Clinical suspicion, diagnosis and management of cardiac amyloidosis: update document and executive summary.

In recent years, the interest in cardiac amyloidosis has grown exponentially. However, there is a need to improve our understanding of amyloidosis in order to optimise early detection systems. Therefore, it is crucial to incorporate solutions to improve the suspicion, diagnosis and follow-up of cardiac amyloidosis. In this sense, we designed a tool following the different phases to reach the diagnosis of cardiac amyloidosis, as well as an optimal follow-up: a) clinical suspicion, where the importance of the "red flags" to suspect it and activate the diagnostic process is highlighted; 2) diagnosis, where the diagnostic algorithm is mainly outlined; and 3) follow-up of confirmed patients. This is a practical resource that will be of great use to all professionals caring for patients with suspected or confirmed cardiac amyloidosis, to improve its early detection, as well as to optimise its accurate diagnosis and optimal follow-up.

Design and baseline characteristics of SALT-HF trial: hypertonic saline therapy in ambulatory heart failure.

AIMS: Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. METHODS AND RESULTS: 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). RESULTS: A total of 167 participants [median age, 81 years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969 pg/mL, IQR: 2508-9328; median CA125 46 U/L, IQR: 20-114). CONCLUSIONS: SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

Sex differences in clinical characteristics and outcomes in the CLOROTIC (combining loop with thiazide diuretics for decompensated heart failure) trial.

AIMS: The addition of hydrochlorothiazide (HCTZ) to furosemide improved the diuretic response in patients with acute heart failure (AHF) in the CLOROTIC trial. Our aim was to evaluate if there were differences in clinical characteristics and outcomes according to sex. METHODS: This is a post-hoc analysis of the CLOROTIC trial, including 230 patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The primary and secondary outcomes included changes in weight and patient-reported dyspnoea 72 and 96 h after randomization, metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. The influence of sex on primary, secondary and safety outcomes was evaluated. RESULTS: One hundred and eleven (48%) women were included in the study. Women were older and had higher values of left ventricular ejection fraction. Men had more ischemic cardiomyopathy and chronic obstructive pulmonary disease and higher values of natriuretic peptides. The addition of HCTZ to furosemide was associated to a greatest weight loss at 72/96 h, better metrics of diuretic response and higher 24-h diuresis compared to placebo without significant differences according to sex (all p-values for interaction were not significant). Worsening renal function occurred more frequently in women (OR [95%CI]: 8.68 [3.41-24.63]) than men (OR [95%CI]: 2.5 [0.99-4.87]), p = 0.027. There were no differences in mortality or rehospitalizations at 30/90 days. CONCLUSION: Adding HCTZ to intravenous furosemide is an effective strategy to improve diuretic response in AHF with no difference according to sex, but worsening renal function was more frequent in women. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT01647932; EudraCT Number: 2013-001852-36.

Executive summary of the 2023 update on the consensus regarding basic conduct during hospital admission for patients with acute heart failure.

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) Upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease. (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response. (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors. (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge.

Consensus on basic conduct during the hospital admission of patients with acute heart failure.

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45 years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65 years in Spain, a quarter of whom die within 1 year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30 days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: 1) At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. 2) During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. 3) To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers and aldosterone antagonists). 4) At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge.

Consensus on basic conduct during the hospital admission of patients with acute heart failure. / Consenso de actuación básica durante el ingreso hospitalario por insuficiencia cardiaca aguda.

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65years in Spain, a quarter of whom die within 1year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: (1)At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. (2)During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. (3)To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensinII receptor blockers, beta blockers and aldosterone antagonists). (4)At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge.

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.

In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

Reduction in hospitalisations and emergency department visits for frail patients with heart failure: Results of the UMIPIC healthcare programme.

OBJECTIVES: Heart failure (HF) is a disease with high morbidity and mortality. We evaluated the usefulness of the Comprehensive Management Units for Patients with HF (Unidades de Manejo Integral para Pacientes con IC [UMIPIC]) programme. PATIENTS AND METHOD: We analysed the patient data from the UMIPIC programme, which was recorded in the HF registry (RICA) of the Spanish Society of Internal Medicine. We compared emergency department visits and hospitalisations for any cause and for HF during the year prior to inclusion in the programme against those that occurred during the subsequent follow-up year, using the chi-squared test. RESULTS: A total of 258 patients (mean age, 80years; 51.9% women) were included in the study. During the previous year, there were 693 hospitalisations for all causes and 174 hospitalisations during the follow-up (75% reduction, P<.001). There were 613 hospitalisations for HF during the previous year and 92 during the follow-up (85% reduction, P<.001); 655 vs. 302 in terms of emergency department visits for any cause (53.9% reduction, P<.001); and 440 vs. 120 for emergency department visits for HF (72% reduction, P<.001). There were no significant differences in the number of hospitalisations or emergency department visits for causes other than HF. CONCLUSIONS: The UMIPIC programme based on the comprehensive care of elderly patients with HF and comorbidity reduces the rate of hospital readmissions and emergency department visits during the first year of follow-up.

Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia.

In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

Evaluation of chromosomal abnormalities by cIg-FISH and association with proliferative and apoptotic indexes in multiple myeloma.

Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

Application of real-time PCR and melting curve analysis in rapid Diego blood group genotyping.

The paucity of appropriate reagents for serologic typing of the Diego blood group antigens has prompted the development of a real-time PCR and melting curve analysis for Diego blood group genotyping. In this study, we phenotyped 4326 donor blood samples for Di(a) using semiautomated equipment. All 157 Di(a+) samples were then genotyped by PCR using sequence-specific primers (PCR-SSP) for DI*02 because of anti-Di(b) scarcity. Of the 4326 samples, we simultaneously tested 160 samples for Di(a) and Di(b) serology, and DI*01 and DI*02 by PCR-SSP and by real-time PCR. We used the same primers for Diego genotyping by real-time PCR and PCR-SSP. Melting curve profiles obtained using the dissociation software of the real-time PCR apparatus enabled the discrimination of Diego alleles. Of the total samples tested, 4169 blood donors, 96.4 percent (95% confidence interval [CI], 95.8-96.9%), were homozygous for DI*02 and 157, 3.6 percent (95% CI, 3.1%-4.2%), were heterozygous DI*01/02. No blood donor was found to be homozygous for DI*01 in this study. The calculated DI*01 and DI*02 allele frequencies were 0.0181 (95% CI, 0.0173-0.0189) and 0.9819 (95% CI, 0.9791-0.9847), respectively, showing a good fit for the Hardy-Weinberg equilibrium. There was full concordance among Diego phenotype results by PCR-SSP and real-time PCR. DI*01 and DI*02 allele determination with SYBR Green I and thermal cycler technology are useful methods for Diego determination. The real-time PCR with SYBR Green I melting temperature protocol can be used as a rapid screening tool for DI*01 and DI*02 blood group genotyping.

ABO genotyping in leukemia patients reveals new ABO variant alleles.

The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic myeloid leukemia (N = 69), chronic lymphoid leukemia (N = 13), acute myeloid leukemia (N = 15), and acute lymphoid leukemia (N = 11). ABO genotyping was carried out using allele specific primer polymerase chain reaction followed by DNA sequencing. ABO*O01 was the most common allele found, followed by ABO*O22 and by ABO*A103. We identified 22 new ABO*variants in the coding region of the ABO gene in 25 individuals with leukemia (23.2%). The majority of ABO variants was detected in O alleles (15/60.0%). In 5 of 51 samples typed as blood group O (9.8%), we found non-deletional ABO*O alleles. Elucidation of the diversity of this gene in leukemia and in other diseases is important for the determination of the effect of changes in an amino acid residue on the specificity and activity of ABO glycosyltransferases and their function. In conclusion, this is the first report of a large number of patients with leukemia genotyped for ABO. The findings of this study indicate that there is a high level of recombinant activity in the ABO gene in leukemia patients, revealing new ABO variants.

ABO genotyping in leukemia patients reveals new ABO variant alleles

The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic myeloid leukemia (N = 69), chronic lymphoid leukemia (N = 13), acute myeloid leukemia (N = 15), and acute lymphoid leukemia (N = 11). ABO genotyping was carried out using allele specific primer polymerase chain reaction followed by DNA sequencing. ABO*O01 was the most common allele found, followed by ABO*O22 and by ABO*A103. We identified 22 new ABO* variants in the coding region of the ABO gene in 25 individuals with leukemia (23.2%). The majority of ABO variants was detected in O alleles (15/60.0%). In 5 of 51 samples typed as blood group O (9.8%), we found non-deletional ABO*O alleles. Elucidation of the diversity of this gene in leukemia and in other diseases is important for the determination of the effect of changes in an amino acid residue on the specificity and activity of ABO glycosyltransferases and their function. In conclusion, this is the first report of a large number of patients with leukemia genotyped for ABO. The findings of this study indicate that there is a high level of recombinant activity in the ABO gene in leukemia patients, revealing new ABO variants.

Results of CHOP chemotherapy for diffuse large B-cell lymphoma

Patients with diffuse large B-cell lymphoma treated in a University Hospital were studied from 1990 to 2001. Two treatment regimens were used: ProMACE-CytaBOM and then, from November 1996 on, the CHOP regimen. Complete remission (CR), disease-free survival (DFS), and overall survival (OS) rates were determined. Primary refractory patients and relapsed patients were also assessed. A total of 111 patients under 60 years of age were assessed and ranked according to the international prognostic index adjusted to age. Twenty (18 percent) of them were classified as low risk, 40 (36 percent) as intermediate risk, 33 (29.7 percent) as high intermediate risk, and 18 (16.3 percent) as high risk. Over a five-year period, OS and DFS rates were 71 and 59 percent, respectively, for all patients. For the same time period, OS and DFS rates were 72.8 and 61.3 percent, respectively, for 77 patients treated with CHOP chemotherapy and 71.3 and 60 percent for patients treated with the ProMACE-CytaBOM protocol. There was no significant difference in OS or DFS between the two groups. Eleven of 50 refractory and relapsed patients were consolidated with high doses of chemotherapy. Three received allogenic and 8 autologous bone marrow transplantation. For the latter, CR was 62.5 percent and mean OS was 41.1 months. The clinical behavior, CR, DFS, and OS of the present patients were similar to those reported in the literature. We conclude that both the CHOP and ProMACE-CytaBOM protocols can be used to treat diffuse large B-cell lymphoma patients, although the CHOP protocol is preferable because of its lower cost and lower toxicity.

Results of CHOP chemotherapy for diffuse large B-cell lymphoma.

Patients with diffuse large B-cell lymphoma treated in a University Hospital were studied from 1990 to 2001. Two treatment regimens were used: ProMACE-CytaBOM and then, from November 1996 on, the CHOP regimen. Complete remission (CR), disease-free survival (DFS), and overall survival (OS) rates were determined. Primary refractory patients and relapsed patients were also assessed. A total of 111 patients under 60 years of age were assessed and ranked according to the international prognostic index adjusted to age. Twenty (18%) of them were classified as low risk, 40 (36%) as intermediate risk, 33 (29.7%) as high intermediate risk, and 18 (16.3%) as high risk. Over a five-year period, OS and DFS rates were 71 and 59%, respectively, for all patients. For the same time period, OS and DFS rates were 72.8 and 61.3%, respectively, for 77 patients treated with CHOP chemotherapy and 71.3 and 60% for patients treated with the ProMACE-CytaBOM protocol. There was no significant difference in OS or DFS between the two groups. Eleven of 50 refractory and relapsed patients were consolidated with high doses of chemotherapy. Three received allogenic and 8 autologous bone marrow transplantation. For the latter, CR was 62.5% and mean OS was 41.1 months. The clinical behavior, CR, DFS, and OS of the present patients were similar to those reported in the literature. We conclude that both the CHOP and ProMACE-CytaBOM protocols can be used to treat diffuse large B-cell lymphoma patients, although the CHOP protocol is preferable because of its lower cost and lower toxicity.

Use of gel microcolumn assay for the detection of drug-induced positive direct antiglobulin tests.

Drugs can result in broad variety of hematologic abnormalities including positive direct antiglobulin test. In this study, we evaluated gel microcolumn assay for the detection of drug-induced antibodies. Direct antiglobulin test was performed by conventional tube and by gel microcolumn assay in 139 hospitalized patients. Drug in vitro studies were done in 34 patients with positive direct antiglobulin test by tube test and gel microcolumn assay using serum and eluate. None of them had signs of hemolytic anemia. A total of 1,000 blood samples from donors were used as control group. Gel microcolumn assay was more sensitive than in tube test for direct antiglobulin test (P<0.01). Positive direct antiglobulin test was more frequent in patients than in donors (P<0.01). Drug in vitro studies were positive with at least one drug in 76.5% of patients with positive direct antiglobulin test by immune complex and/or adsorption mechanisms. We found a high incidence of positive drug in vitro tests in positive direct antiglobulin test patients. Gel microcolumn assay showed appropriate results for drug in vitro studies. The combination of tube and gel microcolumn assay can improve detection of drug-induced positive direct antiglobulin tests.

Comparison of conventional tube test technique and gel microcolumn assay for direct antiglobulin test: a large study.

Gel microcolumn assay (GMA) is a modified serological technique that has been used for ABO and Rh typing, direct antiglobulin test (DAT), detecting alloantibodies, red cell phenotyping, and other applications. However, for DAT, the role of GMA is controversial. The purpose of this large study was to compare the performance of the conventional tube test (CTT) to GMA for detecting potentially significant antibodies coating red blood cells in vivo. From January 1996 to May 2002, we performed DATs by GMA and CTT on 9,862 blood samples submitted to our reference laboratory, using LISS/Coombs cards (DiaMed-Latino America, Lagoa Santa-MG, Brazil) for GMA and polyspecific and monospecific anti-IgG reagents for CTT. Acid eluates were prepared from all positive DAT samples. The specificity of eluates was determined by GMA. We detected nonconcordant results in 2,079 out of 3,163 positive DATs (65.7%). All of these tests were only positive in GMA. Sensitivity and specificity for DATs was 100% and 83.0% for gel, and 50.7% and 97.8% for tube, respectively. Based on this study GMA showed to be more sensitive than CTT for detecting potentially significant antibodies coating red blood cells in vivo.

Comparison of conventional tube test with diamed gel microcolumn assay for anti-D titration.

Anti-D titration is the first step in the evaluation of the RhD-sensitized patient. Traditionally, anti-D titration has been performed by tube agglutination. Gel microcolumn assay is a method that has gained widespread usage throughout the world, mainly for ABO/Rh typing, unexpected antibody screening and direct antiglobulin tests. As gel assay has become widely used as a routine method to detect red blood cell alloantibodies, a critical anti-D titer needs to be established. Seventy-nine known blood samples with anti-D (titers 1-32) were titrated simultaneously by the conventional tube test and the gel microcolumn assay. Red blood cells (R0r phenotype) were used, with a final concentration of 3% for tube and 0.8% for gel. Serial twofold dilutions (2-2.048) were prepared for each technique, followed by reading in antiglobulin phase. Anti-D titration in the gel microcolumn assay showed significantly higher titers (mean 3.4-fold) than the conventional tube test in all samples studied. Based on these data, it was not possible to determine a critical titer for anti-D titration by the gel microcolumn assay.