnosis). RESULTS: Patients (five females, two males, average age 26.2 years, range 18-40 years), in clinical stage IIBX at diagnosis, were treated with eight cycles of R-CHOP-14 regimen, with radiotherapy consolidation (7/7) and central nervous system prophylaxis (6/7). The observed decrease in tumour volume between the initial staging and the interim PET ranged 72-89%. The mean ΔSUVmax reduction between initial (when available) and interim PET was 87% (range 84-89%). In 3/7 cases in the interim PET/CT, the uptake of the tumour was higher than the liver (Deauville Criteria score 4-5), and in 4/7 it was lower than the liver but higher than mediastinal blood pool structures (score 3 according to Deauville Criteria). After a median follow-up of 58 months - OS and EFS is 100%. CONCLUSIONS: The excellent clinical outcome in the study group corresponds with very good metabolic and volumetric response in the interim PET. The ΔSUVmax seems to be easier in implementation and has a more significant impact than other measurements.

Efficacy and safety of stem cell mobilization with cyclophosphamide plus etoposide versus cyclophosphamide alone.

The use of the combination of two cytostatics cyclophosphamide (CTX) and etoposide (VEP) and G-CSF is a reasonable alternative, especially for stem mobilization in multiple myeloma (MM) patients from countries in which newer treatments are limited due to financial constraints. The aim of this study was to compare the efficacy and safety of CTX-VEP versus CTX alone for mobilization of hematopoietic stem cells in MM patients. The analysis included 48 consecutive MM patients mobilized with CTX-VEP compared to 43 consecutive historical controls mobilized with CTX alone. The two groups of MM patients did not differ in terms of the median number of apheresis procedures, median yield the first day, median numbers of harvested CD34+ cells, proportion of patients with at least 5 x 106/kg yield and incidence of non-hematological complications. The median cumulative dose of G-CSF given to individuals in the CTX-VEP group was significantly lower than in the CTX group (p < 0.001). The incidence of post-mobilization thrombocytopenia was higher in the CTX group (p<0.001). The median time to platelet count > 20 x 109/l (10 vs. 11 days, p = 0.004) and the median time to neutrophil count > 50 x 109/l (11 vs. 13 days, p < 0.001) were significantly shorter among the patients mobilized with CTX-VEP than in those treated with CTX alone. These findings suggest that CTX-VEP is as efficacious and possibly safer than CTX alone.

Immediate Response to Brentuximab Vedotin in a Patient with Localized MF-LCT.

The large cell transformation of mycosis fungoides (MF-LCT) is a phenomenon observed in the advanced stages of mycosis fungoides (MF), which is the most common primary cutaneous lymphoma. The diagnostic criteria of MF-LCT are a minimum of 25% of large cells or a formation of microscopic nodules of them in the histological examination of skin samples. The clinical outcomes for MF-LCT are poor, as less than 20% of patients survive 5 years after diagnosis, but the expression of the CD30 antigen is generally considered to be associated with a better prognosis. We present a case of a patient with the diagnosis of MF with LCT, with an ulcerated tumor lesion approximately 30 × 20 cm in size on the right lateral abdominal wall. Brentuximab vedotin (BV) treatment was started due to the presence of the CD30 antigen, with a quick and impressive regression of the cutaneous lesion and tumor mass and good treatment tolerance. After follow-up of 20 months, patient remains in complete remission. A schedule of treatment for MF-LCT is directed mainly by the clinical stage of the disease and the comorbidities; the more severe clinical course of the disease requires systemic treatment. If at least 5% of the cells found in the skin lesions biopsy sample express the CD30 antigen, a beneficial effect of BV treatment could be expected. It may seem that the use of BV is one of the optimal therapeutic options in patients with advanced MF-LCT showing expression of CD30.

Autoimmune cytopenias in patients with malignant lymphoma: A multicenter report by the Polish Lymphoma Research Group.

BACKGROUND: Autoimmune cytopenias (ACs), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and autoimmune granulocytopenia, are rare complications observed in lymphoma patients. They may appear before, during or after lymphoma diagnosis, whether the patients had disease progression or not. OBJECTIVES: This study aims to correlate ACs with lymphoma type, disease course and prognosis. We performed a multicenter retrospective analysis of adult patients with malignant lymphoma and ACs coexistence diagnosed and treated in centers aligned with the Polish Lymphoma Research Group (PLRG). MATERIAL AND METHODS: The analysis covers the years 2016-2022 and included 51 patients comprised of 23 women and 28 men. Of these, 35 patients were diagnosed with AIHA, 15 patients with ITP and 1 patient with both AIHA and ITP. RESULTS: The most common type of lymphoma was Hodgkin lymphoma (HL) (12 patients) and diffuse large B-cell lymphoma (DLBCL) (14 patients). At the time of diagnosis, 31 (61%) of patients had stage 4 of HL or DLBCL, according to Ann Arbor classification. In total, the response to treatment was evaluated in 50 patients, with 25 being in complete remission and 6 in partial remission. We observed that B cell symptoms (p = 0.036), bone marrow involvement (p = 0.073), splenomegaly (p = 0.025), and more than 2 lines of treatment were more common in AIHA compared to ITP patients. Conversely, eucopenia (p = 0.056) and ACs without lymphoma progression (p = 0.002) were more often diagnosed in ITP patients. CONCLUSIONS: In the study group, relapsed and refractory disease was observed more often, and shorter overall survival (OS) was noted in patients with DLBCL. We found that AC is associated with a worse prognosis in comparison to the general population of lymphoma patients. There were no differences in response to AC therapy. To have more accurate data, a larger group, as part of a multicenter study, should be evaluated.

A survey across orbital lymphoma in Poland: Multicenter retrospective study of polish lymphoma research group (PLRG).

OBJECTIVE: To investigate the prevalence of histopathological subtypes, the clinical stage at presentation and treatment modalities in Polish patients with orbital lymphoma (OL) and to determine prognostic outcomes. METHODS: The retrospective study of 107 patients with OL treated in a 14-year period in Polish hematological centers. The analysis included histopathological subtype, disease clinical advancement, treatment modalities, progression-free survival (PFS), and overall survival (OS). RESULTS: The median patient age was 60 years (range 51-71). Mucosa-associated lymphoid tissue (MALT) lymphoma accounted for slightly more than half of all cases of orbital lymphoma (51%). The second most common subtype was diffuse large B-cell lymphoma (DLBCL) (29%). Primary orbital lymphoma was diagnosed in 48% of all patients. According to the Ann Arbor, localized stage IE of orbital lymphoma was diagnosed only in 39% of all patients. Systemic involvement was observed in more than half of all patients (52%). The median follow-up period was 30 months (range 0-160 months). Patients with non-MALT lymphoma had a significantly inferior PFS compared to patients with MALT lymphoma, (p = 0.047). Patients with primary orbital lymphoma had a superior PFS compared to patients with secondary orbital lymphoma [median PFS 104.5 months vs. 33.4 months], (p = 0.069). Younger patients with MALT lymphoma were characterized by superior PFS (median PFS not reached) compared to other studied subgroups of patients (older patients with MALT lymphoma, younger and older non-MALT lymphoma patients) with a median PFS of 30.5, 32.2, 32.6 months respectively (p = 0.039). Patients treated with chemotherapy alone had inferior PFS compared to patients treated with combined therapies (p = 0.034). The median PFS across patients who received chemotherapy alone was 23.7 months, whereas across other patients was 73.9 months. CONCLUSIONS: Secondary lymphoma accounts for more than half of the orbital lymphoma in Polish population. The advanced clinical stage of the disease (non-IE according to Ann Arbor) concerns two-thirds of the overall population of patients with orbital lymphomas and one-third of MALT lymphoma patients. The high incidence of advanced stages of orbital lymphoma may indicate the need for combined treatment. Combined orbital lymphoma treatment is associated with superior PFS compared to chemotherapy alone in overall population of patients with orbital lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in Poland: analysis of patient series and practical guidelines for breast surgeons.

Introduction: Although breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is infrequent, with less than 1000 noted cases worldwide, patients consenting for breast implant surgery should be aware of its risk. We describe the first Polish multicenter case-series data on BIA-ALCL patients and present diagnostic and treatment recommendation for breast surgeons. Material and methods: In cooperation with the Polish Society of Surgical Oncology and Polish Lymphoma Research Group, we collected BIA-ALCL cases in Poland. Results: We retrospectively reviewed clinical data of seven BIA-ALCL patients, diagnosed between July 2013 and November 2019. The median time from implant placement to the first BIA-ALCL symptoms was 65 months (range: 33-96 months). All the patients were exposed to textured implants at presentation. Capsulectomy with implant removal was performed in all the patients with immediate reimplantation in 2 cases. In a median follow-up of 19 months (range 5-81 months), there was no recurrence and all the patients stayed alive. Between 2013 and 2019, the incidence of BIA-ALCL in Polish female population age 30 and above ranged from 0 to 0.021/100 000/year. Conclusions: BIA-ALCL is scarce in the Polish population. In a short-term follow-up, patients' prognosis remains excellent. Due to the withdrawal of roughly textured implants from the market and the exclusion of likely the most potent etiologic factor, it might be expected that the incidence of BIA-ALCL will become even rarer.

Early efficacy and safety of obinutuzumab with chemotherapy in previously untreated patients with follicular lymphoma: A real-world retrospective report of the Polish Lymphoma Research Group.

BACKGROUND: The first-line obinutuzumab-based immunochemotherapy improves the outcome of patients with follicular lymphoma (FL) compared with rituximab-based regimens. However, infusion-related reactions occur in almost half of patients during the 1st obinutuzumab administration. OBJECTIVES: The study aimed to evaluate the early effectiveness and safety of obinutuzumab-based induction regimens in a real-world setting. MATERIAL AND METHODS: Outcomes of patients diagnosed with FL and treated with obinutuzumab between January 2020 and September 2021 were analyzed. RESULTS: The study group included 143 treatment-naïve patients with FL. The median age was 52 years (range: 28-89 years); 45.1% of patients had a high-risk disease as assessed using the Follicular Lymphoma International Prognostic Index (FLIPI). Induction chemotherapy included: O-CVP (obinutuzumab, cyclophosphamide, vincristine, prednisolone) in 49.0% of patients, O-CHOP (O-CVP plus doxorubicin) in 28.7% and O-BENDA (obinutuzumab, bendamustine) in 22.4%. Complete response (CR) and partial response (PR) rates were 69.9% and 26.5%, respectively. There was no difference in response rates between different regimens (p = 0.309). Maintenance was started in 115 patients (85.2%). In the 1st cycle, obinutuzumab was administered as a single 1000-milligram infusion in 47.9% of patients, whereas in 52.1%, initial infusions were split over 2 days (100 mg/900 mg). Infusion-related reactions were reported only during the 1st administration of obinutuzumab in 9.1% of patients, with a similar incidence in those receiving the total dose on a single day or split over 2 days (p = 0.458). The most common adverse events were hematological. Five patients died from coronavirus disease 2019 (COVID-19). CONCLUSION: The early responses to induction regimens and adverse events profile were similar for every type of induction treatment. The infusion-related reactions were rare and limited to the 1st dose of obinutuzumab.

[Escalated BEACOPP as an alternative in high risk Hodgkin lymphoma]. / Eskalowany BEACOPP jako alternatywa dla ABVD w chorobie Hodgkina o wysokim ryzyku.

Hodgkin Disease is one of the common lymphoma subtypes: every year over 750 new cases are diagnosed in Poland. It is most frequent in young adults between 25 - 30 years of age. In a low risk cases prognosis is excellent, and the treatment may be limited to short chemotherapy consolidated by involved field radiotherapy. In high risk cases with a large tumor burden prognosis depends from the choice of the initial therapy. Results of 8 years experience with escalated BEACOPP in UJ CM Department of Hematology are summarized in the paper. Monitoring the early response in imaging studies, particularly in positron emission tomography, allows in the majority of cases to decrease the duration of intensive therapy, without loosing it's efficacy.

[Hematological toxicity of radioimmunotherpy with 90Y Ibritumomab]. / Toksycznosc hematologiczna radioimmunoterapii z zastosowaniem 90Y Ibritumomabu.

Radioimmunotherapy with 90Y Ibritumomabu (Zevalin, BSP) is a new method of systemic radiotherapy applicable to B-cell lymphoma patients. It may be delivered as a short outpatient procedure, with few adverse effects other than hematological toxicity. In the paper, we present length and depth of cytopenias, together with the results of additional tests performed to reveal the possible pathomechanisms, based on 102 patients treated at the University Hospital in Krakow.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with probable mesentery involvement with associated hemophagocytic syndrome (HPS) - how to treat it?

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare, cutaneous lymphoma involving subcutaneous adipose tissue. SPTL is associated in less than 20% with hemophagocytic syndrome (HPS). A 5-year overall survival rate is inferior in patients with SPTL and HPS (46%) as compared with 91% in patients without HPS. No standardized therapy for SPTCL has yet been established. This is a case of 35-year-old Caucasian man with a one-month history of B symptoms with the suspicion of Still's disease, at admission with leucopenia, high LDH, ferritin, sIl-R2, and triglycerides levels, hepatosplenomegaly, small right supraclavicular nodule, and irregular thickening of trunk subcutaneous tissue. The abdomen MRI showed generalized thickening of mesentery and colonic mucosa. In the patient, diagnosis of SPTCL was established with secondary HPS. CHOEP chemotherapy and modified HLH 2014 protocol were applied with subsequent high dose chemotherapy (BEAM) supported by autologous stem cells transplantation. Treatment was complicated by pancytopenia and pneumonia. The outcome of the disease treated by intensive protocol seems to be good.

Design, Synthesis and Biological Activity of New Amides Derived from 3-Benzhydryl and 3-sec-Butyl-2,5-dioxo-pyrrolidin-1-yl-acetic Acid.

The aim of this study was to design and synthesize two new series of pyrrolidine-2,5-dione-acetamides with a benzhydryl or sec-butyl group at position 3 as potential anticonvulsants. Their anticonvulsant activity was evaluated in standard animal models of epilepsy: the maximal electroshock (MES), the 6 Hz, and the subcutaneous pentylenetetrazole (scPTZ) tests. The in vivo studies revealed the most potent anticonvulsant activity for 15 (3-(sec-butyl)-1-(2-(4-(3-trifluoromethylphenyl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione), with ED50 values of 80.38 mg/kg (MES) and 108.80 mg/kg (6 Hz). The plausible mechanism of action was assessed in in vitro binding assays, in which 15 interacted effectively with voltage-gated sodium (site 2) and L-type calcium channels at a concentration of 100 µM. Subsequently, the antinociceptive activity of compounds 7 and 15 was observed in the hot plate test of acute pain. Moreover, compounds 7, 11 and 15 demonstrated an analgesic effect in the formalin test of tonic pain. The hepatotoxic properties of the most effective compounds (7, 11 and 15) in HepG2 cells were also investigated.

Post-transplant Lymphoproliferative Disorder in a Patient After Kidney Transplant, 5-Year Follow-up: A Case Report.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a serious, life-threatening complication in organ transplant patients receiving immunosuppressive therapy. The risk factors include Epstein-Barr virus infection and a cumulative dose of the immunosuppression. CASE REPORT: We present a 5-year follow-up case of a 28-year-old patient with PTLD in the gastrointestinal tract. In the ninth month after kidney transplant, the patient was hospitalized for pain in the abdomen and diarrhea. Physical examination demonstrated tenderness in the area of the cecum, and colonoscopy revealed ulcerations in the large intestine. Polymorphic lymphoma (PTLD) was found in the collected samples. The patient received monotherapy treatment with anti-CD20 antibodies, resulting in complete remission of disease, confirmed by computed tomography scan and colonoscopy. CONCLUSION: PTLD may have a different clinical course and should be considered in the differential diagnosis of patients after organ transplant.

Type 2 diabetes mellitus compromises the survival of diffuse large B-cell lymphoma patients treated with (R)-CHOP - the PLRG report.

Comorbidities impair the prognosis of diffuse large B-cell lymphoma (DLBCL). Type 2 diabetes mellitus (DMT2) increases the risk of other comorbidities, e.g., heart failure (HF). Thus, we hypothesized that pre-existing DMT2 may negatively affect the outcome of DLBCL. To verify this, DLBCL patients treated with (R)-CHOP were enrolled. 469 patients were eligible, with a median age of 57 years; 356 patients had advanced-stage DLBCL. 126 patients had high-intermediate and 83 high-risk international prognostic index (IPI). Seventy-six patients had DMT2, 46 HF; 26 patients suffered from both DMT2 and HF. In the analyzed group DMT2 or HF significantly shortened overall survival (OS) and progression free survival (PFS): the 5-year OS for patients with DMT2 was 64% vs 79% and for those with HF: 49% vs 79%. The 5-year PFS for DMT2 was 50.6% vs 62.5% and for HF 39.4% vs 63.2%. The relapse/progression incidence was comparable between groups; the non-relapse/progression mortality (NRPM) was significantly higher solely in DMT2 patients (5-year NRPM 22.5% vs 8.4%). The risk of death was higher in patients with higher IPI (HR = 1.85) and with DMT2 (HR = 1.87). To conclude, pre-existing DMT2, in addition to a higher IPI and HF, was a negative predictor for OS and PFS.