Indolent B-cell non-Hodgkin lymphomas in children: high association with inborn errors of immunity.

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively.

Coping and Perception of Prognosis in Patients With Indolent Non-Hodgkin's Lymphoma.

BACKGROUND: Indolent non-Hodgkin's lymphomas (iNHL) are a heterogenous group of mostly incurable diseases with prolonged illness courses and prognostic uncertainty. Yet, studies evaluating coping and perception of prognosis are limited. METHODS: We conducted a cross-sectional study of adults newly diagnosed with iNHL in the past 3 months at a single academic center. We assessed quality of life (QOL: Functional Assessment of Cancer Therapy-General), psychological symptoms (Hospital Anxiety and Depression Scale), coping (Brief-COPE), and perception of prognosis (Prognosis Awareness Impact Scale). RESULTS: We enrolled 70.6% (48/68) of eligible patients. Patients had older age (mean = 66.9,sd = 10.5), were female (60.4%), predominantly identified as White (85.4%), and had at least received a college degree (75%). Chronic lymphocytic leukemia (39.6%) and follicular lymphoma (33.3%) were the most common diagnoses. Overall, 27.1% and 14.6% of patients reported clinically significant anxiety and PTSD symptoms, respectively. Patients highly utilized acceptance (56.2%), seeking emotional support (47.9%), and denial (47.9%) as coping strategies at diagnosis. While 66.7% of patients recalled their oncologist assessment of illness as incurable, only 35.4% reported that the illness is unlikely to be cured. Overall, 45.8% indicated that they were worried about prognosis and 31.2% reported perseverating on their prognosis. Higher emotional coping with prognosis was associated with fewer anxiety (B = -0.6, SE = 0.2, P < .001), depression (B = -0.3, SE = .1, P = .005), and PTSD (B = -1.3, SE = 0.4, P < .001) symptoms and better QOL (B = 1.7, SE = 0.4, P < .001). DISCUSSION: Patients with iNHL report substantial psychological distress, a diversity of coping strategies, and complex cognitive understanding of their prognosis. Interventions, which address prognostic uncertainty and promote positive emotional coping with prognosis, may ameliorate psychological distress in this population.

The utility of CONUT score in indolent lymphoma patients.

Background and Aim: Similar to the uncertainties in the treatment criteria for indolent non-Hodgkin lymphoma (iNHL), the prognostic criteria have not been fully clarified. The Controlled Nutritional Status (CONUT) score is not only used as a predictor of malnutrition but also indicates prognosis in many chronic or malignant diseases. The aim of this study is to investigate the predictive and prognostic significance of the CONUT score in patients with iNHL. Patients and Methods: A retrospective evaluation was made of 109 patients with iNHL. The CONUT scores of the patients were compared between those with an indication for treatment and those followed without treatment. The same analysis was performed between patients who developed relapse after treatment. Survival analysis was performed on all patients, and associations between survival and the CONUT score were examined. Results: The median CONUT score was found to be higher in those who had treatment indications compared to those who did not (2 vs 1; P = 0.014). In the regression model, a CONUT absolute value above 5 was found as an independent risk factor predicting relapse. In the whole study population, a CONUT absolute value >2 predicted the risk of mortality with 53.9% sensitivity and 68.7% specificity (AUC ± SE = 0.639 ± 0.07; +PV = 35%; -PV = 82.6%; P = 0.034). Conclusion: CONUT score is a predictive and prognostic factor for patients with iNHL. The development of simple, low-budget prognostic and predictive biomarkers is critical not only for determining the course of the disease but also for follow-up and treatment management.

How to treat splenic marginal zone lymphoma (SMZL) in patients unfit for surgery or more aggressive therapies: experience in 30 cases.

Splenic marginal zone lymphoma (SMZL) is an indolent disease that typically affects elderly patients. Thanks to its outcome, most patients don't need any specific therapy and 'a watch and wait' policy is frequently employed. Treatment is required in symptomatic cases. Splenectomy remains one of the first line options in patients fit for surgery. The best pharmacological strategy has not yet been identified for poor surgical risk cases. Amongst different possible chemotherapeutic approaches, alkylating agents, alone or in association with Rituximab, could employ in 'frail' patients. In the present study, the role of oral cyclophosphamide (100 mg per day for 15 consecutive days, every 30 for a total of six cycles) associated with anti-CD20 monoclonal antibody has been evaluated in 30 newly diagnosed SMZL patients, not fit for splenectomy or more toxic chemotherapic regimens. Overall response rate was 87% (CR 70%; PR 17%). Median PFS was 20 months (range, 1-53), with better outcome for low-risk cases according to IIL score prognostic index. Toxicity profile resulted mild.

Novel agents in indolent lymphomas.

Indolent non-Hodgkin's lymphomas (iNHLs) include follicular lymphomas (FL), marginal-zone lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and small lymphocytic lymphoma. First-line standard therapy in advanced, symptomatic iNHL consists of rituximab-based immunochemotherapy. The recent rediscovery of the 'old' chemotherapeutic agent bendamustine, an alkylating agent with a peculiar mechanism of action, has added a new effective and well-tolerated option to the therapeutic armamentarium in iNHL, increasing response rates and duration. However, patients invariably relapse and subsequent active and well-tolerated agents are needed. In recent years a large number of new targeted agents have been tested in preclinical and clinical experimentation in FL and indolent nonfollicular lymphoma (iNFL), including the new monoclonal antibodies binding CD20 or other surface antigens, immunoconjugates and bispecific antibodies. Moreover novel agents directed against intracellular processes such as proteasome inhibitors, mTOR inhibitors and agents that target the tumour microenvironment, notably the immunomodulatory agent lenalidomide, are under active clinical investigation. The development of these new drugs may change in the near future the approach to iNHL patients, leading to better tolerated and effective therapy regimens.

[Intronic polymorphisms of аntionkogene TP53 in patients with indolent variants of Non-Hodgkin's lymphomas].

The frequency of distribution of alleles and genotypes of single nucleotide substitution G13494A in intron 6 and duplications dup16bp in intron 3 of the gene TP53 in 56 patients with indolent non-Hodgkin's lymphoma and variants in the controls was studied. The increase of the frequency of G-allele and G/G genotype of intron 6 of the gene TP53 in lymphoma patients compared with controls (91 and 84 % vs. 79 (p<0,01) and 63 % (p<0,01), respectively) was determined. It was found that individuals carrying the rare A-allele (i.e., having A/G or A/A genotype), had the risk of disease 3,23 times (OR=3,23; [95 % CI 1,50; 6,92], p<0,05) higher than the general population. No significant differences in the distribution of alleles and genotypes of dup16bp intron 3 of the TP53 gene between cases and controls were identified. The results indicate that the oligonucleotide G13494A substitution in intron 6 proapoptotic gene TP53 in older individuals may have a modulating effect on the risk of indolent lymphoma.

O transplante de células-tronco hematopoéticas no tratamento dos linfomas não Hodgkin / Hematopoietic stem cell transplantation for non-Hodgkin lymphomas

No final da década de 70, ocorreu o primeiro relato de sucesso com a utilização de quimioterapia de alta dose, seguida de transplante de células-tronco hematopoéticas autólogo (TCTH auto), em pacientes com linfoma não Hodgkin (LNH). Desde então, o TCTH autólogo vem se constituindo em um importante instrumento na estratégia de tratamento dos LNH. Inúmeros estudos, em vários subtipos de linfomas, têm consolidado o papel do TCTH autólogo, principalmente como resgate em recidivas de doença. O melhor momento para a incorporação desta estratégia depende do subtipo do linfoma, do status de doença previamente ao transplante (sensível ou resistente) e de fatores clínico-biológicos associados à doença. Em recidiva sensível de linfoma difuso de grandes células, o TCTH autólogo é a terapia de escolha. Nestes pacientes, o transplante promove taxas de resposta completa em até 50 por cento dos casos, comparado a aproximadamente 15 por cento, quando esse resgate é realizado com protocolos quimioterápicos convencionais. O seu papel como parte da terapia de indução de remissão não está totalmente estabelecido. Em linfomas indolentes, principalmente folicular, é a terapia de escolha nas recidivas sensíveis à quimioterapia de resgate. Em linfomas de células do manto, o TCTH autólogo tem se incorporado à terapia de primeira linha, como consolidação de remissão. As indicações de TCTH alogênico em LNH têm se limitado aos casos de refratariedade ao tratamento convencional e recidiva pós-transplante autólogo, em pacientes jovens e sem comorbidades, em decorrência da alta toxicidade associada à utilização de regimes de condicionamento mieloablativos. A utilização de regimes de condicionamento de intensidade reduzida tem reduzido a toxicidade e ampliado o seu uso nos LNH recidivados ou refratários.

High-dose chemotherapy (HDT) followed by autologous bone marrow transplantation (ABMT) has proved to provide significant advantage regarding event-free and overall survival in patients with chemosensitive relapses of aggressive non-Hodgkin's lymphoma (NHL) after conventional therapy. These results encouraged many investigators to use HDT as part of first-line therapy but the results are contradictory. There is no consensus regarding management of relapsed or refractory DLBCL. In follicular lymphomas, autologous stem cell transplantation (SCT) is considered the treatment of choice for young patients with relapsed disease. Autologous SCT has also been evaluated in prospective trials as first-line treatment for high risk patients at diagnosis, but the results are not yet conclusive. In mantle cell lymphoma, autologous stem cell transplantation has been employed as part of first-line therapy. Allo-SCT for patients with lymphoma was first performed in the mid-1980s. The high transplant-related mortality, seen after myeloablative conditioning, discouraged broader interest in this approach and made further research difficult. The generally lower relapse rates after allo-SCT, the association of GvHD with reduced relapse rates, the increase of relapse rates after ex vivo or in vivo T-cell depletion, and the frequent responses to DLIs all support the existence of a graft-vs.-lymphoma effect. However, further data analysis supports the view that not all lymphomas are equal. While slowly proliferating diseases such as follicular lymphoma seem particularly sensitive targets for allogeneic T-cells, results of allo-SCT with aggressive B-cell lymphomas have been less convincing. Patients with these latter diseases obviously need vigorous debulking of their tumor prior to conditioning. Reduced-intensity conditioning fueled a renaissance of allo-SCT as treatment of lymphoma because the lower expected TRM was highly attractive for a patient population where...