RESUMO
Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment.
RESUMO
BACKGROUND: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia. METHODS: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020. The study was approved by the ethics committee of the participating institution and was conducted in accordance with the Declaration of Helsinki. The effectiveness and toxicity of venetoclax + HMA in 190 (43 newly diagnosed, 68 refractory, and 79 relapsed) patients with AML are reported here. RESULTS: In the newly diagnosed AML, the overall response rate and survival confirmed the brilliant results demonstrated in VIALE-A. In the relapsed or refractory AML, the combination demonstrated a surprisingly complete remission rate (44.1% in refractory and 39.7% in relapsed evaluable patients) and conferred to treated patients a good expectation of survival. Toxicities were overall manageable, and most incidents occurred in the first 60 days of therapy. Infections were confirmed as the most common nonhematologic adverse event. CONCLUSIONS: Real-life data show that the combination of venetoclax and HMA offers an expectation of remission and long-term survival to elderly, newly diagnosed patients, and to relapsed or chemoresistant AML, increasing the chance of cure through a different mechanism of action. The venetoclax + HMA combination is expected to constitute the base for triplet combinations and integration of target therapies. Our data contribute to ameliorate the understanding of venetoclax + HMA effectiveness and toxicities in real life.
Assuntos
Leucemia Mieloide Aguda , Humanos , Idoso , Estudos de Coortes , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Sulfonamidas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
The combination approach based on venetoclax (VEN) with azacytidine (AZA) has significantly improved outcomes for elderly patients with acute myeloid leukemia (AML). This innovative approach has led to higher rates of overall response, measurable residual disease (MRD)-negative remissions, and overall survival compared with AZA monotherapy. As a result, this combination has emerged as the gold-standard treatment for elderly or unfit patients with AML who are not eligible for intensive therapy. In younger, fit patients with AML, intensive induction and consolidation chemotherapy is commonly used as a first-line approach; however, relapse continues to be the main reason for treatment failure in approximately 30-40% of patients. Efforts to improve MRD-negative response rates and to facilitate the transition to allogeneic hematopoietic stem cell transplantation, particularly in high-risk AML, have inspired trials exploring the combination of intensive chemotherapy with targeted agents. VEN, a first-in-class anti-BCL2 agent, combined with intensive chemotherapy regimens has shown deep MRD-negative remissions, producing prolonged event-free survival and enhancing the transition to allogeneic transplant in first-complete-remission patients. These benefits support the incremental advantages of adding VEN to intensive chemotherapy approaches across ELN risk subcategories, and provides a robust benchmark to design future trials. In this review, we will discuss current studies assessing the efficacy of frontline regimens integrating VEN into intensive chemotherapy in younger patients with AML and specific molecularly defined subgroups.
RESUMO
Systemic mastocytosis (SM) is a rare disease with a range of clinical presentations, and the vast majority of patients have a KIT D816V mutation that results in a gain of function. The multikinase/KIT inhibitor midostaurin inhibits the D816V mutant and has a well-established role in treating advanced SM. Even if considered the standard of therapy, some open questions remain on optimizing midostaurin management in daily practice. The current review presents the opinions of a group of experts who met to discuss routine practice using midostaurin in patients with advanced SM. The efficacy and safety of midostaurin in Phase 2 trials are overviewed, followed by practical guidance for optimal therapy management and adverse events during therapy with midostaurin. Specific guidance is given for initiating therapy and evaluating response with midostaurin as general assessment and laboratory, instrumental, pathological, and molecular exams. Special consideration is given to dose interruption, reduction, and discontinuation of therapy, as well as adverse event management and supportive therapy. Patients should be informed about possible side effects and receive practical advice to avoid or limit them and antiemetic prophylaxis so that therapy with midostaurin can continue as long as clinical benefit is observed or until unacceptable toxicity occurs. Lastly, considerations on the use of midostaurin during the ongoing Covid-19 pandemic are made. The overall scope is to provide guidance that can be useful in daily practice for clinicians using midostaurin to treat patients with advanced SM.
RESUMO
Decitabine, a DNA hypomethylating agent, was approved for use in adults with acute myeloid leukemia (AML) not eligible for standard chemotherapy and is now widely accepted as standard treatment. Although a number of clinical trials demonstrated its benefits in elderly AML patients, older adults and patients with frequent comorbidities are typically under-represented in such settings. Thus, the aim of the present study is to evaluate, in a real-world setting, the effectiveness and toxicity of decitabine administered as a single agent in unselected previously untreated elderly AML patients not eligible for intensive chemotherapy. In nine hematological departments of the Apulian Hematological Network (REP), we enrolled 199 patients (median age: 75.4 years; range: 61-91) with de novo (n = 94) or secondary/therapy-related (n = 105) AML treated with decitabine 20 mg/m2 for five days every 4 weeks. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using multivariate Cox regression. The average number of cycles administered per patient was 6.3 (SD: 6.0; median: 5 cycles). Complete response was achieved by 31 patients (15.6%) and partial response by 57 (28.6%), for a total of 88 responders overall (44.2%). After a median follow-up of 33.6 months, median OS was 8.7 months (95% CI: 7.4-10.3), and the 6-month, 1-year, and 3-year OS rates were 62.7%, 37.0%, and 7.1%, respectively. Mortality was increased in AML patients with ≥3 comorbidities (HR = 2.45; 95% CI: 1.18-5.08) vs. no comorbidities and in those with adverse karyotype (HR = 1.58; 95% CI: 1.05-2.38) vs. favourable or intermediate profile. Infection was the main registered adverse event (46.0%). In conclusion, this REP real-life study demonstrates, after a follow-up of almost 3 years, how decitabine administered to AML patients not suitable for intensive chemotherapy is effective and well tolerated, even in a population of truly elderly patients with frequent comorbidities.
RESUMO
PURPOSE: Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT. METHODS: This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma. Eighty-one patients participated. RESULTS: Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported. CONCLUSION: NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT.
Assuntos
Antieméticos , Linfoma não Hodgkin , Náusea , Palonossetrom , Vômito , Antieméticos/efeitos adversos , Antineoplásicos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Palonossetrom/efeitos adversos , Transplante Autólogo , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito/prevenção & controleRESUMO
Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment [gastrointestinal toxicity (36.3%) and skin rash (10.3%)]. Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.
RESUMO
Despite the availability of several antiemetics, clinical findings show that control of chemotherapy-induced nausea and vomiting (CINV) continues to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT). For CINV prophylaxis, 5-hydroxytryptamine type-3 receptor antagonists (5HT3-RAs) and neurokinin 1 receptor antagonists (NK1-RAs) are usually administered together with dexamethasone, which may increase the risk of serious infections in patients undergoing myeloablative treatment. The rationale of this multicenter, open-label and phase IIa study was to explore the efficacy of multiple doses of NEPA (netupitant/palonosetron) given as an every-other-day regimen without dexamethasone in preventing CINV in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma (R/R-NHL), eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6), and 98.6% (delayed phase: days 7-8), while complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase), and 95.7% (delayed phase). Moderate and severe episodes of nausea were reported by less than 10% of patients in the overall phase and less than 5% in both the acute and delayed phases. Regarding safety, NEPA was well tolerated with only one adverse event (constipation) evaluated as possibly related to NEPA administration. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone is highly effective for preventing nausea and vomiting in this difficult setting, with a good tolerability profile.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Dexametasona , Combinação de Medicamentos , Humanos , Isoquinolinas , Linfoma não Hodgkin/terapia , Náusea , Recidiva Local de Neoplasia , Piridinas , Quinuclidinas , Transplante Autólogo , VômitoRESUMO
Mammalian target of rapamycin (mTOR) is a key protein kinase that regulates cell growth, metabolism, and autophagy to maintain cellular homeostasis. Its activity is inhibited by adverse conditions, including nutrient limitation, hypoxia, and DNA damage. In this study, we demonstrate that Che-1, a RNA polymerase II-binding protein activated by the DNA damage response, inhibits mTOR activity in response to stress conditions. We found that, under stress, Che-1 induces the expression of two important mTOR inhibitors, Redd1 and Deptor, and that this activity is required for sustaining stress-induced autophagy. Strikingly, Che-1 expression correlates with the progression of multiple myeloma and is required for cell growth and survival, a malignancy characterized by high autophagy response.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/fisiologia , Mieloma Múltiplo/patologia , Proteínas Repressoras/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos Nus , Mieloma Múltiplo/metabolismo , Complexos Multiproteicos/metabolismo , Fosforilação , Proteínas Repressoras/genética , Estresse Fisiológico , Serina-Treonina Quinases TOR/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
AIMS AND BACKGROUND: Multiple myeloma is the second most common hematological cancer. Although it accounts for only a relatively small percentage of all cancer types, the costs associated with managing multiple myeloma are considerable. Available studies are mainly focused on health care costs. The Costo del Mieloma Multiplo (Cost of MM, CoMiM) study investigated the cost of illness of multiple myeloma in Italy during one year of disease management. METHODS: CoMiM is a retrospective, prevalence-based, multi-center, cross-sectional study based on a stratified sample of patients seen during normal clinical practice (asymptomatic; symptomatic on drugs; symptomatic receiving autologous stem cell transplantation; plateau/remission). Demographics, clinical history, health care and non-health care resource consumption data were collected. Costs were evaluated from the societal viewpoint and expressed in Euro 2008. RESULTS: Data on 236 patients were analyzed (39 asymptomatic, 17%; 29 symptomatic receiving autologous stem-cell transplantation, 12%; 105 symptomatic receiving drugs, 44%; 63 plateau/remission, 27%). The total cost of illness reached 19,267.1 ± 25,078.6 (asymptomatic, 959.3 ± 1091.6; symptomatic receiving drugs, 21,707.8 ± 21,785.3; symptomatic receiving autologous stem-cell transplantation, 59,243.7 ± 24,214.0; plateau/remission, 8130.7 ± 15,092.5). The main cost drivers of total cost of illness were drugs and hospital admissions (46.1% and 29.4%, respectively). Antineoplastics and immunomodulators drove the cost of drugs (21.6% and 21.1% of the total cost of illness). Cost of antineoplastics was led by bortezomib (97.4%), whereas the cost driver for immunomodulators was lenalidomide (99.4%). Cost of hospitalization funded by the Italian National Health Service was strongly influenced by transplantation (94.6%), whereas chemotherapy and skeletal fractures did not exceed 1% and 2%, respectively. CONCLUSIONS: Despite some limitations, the CoMiM study provides Italian health care decision-makers with an insight into the stratified cost of illness of multiple myeloma patients.
Assuntos
Antineoplásicos/economia , Efeitos Psicossociais da Doença , Mieloma Múltiplo/economia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/economia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Estudos Transversais , Feminino , Custos de Cuidados de Saúde , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Estudos Retrospectivos , Transplante AutólogoRESUMO
Engagement of NKG2D and DNAX accessory molecule-1 (DNAM-1) receptors on lymphocytes plays an important role for anticancer response and represents an interesting therapeutic target for pharmacological modulation. In this study, we investigated the effect of inhibitors targeting the glycogen synthase kinase-3 (GSK3) on the expression of NKG2D and DNAM-1 ligands in multiple myeloma (MM) cells. GSK3 is a pleiotropic serine-threonine kinase point of convergence of numerous cell-signaling pathways, able to regulate the proliferation and survival of cancer cells, including MM. We found that inhibition of GSK3 upregulates both MICA protein surface and mRNA expression in MM cells, with little or no effects on the basal expression of the MICB and DNAM-1 ligand poliovirus receptor/CD155. Moreover, exposure to GSK3 inhibitors renders myeloma cells more efficient to activate NK cell degranulation and to enhance the ability of myeloma cells to trigger NK cell-mediated cytotoxicity. We could exclude that increased expression of ß-catenin or activation of the heat shock factor-1 (transcription factors inhibited by active GSK3) is involved in the upregulation of MICA expression, by using RNA interference or viral transduction of constitutive active forms. On the contrary, inhibition of GSK3 correlated with a downregulation of STAT3 activation, a negative regulator of MICA transcription. Both Tyr(705) phosphorylation and binding of STAT3 on MICA promoter are reduced by GSK3 inhibitors; in addition, overexpression of a constitutively active form of STAT3 significantly inhibits MICA upregulation. Thus, we provide evidence that regulation of the NKG2D-ligand MICA expression may represent an additional immune-mediated mechanism supporting the antimyeloma activity of GSK3 inhibitors.
Assuntos
Quinase 3 da Glicogênio Sintase/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Células Matadoras Naturais/imunologia , Mieloma Múltiplo/imunologia , Fator de Transcrição STAT3/imunologia , Western Blotting , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Citotoxicidade Imunológica/imunologia , Citometria de Fluxo , Imunofluorescência , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/imunologia , Mieloma Múltiplo/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/metabolismo , Transdução Genética , TransfecçãoRESUMO
AIM: To address the incidence and the prognostic role of a very early standard complete cytogenetic response (CCyR) or all Ph- metaphases (MET-, when <20 cells were evaluable). METHODS: We revised 182 chronic phase chronic myelogenous leukemia patients treated with frontline imatinib (IM) at two institutions from June 2002 to June 2011. RESULTS: After 3 months of treatment, 138 patients (75.8%) achieved CCyR/MET- while 44 patients (24.2%) still presented Ph+ metaphases (MET+) (<33%, 24 patients; ≥33%, 20 patients). On univariate analysis, palpable spleen enlargement (p < 0.001), WBC count >100.0 × 10(9)/l at onset (p < 0.001), and male gender (p = 0.019) had a negative impact on achievement of CCyR/MET- at 3 months. Among patients with CCyR/MET- after 3 months, there were 15 failures (10.8%) compared to 21 (47.7%) among patients with MET+ (p < 0.001). The 5-year overall survival was 97.0% in patients CCyR/MET- at 3 months and 91.8% in patients MET+ at 3 months (p = 0.277); the 5-year progression-free survival was 88.2% in patients CCyR/MET- at 3 months and 48.4% in patients MET+ at 3 months (p < 0.001). CONCLUSIONS: The achievement of CCyR/MET- at 3 months seems to have prognostic relevance and could be a very early and useful indicator of an excellent response to IM beyond European LeukemiaNet guidelines.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia/efeitos dos fármacos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Idoso , Benzamidas , Intervalo Livre de Doença , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Metáfase/efeitos dos fármacos , Pessoa de Meia-Idade , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidoresRESUMO
PURPOSE: Bortezomib, a proteasome inhibitor drug very effective against multiple myeloma, may induce the so-called bortezomib-induced peripheral neuropathy (BIPN), hardly manageable with common analgesic drugs. This study assessed the effectiveness of controlled-release (CR) oral oxycodone in controlling pain and its interference on daily functions of patients with hematologic malignancies affected by BIPN. METHODS: Forty-six patients (median age, 62 years) affected by myeloma and lymphoma, complaining of BIPN-related pain of moderate-to-severe intensity and unresponsive to previous analgesic treatments, were treated with CR oxycodone. The intensity of continuous and brief pain (BP) along with interference of pain with the common daily dimensions of feeling and function were evaluated by using an 11-point numerical rating scale (NRS); a global patient evaluation of efficacy was also performed. RESULTS: The daily average dose of CR oxycodone administered was 28.46 mg (range, 20-80 mg). The pain intensity decreased from a mean NRS value of 7.6 at baseline to 1.3 on day 14. The frequency of BP was reduced from 61 to 47% of patients and its intensity from 7.4 to 3.1 NRS score. A similar trend to decreasing values was observed for all the daily life functions. Slight- or mild-intensity side effects were observed in 23 patients (51%). At the end of the study, 75% of patients found the treatment effective or very effective. CONCLUSION: CR oxycodone for relief of BIPN-related pain was effective and well tolerated. The pain control significantly improved also the quality of the daily life functions, which are usually compromised in these suffering patients.
Assuntos
Analgésicos Opioides/administração & dosagem , Antineoplásicos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Oxicodona/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Pirazinas/efeitos adversos , Administração Oral , Idoso , Bortezomib , Preparações de Ação Retardada , Humanos , Pessoa de Meia-Idade , Cidade de RomaRESUMO
INTRODUCTION: Bortezomib is a proteasome inhibitor that targets myeloma cell and its bone marrow microenvironment. Intravenous Bortezomib with or without dexamethasone, is effective and well tolerated in patients with relapsed/refractory multiple myeloma (MM). METHODS: We used Bortezomib without corticosteroids, to avoid the risk of lung infection reactivations due to patient's Pseudomonas aeruginosa colonization, in a MM patient with Cystic Fibrosis. Four 21-day cycles of Bortezomib were administrated at 1.3 mg/m(2) on days 1,4,8 and 11 with a 10 day rest period. Treatment response and toxicity were evaluated. RESULTS: After four cycles of therapy the patient achieved a very good partial response (VGPR) according to the IMWG response criteria, without clinically significant side effects. CONCLUSIONS: Bortezomib can be successfully utilized for the management of this difficult disease situation.
Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Pirazinas/uso terapêutico , Adulto , Bortezomib , Feminino , Humanos , Mieloma Múltiplo/complicações , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologiaRESUMO
We here describe a single-institution experience on 40 patients with myelodysplastic syndromes (MDS) consecutively treated with deferasirox at the dose of 10-30 mg/kg/day according to Consensus Guidelines on Iron Chelation Therapy, outside of clinical trials. Serum ferritin (SF) was measured monthly, and safety assessment included monitoring of adverse events during treatment and of liver and renal parameters. Median SF at baseline of the 40 patients was 2,878 ng/ml. Median dose of deferasirox was 1,125 mg/day. At a median follow-up of 12 months of treatment, there was a significant reduction in SF from baseline, the median value being 1,400 ng/ml (p = 0.001). Interruptions due to toxicity were recorded in 40 % of patients: most common adverse events were diarrhoea (five patients, 12.5 %) and skin rash (four patients, 10 %). Seven patients had increased serum creatinine values >33 % above baseline, but there were no progressive increases. Four patients (three refractory anaemia and one refractory anaemia with excess blasts type 1) had a reduction of transfusion requirement (from a median of 5 to 1 unit/month) according to International Working Group 2006 criteria, with mean Hb value increasing from 8.5 to 10.5 g/dl, and mean Hb improvement being 2 g/dl (p = 0.02). No increased toxicity was noted when deferasirox was used concomitantly with azacitidine (eight patients who were intermediate 2 International Prognostic Scoring System risk) or lenalidomide (two patients with del(5q)). In conclusion, the oral iron chelator deferasirox is effective and safe when used in MDS patients with transfusion requirement, also if administered concomitantly with other drugs.
Assuntos
Benzoatos/uso terapêutico , Quelantes/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos/uso terapêutico , Azacitidina/uso terapêutico , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Quelantes/administração & dosagem , Quelantes/efeitos adversos , Deferasirox , Toxidermias/etiologia , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Gastroenteropatias/induzido quimicamente , Hematínicos/efeitos adversos , Hematínicos/uso terapêutico , Humanos , Sobrecarga de Ferro/prevenção & controle , Nefropatias/induzido quimicamente , Lenalidomida , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/efeitos adversosRESUMO
In the last decades, the global epidemiological impact of invasive candidiasis (IC) in patients with hematologic malignancies (HM) and in hematopoietic stem cell transplant (HSCT) recipients has decreased and the incidence of invasive aspergillosis exceeded that of Candida infections. The use of prevention strategies, first of all antifungal prophylaxis with triazoles, contributed to the reduction of IC in these populations as demonstrated by several epidemiological studies. However, relatively little is known about the current epidemiological patterns of IC in HM and HSCT populations, because recent epidemiological data almost exclusively derive from retrospective experiences and few prospective data are available. Several prospective, controlled studies in the prophylaxis of invasive fungal diseases have been conducted in both the HM and HSCT setting. On the contrary, most of the prospective controlled trials that demonstrated the efficacy of the antifungal drugs echinocandins and voriconazole in the treatment of candidemia and invasive candidiasis mainly involved patients with underlying conditions other than HM or HSCT. For these reasons, international guidelines provided specific indications for the prophylaxis strategies in HM and HSCT patients, whereas the recommendations on therapy of documented Candida infections are based on the results observed in the general population and should be considered with caution.
RESUMO
BACKGROUND: Imatinib has become first line therapy in chronic myeloid leukemia patients. Little is known about the infective consequences during the treatment with this drug in large series of chronic phase patients. MATERIAL AND METHODS: From January 2001 to September 2006 we treated with imatinib 250 patients in first line (early CP) or after interferon failure (late CP), out of clinical trials and recorded all the bacterial and viral infections occurred. RESULTS: We recorded a similar incidence of bacterial and viral infections both in first line and late CP patients (respectively, 16% and 13%) during 3.5 years of follow-up. Analysis of presenting features predisposing to infections revealed differences only in late CP patients, with elevated percentage of high Sokal risk patients and a more longer median time from diagnosis to start of imatinib. CONCLUSIONS: Opportunistic infections and reactivation of Herpes Zoster are observed during imatinib therapy at very low incidence.