Rare T-cell Lymphoma Research Articles

[Artículo traducido] Diferencias en el perfil mutacional del linfoma T paniculítico y la paniculitis lúpica. Nueva serie de casos

BackgroundSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. ObjectivesThe aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. Materials and methodsWe studied a total of 10 SPTCL and 10 LEP patients using targeted next-generation sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString® technology. Clinical data were collected, and correlations sought with the molecular data obtained. ResultsThe mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53(P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53(P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. ConclusionsThe mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53(P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma

BackgroundAnaplastic Large Cell Lymphoma (ALCL) is a rare and aggressive T-cell lymphoma, classified into ALK-positive and ALK-negative subtypes, based on the presence of chromosomal translocations involving the ALK gene. The current standard of treatment for ALCL is polychemotherapy, with a high overall survival rate. However, a subset of patients does not respond to or develops resistance to these therapies, posing a serious challenge for clinicians. Recent targeted treatments such as ALK kinase inhibitors and anti-CD30 antibody-drug conjugates have shown promise but, for a fraction of patients, the prognosis is still unsatisfactory.MethodsWe investigated the genetic landscape of ALK + ALCL by whole-exome sequencing; recurring mutations were characterized in vitro and in vivo using transduced ALCL cellular models.ResultsRecurrent mutations in FAT family genes and the transcription factor RUNX1T1 were found. These mutations induced changes in ALCL cells morphology, growth, and migration, shedding light on potential factors contributing to treatment resistance. In particular, FAT4 silencing in ALCL cells activated the β-catenin and YAP1 pathways, which play crucial roles in tumor growth, and conferred resistance to chemotherapy. Furthermore, STAT1 and STAT3 were hyper-activated in these cells. Gene expression profiling showed global changes in pathways related to cell adhesion, cytoskeletal organization, and oncogenic signaling. Notably, FAT mutations associated with poor outcome in patients.ConclusionsThese findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.

Subcutaneous Panniculitis-like T-cell Lymphoma

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a primary, rare cutaneous T-cell lymphoma that resembles panniculitis and accounts for <1% of all peripheral T-cell lymphomas. It is characterized by multiple subcutaneous nodules and plaques, which usually involve the extremities. Histopathological findings include the presence of neoplastic T-cell surround and disrupt individual adipocyte membranes. Immunohistochemistry will confirm diagnosis by CD8+ and CD56− cells. Here, we report a case of a 29-year-old female who presented with cutaneous panniculitis-like lesions diagnosed with cutaneous T-cell lymphoma with the help of histopathology and immunohistochemistry.

Different Mutational Profiles of Subcutaneous Panniculitis-like T-cell Lymphoma and Lupus Panniculitis: An Additional Case Series

BackgroundSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. ObjectivesThe aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. Materials and methodsWe studied a total of 10 SPTCL and 10 LEP patients using targeted next-generation sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. ResultsThe mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. ConclusionsThe mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

Characteristics and distinct prognostic determinants of individuals with hepatosplenic T-cell lymphoma over the past two decades.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes, representing less than one percent of non-Hodgkin lymphomas. Given its rarity, the true incidence of HSTCL is unknown and most data have been extrapolated through case reports. To the best of our knowledge, the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014, with a sample size of 122 patients. To paint the most updated epidemiological picture of HSTCL. A total of 186 patients diagnosed with HSTCL, between 2000 and 2017, were ultimately enrolled in our study by retrieving data from the Surveillance, Epidemiology, and End Results database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of HSTCL. Variables with a P value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio of greater than 1 representing adverse prognostic factors. Male gender was the most represented. HSTCL was most common in middle-aged patients (40-59) and less common in the elderly (80+). Non-Hispanic whites (60.75%) and non-Hispanic blacks (20.97%) were the most represented racial groups. Univariate Cox proportional hazard regression analysis of factors influencing all-cause mortality showed a higher OM among non-Hispanic black patients. CSM was also higher among non-Hispanic blacks and patients with distant metastasis. Multivariate Cox proportional hazard regression analysis of factors affecting CSM revealed higher mortality in patients aged 80 or older and non-Hispanic blacks. Overall, the outlook for this rare malignancy is very grim. In this retrospective cohort study of the United States population, non-Hispanic blacks and the elderly had a higher CSM. This data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group, such as treatment delays, which have been shown to increase mortality in this racial/ethnic group for other cancers.

Real-life efficacy of immunotherapy for Sézary syndrome: a multicenter observational cohort study

Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p=0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p=0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p=0.013). Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.

Sézary Syndrome in West Sweden: Exploring Epidemiology, Clinical Features, and Treatment Patterns in a Registry-Based Retrospective Analysis.

Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches.

Primary cutaneous anaplastic large-cell lymphoma resembling infratemporal space infection: a case report

BackgroundPrimary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma belonging to the CD30 + T-cell lymphoproliferative disorders. The case of PC-ALCL in the temporal region is exceedingly rare. Herein, we report a case of PC-ALCL involving the temporal region mimicking infratemporal space infection.Case presentationA 78-year-old woman presented to maxillofacial surgery service with a 6-month history of swelling and pain in the left side of her face. Laboratory investigations found an elevated C-reactive protein (CRP). Imaging findings showed enlarged lymph nodes and extensive thickening of subcutaneous tissue of the left temples. Based on these findings, the infratemporal space infection was suspected initially. The patient underwent incision and drainage, and we unexpectedly found no pus in the lesion area. Incisional biopsy showed necrosis and extensive involvement of the left temples by a diffuse infiltrate containing large, atypical cells. The tumor cells were positive for CD30, CD3, Ki67. They were negative for ALK (SP8), CD5, CD8, CD20 and PAX5. After considering these findings, a diagnosis of PC-ALCL was rendered. The patient was admitted to the lymphoma department for systemic chemotherapy and no relapse occurred during a follow-up period of six months.ConclusionsThis report suggests that if there are suspicious intraoperative manifestations, carrying out a biopsy simultaneously, using Hematoxylin and eosin (HE) staining, and a comprehensive Immunohistochemistry (IHC) panel are essential to diagnosing PC-ALCL to prevent misdiagnosis.

Clinicopathological and molecular genetic alterations in monomorphic–epitheliotropic intestinal T-cell lymphoma of the small intestine

BackgroundSmall intestinal monomorphic–epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL.MethodsThe clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein–Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed.ResultsOf the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up.ConclusionsOur findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

A rare T-cell lymphoma in an ankylosing spondylitis patient under immunosuppression with tumor necrosis factor inhibitor

A rare T-cell lymphoma in an ankylosing spondylitis patient under immunosuppression with tumor necrosis factor inhibitor

Epidemiology and Independent Prognostic Factors of Patients with Hepatosplenic T-Cell Lymphoma over the Past 2 Decades

Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes, representing less than one percent of non-Hodgkin lymphomas. Given its rarity, the true incidence of HSTCL is unknown and most data have been extrapolated through case reports. To the best of our knowledge, the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014, with a sample size of 122 patients. The aim of this study is to investigate the clinical characteristics, survival outcomes, and independent prognostic factors of patients with neuroblastoma over the past two decades with a larger sample size. Methods: A total of 186 patients diagnosed with HSTCL, between 2000 and 2017, were ultimately enrolled in our study by retrieving data from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of HSTCL. Variables with a p value &amp;lt;0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Our cohort had a male predominance (68.82%). Most patients were diagnosed between the age of 40- and 59-year-old (36.02%) and HSTCL was least common among patients 80 years old and older (6.45%). Non-Hispanic whites (60.75%) and non-Hispanic blacks (20.97%) were most represented. Univariate cox proportional hazard regression analyses of factors affecting all-cause mortality revealedhigher overall mortality among non-Hispanic black patients (HR= 1.97, 95% CI 1.27-3.07, p&amp;lt;0.01). CSM was higher among non-Hispanic blacks (HR= 2.34, 95% CI 1.47-3.72, p&amp;lt;0.01) and patients with distant metastasis (HR= 2.23, 95% CI 1.24-4.02, p&amp;lt;0.01). Multivariate cox proportional hazard regression analyses of factors affecting CSM revealedhigher mortality in patients aged 80 or older (HR= 4.72, 95% CI 1.14-19.54, p&amp;lt;0.05) and non-Hispanic blacks (HR= 2.02, 95% CI 1.08-3.7, p&amp;lt;0.05). Surgery, radiation and B symptoms did not affect the overall mortality, nor did they affect the CSM. Conclusion: Overall the prognosis of this rare malignancy is very dismal. In this United States population-based retrospective cohort study using the SEER database, we found that non-Hispanic blacks and patients 80 and above had a higher CSM. Furthermore, cancer directed surgery, marital status and distant metastasis did not affect mortality. While one would expect older patients to have a poorer prognosis, it remains unclear why one racial/ethnic group would be at higher risk as well. This data paves the way for larger prospective studies addressing factors associated with worse prognosis in non-Hispanic blacks, such as delay in treatment, which has been shown to worsen mortality in this racial/ethnic group in other malignancies.

Hyperpigmented Mycosis Fungoides Masquerading as Longstanding Lichen Planus Pigmentosus: A Diagnostic Pitfall.

Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma, accounting for 50%-60% of all cutaneous T-cell lymphoma cases. It has a prevalence of approximately 5-6 cases per 1 million people annually and a higher incidence in dark-skinned populations. We report a case of hyperpigmented MF in a 72-year-old dark-skinned man with a 5-year history of progressive, widespread poikilodermatous patches and thin plaques on the back and bilateral legs. The patient had been treated for lichen planus pigmentosus for 5 years without significant response to therapy. Multiple biopsies revealed a band-like lymphoid infiltrate in the dermis, accompanied by intraepidermal lymphocytes, some of which had larger hyperchromatic nuclei. CD4 + T lymphocytes were predominant over CD8 + T-positive cells located along the epidermis, dermoepidermal junction, and in the dermis. A diagnosis of hyperpigmented MF was made based on the clinical, histopathological, and immunohistochemical findings. This case report highlights the importance of considering hyperpigmented MF as a differential diagnosis in patients with longstanding lichen planus pigmentosus, particularly when there is a lack of response to therapy.

Identifying racial and ethnic disparities in patients diagnosed with mycosis fungoides/Sezary syndrome in the United States: A contemporary SEER analysis.

7544 Background: Mycosis fungoides (MF) and Sezary syndrome (SS) are rare cutaneous T-cell lymphomas. In this study, we compare demographics, treatment, and survival patterns in Hispanic (HI) vs. Non-Hispanic (NH) patients diagnosed with MF and SS. Methods: Data were analyzed on MF and SS patients in the US reported to SEER 18 database between 2000 and 2018. SEER 18 contains the most comprehensive population-based cancer information in the US, covering approximately 27% of the total US population, and up to 36% of HI. Racial groups analyzed included NH whites, HI whites, blacks, and Asians/Pacific Islanders. Patient characteristics, age-adjusted incidence rate, and survival rate were compared across ethnic groups, HI vs NH. Stratification by age, gender, and stage at diagnosis were considered. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between HI and NH. Multivariate analysis and propensity score matching were performed with adjustment for age, stage, and B-symptoms. Results: 8578 patients with MF and 275 patients with SS were identified. Of patients with MF, 11% were HI and 89% were NH; of patients with SS, 12% were HI and 88% were NH. In NH patients with MF, most patients were male (58%); for HI patients with MF, a male predominance was not observed (p &lt; 0.001). In patients with SS, most patients were male in both NH and HI (56% NH, 56% HI; p = 0.989). In both MF and SS, HI were diagnosed at younger ages compared to NH, 49 y.o vs 60 y.o (p &lt; 0.001) and 59 y.o vs 71 y.o (p = 0.009) respectively. Most HI and NH with MF and SS did not receive radiotherapy (91% of NH and 92% of HI for MF; 92% of NH and 91% of HI for SS; p values 0.166 and 0.760, respectively). On survival analysis, for patients with MF, the survival probability (SP) at 2, 5, and 10 years for HI vs NH were 94%, 87%, and 77% vs. 91%, 81%, and 69%, respectively. The survival difference observed favored HI (p &lt; 0.001). For patients with SS, there was no statistically significant survival difference between HI and NH with 2, 5, and 10 year SP at 65%, 42%, and 17% for HI and 62%, 36%, and 16% for NH, respectively (p = 0.99). In patients with SS, the median survival time in years was 3.3 and 3.2 in NH and HI patients, respectively. In patients with MF, the median survival time was not reached. On multivariate analysis, when adjusted for age, those patients with MF and SS who were older than 80 y.o and between 60 to 80 y.o, had worse OS compared to those younger than 60 y.o, with HR 17.6 (95%: 13.8 – 22.3 ) and 4.2 (95 % CI: 3.6 – 5) respectively for MF; and HR 1.8 (95% CI: 0.9 – 3.7) and 1.64 (CI 95% 1 – 2.8) respectively for SS. Conclusions: We identified ethnic differences in incidence, age at diagnosis, sex, and survival outcomes in patients with MF and SS. Notably, we identified a survival advantage in patients with MF that favored HI. In patients with SS, there was no ethnic difference in survival.

TMEM244 Is a Long Non-Coding RNA Necessary for CTCL Cell Growth.

Transmembrane protein 244 (TMEM244) was annotated to be a member of the TMEM family, which are is a component of cell membranes and is involved in many cellular processes. To date, the expression of the TMEM244 protein has not been experimentally confirmed, and its function has not been clarified. Recently, the expression of the TMEM244 gene was acknowledged to be a diagnostic marker for Sézary syndrome, a rare cutaneous T-cell lymphoma (CTCL). In this study, we aimed to determine the role of the TMEM244 gene in CTCL cells. Two CTCL cell lines were transfected with shRNAs targeting the TMEM244 transcript. The phenotypic effect of TMEM244 knockdown was validated using green fluorescent protein (GFP) growth competition assays and AnnexinV/7AAD staining. Western blot analysis was performed to identify the TMEM244 protein. Our results indicate that TMEM244 is not a protein-coding gene but a long non-coding RNA (lncRNA) that is necessary for the growth of CTCL cells.

499 - The Impact of Stem Cell Transplant on Clinical Outcomes of Primary Cutaneous Gamma-Delta T-Cell Lymphoma, Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma, and Subcutaneous Panniculitis-like T-Cell Lymphoma: Analysis of Pooled Databases of Rare Cutaneous Extra-Nodal T-Cell Lymphoma Entities

499 - The Impact of Stem Cell Transplant on Clinical Outcomes of Primary Cutaneous Gamma-Delta T-Cell Lymphoma, Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma, and Subcutaneous Panniculitis-like T-Cell Lymphoma: Analysis of Pooled Databases of Rare Cutaneous Extra-Nodal T-Cell Lymphoma Entities

501 - The Impact of Stem Cell Transplant on Clinical Outcomes of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma and Hepatosplenic T-Cell Lymphoma: Analysis of Pooled Databases of Rare Extra-Nodal Peripheral T-Cell Lymphoma Subtypes

501 - The Impact of Stem Cell Transplant on Clinical Outcomes of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma and Hepatosplenic T-Cell Lymphoma: Analysis of Pooled Databases of Rare Extra-Nodal Peripheral T-Cell Lymphoma Subtypes

A Rare Case of CD4 Positive Cytotoxic PTCL, NOS With Leukemic Presentation.

Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a relatively rare mature T-cell lymphoma that cannot be categorized under any of the well-defined category. This type of aggressive lymphoma mostly involves the lymph nodes, though any other organ can be affected. Leukemic presentation is extremely rare. No case report of isolated leukemic presentation was found after detail literature search. Herein we present a case of PTCL, NOS with leukemic presentation.

Primary Cutaneous Gamma-Delta T-Cell Lymphoma (PCGDTCL) Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Introduction Primary Cutaneous Gamma-Delta T-cell Lymphoma (PCGDTL) is a rare clinical entity that represents <1% of all cutaneous lymphomas. It is characterized by clonal proliferation of mature, activated T-cells expressing the T-cell receptor (TCR) γ/δ and cytotoxic molecules. PCGDTL is often resistant to conventional chemotherapy and is usually associated with poor prognosis. We have conducted this pooled database analysis to delineate key disease characteristics and clinicopathologic determinants of survival in this rare cutaneous T-cell lymphoma. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 140 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results A total of 140 patients with confirmed PCGDTCL were identified. The median age was 54 years with peak incidence between ages 52 and 65 years. There was no sex preponderance. The median duration of symptoms prior to diagnosis was 9 months. Eighty percent of patients presented with >4 lesions with an average size of 3.4cm. The disease involved mostly the lower extremities followed by the upper extremities, trunk, and lastly the face. Almost all the lesions involved the dermis with 48% involving the epidermis. Twenty-four percent of the lesions presented with ulceration and 30% had fat necrosis. Patients presented with constitutional symptoms in 28%, splenomegaly 6%, lymphadenopathy 16%, and hemophagocytic syndrome (HPS) 13%. Compared to no treatment, combination chemotherapy and stem cell transplant (SCT) were statistically superior with median OS months of 2, 16, and not reached respectively (p<0.0001). Age inversely correlated with survival while time from symptoms to diagnosis has a positive correlation. CD30+ imparted a survival advantage while HPS was detrimental to OS, both at borderline significance. Visceral involvement was also associated with a worse median OS (9.5 vs 18 months). OS was not impacted by sex, size of the lesions, or subcutaneous involvement. While solitary disease and absence of constitutional symptoms and bone marrow involvement seemed to have better OS, they did not reach statistical significance. Conclusions This study presents an updated clinicopathologic data from a pooled cohort of patients with PCGDTCL. It details the features of this rare disease and identifies the clinical, immunohistochemical, and treatment modalities that are major determinants of OS.

Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma (PCAECTCL) Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Introduction: Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-cell lymphoma (PCAECTCL) is a rare provisional clinical entity and a subtype of cutaneous T-cell lymphoma. It is characterized by cytotoxic T-cells that primarily involve the epidermis causing rapidly progressive epidermal necrosis and extensive skin ulcers. PCAECTCL is often resistant to conventional chemotherapy and is usually associated with a poor prognosis. We conducted this pooled database analysis to delineate key disease characteristics and clinicopathologic determinants of survival in this rare provisional cutaneous T-cell lymphoma. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 128 cases. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assessing the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 128 patients with confirmed PCAECTCL were identified. The median age was 62, with a peak incidence between 60 and 75 years. There was a male predominance with M:F ratio of 1.9. The median duration of symptoms prior to diagnosis was 6 months. Most of the patients presented with stage IIB (75%), followed by IB (13%), IA(7%), IVB(3%), and IIA(1%). Constitutional symptoms (CS), hemophagocytic syndrome, and ulceration/necrosis were present in 6%, 33%, 1.5%, and 45%, respectively. PCAECTCL widely metastasized in 62% of the cases, mainly to mucocutaneous tissues and visceral organs (83%), which included testicles (11%) and CNS (22%). PCAECTCL immunophenotype consisted of: CD2(37%), CD3(99%), CD5(40%), CD7(66%), CD30(16%), CD45RA(77%), CD56(6%), Granzyme B(72%), TIA-1(100%), and a median Ki-67 score of 70%. The median OS of the whole group was 20 months. OS was significantly impacted as age increased from <40 to 40-59 and > 60 (34 vs. 27 vs. 12 months, p=0.0003). Combination chemotherapy and stem cell transplant were statistically superior to no treatment, with a median OS of 17, 50, and 1 months, respectively (p=0.0002). Males tended to have shorter OS than females (13 vs. 24 months). Similarly, the presence of CS tended to have a shorter OS (6 vs. 21 months). OS was not impacted by stage or immunohistochemical features. Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with PCAECTCL. It details the features of this rare provisional entity and identifies the clinical, immunohistochemical, and treatment modalities that are major determinants of OS.

Autologous Hematopoietic Cell Transplantation for T-Cell Prolymphocytic Leukemia - a Retrospective Study on Behalf of the Chronic Malignancies Working Party of the EBMT

Introduction: T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma with a dismal prognosis. Treatment options for T-PLL are extremely limited. Alemtuzumab is the mainstay of the first-line treatment with a progression-free survival (PFS) of approximately one year. Eligible patients are offered allogeneic hematopoietic cell transplantation (allo-HCT) in consolidation as the only curative approach. Autologous hematopoietic transplantation (auto-HCT) is cited as an option in T-PLL management, e.g., (Staber, Blood 2019; Dearden, Hematology Am Soc Hematol Educ Program 2015), however, extremely scarce data is available on this therapeutic option (Krishnan, Br J Haematol 2010; Dearden, Blood 2001). We hereby present characteristics and outcomes in a cohort of patients with T-PLL undergoing auto-HCT. Methods: Patients aged at least 18 years old with a T-PLL diagnosis who underwent an auto-HCT between 2000 and 2019 were selected from the EBMT database. Additional data to verify the diagnosis (e.g., immunophenotype, cytogenetics, molecular markers), as well as clarification on treatment prior to and post auto-HCT, HCT-CI score, and cause of death, was requested from participating centres. Overall survival (OS) and PFS were analysed using Kaplan-Meier methods. Cumulative incidence of relapse (RI) and non-relapse mortality (NRM) were analysed together in a competing risks framework. Prognostic factors (sex, interval from diagnosis to auto-HCT, Karnofsky performance score (KPS), number of lines of prior therapy, use of TBI and calendar year, disease status, and age at auto-HCT) were evaluated in univariate analyses. Results: Forty patients from 31 centers were included out of 42 initially identified. Two patients were excluded based on immunophenotype (positive CD57 or CD34). Additional data was obtained for 19 patients. Median age at auto-HCT was 62 years (IQR 53-67) with males accounting for 58% of the cohort. Median interval between diagnosis and auto-HCT was 8.8 months (IQR 6.4-17.7), and the median calendar year of auto-HCT was 2011 (IQR 2007-2014). A total of 22% of patients had a KPS of ≤80% and 27% an HCT-CI score of 3 or more. Regarding lines of therapy, 80% received only 1 previous therapy and 96% had been exposed to alemtuzumab. At time of auto-HCT, 68% were in complete remission (CR) and 25% in partial remission (PR). Conditioning was chemotherapy-based in the majority with TBI administered to 10%, at an average dose of 10.4-13 Gy. Engraftment was achieved in all analysed patients. CR rate at 100 days post auto-HCT was 88% (95% CI 73-97%). With a median follow-up of 87.7 months (95% CI, 42.3-89.9) the 2-year OS was estimated at 44% (95% CI, 28-59%) (Figure 1a), with a 2-year PFS of 36% (95% CI, 21-51%) (Figure 1b). 2-year RI was 59% (95% CI, 44-75%), while 2-year NRM was 5% (95% CI, 0-12%). None of the prognostic factors evaluated were significantly associated with OS, PFS, RI, or NRM. For 19 patients (76%), for whom auto-HCT was used as consolidation of response after 1st line alemtuzumab, the CR rate at 100 days after auto-HCT was 85% (95% CI 65-96%). The 2-year estimates for OS and PFS were 47% (95% CI 25-70%) and 47% (95% CI 25-70%), respectively. For the whole group, progressive disease was the most frequent cause of death (55%). Second malignancies developed in 10% of patients. Conclusions: Auto-HCT is associated with acceptable efficacy with low NRM and might significantly extend response duration after alemtuzumab. As already suggested in position papers it may represent an important alternative to allo-HCT. Auto-HCT could possibly be used as a tandem option to maintain or increase disease control prior to reduced-intensity allo-HCT. Figure 1a) Overall survival (OS) and 1b) progression-free survival (PFS) of patients undergoing autologous hematopoietic cell transplantation (auto-HCT). Grey areas represent the 95% confidence intervals. The figures below the graph are the number of patients at risk. The "Consolidation” patients (blue line) are patients with available detailed data receiving auto-HCT as a consolidation of response after first line alemtuzumab. This group is a subset of "All” patients (red line). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal