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Castleman's disease (CD) is a rare and heterogeneous lymphoproliferative disorder, with limited available clinical information in Brazil. A retrospective study was carried out through information contained in the medical records of 51 patients, between July 1999 and June 2020. Seven patients were excluded, and 44 were analyzed in total. The average age of unicentric CD (UCD) patients was 35 years old and of multicentric CD (MCD) patients was 49 years old (p = 0.013). Regarding gender, there was a predominance of females among patients with UCD (68.4%) and males in patients with MCD (57.9%) (p = 0.103). The most common site of involvement in UCD was the cervical region (36.8%). A total of 73.7% of patients with UCD and 68.4% of patients with MCD presented the histological form hialyne-vascular (HV) (p = 0.499). Most patients with laboratory abnormalities had MCD. A total of 78% of the patients were asymptomatic, with the majority of symptomatic patients with MCD (p = 0.042). Only two of the 27 patients evaluated for the presence of human immunodeficiency virus (HIV) had positive serology. HHV-8 was evaluated in 14 cases, being positive in two. Of the patients with UCD, 94.7% underwent excisional biopsy, against only 41.2% of patients with MCD (p = 0.01). The mean follow-up was 61 months. We observed similarities in the clinical profile between patients in our study and patients described in the literature, such as gender, mean age, B symptoms, visceromegaly, fluid accumulation, and treatment. Unlike the literature, the cervical region was the most affected site, besides the greater association of the HV histological subtype among patients with MCD.
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Hiperplasia do Linfonodo Gigante , Herpesvirus Humano 8 , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Hiperplasia do Linfonodo Gigante/diagnóstico , Brasil/epidemiologia , Estudos Retrospectivos , HIVRESUMO
OBJECTIVES: Single nucleotide variants (SNVs) in vascular endothelial growth factor A (VEGFA) and VEGFA receptor (KDR) genes confer different inherited abilities in angiogenesis (AG) pathway. We aimed in the present study to evaluate influence of six VEGFA and four KDR SNVs in clinical features and survival of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: One hundred and sixty-eight DLBCL patients diagnosed between June 2009-September 2014 were enrolled in the study. Patients were homogeneously treated with R-CHOP. Genotypes were identified in genomic DNA by real-time polymerase chain reaction. RESULTS: Patients with VEGFA -634CC and +936CT or TT genotypes were at increased risk of showing grade III / IV toxicities and not achieving complete remission with treatment, and shorter event-free and overall survival were seen in patients with VEGFA -1154GA or AA genotype and VEGFA ATAGCC haplotype. CONCLUSION: Our data suggest that inherited abnormalities in AG's gene modulate clinical features and prognosis of DLBCL patients homogeneously treated with R-CHOP.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/patologia , Neovascularização Patológica/patologia , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Prednisona/administração & dosagem , Prognóstico , Estudos Prospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
BACKGROUND: There is evidence to consider that the tumor microenvironment (TME) composition associates with antitumor immune response, and may predict the outcome of various non-Hodgkin lymphoma subtypes. However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients' samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL. METHODS: We assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, IL17F) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models. RESULTS: High FOXP3/CD3 ratios (p = 0.001), high IL17A levels (p = 0.003) and low IL2 levels (p = 0.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (p = 0.02). In the SNV model, the CC haplotype of IL10 (p < 0.01), the GG genotype of IL2 rs2069762 (p = 0.02) and the AA+AG genotypes of TGFBR2 rs3087465 (p < 0.01) were independent predictors of outcome. Finally, the GG genotype of TGFB1 rs6957 associated with lower tumor TGFß levels (p = 0.03) and less CD163+ macrophages (p = 0.01), but did not modulate patients' survival. CONCLUSIONS: Our results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in IL10, TGFBR2 and IL2, may represent novel prognostic factors in this disease, following future validations.
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Imunidade/genética , Linfoma de Célula do Manto/genética , Polimorfismo de Nucleotídeo Único , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Terapia Combinada , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Estudos de Associação Genética , Genótipo , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressores/uso terapêutico , Interleucinas/genética , Estimativa de Kaplan-Meier , Linfoma de Célula do Manto/imunologia , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Análise de Componente Principal , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Fatores de Crescimento Transformadores beta/genética , Rituximab/uso terapêutico , Fatores de Transcrição SOXC/análise , Fator de Crescimento Transformador beta1/genéticaRESUMO
Early reduction of BCR-ABL1 transcript levels has been associated with improved outcome in chronic myeloid leukemia (CML) treatment. We evaluated 54 chronic-phase CML patients treated with imatinib who switched therapy to dasatinib (n = 33) or nilotinib (n = 21). BCR-ABL1 transcript levels were measured in peripheral blood using real-time quantitative PCR (RQ-PCR) every 3 months from the start of second-line treatment. Patients with BCR-ABL transcript levels >10% at 3 months and >1% at 6 months had significantly inferior progression-free (PFS) and event-free survival (EFS) than patients with RQ-PCR <10% at 3 months and <1% at 6 months (66 vs. 100%, p = 0.01, and 33 vs. 73%, p = 0.02, respectively). Patients with RQ-PCR <10% at 3 months and >1% at 6 months also had inferior PFS and EFS than patients with RQ-PCR <10% at 3 months and <1% at 6 months (48 vs. 100%, p = 0.002, and 25 vs. 73%, p < 0.0001, respectively). Two measurements of BCR-ABL levels were better than a single one to stratify chronic-phase CML patients as failure after second-line therapy.
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Proteínas de Fusão bcr-abl/sangue , Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".
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Background: Marginal zone lymphomas (MZL), comprised of three unique but related subtypes, lack a unifying prognostic score applicable to all the patients in need for systemic chemotherapy and/or immunotherapy. Methods: Patients from the prospective NF10 study (NCT02904577) with newly diagnosed MZL and receiving frontline systemic therapy at diagnosis or after observation were used to train a prognostic model. The primary endpoint was progression-free survival (PFS) from start of treatment. The model was externally validated in a pooled analysis of two independent cohorts from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource and the University of Miami. Findings: We identified 501 eligible patients. After multivariable modeling, lactate dehydrogenase (LDH) above upper normal limit, hemoglobin <12 g/dL, absolute lymphocyte count <1 × 109/L, platelets <100 × 109/L, and MZL subtype (nodal or disseminated) were independently associated with inferior PFS. The proposed MZL International Prognostic index (MZL-IPI) combined these 5 factors, and we defined low (LRG, 0 factors, 27%), intermediate (IRG, 1-2 factors, 57%) and high (HRG, 3+ factors, 16%) risk groups with 5-y PFS of 85%, 66%, and 37%, respectively (c-Harrell = 0.64). Compared to the LRG, the IRG (Hazard Ratio [HR] = 2.30, 95% CI 1.39-3.80) and HRG (HR = 5.41, 95% CI 3.12-9.38) had inferior PFS. Applying the MZL-IPI to the pooled US cohort (N = 353), 94 (27%), 192 (54%), and 67 (19%) patients were classified as LRG, IRG, and HRG, respectively, and the model was validated for PFS (log-rank test p = 0.0018; c-Harrell = 0.578, 95% CI 0.54-0.62). The MZL-IPI was also prognostic for OS in both the training and the external validation sets. Interpretation: MZL-IPI is a new prognostic score for use in all patients with MZL considered for systemic treatment. Funding: The MER was supported by P50 CA97274 and U01 CA195568.
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Hodgkin lymphoma (HL) is one of the most common types of cancer in the young and one of the most curable forms of cancer. Therefore, there has been an increasing interest in the study of long-term morbidities. The aims of the present study were to evaluate the prevalence and risk factors for impaired gonadal function in a retrospective cohort of 238 HL female survivors from Italy and Brazil and to analyse the role of oral contraceptives (OC) and GnRH-analogues. Besides data collection from HL databases, a specific questionnaire was administered to collect data on gonadal function. The median age at diagnosis was 25 years and the median follow-up was 7 years. Overall, 25% of the patients developed impaired gonadal function. Older age at diagnosis, front-line therapies containing alkylating agents and more than one treatment were independent risk factors, whereas the use of OC or GnRH-a reduced independently the risk of impaired gonadal function. The fertility rate among fertile survivors was low when compared with the general population. We confirmed that older age, type of front-line chemotherapy and a higher number of therapies are associated with gonadal function impairment in terms of infertility and premature menopause in female HL survivors. Also, the use of GnRH-a or OC was independently identified as a protective factor. Further prospective studies are needed to better understand the barriers to parenthood in HL survivors.
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Doença de Hodgkin/fisiopatologia , Infertilidade/etiologia , Ovário/fisiopatologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brasil , Anticoncepcionais Orais , Feminino , Preservação da Fertilidade , Doença de Hodgkin/terapia , Humanos , Itália , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto JovemRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and dependent on angiogenesis (AG), whose main effectors are VEGFA and VEGFR2. Functional single nucleotide variants (SNVs) are described in VEGFA and KDR genes. However, it still unknown whether VEGFA - 2578C/A, -2489C/T, -1154G/A, -634G/C, -460C/T and KDR-604T/C, -271G/A, +1192G/A and +1719A/T SNVs act on DLBCL risk and angiogenic features. Genomic DNA from 168 DLBCL patients and 205 controls was used for SNV genotyping. Angiogenesis was immunohistochemically assessed in tumor biopsies, with reactions for VEGFA, VEGFR2, and CD34. VEGFA -1154GG genotype were associated with 1.6-fold higher DLBCL risk. KDR + 1192GG plus KDR + 1719 TT and KDR + 1192GG plus VEGFA - 2578CC combined genotypes are associated with 2.19- and 2.04-fold higher risks of DLBCL, respectively. VEGFA - 634GG or GC genotypes are associated with increased microvessel density and VEGFA levels. No relationship was observed between SNVs and cell-of-origin classification of DLBCL, but higher VEGFA and VEGFR2 were seen in non-germinal center tumors.
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Predisposição Genética para Doença , Linfoma Difuso de Grandes Células B , Humanos , Polimorfismo de Nucleotídeo Único , Genótipo , Linfoma Difuso de Grandes Células B/genética , Nucleotídeos , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaAssuntos
Alelos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Rituximab , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
PURPOSE: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS: We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050). RESULTS: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. CONCLUSION: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.
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Linfoma Difuso de Grandes Células B/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Avaliação Geriátrica , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: Although the increased use of combined antiretroviral therapy (cART) has decreased the incidence of lymphomas HIV-associated, Burkitt lymphoma (BL) incidence remains stable. Reported outcomes on HIV-associated BL from developed countries seem to corroborate that the regimens do not need to be tailored to the HIV-positive population. MATERIALS AND METHODS: This is a retrospective multicenter cohort study from Brazil, including HIV-positive patients aged 15 years and above diagnosed with BL. RESULTS: A total of 54 patients were included. Median age was 39 years (range, 15-64). At diagnosis, advanced disease was found in 86% and 52% had a CD4+ count lower than 200 cells/mm3. Five patients died before starting any regimen. Among the remaining 49 patients, most were treated with Hyper-CVAD (53%) and CODOX-M IVAC (18%). Rituximab was used in frontline in only 16% of the patients. Primary refractory disease was found in 14%. A treatment-related mortality of 38.7% and a complete response rate of 44.9% were found. At 4 years, estimated overall survival (OS) was 39.8%. All relapsed and primary refractory patients eventually died. Remaining patients died from infections (24/34), despite antimicrobial prophylaxis and associated cART. CONCLUSION: Early mortality and toxicity were higher in our cohort than in developed countries. A faster diagnosis, better understanding of the biology of the disease, establishment of low toxicity regimens, inclusion of rituximab and improvement of supportive care may decrease the mortality of HIV-associated BL in developing countries.
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Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/etiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Brasil/epidemiologia , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/terapia , Comorbidade , Gerenciamento Clínico , Suscetibilidade a Doenças , Resistencia a Medicamentos Antineoplásicos , Feminino , Infecções por HIV/virologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Vigilância em Saúde Pública , Estudos Retrospectivos , Adulto JovemRESUMO
The study of the tumor microenvironment (TME) in follicular lymphoma (FL) has produced conflicting results due to assessment of limited TME subpopulations, and because of heterogeneous treatments among different cohorts. Also, important genetic determinants of immune response, such as single-nucleotide polymorphisms (SNPs), remain underexplored in this disease. We performed a detailed study of the TME in 169 FL biopsies using immunohistochemistry, encompassing lymphocytes, macrophages, and cytokines. We also genotyped 16 SNPs within key immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, and IL17F) in 159 patients. We tested associations between SNPs, clinicopathological features and TME composition, and proposed survival models in R-CHOP/R-CVP-treated patients. Presence of the IL12A rs568408 "A" allele associated with the follicular pattern of FOXP3+ cells. The IL12A AA haplotype included rs583911 and rs568408 and was an independent predictor of worse survival, together with the follicular patterns of T-cells (FOXP3+ and CD8+) and high IL-17F tumor levels. The patterns of CD3+, CD4+ and CD8+ cells, displayed as a principal component, also associated with survival. Hierarchical clustering of the TME proteins demonstrated a cluster that was associated with worse prognosis (tumors enriched in IL-17A, IL-17F, CD8, PD1, and Ki-67). The survival of FL patients who were treated in the rituximab era shows a strong dependence on TME signals, especially the T-cell infiltration patterns and IL-17F tumor levels. The presence of the AA haplotype of IL12A in the genome of FL patients is an additional prognostic factor that may modulate the composition of T-reg cells in this disease.
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The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.
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BACKGROUND: Cardiovascular events (CVEs) have been observed in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors. PATIENTS AND METHODS: We retrospectively evaluated the incidence of CVEs on 233 consecutive patients with chronic myeloid leukemia, of which 116 were treated with imatinib, 75 with dasatinib, and 42 with nilotinib. The median follow-up was 2047, 1712, and 1773 days, respectively. RESULTS: The cumulative incidence of CVEs was 4.29%. Three events occurred during dasatinib treatment, 6 during nilotinib treatment, and none during imatinib treatment (P ≤ .001). Arterial occlusive events occurred in 2 (2.6%) of 75 patients treated with dasatinib and in 6 (14.2%) of 42 patients treated with nilotinib (P ≤ .001). Furthermore, all of them occurred in patients with high-risk (n = 2) and very high-risk (n = 6) cardiovascular risk, contributing to 4.3% of mortality. CONCLUSION: CVEs were more frequent in patients treated with second-generation tyrosine kinase inhibitors. Arterial occlusive events were more frequent in patients treated with nilotinib, with high and very high cardiovascular risk.
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Doenças Cardiovasculares/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Adulto , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
We describe the case of a female patient, 52 years old, with dizziness and left motor incoordination for 2 weeks. Brain MRI magnetic resonance imaging) revealed a hyperintense lesion on T2-weighted images, without restricted diffusion, in the left middle cerebellar peduncle. Spectroscopy demonstrated peak of lipids and perfusion did not show any elevation in relative cerebral blood volume (rCBV). The patient underwent an open biopsy and resection, and the diagnosis of diffuse large B-cell lymphoma (DLBCL) was established. The patient received intravenous dexamethasone with symptoms remission, followed by four cycles of methotrexate plus cytarabine. After 3 months, the patient returned with decreased consciences level and a new MRI revealed a right superior frontal gyrus lesion with features suggesting a lymphomatous lesion. The patient died five days after her relapse.
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Neoplasias Encefálicas/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Imunocompetência , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
We analyzed the management and outcomes of pregnancies of patients with chronic myeloid leukemia at a single center over fifteen years. Among the 203 CML female patients, there were ten pregnancies in seven women, all of them not planned. In three cases, the chronic myeloid leukemia diagnosis was made during pregnancy. Five patients received tyrosine kinase inhibitors in the first weeks of pregnancy and the drug was interrupted until delivery. One patient lost complete cytogenetic response, and two patients lost the hematological response. A patient with a stable major molecular response had two successful pregnancies without loss of response. There were four premature births. There were no maternal adverse events, fetal malformation or death. All patients received Interferon-alpha during gestation, and two received hydroxyurea for a short period. Leukapheresis was performed in two patients for hyperleukocytosis control. One patient with sickle cell disease died from disease progression six months after delivery. CONCLUSIONS: The tyrosine kinase inhibitors ministration should be interrupted during pregnancy. Patients should be advised to achieve a stable and deep molecular response if they plan to conceive, to avoid the risk of disease progression.
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INTRODUCTION: The incidence of grade 3-4 anemia was reported to be 3% with imatinib therapy for newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP). However, there are few data regarding the causes and the development of anemia after long-term treatment. This study aimed to evaluate the incidence of anemia after at least two years of imatinib treatment of CML patients in the CP and to identify other contributing causes of anemia in this population. PATIENTS AND METHODS: We performed a retrospective analysis of 97 CML patients in the CP treated with imatinib for at least two years. We analyzed the hemoglobin (Hb) levels of CML patients at diagnosis, upon initiation of treatment with imatinib and after two years of imatinib treatment, and investigated other causes of anemia in this population. RESULTS: Most of the patients presented Hb levels below the normal range (80.4%) after the second year of treatment, 17.9% grade 2 and 1.3% grade 3. In 13 cases (16.7%), anemia was attributed to resistance and in 13 cases (16.7%) the following causes were identified: iron deficiency (n=5), hypothyroidism (n=2), vitamin B12 deficiency (n=3), acquired immune deficiency syndrome (AIDS) (n=1), pulmonary tuberculosis (n=1) and renal toxicity (n=1). In 52 patients (66.6%), there were no other factors contributing to anemia, except imatinib treatment. CONCLUSION: Regular follow-up is required to identify the causes of anemia not related to CML or imatinib toxicity. The importance of investigating secondary causes of anemia should be emphasized, especially in patients with good adherence to treatment and satisfactory therapeutic response.
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This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients <65 years of age, with good prognosis (136 per arm) were randomized (1:1) to receive six cycles of either RTXM83 or R-rituximab. The primary efficacy endpoint was achieved (overall response rate of 83.6% for RTXM83 and 82.9% for R-rituximab) with a difference 0.7% between arms (95%CI: [-8.77% to 10.17%]) fulfilling the predefined non-inferiority margin (-13%). Similar number of patients reported at least one adverse event (AE) (131 per arm) or one serious AE (47 with RTXM83 and 45 with R-rituximab). Anti-drug antibody development was comparable between the arms. PK/PD secondary endpoint results support similarity between the compounds. RTXM83 exhibits non-inferior efficacy and similar safety/immunogenicity to R-rituximab, being an accessible alternative for the treatment of patients with previously untreated DLBCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Medicamentos Biossimilares/administração & dosagem , Ciclofosfamida/administração & dosagem , Método Duplo-Cego , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagem , Adulto JovemRESUMO
OBJECTIVE: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. METHODS: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. RESULTS: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value < 0.01 for overall and event-free survival) and high-risk Follicular Lymphoma International Prognostic Index (p-value < 0.01 for overall survival) were independently associated to worse prognosis. Maintenance with rituximab improved the prognosis (p-value < 0.01 for overall survival). For mantle cell lymphoma, B-symptoms (p-value = 0.03 for overall survival and event-free survival) and bone marrow infiltration (p-value = 0.01 for overall survival) independently predicted reduced survival, and rituximab at induction increased both event-free and overall survival (p-value < 0.01 in both analyses). Combinations of these deleterious features could identify extremely poor prognostic subgroups. The administration of rituximab was more frequent in the AC. Camargo Cancer Center, which was the institution associated with better overall survival for both neoplasias. CONCLUSION: This study represents the largest cohort of follicular and mantle cell lymphoma in South America thus far. Some easily assessable clinical variables were able to predict prognosis and should be considered in low-income centers. In addition, the underuse of rituximab in the Brazilian public health system should be reconsidered in future health policies.