Diffuse Large B-cell Lymphoma Leg Research Articles

Characteristics of Primary Cutaneous Lymphoma in Italy: A Tertiary Care, Single-Center Study.

Data on primary cutaneous lymphomas (PCLs) patients in the Italian population are limited, and, despite the existence of several treatment options, the management of those patients remains challenging. Our study aimed to investigate the clinical and therapeutic features of PCL patients in a referral center in Italy. We conducted a retrospective study on 100 consecutive PCL patients between January 2017 and December 2022. The mean (SD) age of our cohort was 70.33 (14.14) years. Cutaneous T-cell lymphomas (CTCLs) represented 65% of all cases; the majority were mycosis fungoides (42%), followed by cases of Sezary syndrome (10%) and primary cutaneous anaplastic large cell lymphoma (4%). Cutaneous B-cell lymphomas (CBCLs) accounted for 35 % of PCLs, with 15 cases of primary cutaneous follicle center lymphoma, 10 cases of primary cutaneous diffuse large B-cell lymphoma leg type, and 9 cases of marginal zone B-cell lymphoma. A higher frequency of pruritus (p = 0.008) and higher peripheral blood levels of beta-2 microglobulin (p ≤ 0.001) and lactate dehydrogenase (p = 0.025) were found in CTCLs compared to those of CBCLs. Considering all therapeutic lines performed, treatments were extremely heterogeneous and skin-directed therapies represented the most frequently used approach. Our study confirms the distribution of PCL subtypes formerly reported in the literature and highlights the utility of real-life data in treatments to improve the current management of PCL patients.

O-127 - Cutaneous relapses location in diffuse large B-cell lymphoma leg type after immunochemotherapy

O-127 - Cutaneous relapses location in diffuse large B-cell lymphoma leg type after immunochemotherapy

Orbital Involvement by Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type.

Orbital Involvement by Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type.

1421 Primary cutaneous diffuse large B-cell lymphoma–leg type masquerading as a mucocele

1421 Primary cutaneous diffuse large B-cell lymphoma–leg type masquerading as a mucocele

Assessment of Liquid Biopsy in Primary Cutaneous Diffuse Large B-Cell Lymphoma–Leg Type

Liquid biopsy assessment has been first established in solid tumors, allowing the detection of either circulating tumor cells, cell-free vesicles and/or circulating tumor cell-free DNA (ctDNA), in the plasma or other biological fluids. In systemic diffuse large B-cell lymphomas (DLBCL), ctDNA is detectable, reflecting tumor mutational status, and may predict clinical outcome ( Bohers et al., 2018 Bohers E, Viailly P-J, Becker S, Marchand V, Ruminy P, Maingonnat C, et al. Non-Invasive Monitoring of Diffuse Large B-Cell Lymphoma by Cell-Free DNA High-Throughput Targeted Sequencing: Analysis of a Prospective Cohort. Blood Cancer J. 2018;1;8(8):74. Google Scholar ). In addition, dynamics of ctDNA correlates with clinical response ( Kurtz et al., 2019 Kurtz D.M. Esfahani M.S. Scherer F. Soo J. Jin M.C. Liu C.L. et al. Dynamic risk profiling using serial tumor biomarkers for personalized outcome Prediction. Cell. 2019; 178: 699-713.e19 Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar ; Deng et al., 2020 Deng Q, G Han, N Puebla-Osorio, M Chun John Ma, P Strati, B Chasen, et al. Characteristics of Anti-CD19 CAR T Cell Infusion Products Associated with Efficacy and Toxicity in Patients with Large B Cell Lymphomas. Nat Med. 2020;26 (12): 1878-1887. Google Scholar ; Kurtz et al. 2018). Primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT) is an aggressive cutaneous lymphoma, presenting as rapid progressive tumor(s) in elderly ( Willemze et al., 2019 Willemze R. Cerroni L. Kempf W. Berti E. Facchetti F. Swerdlow S.H. Jaffe E.S. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019; 133: 1703-1714 Crossref PubMed Scopus (535) Google Scholar ). Mutational landscape of PCDLBCL-LT showed Activated B-cell-like DLBCL canonical mutations, ( Mareschal et al., 2017 Mareschal S. Pham-Ledard A. Viailly P.J. Dubois S. Bertrand P. Maingonnat C. et al. Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing. J Invest Dermatol. 2017; 137: 1984-1994 Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar ; Zhou et al. 2018) especially with high prevalence of MYD88L265P (70%) and CD79B (40%) mutations that allows its classification in MCD or C5 subgroup among DLBCL ( Schmitz et al., 2018 Schmitz R. Wright G.W. Huang D.W. Johnson C.A. Phelan J.D. Wang J.Q. et al. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Eng J Med. 2018; 378: 1396-1407 Crossref PubMed Scopus (936) Google Scholar ) ( Chapuy et al., 2018 Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, et al. 2018. Molecular Subtypes of Diffuse Large B-cell Lymphoma are Associated with Distinct Pathogenic Mechanisms and Outcomes ». Nat Med. 2018;24(5):679-690. Google Scholar ). Genetic analysis on primary tumors may be limited by tumor site, sample size but also by spatial and temporal mutational heterogeneity (Condoluci et Rossi 2019; Phallen et al., 2017 Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, et alDirect detection of early-stage cancers using circulating tumor DNA. Sci Transl Med. 2017;16;9(403):eaan2415. Google Scholar ). Droplet digital PCR (ddPCR) and its increased sensitivity of 0.01% (Diaz et Bardelli 2014) may detect infraclinical systemic involvement and appears appropriate for single hot-spot mutations detection such as MYD88L265P. Next Generation Sequencing (NGS) may be more appropriate to capture the mutational landscape of ctDNA ( Galimberti et al., 2019 Galimberti S. Genuardi E. Mazziotta F. Iovino L. Morabito F. Grassi S. et al. The Minimal Residual Disease in Non-Hodgkin’s Lymphomas: From the Laboratory to the Clinical Practice. Front Oncol. 2019; 26: 528 Crossref Scopus (14) Google Scholar ).

Molecular Diagnostics for TP53 Is Recommended in B-Cell Lymphomas

Introduction Multiple studies in patients with B-cell lymphomas (BCL) have shown that TP53 is associated with inferior therapeutic efficacy and survival outcomes. Current treatment algorithms for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are tailored for patients harboring a TP53 mutation using a different therapeutic strategy. Regardless, targeted next generation sequencing (tNGS) is not standard practice in the diagnostic workup of lymphomas. In solid malignancies, e.g., ovarian cancer (PMID: 35752743), our institute has shown that p53 immunohistochemistry (IHC) is a good and widely used marker to assess TP53 mutations. In lymphomas however, this correlation is not yet as clearly established. Here we evaluate the accuracy of p53 IHC as a surrogate marker for TP53 mutational analysis in a large cohort of BCL. Method For this retrospective study 278 consecutive patients diagnosed with BCL between 2014-2022 were selected. The cases were diagnosed according to the revised 4th edition WHO classification (2016), and included diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS, n=145), primary cutaneous DLBCL leg type (PCDLBCL LT, n=13), high grade B-cell lymphoma (HGBCL, n=8), primary central nervous system lymphoma (PCNSL, n=11), primary mediastinal B-cell lymphoma (PMBCL, n=3), Burkitt lymphoma (n=4), mantle cell lymphoma (MCL, n=18) and a diverse group of indolent mature B-cell neoplasms (MBCN, n=76, specified in figure 1). P53 IHC staining was performed using the Dako Autostainer Link 48 (Dako Omnis, Glostrup, Denmark), according to standard procedures. For each case, p53 IHC was blindly and independently assigned by one junior (LMH) and one senior (PMJ) hematopathologist to one of the following categories: abnormal (complete absence OR staining > 50% of tumor cells) or wild type (WT) (staining 1-50% of tumor cells). All discordant cases were discussed at a consensus meeting attending both pathologists and assigned a definitive category. The inter-rater reliability was measured with Cohen's kappa coefficient. Pathogenic variants of TP53 for all cases were identified with an in-house developed tNGS panel (LYMFv1), including 52 B-cell lymphoma-relevant genes and covering all exons of TP53, as described before (PMID: 34478526). Results IHC showed 213 p53 WT and 65 abnormal. Kappa correlation of the p53 IHC assessment between the two pathologists was 0,82, indicating a strong level of agreement. tNGS identified a TP53 mutation in 75 patients (26,9%), of which DLBCL NOS was the largest subgroup (n=43), followed by MBCN (n=14) and MCL (n=7). Overall, most TP53 mutations were non-synonymous (80,5%) and localized in exon 7 (36%), as shown in the Oncoprintplot (figure 1). In MBCN the most frequent location was exon 5 (33%), while in DLBCL as the largest subgroup, mainly exon 7 (38%) was affected. The overall accuracy of p53 IHC was 85,6% (95% CI 80,9-89,5%) for the presence of TP53 mutation. The corresponding sensitivity and specificity were 66,7% (95% CI 56,0-77,4%) and 92,2% (95% CI 88,5-95,9%), respectively. 25 BCLs showed a false-negative (FN) p53 WT IHC, despite detection of TP53 mutation. MBCN was the least accurate performing group (8/14 FN), followed by DLBCL NOS (13/43 FN). On the other hand, there were 15 BCLs with a false-positive (FP) abnormal IHC staining without identification of a TP53 mutation (figure 2). Again, MBCN was the lowest performing group (7/62 FP), but the overall specificity was high. Conclusion Our data indicate that the performance of p53 IHC is not sufficient as a surrogate marker for TP53 mutations in the diagnostic workup of lymphoma patients. Although the specificity is high with a low amount of FP, the sensitivity is relatively low with a high number of FN. It seems that misinterpretation of the p53 IHC is not an adequate explanation for the low sensitivity, considering the strong inter-rater reliability and the re-assessment of all discordant cases. By utilizing only p53 IHC there is a significant chance a TP53 mutation is missed, resulting in misevaluation of a high-risk patient. Therefore, molecular analysis is recommended in all patients with BCL, especially for further development of risk-directed therapies based on TP53 mutation status. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Histopathological Features of Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type: A Case Report

Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare and aggressive lymphoma with poor prognostic. It is difficult to diagnose PCDLBCL-LT at an early stage due to its nonspecific manifestations that overlap with other lymphomas. A histopathological examination can be performed to establish the diagnosis.
 Case Presentation: A 74-year-old female presented with itchy red, swollen patches accompanied by a burning sensation on both her legs. Clinical examination revealed a hard ping pong ball-sized lump palpable on her left inner thigh. Haematoxylin eosin staining demonstrated the proliferation of diffused neoplastic cells, homogenous cells with atypical nuclei, and mitoses. Immunohistochemical examination revealed positive for CD 45 as well as CD 20 and negative for CD3. These findings were consistent with a diagnosis of PCDLBCL-LT.
 Conclusion: The presented case demonstrates that skin lesions in patients with diagnosed PCDLBCL-LT may have a variable clinical presentation. Histologically is characterized by a diffuse dermal infiltrate mostly consisting of activated B-cell (centroblast) and activated lymphocyte (immunoblast), with high mitotic activity and a minimal T-reactive component. Immunohistochemical analysis is necessary for establishing the diagnosis of PCDLBCL-LT which shows positive markers for CD 45, CD 20, CD79a, Bcl-2, MUM-1, FOX-P1, CD10, IgM, CD 138, Ki-67, CD 30 and MYC.

Patient-Derived Xenograft and Cell Line Models of Human Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type

Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) is a rare and aggressive malignancy, mostly occurring on the leg of elderly women (Willemze et al., 2019). PCDLBCL-LT harbors an activated B-cell‒like diffuse large B-cell lymphoma (ABC-DLBCL) signature and is enriched for mutations involving the toll-like receptor, B-cell receptor, and NF-κB pathways (Pham-Ledard et al., 2012; Zhou et al., 2018). The high frequency of MYD88L265P mutation in combination with those of CD79B and PIM1 relates these lymphomas to the MCD/C5 subset of diffuse large B-cell lymphomas, which includes ABC-DLBCL occurring in extranodal sites (Danilov et al., 2022).

Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type, a Convoluted Path to Diagnosis

Primary cutaneous diffuse large B cell lymphoma is a rare and aggressive form of primary cutaneous B-cell lymphoma. It typically presents with reddish to brown-nodules on the distal legs. We introduce the case of a 71 year-old female who presented to an urgent care clinic with a new onset of painful nodules on her right lower extremity. After workup and treatment for superficial thrombophlebitis, the patient improved until she presented to her primary care physician with worsening symptoms one month later. Diagnosis of primary cutaneous diffuse large B-cell lymphoma, leg type was confirmed via biopsy. After referral to oncology, further workup showed stage 4 disease. The patient was subsequently scheduled to begin treatment with R-CHOP. Unfortunately, prior to the initiation of chemotherapy she passed away after contracting COVID-19 pneumonia.

Cutaneous Epstein-Barr virus–positive diffuse large B-cell lymphoma, not otherwise specified: A systematic review and comparative analysis with Epstein-Barr virus–negative, leg type

To the Editor: Epstein-Barr virus (EBV)–positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an EBV-associated B-cell lymphoma often presenting in elderly patients without any known immunodeficiencies.1,2 For a systematic review to characterize cutaneous EBV-positive DLBCL-NOS, we searched 5 databases (Supplemental Fig 1; available via Mendeley at https://doi.org/10.17632/dby7kdtzk8.1).3 We also searched the Asan Medical Center database for cases of cutaneous EBV-positive DLBCL-NOS and primary cutaneous EBV-negative DLBCL–leg type for comparative analysis.

18FDG PET/CT in Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type

An 86-year-old woman was referred for a rare but aggressive subtype of primary cutaneous lymphoma of the right lower limb: diffuse large B-cell lymphoma leg type. Initial evaluation by whole-body F-FDG PET/CT showed intense hypermetabolic activity of multiple cutaneous and subcutaneous nodules of the distal third of the right leg. Follow-up evaluations by F-FDG PET/CT showed complete response after 4 and 8 cycles of appropriate rituximab combination with polychemotherapy. Although no specific recommendations are available, our case stresses the major role of F-FDG PET/CT for initial extension and treatment response evaluation in clinical practice of primary cutaneous diffuse large B-cell lymphoma leg type.

Mutations of the B-Cell Receptor Pathway Confer Chemoresistance in Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) preferentially involves the lower limb in elderly subjects. A combination of polychemotherapy and rituximab has improved prognosis. However, about 50% of patients will experience progression or relapse without any predictive biologic marker of therapeutic response. The mutational profile of PCLBCL-LT has highlighted mutations contributing to constitutive NF-κB and B-cell receptor (BCR) signaling pathways but has not demonstrated clinical utility. Therefore, the mutational status of 32 patients with PCLBCL-LT (14 patients with complete durable response and 18 patients with relapsing or refractory disease) was determined with a dedicated lymphopanel. Tumor pairs at diagnosis and relapse or progression were analyzed in 14 relapsing or refractory patients. Patients with PCLBCL-LT harboring one mutation that targets one of the BCR signaling genes, CD79A/B or CARD11, displayed a reduced progression-free survival and specific survival (median 18 months, P= 0.002 and 51 months, P= 0.03, respectively, whereas median duration in the wild-type group was not reached) and were associated with therapeutic resistance (P= 0.0006). Longitudinal analyses revealed that MYD88 and CD79B were the earliest and among the most mutated genes. Our data suggest that evaluating BCR mutations in patients with PCLBCL-LT may help to predict first-line therapeutic response and to select targeted therapies.

Successful Treatment of Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type With Single-Agent Venetoclax.

Successful treatment of primary cutaneous diffuse large B cell lymphoma leg type with single agent venetoclax

Primary Cutaneous Follicle Center Lymphoma.

Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma that is limited to the skin at diagnosis. It has a differential diagnosis that includes systemic/nodal follicular lymphoma secondarily involving the skin; primary cutaneous diffuse large B-cell lymphoma leg type; reactive lymphoid hyperplasia; and primary cutaneous marginal zone lymphoma. To review the clinical, morphologic, immunophenotypic, and genetic features of primary cutaneous follicle center lymphoma; its differential diagnosis; and the evidence that supports use of immunohistochemistry and genetic testing in the diagnosis and prognosis of this entity. Pertinent literature regarding cutaneous B-cell lymphomas is summarized and University of Michigan cases are used to highlight characteristics of primary cutaneous follicle center lymphoma. Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma with distinctive features, although some cases may have elements that overlap with other lymphomas, complicating interpretation.

Primary cutaneous B-cell lymphomas- clinical and histopathologic features, differential diagnosis, and treatment.

Cutaneous B-cell lymphomas (CBCLs) are a heterogeneous group of diseases that can have variable presentations, prognoses, and treatments. The proper identification of a CBCL hinges on proper histopathologic and clinical evaluation. Comprising 25% to 30% of the primary cutaneous lymphomas, incident cases of CBCL are rare. Given the variable natural history of the CBCL, proper classification is critical so that patients are treated appropriately. CBCLs can be divided into 2 main groups: indolent and aggressive. Indolent CBCLs include primary cutaneous follicle center lymphoma and primary cutaneous marginal zone lymphoma. These subtypes usually do not affect a patient's lifespan but can lead to substantial symptomatology, prompting the need for treatment. The aggressive subtypes of CBCL include diffuse large B-cell lymphoma leg type and intravascular large B-cell lymphoma. These are treated as systemic lymphomas, and their prognoses are not as good. In this article, we discuss the clinical features, differential diagnoses, histopathologic features, and treatment options for each of the 4 types of CBCL. The proper categorization of these diseases can allow physicians to properly treat a patient with CBCL, including the avoidance of unnecessary therapy.

Paediatric cutaneous lymphomas: a review and comparison with adult counterparts.

Primary cutaneous lymphomas (CL) in children is rare. Only a few studies focused specifically on paediatric CL and therefore little is known whether primary CL in children are similar to or different from their adult counterparts with respect to the clinicopathological presentation, behaviour and prognosis. An extensive literature search using PubMed/MEDLINE from January 1995 through July 2014 was undertaken for articles reporting cases of paediatric CL. In addition, we identified 31 children with CL in our institutions. Mycosis fungoides and lymphomatoid papulosis are the two most prevalent lymphoma forms in children. A few entities of cutaneous lymphomas such as cutaneous diffuse large B-cell lymphoma leg type, and Sézary syndrome have not been reported so far in children. Other lymphoma entities such as hydroa vacciniforme-like lymphoma are mostly seen in certain geographic areas (Asia, Central and South America). In the paediatric population, low-malignant indolent forms such as primary cutaneous marginal zone lymphoma and primary cutaneous follicle centre lymphoma are very rare, whereas the more aggressive forms of B-cell lymphomas, precursor lymphoblastic lymphomas, and blastic plasmacytoid dendritic cell neoplasm are the most common forms in children, mostly involving the skin secondarily. Most paediatric lymphomas have similar clinicopathological features and course as their adults counterparts, particularly in the group of cutaneous T-cell lymphomas. The spectrum of cutaneous B-cell lymphomas in children significantly differs from the one in adults. Diagnostic work-up and treatment of paediatric patients with lymphomas are best achieved in close collaboration with paediatric haematopathologists and oncologists.

A ‘migrant’ mass of the forehead: Diagnosis and treatment

Primary cutaneous large B-cell lymphoma, leg type, is a rare and aggressive neoplasm as defined by the World Health Organization/European Organisation for Research and Treatment of Cancer classification of cutaneous lymphomas. In some cases this disease may simulate other forms of benign or malignant solid tumours. We present a case of a 74-year-old man showing a quickly 'migrant' mass on his forehead. First skin biopsy, ultrasound and magnetic resonance images were not significant. A deeper biopsy revealed a pathology consistent with a primary cutaneous diffuse large B-cell lymphoma leg type. The patient was successfully treated with only local radiotherapy (total dose: 32.4 Gy). At 1-year follow-up there were no recurrences. To the best of our knowledge, this is the second case of a primary cutaneous diffuse large B-cell lymphoma leg type developed as a quickly 'migrant' lesion. In contrast with the first report, our case developed in a non-leg site. From these two cases, we should bear in mind that aggressive and quickly migrant cutaneous or subcutaneous masses might mask a lymphomatous disease.

Diffuse large B-cell lymphoma leg type secondary to testicular diffuse large cell-B lymphoma

Diffuse large B-cell lymphoma leg type secondary to testicular diffuse large cell-B lymphoma

Primary cutaneous diffuse large B-cell lymphoma leg type presenting with hemophagocytic syndrome

Primary cutaneous diffuse large B-cell lymphoma leg type presenting with hemophagocytic syndrome

Pegylated Liposomal Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (CBVD) in the Treatment of Advanced Primary Cutaneous Lymphomas.

Abstract 3717Poster Board III-653 IntroductionPrimary cutaneous lymphomas (PCL) present in the majority of histologic variants an indolent behaviour and a good prognosis with a prolonged survival. In a very small number of patients (pts), PCL is aggressive at the onset while in pts who are resistant or have relapsed after repeated topic or systemic therapies an advanced disease is more frequently observed. In these patients no therapy is capable of inducing a stable remission of the disease. The efficacy and low toxicity of Pegylated Liposomal Doxorubicin (PLD) as a single agent in second-line therapy of PCL was recently demonstrated. In our study we tested the safety and efficacy of PLD (Caelyx®) (C) in association with three drugs of proven effectiveness in nodal lymphoprolipherative and other primary cutaneous neoplastic disorders: Bleomycin (B), Vinblastine (B) and Dacarbazine (D) (CBVD). Patients and MethodsFrom February 2003 to December 2008 we observed 37 consecutive pts with advanced PCL: 19 Cutaneous T-Cell Lymphomas (CTCL) and 18 cutaneous B-Cell Lymphomas (CBCL). The CTCL pts were: 15 males and 4 females, with median age 59 (27-86) years, of which 7 pts with Anaplastic Large Cell Lymphoma (ALCL) CD30 positive, 7 pts with transformed Mycosis Fungoides (tMF), 3 pts with CD30 negative ALCL, 1pt with Panniculitis-like (Pl) Lymphoma and 1 pt with transformed Sezary Syndrome (tSS), according to the WHO-EORTC consensus classification. Nine pts presented with a nodal involvement and 10 pts were resistant or relapsed after 1 or more systemic treatments. Among the CBCL pts there were: 8 males and 10 females, with median age 61 (42-84) years, 12 pts had a Follicular Centre Lymphoma (FCL), 3 a Marginal Zone Lymphoma (MZL) and 3 a Diffuse Large B-Cell Lymphoma Leg Type (LT). Five pts presented a nodal involvement and 11 pts had received 1 or more previous systemic therapy. All 37 pts received CBVD therapy at following dosage: C: 20 mg/m2, B: 10 mg/m2, V: 6 mg/m2, D: 325 mg/m2 at days 1 and 15, administered intravenously every 4 weeks for a maximum of 6 cycles. Rituximab (R) at dosage of 375 mg/m2 was administered to CBCL pts at 1st day of each cycle. Before the treatment, pts were submitted to a complete staging of disease including TC-scan, bone marrow biopsy, and immunophenotyping of peripheral blood cells. ResultsIn the CTCL group 4 pts received 4 CBVD cycles, 14 pts received 6 CBVD cycles and 1 pt presented a progressive disease after the 1st cycle. Overall Response Rate (ORR) was 94.7% (18/19 pts). Sixteen out of 18 pts (88.8%) had a Complete Remission (CR) with disappearance of nodal involvement and cutaneous lesions, 2/18 pts obtained a Partial Remission (PR) with disappearance of nodal involvement and 75% of cutaneous lesions. In the CBCL group 3 pts received 2 R-CBVD cycles, 3 pts 4 cycles and 11 pts 6 cycles: ORR was 100% and all pts obtained a CR. The occurrence of palmoplantar erytrodisesthesia in 5 pts and grade 2-3 granulocytopenia in 12 pts did not modify the therapy program. Two CTCL pts (1 tSS, 1Pl) and 1 CBCL (LT) pt in CR after therapy received an allogeneic Hemopoietic Stem Cells (HCS) transplant and 1 CBCL(FCL) pt a syngeneic HCS transplant. In CTCL group 11 (61%) pts maintained their response after a median follow up of 15.5 (9-71) months. Among CBCL pts 14 (77.7%) pts are still in CR after a median follow up of 15 (4-36) months. ConclusionsOur experience demonstrates that the CBVD association is an effective and safe therapy for advanced PCL in inducing an important tumour burden reduction with a high CR rate. The assessment of response duration requires a longer observation. A larger number of patients in a multicentric trial are needed to confirm our promising results. Disclosures:Off Label Use: liposomial doxorubicin has a peculiar cutaneous tropism and low cardiac toxicity compared with other anthracyclines.