Castleman disease (CD) was first described in the 1954 by Benjamin Castleman as a rare nonmalignant lymphoproliferative disorder [1]. Multicentric CD (MCD) involves multiple regions of enlarged lym...

Summary: Clinical data on primary central nervous system (CNS) lymphoma (PCNSL) patients is mostly generated from prospective studies, and many frail real‐world patients are not included. Recently,the diagnosis and treatment of PCNSL patients was confounded by the COVID‐19 pandemic. In particular, treatment with high‐dose cytarabine was linked to increased risk of pneumonia and virus persistence. We report on outcome of the induction regimen R‐MIV (rituximab, methotrexate, ifosfamide, and vincristine) involving intensive administration of high‐dose methotrexate (3.5 g/m²) with ifosfamide, every 2 weeks and rituximab once per week for six doses. The median age and performance status (PS) for 64 patients was 58 years and 2 (PS 3; 22%) respectively. The overall response rate by magnetic resonance imaging/computed tomography (MRI/CT) was 73% (n = 46/63), with an additional 17.5% (n = 11/63) patients without measurable disease at baseline. Grade 3–4 haematological toxicity was low for R‐MIV (neutropenia: 25% and thrombocytopenia: 1%). Three patients (4.7%) died from treatment‐related toxicity. Co‐existence of SARS‐CoV‐2 infection with cytomegalovirus reactivation and the varicella‐zoster virus in two patients was fatal. Fifty patients (78%) were eligible for consolidation. Median progression‐free and overall survival were not reached (median follow‐up: 44 months). In conclusion, the R‐MIV regimen is feasible in routine practice, effective and safe, even during the COVID‐19 pandemic.

(1) Background: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and highly aggressive, with no practical risk model defined yet. The prognostic value of T-LBL immunological subtypes is still a matter of controversy. (2) Methods: We re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) protocols, 05/93 (n = 20) and T-LBL 1/2004 (n = 29), 85.7% of which achieved complete remission (CR). (3) Results: The 5/10-year overall survival (OS) and event-free survival (EFS) were 62%/59% and 48%/43%, respectively. In 96% of patients, flow cytometry analyses defining the WHO 2008 immunophenotypes were available. Cortical, early/pro-T/CD2(−), early/pre-T/CD2(+), and mature subtypes were identified in 59.5%, 19%, 15%, and 6.5% of patients, respectively. Overall, 20% of patients had the early T-cell precursor (ETP)-LBL immunophenotype, as proposed by the WHO 2017 classification. For the early/pro-T/CD2(−) subtype, the five-year OS and EFS were 13% and 13%, while for all the other, non-pro-T subtypes, they were 69% and 67%. By multivariate analysis, only CD2(−) status and age > 35 years emerged as strong, independent factors influencing OS and EFS, while the risk of CR failure was influenced by age only (>35 years). (4) Conclusions: ETP was non-significant for OS, unless an ultra-high-risk pro-T/CD2(−) subtype was concerned.

Background: MYC, BCL2 and BCL6 are known to be altered in high grade B-cell lymphoma (HGBL). Double/triple-hit lymphomas (D/THLs) are characterized by chromosomal rearrangementsof MYC, BCL2 and/or BCL6. D/THLs have been included in the updated 2016 WHO classification, as a new category of "High grade B-cell lymphoma with rearrangements" (HGBL-R) or Diffuse Large B-cell lymphoma (DLBCL) entity, depending on morphology/cytogenetic features. BCL2 protein is expressed in a much higher proportion of DLBCL and HGBL, not otherwise specified (HGBL,NOS), and is often associated with a concomitant expression of MYC and BCL6. Most of HGBLs do not carry BCL2/MYC/BCL6 rearrangements and are referred to as "double/triple-expressor lymphomas" (D/TELs). D/THLs patients usually progress rapidly, are resistant to R-CHOP immunochemotherapy, and have very poor prognosis. D/TELs also have a worse outcome than other DLBCL,NOS. BCL2 overexpression is observed in both germinal centre B-cell-like (GCB) and non-GCB HGBL. We have previously described a diagnostic algorithm for subtypes of HGBL based on flow-cytometry immunphenotyping (FCM) with CD38 overexpression, which correlates with MYC rearrangement assessed in fine needle aspiration biopsy (FNAB) samples. Here, we propose that patients with HGBL/DLBCL,NOS, with BCL2 overexpression, especially those with D/THLs and D/TELs, may benefit from DA-EPOCH-R (dose-adjusted cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone with rituximab) treatment. Methods: 30 patients (male/female 18/12, median age/range 51/35-76/) diagnosed with DLBCL,NOS (13 pts), HGBL-R (11 pts), HGBL,NOS (2 pts), primary mediastinal B-cell lymphoma - PMBL (3 pts) and DLBCL,leg type (1 pt), based on 2016 WHO classification, were treated with DA-EPOCH-R as first-line therapybetween January 2015 - July 2016. Clinical stage III or IV and IPI 3 or more were found in 27 pts (90%) and 22 pts (73%), respectively. All cases were evaluated by histopathological/immunohistochemical/flow-cytometry examination (HP/IHC/FCM), with panels of antibodies, including also CD5/CD10/CD20/CD38/BCL2/BCL6/MYC. In most cases, MYC, BCL2, BCL6 and, in case of relapse, also TP53 status was evaluated by karyotyping (CC) and FISH. Results: Considering the cell-of-origin, there were 20 pts with GCB, 3 non-GCB, 4 CD5+ and 3 PMBL. In addition, 15 pts were DEL, 12 - TEL, 3 - one-expressor lymphoma, 8 - D/THL, 12 - one-hit lymphoma and 10 - non-hit lymphoma, mostly with BCL2 overexpression. Karyotype was successfully assessed in 70%, while BCL2 overexpression was found in 83% of HGBL pts. MYC, BCL2, and BCL6 rearrangement was found in 48%, 35% and 21%, respectively. In 50%, 46% and 54% of cases there was an increase in copy number/amplification of MYC, BCL2 and BCL6, respectively. In 15 evaluable pts., overall and complete response was 80% and 53%, respectively. Median follow-up of HGBL pts treated with DA-EPOCH-R was 5 months (range 1-17), and the probability of one year overall survival was 91%, 95% C.I. (80%,100%). Progression free survival at 1 year was 62%, 95C.I. (36%,90%). 3 of 4 patients with progressive disease had TP53 deletion. The main toxicity was pancytopenia with neutropenia grade 3 or more in 24 pts (80%). Treatment-related mortality due to septic shock occurred in 2 patients (7%). Conclusions: DA-EPOCH-R regimen shows a promising activity considering D/THL and D/TEL-associated drug resistance. DA-EPOCH-R regimen seems to overcome drug resistance associated with BCL2/MYC/BCL6 overexpression, but not with TP53 deletion. Combining HP/IHC with FNAB/FCM/CC/FISH is a reliable method for D/THL and D/TEL diagnosis but the most sensitive method for fast MYC/BCL2 rearrangement assessment in DHL is FNAB/FCM CD38 and BCL2 overexpression.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma which is associated with a relatively poor prognosis compared to other diffuse large B-cell lymphomas. Population-based cancer registry data demonstrates that there has been a significant improvement in the survival of patients with PCNSL over the past two decades. This improvement likely reflects the introduction of high-intensity chemotherapy based on an induction regimen with high-dose methotrexate, and consolidation strategy including autologous stem cell transplantation. As a result, the improvement has been mainly observed in younger patients. New approaches such as Bruton tyrosine kinase inhibitor, immunomodulatory agents, immune checkpoint inhibition, and chimeric antigen receptor T-cell therapy are under investigation for PCNSL. In addition, trials combining novel agents in front-line induction treatment are ongoing. Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma which is associated with a relatively poor prognosis compared to other diffuse large B-cell lymphomas. Population-based cancer registry data demonstrates that there has been a significant improvement in the survival of patients with PCNSL over the past two decades. This improvement likely reflects the introduction of high-intensity chemotherapy based on an induction regimen with high-dose methotrexate, and consolidation strategy including autologous stem cell transplantation. As a result, the improvement has been mainly observed in younger patients. New approaches such as Bruton tyrosine kinase inhibitor, immunomodulatory agents, immune checkpoint inhibition, and chimeric antigen receptor T-cell therapy are under investigation for PCNSL. In addition, trials combining novel agents in front-line induction treatment are ongoing.

The aim of this prospective, observational study was to evaluate the safety and efficacy of high-dose chemotherapy (HDC) with carmustine, etoposide and thiotepa (BET) followed by autologous stem-cell transplantation (ASCT) for transplant eligible primary central nervous lymphoma (PCNSL) patients. High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is a recommended consolidation strategy for eligible primary CNS lymphoma patients; however, more data on its efficacy and safety in real-world patients are still needed. We report the outcomes of 60 patients treated in five hemato-oncology centers within the Polish Lymphoma Research Group, considered eligible for HDC-BET-ASCT after R-MIV (rituximab, methotrexate, ifosfamide, vincristine) induction with one cycle of AT (cytarabine and thiotepa) at the end of induction. The median age (range) was 58 (19-70) years, with 24 (40%) patients aged ≥ 60 years. Two patients (3.3%) died from transplant-related toxicity. At a median follow-up of 51 months, 4-year progression-free (PFS) and overall survival (OS) were 66% and 74%, respectively. Fifteen (25%) patients relapsed: 10 within the first 12 months, while 2 patients (13.3%) 3.6 years and 7 years after ASCT. Five patients (33%) achieved a second complete remission, with two patients eligible for a second HDC-ASCT. Eighteen patients were transplanted during the COVID-19 pandemic, with more relapses shown during this period (44.4% vs. 16.6%), but with no impact on 4-year OS (p = 0.49) and PFS (p = 0.1) compared to patients treated outside the pandemic. Strategy based on R-MIV induction and HDC-BET-ASCT was feasible and had acceptable safety in daily practice.