Clinical Outcomes of Advanced-Stage Cutaneous Lymphoma under Low-Dose Gemcitabine Treatment: Real-Life Data from the German Cutaneous Lymphoma Network

Background: Gemcitabine is an effective single-agent chemotherapy used in advanced stages of cutaneous T-cell lymphoma (CTCL). However, gemcitabine used in the current standard regimen is frequently associated with adverse events (AE), such as an increased risk for myelosuppression and severe infections. Objectives: We investigated in this retrospective study the effect of low-dose gemcitabine in pretreated advanced-stage CTCL and in blastic plasmacytoid dendritic cell neoplasia (BPDCN) regarding overall response (OR), progression-free survival (PFS), and AE. Material and Methods: A retrospective, multicenter study was conducted on 64 CTCL and BPDCN patients treated with gemcitabine in average absolute dosage of 1,800 mg/m(2) per cycle, which is 50% lower compared to standard dosage of 3,600 mg/m(2) per cycle (1,200 mg/m² day 1, 8, 15). Evaluation of response to therapy and AE was done 4-6 weeks after the sixth cycle. Results: OR was 62% with 11% demonstrating a complete response. The median time of PFS was 12 months and median time to next treatment was 7 months. Only 3/63 patients showed serious side effects, e.g., port infection or acute renal failure. Almost 73% of the patients experienced minor to moderate side effects (CTCAE grade 0-2). Fatigue (27.2%), fever (22.7%), and mild blood count alteration (18.2%) were the most common AE. Conclusions: This retrospective analysis supports the use of low-dose gemcitabine therapy in CTCL, demonstrating with 62% OR and PFS of 12 months an almost identical response rate and survival as compared to the standard dose therapy reported in previous studies but with a significantly improved safety profile and tolerability

Molecular pathogenesis of cutaneous lymphoma-Future directions

Stadler R, Hain C, Cieslak C, Stranzenbach R. Molecular pathogenesis of cutaneous lymphoma-Future directions. Experimental Dermatology . 2020.The pathogenesis of cutaneous T-cell lymphomas is not clear. In recent years, the genetic changes in CTCL were explored. The detected mutations showed a great deal of heterogeneity between individual patients. The studies documented various copy number variations (CNV) and single nucleotide variations (SNV) in multiple genes involved in multiple signalling pathways. Recurrently mutated signalling pathways include JAK-STAT, MAPK, T-cell receptor, TNF receptor and NF kappa B signalling. In the period between 2018 and today, additional studies towards the genetic changes in CTCL were carried out. Genetic changes in gamma delta T-cell lymphoma are also shown in genes of the JAK-STAT, MAPK, MYC and chromatin signalling pathways. These studies might indicate a shift away from targeted sequencing approaches towards whole-genome sequencing. This approach demands additional resources in terms of funding but has the advantage of finding mutations in non-coding regions. These mutations were neglected for a long time, but as shown in contemporary research these regions harbour highly recurrent mutations affecting gene expression and regulation. Nevertheless, the detection of specific molecular changes in known pathways enables considerations for targeted therapies

BASCULE Syndrome Associated with Autoantibodies

Dear Editors: In 2016, Bessis and coworkers first reported Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome [...

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

PURPOSE: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. PATIENTS AND METHODS: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). RESULTS: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). CONCLUSION: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and S\ue9zary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

Abstract PURPOSE: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and S\ue9zary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. PATIENTS AND METHODS: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). RESULTS: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). CONCLUSION: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients