18F-FDG-PET/CT response after first-line treatment as a prognostic factor for survival in peripheral T-cell lymphoma: a Spanish retrospective study.

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.

Guideline Concordance of Treatment and Outcomes Among Adult Non-Hodgkin Lymphoma Patients in Sub-Saharan Africa: A Multinational, Population-Based Cohort.

BACKGROUND: Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. METHODS: We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. FINDINGS: Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. INTERPRETATION: This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.

Clinicopathologic characteristics, outcomes, and prognostic factors of angioimmunoblastic T-cell lymphoma in China.

BACKGROUND: This study aimed to better characterize the clinicopathologic characteristics, outcomes, and prognostic factors of AITL in China. METHODS: We retrospectively analyzed 312 patients with AITL enrolled between January 2011 and December 2020 from five institutions in China. RESULTS: The median age was 65 years, with 92.6% advanced stage, 59.7% elevated LDH, 46.1% anemia, and 44.0% hypergammaglobulinemia. The majority of patients (84.9%) received anthracycline-based regimens with or without etoposide, and only 6.1% underwent autologous stem cell transplantation following first remission. The 5-year OS and PFS estimates were 43.4% and 25.0% with no significant improvement of survival between patients treated during 2011-2015 and 2016-2020, respectively. Both the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT), were predictive for OS. In multivariate analysis, age >70 years, elevated LDH, and albumin level <35 g/L were independent prognostic factors for OS. Combining these three factors, a novel prognostic model (the Chinese AITL score) was constructed, which stratified patients into low-, intermediate-, and high-risk groups, with 5-year OS rates of 69.0%, 41.5%, and 23.7%, respectively. This new model was successfully validated in an independent cohort. CONCLUSIONS: Patients with AITL were mainly treated with anthracycline-based regimens, and the outcomes were still unsatisfactory in China. Our novel prognostic model may improve our ability to identify patients at different risks for alternative therapies.

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide for Peripheral T Cell Lymphoma: The Importance of Graft Source.

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus host-disease (GVHD) prophylaxis has revolutionized allogeneic blood or marrow transplantation (alloBMT), but there is limited published experience in peripheral T cell lymphoma (PTCL). We sought to assess outcomes in patients with PTCL who underwent alloBMT with PTCy. We reviewed the charts of all adult patients age ≥18 years who underwent alloBMT with nonmyeloablative conditioning and PTCy-based GVHD prophylaxis at the Sidney Kimmel Comprehensive Cancer Center between January 2004 and December 2020. Sixty-five patients were identified. The median age was 59 years (range, 24 to 75 years). Lymphoma histology included PTCL not otherwise specified (n = 24), anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n = 14), angioimmunoblastic T cell lymphoma (n = 7), enteropathy-associated T cell lymphoma (n = 6), hepatosplenic T cell lymphoma (n = 4), and others (n = 10). Eleven patients were in first complete remission (17%); the remaining patients were in first partial remission or underwent salvage therapy to at least PR prior to transplantation. Forty-eight patients underwent alloBMT from a haploidentical related donor (74%), 10 from a fully matched donor (15%), and 7 from a mismatched unrelated donor (11%). All patients received fludarabine, cyclophosphamide, and total body irradiation (TBI). The graft source was bone marrow (BM) in 46 patients (71%) and peripheral blood (PB) in 19 patients (29%); all patients in the BM cohort received 200 cGy TBI, and most patients in the PB cohort (15 of 19) received 400 cGy TBI. GVHD prophylaxis comprised PTCy, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. With a median follow-up of 2.8 years (range, 290 days to 14.2 years), the 2-year progression-free survival (PFS) for the entire cohort was 49% (95% confidence interval [CI], 38% to 64%), and the 2-year overall survival (OS) was 55% (95% CI, 44% to 69%). Outcomes were significantly improved in those receiving PB compared to those receiving BM, including a 2-year PFS of 79% (95% CI 63% to 100%) versus 39% (95% CI, 27% to 56%), 2-year OS of 84% (95% CI, 69% to 100%) versus 46% (95% CI, 33% to 63%), and 1-year cumulative incidence of relapse of 5% (95% CI, 0 to 16%) versus 33% (95% CI, 19% to 46%), with no difference in GVHD and nonrelapse mortality. AlloBMT with PTCy is safe and well-tolerated in patients with PTCL. Our data suggest that increasing the TBI dose to 400 cGy and using PB allografts may offer improved disease control and better survival outcomes, though additional studies are needed to confirm these findings.

Eficacia y seguridad de uso de brentuximab para el tratamiento de linfoma periférico de células T, subtipo anaplásico de células grandes sistémico, CD30 positivo y ALK negativo, en pacientes sin tratamiento previo / Efficacy and safety of using brentuximab for the treatment of peripheral t-cell lymphoma, systemic anaplastic large cell subtype, cd30 positive and alk negative, in treatment-naïve patients

ANTECEDENTES: Este dictamen ha sido elaborado en el marco de la metodología ad hoc para evaluar solicitudes de tencologías sanitarias, la cual fue aprobada mediante la Resolución N° 111-IETSI-ESSALUD-2021 del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI). Bajo dicho contexto, el presente documento expone la evaluación de la eficacia y seguridad del uso de brentuximab más quimioterapia para el tratamiento de linfoma periférico de células T, subtipo anaplásico de células grandes, sistémico, CD30+ ALK-, en pacientes sin tratamiento previo. ASPECTOS GENERALES: En el Dictamen Preliminar N° 003-SDEPFYOTS-DETS-IETSI-2017 se detalla los aspectos generales de los linfomas no Hodgkin de células T anaplásicos. Brevemente, los linfomas son neoplasias del sistema linfático. Éstos se dividen en los linfomas de ........ Hodgkin (LH) y linfomas no Hodgkin (LNH). Específicamente, dentro de los LNH, los 04. linfomas periféricos de células T (LPCT) son agresivos y raros y se encuentran dentro del grupo de los trastornos linfoproliferativos CD30 positivo que afectan a los ganglios linfáticos y las regiones extraganglionares. Por otro lado, los linfomas anaplásicos de células grandes (ALCL, por sus siglas en inglés) constituyen aproximadamente el 3 % de los LNH y cerca del 15 % de los linfomas periféricos (Morton et al., 2006). La presencia de la mutación (translocación cromosómica) en el gen ALK se ha asociado con un mejor pronóstico clínico que aquellos tumores que no presentan dicha mutación (ALK negativo). En un análisis de sobrevida a los cincos años, publicado por Gayscone et al., se observó que la sobrevida de los pacientes ALK positivo era de aproximadamente 93 %, mientras que en los pacientes ALK negativo éste fue de alrededor de 37 %. Asimismo, se estima que aproximadamente el 60 % de los ALCL, CD30 positivo son ALK positivo (Gascoyne et al., 1999). En general, los pacientes con ALCL tienen características clínicas similares a otros linfomas agresivos con adenopatías de rápido crecimiento, y aproximadamente dos tercios de los pacientes debutan con estadio III o IV y compromiso extra-nodal (Kadin & Carpenter, 2003). El ALCL representa cerca del 3 % de los LNH en adultos y del 10 al 20 % de los LNH en niños. No obstante, el ALCL ALK negativo suele ocurrir en adultos mayores con una edad media de 55 años (Stein et al., 2000). METODOLOGÍA: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad del uso de brentuximab en el tratamiento de linfoma de células T anaplásico, ALK negativo. Esta búsqueda se realizó utilizando las bases de datos PubMed, Cochrane Library y LILACS. Adicionalmente, se realizó una búsqueda manual del listado de referencias bibliográficas de los estudios seleccionados a fin de identificar otros estudios que pudieran ser útiles para la presente evaluación. Por otro lado, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como el Cochrane Group, The National Institute for Health and Care Excellence (NICE), The Agency for Health Care Research and Quality (AHRQ), The Scottish Medicines Consortium (SMC), y The Canadian Agency for Drugs and Technologies in Health (CADTH). Esta búsqueda se completó revisando publicaciones de grupos dedicados a la educación, investigación y mejora de la práctica clínica oncológica y hematológica dentro de América y Europa, como The National Comprehensive Cancer Network (NCCN), The American Society of Clinical Oncology (ASCO), The European Society of Medical Oncology (ESMO), y The American Society of Hematology (ASH). Finalmente, se hizo una búsqueda adicional en la página web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.gov/) y The International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/), para poder identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados para, de este modo, disminuir el riesgo de sesgo de publicación. Las estrategias de la búsqueda para identificar la evidencia de ensayos clínicos aleatorizados (ECA) se encuentran en las Tablas 1, 2 y 3 del Material Suplementario. La búsqueda de literatura consideró GPC, priorizando aquellas que elaboraran recomendaciones basadas en la evidencia; considerando además aquellas guías de referencia para los servicios de oncología y hematología de la institución; ETS; revisiones sistemáticas con meta-análisis de ECA; y ECA que abordaran la pregunta PICO del presente dictamen. Se incluyeron las publicaciones en inglés y español. Se excluyeron los ensayos clínicos no aleatorizados, los estudios observacionales, las series de casos, los reportes de casos, las cartas al editor, los comentarios, las editoriales y los resúmenes de congresos. La selección de los estudios fue llevada a cabo en dos fases. La primera fase por título y resúmenes fue realizada por dos evaluadores de manera independiente a través del aplicativo web Rayyan (https://rayyan.qcri.org), la cual permitió preseleccionar los estudios a incluir y/o los que requerían más información para decidir. La segunda fase fue realizada por un evaluador y consistió en la revisión de los criterios de elegibilidad empleando el texto completo de los estudios que fueron preseleccionados. RESULTADOS: La búsqueda de literatura permitió identificar seis publicaciones que aportan información de relevancia para fines de la presente actualización: dos GPC, la guía de National Comprehensive Cancer Network (NCCN, 2021) y la guía de British Society for Hematology(Fox et al., 2021); dos ETS(CADTH, 2020; NICE, 2020), y dos publicaciones del ECA ECHELON-2 (Horwitz et al., 20191, 2021). Este ensayo ha sido utilizado como la evidencia central en las recomendaciones de las GPC y en las ETS, y es considerado como la evidencia central de la presente evaluación. CONCLUSIÓN: Por todo lo expuesto, el IETSI no aprueba el uso de brentuximab para el diagnóstico de linfoma periférico de células T, anaplásico de células grandes sistémico, CD30 positivo y ALK negativo, en pacientes sin tratamiento previo.

Rare non-Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric-type follicular lymphoma, marginal zone lymphoma, and nonanaplastic peripheral T-cell lymphoma.

Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for <2% of childhood non-Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype-dependent and ranges from a block-like anaplastic large cell lymphoma (ALCL)-derived and, alternatively, leukemia-derived therapy in PTCL not otherwise specified and subcutaneous panniculitis-like T-cell lymphoma to a block-like mature B-NHL-derived or, preferentially, ALCL-derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T-cell lymphoma.

Prognostic Values of Baseline 18F-FDG PET/CT in Patients with Peripheral T-Cell Lymphoma.

PURPOSE: In the present study, we aimed to investigate whether the metabolic parameters on baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) could be used to predict prognosis in peripheral T-cell lymphomas (PTCL). METHODS: A total of 51 nodal PTCL patients who underwent baseline 18F-FDG PET/CT were retrospectively evaluated in the present study. Total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were also assessed. Besides, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) was also included. Log-rank test and Cox regression analysis were used to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up was 18 months. Patients with low TLG, TMTV, and SUVmax levels had a significantly better clinical outcome than those with high TLG, TMTV, and SUVmax levels. The 2-year PFS rates of the high- and low-TMTV groups were 34.62% and 80%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (p < 0.001), whereas the corresponding 2-year OS rates were 46.15% and 84.00%, respectively (n = 10), intermediate-risk group with TMTV > 62.405 or NCCN-IPI score of 4-8 (2-year PFS and OS were 52.4% and 66.7%, respectively, n = 10), intermediate-risk group with TMTV > 62.405 or NCCN-IPI score of 4-8 (2-year PFS and OS were 52.4% and 66.7%, respectively, n = 10), intermediate-risk group with TMTV > 62.405 or NCCN-IPI score of 4-8 (2-year PFS and OS were 52.4% and 66.7%, respectively. CONCLUSIONS: Baseline TMTV and TLG were independent predictors of PFS and OS in PTCL patients, and SUVmax and NCCN-IPI scores were also independent predictors of OS. Moreover, the combination of TMTV and NCCN-IPI scores improved patient risk-stratification at the initial stage and might contribute to the adjustment of the therapeutic regime. This trial is registered with ChiCTR1900025526.

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Recent analyses of the genetics of peripheral T-cell lymphoma (PTCL) have shown that a large proportion of cases are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. Here we demonstrate the usefulness of Roquinsan/+ animals as a pre-clinical model of Tfh lymphoma. Long latency of development and incomplete penetrance in this strain suggests the lymphomas are genetically diverse. We carried out preliminary genetic characterisation by whole exome sequencing and detected tumor specific mutations in Hsp90ab1, Ccnb3 and RhoA. Interleukin-2-inducible kinase (ITK) is expressed in Tfh lymphoma and is a potential therapeutic agent. A preclinical study of ibrutinib, a small molecule inhibitor of mouse and human ITK, in established lymphoma was carried out and showed lymphoma regression in 8/12 (67%) mice. Using T2-weighted MRI to assess lymph node volume and diffusion weighted MRI scanning as a measure of function, we showed that treatment increased mean apparent diffusion coefficient (ADC) suggesting cell death, and that change in ADC following treatment correlated with change in lymphoma volume. We suggest that heterozygous sanroque mice are a useful model of Tfh cell derived lymphomas in an immunocompetent animal.

Risk factors and timing of autologous stem cell transplantation for patients with peripheral T-cell lymphoma.

High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) is an option for patients with peripheral T-cell lymphoma (PTCL); however, neither prospective nor retrospective studies support proceeding with ASCT upfront, and the timing of HDC-ASCT remains controversial. We retrospectively analyzed the risk factors for outcomes of 570 patients with PTCL, including PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL), who received ASCT for frontline consolidation (n = 98 and 75, respectively) or alternative therapies after either relapse (n = 112 and 75) or primary induction failure (PIF; n = 127 and 83) between 2000 and 2015. Significant risk factors for overall survival (OS) after upfront ASCT were a ≥ 2 prognostic index for T-cell lymphoma (P < 0.001) and partial response (PR) at ASCT (P = 0.041) in PTCL-NOS patients, and > 60 years of age (P = 0.0028) and PR at ASCT (P = 0.0013) in AITL patients. Performance status of ≥ 2 at ASCT (P < 0.001), receiving ≥ 3 regimens before ASCT (P = 0.018), and PR at ASCT (P = 0.018) in PTCL-NOS patients and > 60 years of age at ASCT (P = 0.0077) in AITL patients were risk factors for OS after ASCT with a chemosensitive PIF status. Strategies that carefully select PTCL patients may allow identification of individuals suitable for ASCT.

Can folate replacement induce lymphoma progression?

A 43-year-old Japanese man with a low haemoglobin level of 1.3 g/dL and multiorgan dysfunction syndrome (MODS) was admitted to our hospital. He was diagnosed with folate deficiency, which was initially attributed to his malnutrition. He was transfused with several units of packed red blood cells and treated with folate, thiamine and vitamin B12 supplements; he showed a prompt haematological response and recovery from MODS. However, 3 weeks after the initial recovery, he had a relapse of pancytopenia and developed high-grade fever along with rapidly enlarging, generalised lymphadenopathy. Bone marrow biopsy revealed hemophagocytosis, and lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified. Folate supplementation may have promoted lymphoma progression.

A risk stratification model for nodal peripheral T-cell lymphomas based on the NCCN-IPI and posttreatment Deauville score.

PURPOSE: The aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs. METHODS: We retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients. RESULTS: Posttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47-3.18) vs. 7.86 (5.66-10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20-4.41) vs. 4.42 (2.36-8.26) vs. 7.09 (3.57-14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort. CONCLUSION: The risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs.

[Prognostic significance of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma treated with CHOP-based chemotherapy].

Objective: To validate the prognostic value of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma (PTCL) treated with CHOP-based chemotherapy. Methods: A retrospective analysis in 162 PTCL patients who were initially diagnosed and treated in Rui Jin Hospital from January 2003 to May 2013 was conducted. Baseline characteristics were collected, and survival analysis was performed according to the IPI and NCCN-IPI model. Results: The estimated 5-year overall survival (OS) rate and progression free survival (PFS) rate were 33% and 20%, with median OS and PFS of 17.0 months and 9.2 months, respectively. Multivariate analysis indicated ECOG score (PFS: HR=2.418, 95%CI 1.535-3.809, P<0.001; OS: HR=2.347, 95%CI 1.435-3.839, P= 0.001) , specific extra-nodal sites (PFS: HR=1.800, 95%CI 1.216-2.665, P=0.003; OS: HR=1.608, 95% CI 1.054-2.454, P=0.027) and pathology type (PFS: HR=0.424, 95% CI 0.184-0.975, P=0.043; OS: HR=0.276, 95% CI 0.087-0.877, P=0.029) were independent prognostic factors of OS and PFS for the patients with PTCL. The survival rates of low risk patients based on NCCI-IPI were remarkably higher than the counterparts based on IPI (5-year OS 74% vs 54%, χ(2)=5.041, P=0.025, 5-year PFS 50% vs 38%, χ(2)= 5.295, P=0.021) . NCCN-IPI was outstanding to identify the subgroup of low risk patients with PTCL, who may benefit from conventional chemotherapy such as CHOP or CHOP-like regimen. Conclusion: NCCN-IPI is more powerful for low risk PTCL patients and a strong supplement for IPI.

Adult T-cell leukemia/lymphoma treatment in Bahia, Brazil

Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral) with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP); doxorubicin, ranimustine, and prednisolone (AMP); and vindesine, etoposide, carboplatin, and prednisolone (VECP)]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late probably due to lack of knowledge of adult T-cell leukemia/lymphoma by primary healthcare doctors and a Brazilian treatment protocol needs to be established.

The role of alisertib in treatment of peripheral T-cell lymphomas.

Peripheral T-cell lymphomas are aggressive lymphomas with poor outcomes for which novel treatments are urgently needed. Alisertib (MLN8237) is a second-generation oral Aurora A kinase inhibitor. Treatment with alisertib results in an accumulation of cells with abnormal mitotic spindles, leading to decreased proliferation and apoptosis in a range of human tumor cell lines. Alisertib has shown single-agent antitumor activity in animal xenograft models and promising antitumor activity alone or in combination with other agents in patients with solid and hematologic cancers, and T-cell lymphomas in particular. It is currently being tested in randomized controlled Phase III trials in relapsed/refractory peripheral T-cell lymphoma.

Preemptive leucovorin administration minimizes pralatrexate toxicity without sacrificing efficacy.

Balancing efficacy and safety of drugs is key for successful cancer therapy, as adverse reactions can prohibit the use of efficacious treatments. Pralatrexate (PDX) is a novel antifolate with a higher affinity for tumor cells than methotrexate, Food and Drug Administration (FDA) approved for use in relapsed and refractory peripheral T-cell lymphoma (PTCL) and transformed mycosis fungoides (T-MF). Patients with T-MF have a higher incidence of adverse events than patients with other lymphomas, necessitating a lower recommended dose of 15 mg/m(2) (vs. 30 mg/m(2) for PTCL). Dose-limiting toxicity (DLT) mucositis occurs in about 25% of patients with T-MF, but milder mucositis is observed in almost all patients with T-MF, frequently leading to therapy discontinuation despite clinical response. Leucovorin rescue is the standard of care for high-dose methotrexate therapy, but has not been studied or recommended for use with PDX. We report our clinical experience using leucovorin with PDX (30 mg/m(2)) with good clinical response and no DLTs. Prophylactic leucovorin deserves further investigation in prospective clinical trials to allow patients with cutaneous lymphomas to receive the full benefit of PDX therapy without intolerable toxicity.

Pralatrexate: a novel synthetic antifolate for relapsed or refractory peripheral T-cell lymphoma and other potential uses.

PURPOSE: The pharmacology, pharmacokinetics, clinical trials, adverse effects, dosage, and economic considerations of pralatrexate (PDX) are reviewed. SUMMARY: Peripheral T-cell lymphoma (PTCL) comprises approximately 15-20% of all aggressive lymphomas and 5-10% of all non-Hodgkin's lymphomas. Advanced PTCL is often refractory to traditional first-line chemotherapy regimens. PDX was developed as a synthetic folate analog antimetabolite that competitively inhibits dihydrofolate reductase (DHFR). This results in the depletion of thymidine, leading to interference with deoxyribonucleic acid synthesis and cancer cell death. PDX has a higher potency than methotrexate and edatrexate (EDX). The efficacy and safety of PDX have been demonstrated in the PROPEL trial, a prospective phase II trial in patients with relapsed or refractory PTCL. Patients with prior stem cell transplantation receiving PDX also had similar response rates (RRs). PDX was investigated on the treatment of relapsed or refractory cutaneous T-cell lymphoma, previously treated advanced non-small cell lung cancer and other solid malignancies. PDX has similar side effects to other DHFR inhibitors. The most common side effect of PDX is mucositis. The recommended dose of PDX is 30 mg/m(2) weekly once for 6 weeks in 7-week cycle until disease progresses or unacceptable toxicity for PTCL and may require dose reduction or discontinuation. Patients should be supplemented with oral folic acid and intramuscular vitamin B(12) injections. CONCLUSION: PDX provides clinical benefit to patients with relapsed or refractory PTCL with durable complete and partial responses in patients who had not responded to multiple prior treatment regimens.

Therapies for peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders that, for the most part, are associated with a very poor prognosis. The standard therapy for PTCLs is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or a comparable CHOP-like regimen that incorporates anthracyclines. With the exception of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK(+) ALCL), the cure rate for PTCLs with CHOP is low, and limited evidence suggests that anthracyclines do not improve the prognosis. However, there is no compelling evidence that any other regimen or approach is superior. It remains challenging to compare alternative therapies or treatment strategies with CHOP because the majority of data are retrospective and include diverse patient populations. Recently, prospective studies have been initiated exclusively for PTCL, and in some, select histologic subtypes are evaluated in an effort to remove heterogeneity. Encouragingly, there have been several new therapies emerging with activity in PTCLs and exciting novel combinations under consideration that will hopefully move the field forward and improve outcome in this challenging group of diseases.

Enhancing existing approaches to peripheral T-cell lymphoma.

The National Comprehensive Cancer Network (NCCN) practice guidelines for peripheral T-cell lymphoma (PTCL) accentuate the lack of standard treatment options for this disease. Outcomes with conventional therapies, many of which are borrowed from B-cell lymphoma, are poor. Strategies to enhance existing approaches include creating a new platform for first-line therapy and adding novel agents, such as denileukin diftitox, to existing chemotherapy platforms. Furthermore, to improve outcomes, patients must reach transplant through effective first-line therapies. Additionally, treatment should be individualized based on histopathologic subtype, as all PTCL patients will not respond to the same treatment regimen.