Disease Overview
Mantle cell lymphoma (MCL) is a non‐Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard ...therapies and a median overall survival (OS) of 4‐5 years.
Diagnosis
Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX‐11 or a low Ki‐67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma.
Risk Stratification
The MCL International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki‐67 proliferative index if available. The median OS for the low‐risk group was not reached (5‐year OS of 60%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group.
Risk‐Adapted Therapy
For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytotoxic
Regimen followed by autologous stem cell transplantation should be considered. Rituximab maintenance after autologous stem cell transplantation has also improved the progression‐free and overall survival. For older symptomatic MCL patients with intermediate or high risk MIPI, combination chemotherapy with R‐CHOP, R‐Bendamustine, or a clinical trial should be considered. In addition, rituximab maintenance therapy may prolong the progression‐free survival. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), lenalidamide (anti‐angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase BTK inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Clinical trials with novel agents are always a consideration for MCL patients.
Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of mature peripheral T-cell lymphoma (PTCL). The history of AITL is much longer and deeper than the literature would suggest given the ...many names that have preceded it. Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL. The 2016 World Health Organization classification of lymphoid neoplasms recently acknowledged the complexity of this diagnosis with the addition of other AITL-like subsets. AITL now resides under the umbrella of nodal T-cell lymphomas with follicular T helper phenotype. Induction strategies continue to focus on increasing complete remission rates that allow more transplant-eligible patients to proceed toward consolidative high-dose therapy and autologous stem cell rescue with improving long-term survival. There are several clinical trials in which recently approved drugs with known activity in AITL are paired with induction regimens with the hope of demonstrating long-term progression-free survival over cyclophosphamide, doxorubicin, vincristine, and prednisone. The treatment of relapsed or refractory AITL remains an unmet need. The spectrum of AITL from diagnosis to treatment is reviewed subsequently in a fashion that may one day lead to personalized treatment approaches in a many-faced disease.
During the height of the coronavirus disease 2019(COVID-19) pandemic, many health care facilities needed to focus on screening for and treating patients with known or suspected COVID-19. This ...resulted in the diversion of health care workers and resources.
Summary
Peripheral T‐cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti‐folate pralatrexate, the ...first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front‐line setting. This phase 2 study evaluated a novel front‐line combination whereby cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternated with pralatrexate (CEOP‐P) in PTCL. Patients achieving a complete or partial remission (CR/PR) were eligible for consolidative stem cell transplantation (SCT) after 4 cycles. Thirty‐three stage II‐IV PTCL patients were treated: 21 PTCL‐not otherwise specified (64%), 8 angioimmunoblastic T cell lymphoma (24%) and 4 anaplastic large cell lymphoma (12%). The majority (61%) had stage IV disease and 46% were International Prognostic Index high/intermediate or high risk. Grade 3–4 toxicities included anaemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), increased creatinine (12%) and liver transaminases (12%). Seventeen patients (52%) achieved a CR. The 2‐year progression‐free survival and overall survial, were 39% (95% confidence interval 21–57) and 60% (95% confidence interval 39–76), respectively. Fifteen patients (45%) (12 CR) received SCT and all remained in CR at a median follow‐up of 21·5 months. CEOP‐P did not improve outcomes compared to historical data using CHOP. Defining optimal front line therapy in PTCL continues to be a challenge and an unmet need.
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