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TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.
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INTRODUCTION AND OBJECTIVES: The possibility of performing remote-surgery has been the goal to achieve, since the early development of the first surgical robotic platforms. This systematic review aims to analyse the state of the art in the field and to provide an overview of the possible growth of this technology. METHODS: All English language publications on Telementoring and Telesurgery for minimally invasive urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed®, Scopus®, and Web of Science™ databases (up to June 2019). RESULTS: Our electronic search identified a total of 124 papers in PubMed, Scopus, and Web of Science. Of these, 81 publications were identified for detailed review, which yielded 22 included in the present systematic review. Our results showed that remote surgery has been under-utilised until today, mostly due to the lack of appropriate telecommunication technologies. CONCLUSION: Remote live surgery is a growing technology that is catalyzing incremental interest. Despite not being yet reliable today on a regular basis in its most advanced applications, thanks to the advent of novel data-transmission technologies, telepresence might become a critical educational methodology, highly impacting the global healthcare system.
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Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Urológicos/métodos , HumanosRESUMO
PURPOSE: The aim of the present study is to investigate the impact of the near-infrared (NIRF) technology with indocyanine green (ICG) in robotic urologic surgery by performing a systematic literature review and to provide evidence-based expert recommendations on best practices in this field. METHODS: All English language publications on NIRF/ICG-guided robotic urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed®, Scopus® and Web of Science™ databases (up to April 2019). Experts in the field provided detailed pictures and intraoperative video-clips of different NIRF/ICG-guided robotic surgeries with recommendations for each procedure. A unique QRcode was generated and linked to each underlying video-clip. This new exclusive feature makes the present the first "dynamic paper" that merges text and figure description with their own video providing readers an innovative, immersive, high-quality and user-friendly experience. RESULTS: Our electronic search identified a total of 576 papers. Of these, 36 studies included in the present systematic review reporting the use of NIRF/ICG in robotic partial nephrectomy (n = 13), robotic radical prostatectomy and lymphadenectomy (n = 7), robotic ureteral re-implantation and reconstruction (n = 5), robotic adrenalectomy (n = 4), robotic radical cystectomy (n = 3), penectomy and robotic inguinal lymphadenectomy (n = 2), robotic simple prostatectomy (n = 1), robotic kidney transplantation (n = 1) and robotic sacrocolpopexy (n = 1). CONCLUSION: NIRF/ICG technology has now emerged as a safe, feasible and useful tool that may facilitate urologic robotic surgery. It has been shown to improve the identification of key anatomical landmarks and pathological structures for oncological and non-oncological procedures. Level of evidence is predominantly low. Larger series with longer follow-up are needed, especially in assessing the quality of the nodal dissection and the feasibility of the identification of sentinel nodes and the impact of these novel technologies on long-term oncological and functional outcomes.
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Corantes , Verde de Indocianina , Imagem Óptica , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Assistida por Computador/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Consenso , Humanos , Imagem Óptica/normas , Guias de Prática Clínica como Assunto , Procedimentos Cirúrgicos Robóticos/normas , Cirurgia Assistida por Computador/normas , Procedimentos Cirúrgicos Urológicos/normasRESUMO
BACKGROUND: Worldwide, stomas represent a medical and social problem. Data from the literature on stoma management are extensive but not homogeneous. In Italy, no guidelines exist for this topic. Thus, clear and comprehensive clinical guidelines based on evidence-based data and best practice are need. In 2018, the Multidisciplinary Italian Study group for STOmas, called MISSTO, was founded. The aim was to elaborate guidelines for practice management of enteral and urinary stomas in adults. METHODS: A systematic review of the literature was performed using PubMed, National Guideline Clearinghouse, and other databases. The research included guidelines, systematic reviews, meta-analyses, randomized clinical trials, cohort studies, and case reports. Five main topics were identified: "stoma preparation", "stoma creation", "stoma complications", "stoma care", and "stoma reversal". The systematic review was performed for each topic, and studies were evaluated according to the GRADE system, AGREE II tool. RESULTS: Recommendations were elaborated in the form of statements with an established grade of recommendation for each statement. For low levels of scientific evidence statements, a consensus conference composed of expert members of the major Italian scientific societies in the field of stoma management and care was held. After discussing, correcting, validating, or eliminating the statements by the experts, the final version of the guidelines was elaborated and prepared for publication. This manuscript is focused on statements on the surgical management of enteral stomas. CONCLUSIONS: These guidelines are the first Italian guidelines on multidisciplinary management of enteral stomas with the aim of assisting surgeons during stoma management and care.
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Enterostomia/efeitos adversos , Enterostomia/métodos , Hérnia Abdominal/prevenção & controle , Estomas Cirúrgicos , Adulto , Colostomia , Medicina Baseada em Evidências , Hérnia Abdominal/etiologia , Humanos , Ileostomia , Consentimento Livre e Esclarecido , Itália , Educação de Pacientes como Assunto , ProlapsoRESUMO
BACKGROUND: Currently, there are no data available on the best choice of treatment in heavily pretreated patients with advanced breast cancer. However, the combination of oral vinorelbine and capecitabine has been demonstrated to be effective and safe in patients with advanced breast cancer pretreated with anthracycline. Furthermore, some studies assessed the activity of dasatinib, an oral tyrosine kinase inhibitor that inhibits five oncogenic tyrosine kinase families, alone or in combination with different chemotherapy in patients affected with advanced breast cancer. CASE PRESENTATION: A patient with metastatic breast cancer, hormone receptor positive and human epidermal grow factor receptor 2 negative, pretreated with epirubicine, taxanes and nab-paclitaxel, was submitted to third line chemotherapy with vinorelbine 60 mg/m2 on day 1, 8 plus capecitabine 1000 mg/m2 twice daily from day 1 to day 14 every 21 days. The patient was taking also dasatinib 100 mg once daily for chronic myeloid leukemia. The treatment was well tolerated and, after 15 months, computed tomography scan showed a complete response of liver metastases and bone stable disease. After another 28 months, a 18-fluorodeoxyglucose positron emission tomography scan showed a metabolic response of bone metastases without other site of disease. CONCLUSIONS: This is the first case in literature about activity of dasatinib in combination with a chemotherapy schedule of oral vinorelbine and capecitabine in advanced breast cancer. This treatment showed both good tolerability and great activity with a long progression free survival of 54 months.
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Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor, on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity.
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Leucemia Mieloide Aguda/tratamento farmacológico , Trametes/química , Linhagem Celular Tumoral , HumanosRESUMO
Hyperspectral Raman images of human prostatic cells have been collected and analysed with several approaches to reveal differences among normal and tumor cell lines. The objective of the study was to test the potential of different chemometric methods in providing diagnostic responses. We focused our analysis on the ν(CH) region (2800-3100cm-1) owing to its optimal Signal-to-Noise ratio and because the main differences between the spectra of the two cell lines were observed in this frequency range. Multivariate analysis identified two principal components, which were positively recognized as due to the protein and the lipid fractions, respectively. The tumor cells exhibited a modified distribution of the cytoplasmatic lipid fraction (mainly localized alongside the cell boundary) which may result very useful for a preliminary screening. Principal Component analysis was found to provide high contrast and to be well suited for image-processing purposes. Self-Modelling Curve Resolution made available meaningful spectra and relative-concentration values; it revealed a 97% increase of the lipid fraction in the tumor cell with respect to the control. Finally, a univariate approach confirmed significant and reproducible differences between normal and tumor cells.
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Próstata/citologia , Neoplasias da Próstata/patologia , Análise de Célula Única/métodos , Análise Espectral Raman/métodos , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Processamento de Imagem Assistida por Computador/métodos , Análise dos Mínimos Quadrados , Masculino , Análise Multivariada , Análise de Componente Principal , Próstata/química , Processamento de Sinais Assistido por Computador , Razão Sinal-RuídoRESUMO
Human exposure to altitude is a model to study the role of oxygen in different areas of physiology and pathophysiology. The aim of this study was to evaluate whether a short exposure to hypoxia (5 days) combined with exercise, at altitude ranging from 900 m above sea level to 5895 m above sea level (Kilimanjaro Expedition) can modify seminal and reproductive hormonal parameter levels in human beings. During the ascent, blood oxygen saturation at 3.848 m above sea level was found to be decreased when compared to sea level (P < 0.02). The sperm forward motility at sea level after the expedition showed a significant reduction ââ(P < 0.02). There were no changes in other seminal parameters among those compared. Determination of the hormonal plasma concentrations showed that baseline values of follicle-stimulating hormone, total testosterone, prolactin and oestradiol were unchanged at sea level after the hypoxic experience, with respect to baseline values at sea level. On the other hand, luteinising hormone levels after altitudes trekking significantly increased compared to levels before the expedition (P < 0.05). Because of the short-term exposure, we can assume that the reduced forward motility described here may result from the effects of the acute altitude hypoxia on spermatozoa during the epididymal transit where they mature acquiring their motility.
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Hipóxia/fisiopatologia , Hormônio Luteinizante/sangue , Estresse Oxidativo/fisiologia , Oxigênio/sangue , Motilidade dos Espermatozoides/fisiologia , Adulto , Altitude , Estradiol/sangue , Exercício Físico , Hormônio Foliculoestimulante/sangue , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Tanzânia , Testosterona/sangueRESUMO
A rare case of splenic marginal zone lymphoma (SMZL) in a human immunodeficiency virus (HIV)-1 infected patient is described. As an association between SMZL and viral infections has been reported, the presence of the hepatitis C virus and HIV-1 genomes was evaluated. Only HIV-1 DNA levels were detected in enriched splenic B lymphocytes, suggesting a HIV-1 involvement in lymphomagenesis.
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Infecções por HIV/complicações , HIV-1/patogenicidade , Linfoma de Zona Marginal Tipo Células B/etiologia , Neoplasias Esplênicas/etiologia , Transformação Celular Viral , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Pessoa de Meia-Idade , Baço/patologia , Neoplasias Esplênicas/diagnósticoRESUMO
Recently, strategies for acute myeloid leukemia (AML) therapy have been developed that target anti-apoptotic BCL2 family members using BH3-mimetic drugs such as ABT-737. Though effective against BCL2 and BCL-X(L), ABT-737 poorly inhibits MCL-1. Here we report that, unexpectedly, ABT-737 induces activation of the extracellular receptor activated kinase and induction of MCL-1 in AML cells. MEK inhibitors such as PD0325901 and CI-1040 have been used successfully to suppress MCL-1. We report that PD0325901 blocked ABT-737-induced MCL-1 expression, and when combined with ABT-737 resulted in potent synergistic killing of AML-derived cell lines, primary AML blast and CD34+38-123+ progenitor/stem cells. Finally, we tested the combination of ABT-737 and CI-1040 in a murine xenograft model using MOLM-13 human leukemia cells.Whereas control mice and CI-1040-treated mice exhibited progressive leukemia growth, ABT-737, and to a significantly greater extent, ABT-737+CI-1040 exerted major anti-leukemia activity. Collectively, results demonstrated unexpected anti-apoptotic interaction between the BCL2 family-targeted BH3-mimetic ABT-737 and mitogen-activated protein kinase signaling in AML cells: the BH3 mimetic is not only restrained in its activity by MCL-1, but also induces its expression. However, concomitant inhibition by BH3 mimetics and MEK inhibitors could abrogate this effect and may be developed into a novel and effective therapeutic strategy for patients with AML.
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Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas de Membrana/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Nitrofenóis/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Sulfonamidas/farmacologia , Animais , Proteína 11 Semelhante a Bcl-2 , Benzamidas/farmacologia , Linhagem Celular Tumoral , Difenilamina/análogos & derivados , Difenilamina/farmacologia , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Nus , Proteína de Sequência 1 de Leucemia de Células Mieloides , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/fisiologiaRESUMO
The Budd-Chiari Syndrome (BCS) and the splanchnic vein thrombosis are characterized by hepatic venous outflow obstruction, generally due to venous thrombosis. These rare diseases are usually caused by multiple concurrent factors, including acquired and inherited thrombophilias. Since the diagnosis of myeloproliferative neoplasms (MPNs) is often difficult in patients with BCS and splanchnic vein thrombosis because of spleen enlargement, secondary pancytopenia and bleeding disorders, recent observations have included in the diagnostic work-up the analysis of the JAK2 mutation. The revision of several recent reports clarify the importance of the JAK2V617F detection in the diagnostic work-up of the BCS and splanchnic vein thrombosis, allowing the demonstration of masked MPNs among these cases that may benefit, in the near future, of target molecular therapies directed toward the JAK2 mutation.
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Neoplasias da Medula Óssea/diagnóstico , Neoplasias da Medula Óssea/genética , Síndrome de Budd-Chiari/diagnóstico , Síndrome de Budd-Chiari/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Circulação Esplâncnica , Trombose Venosa/diagnóstico , Trombose Venosa/genética , Diagnóstico Diferencial , HumanosRESUMO
Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological properties have been elucidated, including their distinct replicative properties, cell surface phenotypes, their increased resistance to chemotherapeutic drugs and the involvement of growth-promoting chromosomal translocations. Of particular importance is their ability to transfer malignancy to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Furthermore, numerous studies demonstrate that acute myeloid leukemia arises from mutations at the level of stem cell, and chronic myeloid leukemia is also a stem cell disease. In this review, we will evaluate the main characteristics of LSCs elucidated in several well-documented leukemias. In addition, we will discuss points of therapeutic intervention. Promising therapeutic approaches include the targeting of key signal transduction pathways (for example, PI3K, Rac and Wnt) with small-molecule inhibitors and specific cell surface molecules (for example, CD33, CD44 and CD123), with effective cytotoxic antibodies. Also, statins, which are already widely therapeutically used for a variety of diseases, show potential in targeting LSCs. In addition, drugs that inhibit ATP-binding cassette transporter proteins are being extensively studied, as they are important in drug resistance-a frequent characteristic of LSCs. Although the specific targeting of LSCs is a relatively new field, it is a highly promising battleground that may reveal the Holy Grail of cancer therapy.
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Leucemia/tratamento farmacológico , Leucemia/patologia , Células-Tronco Neoplásicas/patologia , Sistemas de Liberação de Medicamentos/métodos , Humanos , Leucemia/etiologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Resultado do TratamentoRESUMO
The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are frequently activated in leukemia and other hematopoietic disorders by upstream mutations in cytokine receptors, aberrant chromosomal translocations as well as other genetic mechanisms. The Jak2 kinase is frequently mutated in many myeloproliferative disorders. Effective targeting of these pathways may result in suppression of cell growth and death of leukemic cells. Furthermore it may be possible to combine various chemotherapeutic and antibody-based therapies with low molecular weight, cell membrane-permeable inhibitors which target the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to ultimately suppress the survival pathways, induce apoptosis and inhibit leukemic growth. In this review, we summarize how suppression of these pathways may inhibit key survival networks important in leukemogenesis and leukemia therapy as well as the treatment of other hematopoietic disorders. Targeting of these and additional cascades may also improve the therapy of chronic myelogenous leukemia, which are resistant to BCR-ABL inhibitors. Furthermore, we discuss how targeting of the leukemia microenvironment and the leukemia stem cell are emerging fields and challenges in targeted therapies.
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Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Leucemia/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Humanos , Leucemia/patologiaRESUMO
Mutations and chromosomal translocations occur in leukemic cells that result in elevated expression or constitutive activation of various growth factor receptors and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are often activated by mutations in upstream genes. The Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways are regulated by upstream Ras that is frequently mutated in human cancer. Recently, it has been observed that the FLT-3 and Jak kinases and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphatase are also frequently mutated or their expression is altered in certain hematopoietic neoplasms. Many of the events elicited by the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways have direct effects on survival pathways. Aberrant regulation of the survival pathways can contribute to uncontrolled cell growth and lead to leukemia. In this review, we describe the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize recent data regarding the regulation and mutation status of these pathways and their involvement in leukemia.
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Leucemia/etiologia , Transdução de Sinais , Humanos , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Quinases/metabolismo , Fatores de Transcrição STAT/metabolismoRESUMO
Olive oil, the most important dietary fat source of the Mediterranean diet, can be contaminated by mycotoxins. An efficient analytical method for the simultaneous determination of aflatoxin B1 (AFB1) and ochratoxin A (OTA) in olive oil is reported. Thirty commercial samples of virgin olive oil, purchased in olive-press plants and supermarkets in southern Italy and North Africa, were analysed to verify the analytical procedure and monitor mycotoxin contamination. A simple, rapid and economic method was set up and tested for both the extractive step and the clean-up procedures for simultaneous AFB1 and OTA determination in olive oil. Data obtained showed that OTA was detected with high frequency (80%) in samples from both geographical areas (up to 17.0 ng g-1), while AFB1 was found from three of four samples from North Africa (up to 2.4 ng g-1). In addition, 'not labelled' oil samples proved to be more contaminated by OTA then 'labelled' samples (mean values of 2.47 and 0.66 ng g-1, respectively). These findings indicate that olive oil can be significantly contaminated by mycotoxins and confirm that a scrupulous application of European Regulation 1019/2002 (European Commission 2002), which prohibits the sale of non-labelled olive oil, is strongly recommended. Conventional qualitative parameters such as peroxide number, spectrophotometric evaluation and acid values were not correlated with mycotoxin occurrence.
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Aflatoxina B1/análise , Ocratoxinas/análise , Óleos de Plantas/análise , Dieta Mediterrânea , Gorduras Insaturadas na Dieta/análise , Humanos , Marrocos , Azeite de OlivaRESUMO
The p.M172K TFR2 mutation was identified in two Italian siblings aged 32 and 40 years old with primary iron overload. The two patients showed a severe increase in serum iron indices. From the age of 25, the male sib also revealed abnormal levels of hepatic enzymes, presumably in relation to iron induced liver damage. Clinical findings seem to evidence that type 3 hemochromatosis can be more serious than classic hemochromatosis. This report adds two more type 3 hereditary hemochromatosis cases which suggest that TFR2 mutations could be more frequently involved in non-HFE hemochromatosis than has been actually thought.
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Predisposição Genética para Doença , Hemocromatose/genética , Sobrecarga de Ferro/metabolismo , Receptores da Transferrina/genética , Adulto , Análise Mutacional de DNA , Família , Feminino , Hemocromatose/metabolismo , Humanos , Itália , Masculino , Transferrina/metabolismoRESUMO
AIMS: To analyze clinical and laboratory features at presentation in correlation to treatment response and overall survival; evaluation of different treatment approaches. METHODS: The data of 151 consecutive HCL patients observed between 1982 and 2005 were retrospectively analyzed. RESULTS: The following data at presentation were analyzed and compared to response, DFS, PFS and OS: Hb < 10 g/dl (observed in 27% of patients); Plt < 100,000/microl (72%); WBC > 10,000/microl (15%); Splenomegaly (75%); Bone marrow involvement > 70% (27%). At univariate analysis only WBC > 10,000/microl resulted significantly correlated to reduced PFS. 88 Pts received as first line treatment alpha2-interferon (IFN) alone, 49 purine analogues (PA) alone or in combination with IFN, 5 were treated with splenectomy. Among IFN treated patients CR, PR and SD were obtained in 21.6%, 73.8%, 4.5% respectively of the patients; while among PA treated patients in: 26.5%, 71.4%, 2.0% respectively. DFS was significantly prolonged in patients treated with PA with respect to IFN. No significant difference in OS was observed. Median PFS was 27.6 months, median OS is projected at 238 months after a median follow up of 131 months. CONCLUSIONS: Among the routine clinical and hematochemical baseline features only the presence of WBC > 10,000/microl was correlated to a lower PFS. First line treatment with purine analogues is correlated to prolonged PFS and DFS with respect to IFN; nevertheless no difference is observed in OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Feminino , Seguimentos , Hemoglobinas/metabolismo , Humanos , Interferon-alfa/administração & dosagem , Leucemia de Células Pilosas/sangue , Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pentostatina/administração & dosagem , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Esplenectomia , Análise de SobrevidaRESUMO
Antibodies capable to recognize antigen expressed on cancer cells represents the ideal approach for targeted anti neoplastic therapies. The CD33 antigen is present on 90% of acute myeloid leukemia blasts and is shared on normal hemopoietic cells only on the non stem dillerentiating fraction. Gemtuzumab Ozogamicin (GO) is an engineered humanized antibody anti-CD33 conjugated with a potent intercalating agent, named calicheamicin, which is release only at intracellular level (lower pH), following a selective binding to CD33-positive cells, thus representing a promising approach for target anti-leukemia therapy. GO was approved conditionally by the Federal Drug Administration in May 2000 as a single therapy for first recurrence of Acute Myeloid Leukemia (AML) in a subset of older patients. Since 2000, treatment trials and pilot studies have revealed potential expanded applications along with potential limitations. Phase II trials have confirmed the activity and the efficacy of GO as single agent in the treatment of relapsed AML. More recently, clinical trials on induction and post-remission treatment of adult AML have shown efficacy of GO in combination chemotherapy. The strong and homogeneous CD33 expression in Acute Promyelocytic Leukemia (APL), have resulted in an effective treatment of this disease with GO used as salvage treatment, as well as innovative approach for molecular relapsed patients. However, the incidence of veno-occlusive disease, better defined as sinusoidal occlusive syndrome (SOS), must be taken into account as potential complication associated with the GO administration, especially in patients treated with ablative regimens. In conclusion, the extension of the approval in Italy to AML CD33+ in relapsed, regardless age limitation, along with the ongoing evaluation by the European EMEA, represent the basis for a large clinical application of GO in myeloid malignancies potentially extended to paediatric patients with AML and to ALL CD33+.