Toxicity and outcome of adults with acute myeloid leukemia receiving consolidation with high-dose cytarabine.

INTRODUCTION: High-dose cytarabine is considered standard of care as consolidation chemotherapy in adults with acute myeloid leukemia (AML) who are not eligible for allogeneic hematopoietic cell transplantation, but may be associated with significant toxicity. We evaluated the toxicity associated with high-dose cytarabine given as consolidation in AML patients treated at a Brazilian public hospital. METHODS: We retrospectively reviewed the charts of all patients with AML treated between 2008 and 2020 who obtained complete remission (CR) after one cycle of induction chemotherapy and received consolidation with at least one cycle of high-dose cytarabine (defined as 3 g/m2 every 12 h days 1, 3 and 5). RESULTS: Among 61 patients who received induction remission, 32 obtained CR and 28 received at least one cycle of high-dose cytarabine, for a total of 67 cycles (median 2 cycles per patient, range 1 - 4). In 45 cycles (67.2%) the patient was discharged after the end of chemotherapy, with a median of 6 days at home (range 3 - 8). Readmission occurred in 31 of the 45 cycles (68.9%). The most frequent toxicities were febrile neutropenia (56.7%), nausea and vomiting (23.9%), oral mucositis (14.9%) and diarrhea (11.9%). Bacteremia was documented in 13 cycles (34.2%). There were three cases of typhlitis and two of invasive fungal disease (aspergillosis and candidemia). Four patients died (14.3%), with two deaths considered treatment-related (candidemia and typhlitis). CONCLUSION: In the setting of a Brazilian public hospital, high-dose cytarabine as consolidation therapy is feasible, with manageable toxicity profile.

Current treatment preferences in acute myeloid leukemia: a survey in Brazil

ABSTRACT Introduction:: Most adults with acute myeloid leukemia (AML) will eventually relapse from their disease. The combination of 7-day cytarabine and an anthracycline on days 1-3 (the so called "7 + 3" regimen) can be considered standard of care of younger patients with AML. However, the treatment of the elderly ineligible for intensive chemotherapy remains a challenge. Low-dose of subcutaneous cytarabine or hypomethylating agents (HMA) have been studied this group. There are no studies investigating physician practice variation in treating AML in Brazil. Methods:: We developed a survey with ten questions in order to explore the approach to AML in Brazil. Results:: The sample size comprised 100 hematologists. Most reported regular (63%) or occasional (29%) treatment of AML patients. Karyotype analysis and polymerase chain reaction were available in 88% and 71% of institutions, respectively. Next generation sequencing analysis was used in 7% of instituitions. Younger patients receive the "7 + 3" protocol with continuous infusion of cytarabine and anthracycline in 98% of cases. The preferred anthracycline is daunorubicin (64%), followed by idarubicin (34%). The most prescribed daunorubicin dose was 60 mg/m2 (56%). Consolidation after CR with high cytarabine doses (HIDAC) was indicated by 84% of hematologists and 70% use 3 g/m2 twice a day for 3 days. Elderly and unfit patients received HMA (47%) as the preferred treatment. Conclusion:: We showed that the most prevalent AML treatments were according to current guidelines. There is room to improve on the availability of diagnostic tools and the capacity to perform bone marrow transplantation.

Current treatment preferences in acute myeloid leukemia: a survey in Brazil.

INTRODUCTION: Most adults with acute myeloid leukemia (AML) will eventually relapse from their disease. The combination of 7-day cytarabine and an anthracycline on days 1-3 (the so called "7 + 3" regimen) can be considered standard of care of younger patients with AML. However, the treatment of the elderly ineligible for intensive chemotherapy remains a challenge. Low-dose of subcutaneous cytarabine or hypomethylating agents (HMA) have been studied this group. There are no studies investigating physician practice variation in treating AML in Brazil. METHODS: We developed a survey with ten questions in order to explore the approach to AML in Brazil. RESULTS: The sample size comprised 100 hematologists. Most reported regular (63%) or occasional (29%) treatment of AML patients. Karyotype analysis and polymerase chain reaction were available in 88% and 71% of institutions, respectively. Next generation sequencing analysis was used in 7% of instituitions. Younger patients receive the "7 + 3" protocol with continuous infusion of cytarabine and anthracycline in 98% of cases. The preferred anthracycline is daunorubicin (64%), followed by idarubicin (34%). The most prescribed daunorubicin dose was 60 mg/m2 (56%). Consolidation after CR with high cytarabine doses (HIDAC) was indicated by 84% of hematologists and 70% use 3 g/m2 twice a day for 3 days. Elderly and unfit patients received HMA (47%) as the preferred treatment. CONCLUSION: We showed that the most prevalent AML treatments were according to current guidelines. There is room to improve on the availability of diagnostic tools and the capacity to perform bone marrow transplantation.

Effect of circadian variation on neutrophil mobilization to the peripheral blood in benign constitutional neutropenia.

Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on neutrophil circadian variation. The objective of this study was to evaluate whether circadian variations of neutrophil counts would result in neutrophil values higher than neutropenia threshold in individuals with BCN. Absolute neutrophil counts (ANCs) were evaluated in 102 patients with BCN (<1500 cells/µL) and 60 age- and sex-matched controls. Paired blood counts were performed in the early morning and in the early afternoon. We observed a significant difference between morning and afternoon ANC in BCN patients (879 cells/µL, 95% CI 745-1028, p < 0.001), as well as in the controls (619 cells/µL, 95% CI 443-796, p < 0.001). The ANC increase between the two evaluations was significantly greater in BCN patients compared with controls: 83% and 27%, respectively (p < 0.001). The ANC increment was higher in the groups with a lower morning ANC: 105%, 63%, and 27% in the <1000, 1000-1500, and >1500 cells/µL groups, respectively (p < 0.001). Of all BCN patients, 73% presented with >1500 cells/µL in the afternoon and 16% improved from the <1000 cells/µL to the 1000-1500 cells/µL category. In conclusion, neutrophil circadian variation measurement allows many BCN patients to be excluded from the neutropenia threshold. We identified a simple, easy, and feasible way to assess neutrophil reserve in patients with BCN with a potential reduction in costs of the assessment.

Feasibility and outcome of the hyper-CVAD regimen in patients with adult acute lymphoblastic leukemia.

BACKGROUND: Current chemotherapy regimens for adults with acute lymphoblastic leukemia (ALL) result in high rates of complete remission (CR), but relapses are still frequent. PATIENTS AND METHODS: In this retrospective single-center study, we evaluated the results of the Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen in 49 ALL patients treated between 2001 and 2013. No exclusion criteria were applied. The primary outcome measure was the CR rate. RESULTS: Forty-six of the 49 patients (93.8%) obtained CR, and 3 (6%) patients died during induction. Philadelphia chromosome was present in 6 patients (12.2%); in all a CR was obtained. Among the 46 patients in CR, 30 (65.2%) received the full planned intensive-phase treatment (8 cycles). Allogeneic hematopoietic cell transplantation was performed in 2 (4%) patients in first CR and in 3 (6%) patients after a second CR. Nonrelapse mortality was observed in 8 patients (16.3%). The median overall survival (OS) and 5-year OS were 24.4 months and 35%, respectively. Initial leukocyte count (> 30 × 10(9)/L) was an important prognostic factor. CONCLUSION: Hyper-CVAD as an induction regimen for adults and adolescents with ALL was feasible and yielded a high rate of CR. Relapse rates and OS were comparable to other series but still unsatisfactory.

Risk factors for unsuccessful peripheral blood stem cell harvesting using granulocyte-colony stimulating factor mobilization in patients with multiple myeloma.

The aim of this study was to determine factors that influence unsuccessful peripheral blood stem cell (PBSC) harvesting in patients with multiple myeloma (MM). Retrospective data of 186 MM patients who received G-CSF as mobilization were analyzed. Patients with successful harvest were compared with those who failed (using 2 definitions of failure <2 and <4 CD34 cells×10(6)/mm(3)). The groups were compared regarding age, gender, body weight, baseline platelet count, receipt of radiotherapy, number of prior chemotherapy regimens, PBSC count before collection, processed and collected volume, collect replace, number of sessions and final number of PBSC collected. By multivariate analysis, a baseline platelet count <161,000 cells/mm(3) was associated with PBSC harvest lower than 2×10(6)/kg, and age >58 years was related to PBSC harvest lower than 4×10(6)/kg CD34 cells/kg. Patients with these parameters should not receive mobilization protocols with G-CSF alone. Alternative protocols should be tested in this high risk harvest failure population.

Factors prompting early central venous catheter removal from cancer patients with candidaemia.

We evaluated clinical factors associated with early central venous catheter (CVC) removal in cancer patients with candidaemia who survived >3 days after the index blood culture. This was a retrospective cohort study from a previous candidaemia database conducted between January 2001 and June 2005. Eligible patients were those whose catheters were removed. Those who died in the first 72 h were excluded. Early CVC removal was defined as withdrawal in the first 72 h. We enrolled 164 patients with a 10.4% mortality rate. Multivariate analysis showed temporary non-tunnelled catheter type (odds ratio 5.06; 95% confidence interval 2.16-11.83) as the only variable associated with early removal. Among the 84 episodes judged not catheter-related, 52 CVCs were removed due to the need for further cancer treatment. No differences in mortality were seen among patients with early or late catheter removal. Stratified analysis showed a survival benefit (p = 0.04) of early removal among patients with a Karnofsky performance status score >60. The study shows a propensity to immediately remove short-term catheters and a tendency for early removal in patients undergoing active cancer treatment. There was no benefit of early catheter removal with regard to overall mortality. The favourable impact of early over late removal on survival among patients without significant illness merits further investigation.

Factors associated with hospital readmission in sickle cell disease.

BACKGROUND: Sickle cell disease is the most frequent hereditary disease in Brazil, and people with the disease may be hospitalised several times in the course of their lives. The purpose of this study was to estimate the hazard ratios of factors associated with the time between hospital admissions. METHODS: The study sample comprised all patients admitted, from 2000 to 2004, to a university hospital in Rio de Janeiro State, south-east Brazil, as a result of acute complications from sickle cell disease (SCD). Considering the statistical problem of studying individuals with multiple events over time, the following extensions of Cox's proportional hazard ratio model were compared: the independent increment marginal model (Andersen-Gill) and the random effects model. RESULTS: The study considered 71 patients, who were admitted 223 times for acute events related to SCD. The hazard ratios for hospital readmission were statistically significant for the prior occurrence of vaso-occlusive crisis and development of renal failure. However, analysis of residuals of the marginal model revealed evidence of non-proportionality for some covariates. CONCLUSION: the results from applying the two models were generally similar, indicating that the findings are not highly sensitive to different approaches. The better fit by the frailty model suggests that there are unmeasured individual factors with impact on hospital readmission.

Obesity and dose individualization in cancer chemotherapy: the role of body surface area and body mass index.

It is generally accepted that anti-neoplastic chemotherapy dose should be calculated according to body surface area (BSA). This approach does not account for the presence of obesity. Hence, patients with the same BSA will receive the same chemotherapy dose, regardless the presence of obesity. Since this may cause of toxicity in some obese patients, practice of limit BSA is usual. Currently, the body mass index (BMI) is largely used as a marker of obesity and both BSA and BMI include only height (h) and weight(w) in their formula. We put forward the hypothesis that the BMI should also be taken in account for calculation of chemotherapy dose for obese patients (BMI > 30 kg/m2). In this article, we present a correction to BSA (CBSA) based on the BMI to be tested in obese patients. Our main result is given by the equationCBSA=K(alpha1h(alpha2+2kappa)w(alpha3-kappa)),whereand kappa, alpha1, alpha2, alpha3 are constants. We show examples of how to calculate the CBSA. This simple strategy may limit drug exposition and maintain greater efficacy than a fixed limitation of BSA.

Expression of Epstein-Barr virus in patients with Hodgkin's disease: report of 64 cases from Rio de Janeiro, Brazil

O vírus Epstein-Barr (EBV) tem sido implicado na fisiopatogenia da doença de Hodgkin (DH) e a associação deste vírus com a DH está relacionada com as condições socioeconômicas da população estudada, com a idade e com o subtipo histológico celularidade mista (CM). A prevalência do EBV na DH é muito variável. Este estudo foi realizado com o objetivo de determinar a prevalência do EBV na DH em uma população brasileira. Foram estudados 64 casos de DH oriundos do Hospital Universitário utilizando-se o método de imunoistoquímica com anticorpo monoclonal contra a proteína latente da membrana (LMP1). O vírus foi encontrado em 35 dos 64 casos estudados (55 por cento) e sua presença correlacionou-se de maneira significativa com o subtipo histológico CM (OR = 9; IC 95 por cento = 1,66 - 66; p = 0,0015). Estes resultados confirmam que o EBV está relacionado com a DH em uma população brasileira.

Intensified ABVP chemotherapy for the primary treatment of Hodgkin's disease.

This report describes the results of a multicenter study designed to determine the efficacy and toxicity of a novel combination (ABVP) in patients with newly diagnosed Hodgkin's disease. The ABVP protocol is a modification of ABVD in which prednisone is substituted for DTIC. In order to attempt an increase in drug intensity, doxorubicin, bleomycin and vinblastine were administered on days 1 and 8 of each cycle, and a new cycle began on day 22. Patients who developed phlebitis were allowed to receive the drugs every two weeks. Patients with bulky mediastinal disease received involved field radiation therapy after chemotherapy. Fifty-one patients were treated. Complete remission was achieved in 40 patients (78%). Actuarial failure-free survival in 55 months was 59%, and overall survival was 81%. The overall survival for the 32 patients treated with the intensified regimen was higher than that for those who switched to the bi-weekly schedule (89% vs. 68%, p=0.03). ABVP appears to be equivalent to ABVD. The higher overall survival rate in patients treated every 21 days suggests that this intensified schedule might be more effective. The placement of a Port catheter is recommended, due to the high incidence of phlebitis.