RESUMO
Primary plasma cell leukemia (pPCL) is a rare and challenging malignancy. There are limited data regarding optimum transplant approaches. We therefore undertook a retrospective analysis from 1998-2014 of 751 patients with pPCL undergoing one of four transplant strategies; single autologous transplant (single auto), single allogeneic transplant (allo-first) or a combined tandem approach with an allogeneic transplant following an autologous transplant (auto-allo) or a tandem autologous transplant (auto-auto). To avoid time bias, multiple analytic approaches were employed including Cox models with time-dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto-first (n=681), regardless of a subsequent second transplant. The allo-first group had a lower relapse rate (45.9%, 95% confidence interval [95% CI]: 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher non-relapse mortality (27%, 95% CI: 15.9-38.1 vs. 7.3%, 5.2-9.4) at 36 months. Patients who underwent allo-first had a remarkably higher risk in the first 100 days for both overall survival and progression-free survival. Patients undergoing auto-allo (n=122) had no increased risk in the short term and a significant benefit in progression-free survival after 100 days compared to those undergoing single auto (hazard ratio [HR]=0.69, 95% CI: 0.52- 0.92; P=0.012). Auto-auto (n=117) was an effective option for patients achieving complete remission prior to their first transplant, whereas in patients who did not achieve complete remission prior to transplantation our modeling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplantation in pPCL to date. We confirm a significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome. This knowledge may help to guide clinical decisions on transplant strategy.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Plasmocitária , Humanos , Estudos Retrospectivos , Transplante Homólogo , Leucemia Plasmocitária/diagnóstico , Leucemia Plasmocitária/terapia , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo , RecidivaRESUMO
With increasingly effective treatments, early death (ED) has become the predominant reason for therapeutic failure in patients with acute promyelocytic leukemia (APL). To better prevent ED, patients with high-risk of ED must be identified. Our aim was to develop a score that predicts the risk of ED in a real-life setting. We used APL patients in the populationbased Swedish AML Registry (n=301) and a Portuguese hospital-based registry (n=129) as training and validation cohorts, respectively. The cohorts were comparable with respect to age (median, 54 and 53 years) and ED rate (19.6% and 18.6%). The score was developed by logistic regression analyses, risk-per-quantile assessment and scoring based on ridge regression coefficients from multivariable penalized logistic regression analysis. White blood cell count, platelet count and age were selected by this approach as the most significant variables for predicting ED. The score identified low-, high- and very high-risk patients with ED risks of 4.8%, 20.2% and 50.9% respectively in the training cohort and with 6.7%, 25.0% and 36.0% as corresponding values for the validation cohort. The score identified an increased risk of ED already at sub-normal and normal white blood cell counts and, consequently, it was better at predicting ED risk than the Sanz score (AUROC 0.77 vs. 0.64). In summary, we here present an externally validated and population-based risk score to predict ED risk in a real-world setting, identifying patients with the most urgent need of aggressive ED prevention. The results also suggest that increased vigilance for ED is already necessary at sub-normal/normal white blood cell counts.
Assuntos
Leucemia Promielocítica Aguda , Estudos de Coortes , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/epidemiologia , Leucemia Promielocítica Aguda/terapia , Contagem de Leucócitos , Fatores de Risco , Resultado do TratamentoAssuntos
Linfo-Histiocitose Hemofagocítica , Linfoma Difuso de Grandes Células B , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/complicações , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Neoplasias Vasculares/complicações , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patologia , Idoso , Feminino , Pessoa de Meia-IdadeRESUMO
Autologous stem cell transplantation (ASCT) is still debatable in treatment of patients over 65 years with multiple myeloma (MM). We performed a retrospective analysis of newly diagnosed MM patients who underwent ASCT between January 2010 and July 2016. A non-transplanted group with similar clinical characteristics, aged 65-70 years old, diagnosed and treated in the same timeline was used for comparison. We analyzed a total of 155 patients, 132 of which underwent ASCT (≤ 65 years, n = 103, median 56 years; > 65 years, n = 29, median 67 years) and 23 non-transplanted (median 68 years). Conditioning consisted of melphalan 200 mg/m2 (MEL200) in younger patients and melphalan 140 mg/m2 (MEL140) in half of elderly patients. Stratifying by age, there were no statistically significant differences concerning transplant-related myelotoxicity and non-hematopoietic toxicity; however, elderly patients conditioned with MEL200 had higher needs of transfusional support and more days of intravenous antibiotics. Those patients also had higher needs of transfusional support, higher grade of mucositis (p = 0.028), and more days of intravenous antibiotics (p = 0.019) than the elderly transplanted with MEL140. Global transplant-related mortality was 3.8%. Survival was not influenced by age. Non-transplanted elderly patients had comparable disease features, and induction response was similar in both groups (before ASCT in the transplanted cohort). Survival of transplanted elderly patients was superior to non-transplanted (OS, 59 months vs 30 months, p = 0.037; EFS, 45 months vs 27 months, p = 0.014). Selected elderly patients when transplanted have similar disease response and survival as younger patients. A higher dose of melphalan has more toxicity, but it is globally a well-tolerated procedure.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Adulto , Fatores Etários , Idoso , Antibacterianos/administração & dosagem , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/etiologia , Mucosite/prevenção & controle , Estudos Retrospectivos , Segurança , Taxa de SobrevidaRESUMO
Patients older than 75 years old with multiple myeloma (MM) have shorter survival and are usually treated differently from what features in clinical trials. In this study, the authors characterized the Portuguese population of MM patients above 75 years old, treated between 2009 and 2016. We compared the outcomes obtained with bortezomib-based protocols (BBP), thalidomide-based protocols (TBP), and chemotherapy (CT) using univariate and multivariate controlling for age, performance status, International Staging System score, renal impairment, and number of comorbidities. We retrieved data from 386 patients, treated in 12 hospitals. Three hundred thirty-one cases were analyzed: 119 patients treated with BBP, 65 with TBP, 147 with CT. Median age was 79 years; CT-treated patients were older, had a worse performance status, and have more comorbidities. The median follow-up was 25 months. The 2-year OS was 58% and the median OS was 29.5 months. Patients treated with BBP had more frequently very good partial response (VGPR) or better response, and the subgroup of more fit patients had a significantly longer progression-free survival (PFS) and OS. The most frequently grade 3-4 toxicities were hematologic, infectious, and neurologic and were significantly lower in TBP and CT groups vs BBP. The most common second line was CT, followed by lenalidomide. Patients treated with lenalidomide had a higher probability of VGPR or better and a superior 1-year PFS. Despite the limitations of a retrospective study, our cohort represents the reality of older patients with MM in a western country. The hazard of death or progression was higher for old, fit patients treated, in first line, with CT and with TBP compared with that of BBP.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Portugal/epidemiologia , Taxa de SobrevidaRESUMO
Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.
O vírus citomegálico (CMV) é um tipo de vírus de ácido desoxirribonucleico de dupla cadeia que pertence à família herpesviridae. Após uma infeção primária, o vírus torna-se latente em vários tipos de glóbulos brancos. A infeção por CMV pode permanecer latente ou tornar-se ativa, especialmente em indivíduos imunodeprimidos, como aqueles submetidos a transplantes de células progenitoras hematopoiéticas (TPH), onde a reativação do CMV pode ocorrer. Neste contexto, a infeção por CMV é comum e associada a elevadas taxas de morbilidade e mortalidade. A pneumonite é uma das complicações mais graves, com taxas de mortalidade superiores a 50%. Além disso, mesmo na ausência de doença específica do órgão, a infeção por CMV está relacionada com um aumento da mortalidade não relacionada com a recidiva da neoplasia hematológica. Dada a frequência e gravidade desta infeção em doentes submetidos a TPH, é crucial implementar estratégias eficazes de monitorização, prevenção e tratamento. Este protocolo foi desenvolvido para identificar os grupos de doentes que se beneficiam de uma abordagem sistematizada para a infeção por CMV e definir a estratégia mais adequada para cada grupo. A monitorização da carga viral de CMV no sangue periférico é fundamental, especialmente em doentes com risco moderado a elevado de infeção ativa. A profilaxia primária com letermovir (fármaco antiviral) é recomendada para reduzir a incidência de infeção ativa, especialmente em doentes com alto risco. A profilaxia secundária com valganciclovir (fármaco antiviral) é recomendada após um episódio de infeção ativa, enquanto o tratamento de antecipação e de doença é baseado na monitorização da carga viral e na resposta clínica. Este protocolo visa melhorar a abordagem da infeção por CMV em doentes submetidos a TPH, garantindo uma abordagem preventiva e terapêutica eficaz e segura.
RESUMO
The treatment of multiple myeloma has profoundly changed with the introduction of several innovative therapies. The optimization of therapeutic sequencing through the combined use of the various drugs developed in recent years and the attention given to the characteristics of patients have allowed the reduction of toxicities and increased survival and quality of life of patients with multiple myeloma. These treatment recommendations from the Portuguese Multiple Myeloma Group offer guidance for first-line treatment and progression/relapse situations. These recommendations are given highlighting the data that justify each choice and referring to the respective levels of evidence that support these options. Whenever possible, the respective national regulatory framework is presented. These recommendations constitute an advance towards the best treatment of multiple myeloma in Portugal.
O tratamento do mieloma múltiplo tem sido amplamente alterado com introdução de várias terapêuticas inovadoras. A otimização da sequenciação terapêutica através do uso combinado dos vários fármacos desenvolvidos nos últimos anos e a atenção dada às características dos doentes têm permitido diminuir toxicidades e aumentar a sobrevivência dos doentes, bem como aumentar a sua qualidade de vida. As presentes recomendações terapêuticas do Grupo Português do Mieloma Múltiplo oferecem orientações para o tratamento de primeira linha e progressão/recaída. As recomendações são fundamentadas evidenciando os dados que justificam cada escolha e referindo os respetivos níveis de evidência que suportam essas opções. Sempre que possível é apresentado o respetivo enquadramento regulamentar nacional. Estas recomendações constituem um avanço para o melhor tratamento do mieloma múltiplo em Portugal.
Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Portugal , Qualidade de Vida , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
A 77-year-old man, otherwise healthy, presented with multiple symmetric yellowish patches in his axillary folds and abdomen that had evolved for 6 months (Figures 1 and 2). The lesions were initially confined to the axillary folds but have since disseminated during last 3 months. The patient was asymptomatic, and the physical examination was normal. Dermatoscopic evaluation of the yellowish patches showed a yellow homogeneous amorphous structure (Figure 3). (SKINmed. 2022;20:228-230).
Assuntos
Xantomatose , Idoso , Humanos , Masculino , Xantomatose/diagnóstico , Xantomatose/patologiaRESUMO
Treatment of acute myeloid leukemia (AML) evolving from myeloproliferative (MPN) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) is challenging. We evaluated disease characteristics, treatment patterns and outcomes in 372 patients diagnosed with AML after MPN or MDS/MPN over a 27-year period. Frontline treatment was intensive chemotherapy (38%), hypomethylating agents [HMAs] (17%), non-intensive chemotherapy (14%), and supportive care (31%). Median overall survival was 4.8 months, with a 5-year survival rate of 4%. Median survival was 2.8, 3.9 and 8.3 months for the 1992-2010, 2011-2015 and 2016-2019 periods, respectively (test for trend p < 0.001). Complete response (CR) rate was higher with intensive chemotherapy (43%) than with non-intensive chemotherapy (12%) or HMAs (8.5%) [p < 0.001], but responses were short-lived without allogeneic hematopoietic cell transplantation. Patients treated with intensive chemotherapy or HMAs had superior survival than those receiving non-intensive chemotherapy (median: 8.5 vs. 8.6 vs. 4.2 months, respectively). No differences in treatment response or survival were observed according to prior disease subtypes. Patients undergoing transplantation in CR had better survival than those transplanted in other response categories (3-year survival rate of 64% vs. 22%, p = 0.002). Our results support the use of intensive chemotherapy followed by transplant whenever possible, and the preferential use of HMAs over attenuated chemotherapy regimens in unfit patients. In spite of the survival improvement in recent years, this subset of AML constitutes an unmet medical need and deserves systematic incorporation in clinical trials.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Doenças Mieloproliferativas-Mielodisplásicas , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Sistema de RegistrosRESUMO
The hypomethylating agents, decitabine (DEC) and azacitidine (AZA), allowed more elderly acute myeloid leukemia (AML) patients to be treated. However, there are little direct comparative data on AZA and DEC. This multicenter retrospective study compared the outcomes of AZA and DEC in terms of response and overall survival (OS). Potential predictors associated with response and OS were also evaluated. A total of 626 AML patients were included (487 treated with AZA and 139 with DEC). Response rates were similar in both groups: CR was 18% with AZA vs. 23% with DEC (p = 0.20), CR/CRi was 20.5% vs. 25% (p = 0.27) and ORR was 32% vs. 39.5% (p = 0.12), respectively. Patients with leukocytes < 10 × 109/L, bone marrow blasts < 50% and ECOG ≥ 2 had higher ORR with DEC than with AZA. OS was similar in both groups: 10.4 months (95% CI: 9.2−11.7) vs. 8.8 months (95% CI: 6.7−11.0, p = 0.455), for AZA and DEC, respectively. Age (≥80 years), leukocytes (≥ 10 × 109/L), platelet count (<20 × 109/L) and eGFR (≥45 mL/min/1.73 m2) were associated with higher OS with AZA compared to DEC. In conclusion, we found no differences in response and OS rates in AML patients treated with AZA or DEC.
Assuntos
Linfócitos B/patologia , Transformação Celular Neoplásica/patologia , Linfoma Difuso de Grandes Células B/patologia , Plasmócitos/patologia , Linfoma Plasmablástico/patologia , Linfócitos B/metabolismo , Biópsia , Transformação Celular Neoplásica/metabolismo , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Imunofenotipagem , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , Plasmócitos/metabolismo , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/terapia , Tomografia Computadorizada por Raios XRESUMO
Monoclonal gammopathy of undetermined significance (MGUS) may be associated with pathologies with severe neuromuscular manifestations such as sporadic late-onset nemaline myopathy (SLONM). We describe a difficult to diagnose case of SLNOM with marked clinical improvement after achieving gammopathy complete hematologic response.
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A 3-year old White boy was referred to our dermatology department with a papular disseminated eruption, evolving for 7 months. Several topical antibiotics and corticosteroids were used without improvement. The dermatosis was locally asymptomatic, and systemic symptoms were absent. Examination revealed multiple, skin-colored to pinkish monomorphic papules with a generalized distribution involving the face, trunk, and limbs (Figure 1). The lesions spared the scalp, palms, and soles. Cervical, axillary, and inguinal lymphatic nodes were not palpable. Cutaneous biopsy of one of the abdominal lesions revealed an unremarkable epidermis but a reticular dermis with clusters of histiocytic, lymphocytic, and rare eosinophil cells. In the immunohistochemical study, expression of CD1a was observed in the histiocytic cells and S100 in the antigen-presenting cells of the dermal infiltrate (Figures 2 and 3). Taking into account the clinical presentation and the histopathologic result, a diagnosis of Langerhans cell histiocytosis (LCH) was established.
Assuntos
Histiocitose de Células de Langerhans , Biópsia , Pré-Escolar , Face , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Masculino , Couro Cabeludo , PeleRESUMO
BACKGROUND: Multiple myeloma (MM) is the second most common hematological cancer worldwide and has significant morbidity and mortality and is increasing in incidence. While MM management costs are considerable, specific economic data at the country level remain scarce. OBJECTIVE: This study assesses the burden and cost of MM in Portugal from the perspective of the National Health Service (NHS) to support the definition of health policies, resource allocation and patient care. METHODS: Developed by the Portuguese Multiple Myeloma Group, this study considers the most recent available data. Burden of disease was measured using disability-adjusted life-years (DALYs). The cost of MM was estimated using a prevalence-based model that estimated direct costs for the NHS considering all costs associated with diagnosis, hospitalizations, surgeries, emergency visits, medical appointments, drugs and transportation. Costs were quantified based on the diagnosis-related group funding price, except for drug usage, which was calculated using the average hospital product stock price. RESULTS: The burden of disease attributable to MM for 2018 was estimated at 8931 DALYs: 8570 resulting from premature deaths and 361 from disability. Average yearly direct costs per patients with MM amounted to 31,449 (year 2018 values). Total direct costs are estimated at 61 million per year. CONCLUSIONS: The mortality rate in MM means that most DALYs are due to years of life lost rather than years lost due to disability. This study generates comprehensive data on the burden and cost of MM in Portugal and provides updated insights into the costs associated with the management of MM.
Assuntos
Efeitos Psicossociais da Doença , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Portugal/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Medicina EstatalRESUMO
Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer, but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in patients with AML at diagnosis and explored the mechanisms involved using the syngeneic MLL-AF9-induced AML mouse model. We found that AML is a disorder with a unique iron profile, not associated with inflammation or transfusion, characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that the AML-induced loss of erythroblasts is responsible for iron redistribution and increased TSAT. We also show that AML progression is delayed in mouse models of systemic iron overload and that elevated TSAT at diagnosis is independently associated with increased overall survival in AML. We suggest that TSAT may be a relevant prognostic marker in AML.
Assuntos
Anemia , Leucemia Mieloide Aguda , Animais , Eritroblastos , Humanos , Ferro , Camundongos , TransferrinaRESUMO
The management of older patients with Multiple Myeloma (MM) is particularly challenging due to the highly heterogeneous nature of this population, both in terms of physical and cognitive functioning. Older patients may be divided into fit, intermediate and frail, with variable abilities to tolerate treatments. A careful and correct assessment of the frailty status is thus paramount for the success of therapy and for improving outcomes. With the aging of the European population, the number of older patients with MM is rapidly growing. We hereby present the deliberations and recommendations from an expert panel of Portuguese hematologists conducted to discuss the management of this population, including how to stratify and treat older patients with MM according to their frailty status. The use of frailty tools is critical for the development of individualized risk-adapted treatment strategies and to minimize the risk of under or overtreatment. Aggressive therapies should be used in fitter patients to improve survival outcomes, while frail patients should generally be treated with less toxic approaches to control symptoms while minimizing toxicity. In intermediate-fit patients, low-dose triplets are recommended to achieve a balance between improving survival and maintaining quality of life. The management of older patients with MM should be performed by a multidisciplinary team in view of their advanced age and high prevalence of comorbidities. The inclusion of older and frail patients in future clinical trials investigating treatment regimens for MM is crucial to evaluate treatment feasibility and to improve clinical decision making in this population.
Assuntos
Idoso Fragilizado , Mieloma Múltiplo , Idoso , Avaliação Geriátrica , Humanos , Mieloma Múltiplo/terapia , Portugal , Qualidade de VidaRESUMO
Extramedullary disease is an aggressive presentation at diagnosis and relapse for multiple myeloma (MM) patients. Central nervous system (CNS) is a very rare manifestation of the extramedullary disease, accounting for less than 1% of MM on diagnosis and relapse. Neurological symptoms are unspecific and usually attributed to other causes. We present two patients with CNS-MM at relapse after autologous stem cell transplant highlighting the importance of clinical suspicion and interdisciplinarity at diagnostic workup as well as the need for intensive therapeutic options on such rare and aggressive cases. The presence of neurological abnormalities in anamnesis and physical examination on a patient with MM should always prompt to suspect of a CNS involvement, and active investigation must be undertaken. MRI is the standard radiological method to detect CNS-MM, with histopathological corroboration by stereotactic biopsy and CSF evaluation alongside. Treatment of CNS-MM should include two essential approaches-be able to cross the BBB and treat the systemic disease. There is no standard therapy for this extramedullary relapse, and a tailored and multiple therapy should be promptly started-intrathecal therapy, radiotherapy, and systemic therapy, including an immunomodulator.
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This study investigated the importance of an oral test dose for busulfan (BU) dose adjustment before a conditioning regimen for hematopoietic stem-cell transplantation (HSCT) and the effect of fludarabine (FLU) on the oral BU pharmacokinetics evaluated after the fifth treatment dose (first BU dose on day 2 of treatment). Twenty-eight patients treated with oral BU (1 mg/kg every 6 hours for 4 days) were divided into 2 groups according to the concomitant administration of FLU (n = 15; 30 mg/m2 for 5 days) or subsequent administration of cyclophosphamide (CY) (n = 13; 60 mg/kg for 2 days). On the day prior to the beginning of the conditioning regimen, blood samples were collected (0-6 hours) after administration of an oral BU test dose of 0.25 mg/kg. Busulfan was quantified in plasma samples by LC-MS/MS, and the pharmacokinetic parameters were calculated using WinNonlin software. Blood samples were collected between the fifth and sixth treatment dose to confirm the mean plasma steady-state concentration (Css ) of BU. The AUC0-6 and apparent clearance of BU did not differ (P < .05) between the groups receiving FLU and CY. In 81% of the patients who received BU doses adjusted based on the test dose (n = 21), the Css was within the target range of 600-900 ng/mL. No association was observed between BU AUC0-6 and clinical outcome in the study group (n = 28). The results suggest that in concomitant administration of FLU and BU during conditioning regimens for HSCT, changes in BU dose should be considered only after the administration of the fifth BU dose.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/administração & dosagem , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/administração & dosagem , Vidarabina/análogos & derivados , Administração Oral , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/sangue , Bussulfano/sangue , Criança , Pré-Escolar , Terapia Combinada/métodos , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Imunossupressores/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/sangue , Adulto JovemRESUMO
Stem cell transplantation affects patient׳s vulnerability to infections due to immunological changes related to chemotherapy. Multiple myeloma is characterized by susceptibility to infections, and IL-6 and TNF-α increased levels affect immune response (IR). Polymorphisms in promoter region of cytokine genes may alter expression levels and affect IR. We performed interaction analysis of IL-6 (-174G/C) and TNF-α (-308G/A) polymorphisms with infection susceptibility in 148 patients classified accordingly to infection status and found an interaction when compared groups with and without bacteremia (p=0.0380). The interaction may be more important than single effects for the IR associated with the infection susceptibility in ASCT.
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Mucormycosis is a rare, highly aggressive and usually fatal infection, which affects immunocompromised patients. This case report describes a patient with acute promyelocytic leukemia who received antifungal therapy for a suspected pulmonary Aspergillus infection. Material from a lobectomy suggested that on histologic grounds the diagnosis had to be changed to mucormycosis. High suspicion of a Mucor infection favors early detection and timely appropriate antifungal therapy, which is crucial for the prognosis of these patients.