Lower doses of dacarbazine (modified BEACODD) as a safer strategy with equal effectiveness in an intensive treatment protocol of Hodgkin's lymphoma: a preliminary retrospective analysis of a single public center in Brazil.

The German Hodgkin Study Group developed the escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) protocol as a treatment strategy for advanced-stage Hodgkin's lymphoma. In Brazil, as well as in other countries, procarbazine has been replaced with dacarbazine due to the limited availability of procarbazine. The Hematology Center at Irmandade da Santa Casa de Misericórdia in São Paulo adopted and modified the escalated BEACOPP protocol, substituting prednisone with dexamethasone and incorporating two different doses of dacarbazine: 375 mg/m2/day on Day 8 or the original dose of 250 mg/m2/day on Days 2 and 3. This adjustment was made in response to the anticipated toxicity profile. This study aimed to compare the two different doses in the protocols (375 mg/m2/cycle versus 500 mg/m2/cycle) administered to patients with advanced Hodgkin's lymphoma in similar periods. This retrospective study analyzed the data of 31 patients at a single center in Brazil from 2019 to 2021. Seventeen of the 31 patients received 500 mg/m2/cycle (500 Group), while 14 received 375 mg/m2/cycle (375 Group). At the end of the protocol, 71% of the patients in the 375 Group and 76% in the 500 Group achieved complete remission. On analyzing the number of cycles that patients presented with febrile neutropenia, the 500 Group had three times more events (17.9%) than the 375 Group (6.09% - p-value = 0.04). In the 500 Group, 47.1% needed to change the protocol to ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine) due to toxicity. In this limited cohort from a single public center in Brazil, the use of 375 mg/m2 of dacarbazine per cycle of the modified escalated BEACOPP protocol emerged as a safer strategy, maintaining treatment efficacy without compromising response in patients with advanced Hodgkin's lymphoma.

Evaluation of C-reactive protein and its prognostic relationship in patients with Hodgkin's Lymphoma.

OBJECTIVES: To assess the prognostic value of C-Reactive Protein (CRP), at diagnosis and during follow-up, of patients with Hodgkin´s Lymphoma treated at the Hematology Service of the Santa Casa de São Paulo Hospital, and to correlate serum CRP levels with disease stage and treatment response. METHODS: A retrospective study involving review of 71 medical records of patients diagnosed with Hodgkin´s Lymphoma between February 2012 and January 2016 was performed. Three patients were subsequently excluded, giving a total of 68 patients for analysis. A level of CRP > 1mg/dl was considered elevated. RESULTS: Patients were predominantly male (61.8%) and mean age was 34 years. Fifty-three (78%) patients had advanced stage and (76.5%) had B symptoms. Elevated baseline CRP was associated with greater likelihood of B symptoms (p= 0.02) and of advanced stage (p= 0.015). Patients with Low CRP level after 5th and 6th cycles of chemotherapy was associated with complete response (p=0.04 and p=0.03, respectively). Treatment-refractory patients had greater risk of death (p=0.002). CONCLUSION: CRP is clinically important for follow-up of patients with Hodgkin´s Lymphoma, where high levels were associated with advanced disease and/or presence of B symptoms. CRP level was considered a predictor of treatment response. Persistence of high CRP values during treatment was associated with refractoriness.

Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

Application of the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice: a retrospective analysis apart from the clinical trial at two centers in Brazil

ABSTRACT Introduction: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. Methods: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. Results: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. Conclusion: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Application of the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice: a retrospective analysis apart from the clinical trial at two centers in Brazil.

INTRODUCTION: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. METHODS: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. RESULTS: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. CONCLUSION: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.

Evaluation of C-reactive protein and its prognostic relationship in patients with Hodgkin's Lymphoma.

OBJECTIVES: To assess the prognostic value of C-Reactive Protein (CRP), at diagnosis and during follow-up, of patients with Hodgkin´s Lymphoma treated at the Hematology Service of the Santa Casa de São Paulo Hospital, and to correlate serum CRP levels with disease stage and treatment response. METHODS: A retrospective study involving review of 71 medical records of patients diagnosed with Hodgkin´s Lymphoma between February 2012 and January 2016 was performed. Three patients were subsequently excluded, giving a total of 68 patients for analysis. A level of CRP > 1 mg/dl was considered elevated. RESULTS: Patients were predominantly male (61.8 %) and mean age was 34 years. Fifty-three (78 %) patients had advanced stage and (76.5 %) had B symptoms. Elevated baseline CRP was associated with greater likelihood of B symptoms (p = 0.02) and of advanced stage (p = 0.015). Patients with Low CRP level after 5th and 6th cycles of chemotherapy was associated with complete response (p = 0.04 and p = 0.03, respectively). Treatment-refractory patients had greater risk of death (p = 0.002). CONCLUSION: CRP is clinically important for follow-up of patients with Hodgkin´s Lymphoma, where high levels were associated with advanced disease and/or presence of B symptoms. CRP level was considered a predictor of treatment response. Persistence of high CRP values during treatment was associated with refractoriness.

Lower access to risk stratification tests and drugs, and worse survival of chronic lymphocytic leukaemia patients treated in public as compared to private hospitals in Brazil: A retrospective analysis of the Brazilian registry of chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) has a highly variable clinical course. In addition to biological factors, socioeconomic factors and health system characteristics may influence CLL outcome. Data from the Brazilian Registry of CLL were analyzed to compare clinical and treatment-related characteristics in patients with CLL, from public or private institutions. A total of 3326 patients from 43 centres met the eligibility criteria, of whom 81% were followed up at public hospitals and 19% at private hospitals. The majority were male (57%), with a median age of 65 years. Comparing public and private hospitals, patients in public hospitals were older, had more advanced disease at diagnosis, and more frequently had elevated creatinine levels. All investigated prognostic markers were evaluated more often in private hospitals. First-line treatment was predominantly based on chlorambucil in 41% of the cases and fludarabine in 38%. Anti-CD20 monoclonal antibody was used in only 36% of cases. In public hospitals, significantly fewer patients received fludarabine-based regimens and anti-CD20 monoclonal antibodies. Patients from public hospitals had significantly worse overall survival (71% vs. 90% for private hospitals, p < 0.0001) and treatment-free survival (32% vs. 40%, for private hospitals, p < 0.0001) at seven years. Our data indicate striking differences between patients followed in public and private hospitals in Brazil. A worse clinical condition and lack of accessibility to basic laboratory tests and adequate therapies may explain the worse outcomes of patients treated in public institutions.

NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial.

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.

Everolimus as a single agent in refractory or relapsed Hodgkin's lymphoma: the Brazilian Named Patient Program Experience

Abstract Background Despite all the scientific progress that has been made on understanding the disease, prognosis for patients with relapsed and refractory Hodgkin's lymphoma remains poor and the treatment is palliative in the majority of the cases. Thus, the aim of this study was to present the results on the compassionate use of everolimus in a group of patients who were monitored at nine different centers in Brazil. Methods A 10-mg oral dose of everolimus was given to each patient daily. Response time was evaluated from the beginning of medication use until loss of response, toxicity or medical decision to cease treatment. Results Thirty-three patients were evaluated. The median age at the beginning of medication administration was 29 years. Patients had received a median of five prior therapies. Overall response rate was 45.4%, with 13 patients achieving partial response, two achieved clinical response, 14 remained with stable disease, two had disease progression, and two were not evaluated. Patients received a median of 14 cycles. Progression-free survival was nine months, and overall survival was estimated to be 36 months. Three patients used the medication for more than four years. The most frequently reported adverse events were thrombocytopenia and hypercholesterolemia. Three patients had pulmonary toxicity. Grade III and IV adverse events occurred in 39% of the patients. Conclusion Everolimus was found to provide a response in a group of patients with refractory or relapsed Hodgkin's lymphoma who had adequate tolerability to the drug.

Everolimus as a single agent in refractory or relapsed Hodgkin's lymphoma: the Brazilian Named Patient Program Experience.

BACKGROUND: Despite all the scientific progress that has been made on understanding the disease, prognosis for patients with relapsed and refractory Hodgkin's lymphoma remains poor and the treatment is palliative in the majority of the cases. Thus, the aim of this study was to present the results on the compassionate use of everolimus in a group of patients who were monitored at nine different centers in Brazil. METHODS: A 10-mg oral dose of everolimus was given to each patient daily. Response time was evaluated from the beginning of medication use until loss of response, toxicity or medical decision to cease treatment. RESULTS: Thirty-three patients were evaluated. The median age at the beginning of medication administration was 29 years. Patients had received a median of five prior therapies. Overall response rate was 45.4%, with 13 patients achieving partial response, two achieved clinical response, 14 remained with stable disease, two had disease progression, and two were not evaluated. Patients received a median of 14 cycles. Progression-free survival was nine months, and overall survival was estimated to be 36 months. Three patients used the medication for more than four years. The most frequently reported adverse events were thrombocytopenia and hypercholesterolemia. Three patients had pulmonary toxicity. Grade III and IV adverse events occurred in 39% of the patients. CONCLUSION: Everolimus was found to provide a response in a group of patients with refractory or relapsed Hodgkin's lymphoma who had adequate tolerability to the drug.

Evaluation correlates C-reactive protein with advanced stage Hodgkin's lymphoma and response to treatment in a tertiary university hospital in Brazil

To demonstrate a correlation of C-reactive protein levels with disease stage and response to treatment in Hodgkin's lymphoma patients of the Hematology Service of Santa Casa de São Paulo.METHODS: A retrospective study based on review of medical records was carried out of 38 patients diagnosed with Hodgkin's lymphoma between October 2010 and December 2012. Three patients met the exclusion criteria, giving a final sample of 35 patients for analysis. C-reactive protein levels >1 mg/dL were considered positive.RESULTS: Among the patients analyzed, median age was 29 years, 65% were male and 85% had the classical nodular sclerosis subtype. Twenty-nine (82%) were in the advanced stage and 28% had bulky mass at diagnosis. Seventeen percent had bone marrow invasion by lymphoma. Baseline C-reactive protein levels were associated with both stage (p-value = 0.0035) and presence or absence of B symptoms (p-value = 0.008). The highest C-reactive protein levels were detected in patients with advanced disease while no patients with localized disease had C-reactive protein >5 mg/dL (p-value = 0.02). After the first treatment cycle, C-reactive protein fell to near-normal levels and no direct association with response pattern was found. As the mean follow-up was only 14 months, it was not possible to determine whether relapse was accompanied by a further increase in C-reactive protein.CONCLUSION: Baseline C-reactive protein levels directly correlated with stage and presence or absence of B symptoms, but the degree of improvement with treatment did not correlate with response pattern. After a longer follow-up, it may be possible to assess whether relapse correlates with a further increase in C-reactive protein levels...

Evaluation correlates C-reactive protein with advanced stage Hodgkin's lymphoma and response to treatment in a tertiary university hospital in Brazil.

OBJECTIVE: To demonstrate a correlation of C-reactive protein levels with disease stage and response to treatment in Hodgkin's lymphoma patients of the Hematology Service of Santa Casa de São Paulo. METHODS: A retrospective study based on review of medical records was carried out of 38 patients diagnosed with Hodgkin's lymphoma between October 2010 and December 2012. Three patients met the exclusion criteria, giving a final sample of 35 patients for analysis. C-reactive protein levels >1mg/dL were considered positive. RESULTS: Among the patients analyzed, median age was 29 years, 65% were male and 85% had the classical nodular sclerosis subtype. Twenty-nine (82%) were in the advanced stage and 28% had bulky mass at diagnosis. Seventeen percent had bone marrow invasion by lymphoma. Baseline C-reactive protein levels were associated with both stage (p-value=0.0035) and presence or absence of B symptoms (p-value=0.008). The highest C-reactive protein levels were detected in patients with advanced disease while no patients with localized disease had C-reactive protein >5mg/dL (p-value=0.02). After the first treatment cycle, C-reactive protein fell to near-normal levels and no direct association with response pattern was found. As the mean follow-up was only 14 months, it was not possible to determine whether relapse was accompanied by a further increase in C-reactive protein. CONCLUSION: Baseline C-reactive protein levels directly correlated with stage and presence or absence of B symptoms, but the degree of improvement with treatment did not correlate with response pattern. After a longer follow-up, it may be possible to assess whether relapse correlates with a further increase in C-reactive protein levels.

Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7%) patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5%) patients of this cohort received rituximab as first-line treatment and nine (7.1%) received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7%) had parenchymal central nervous system involvement; seven (77.7%) had stage III or IV disease; one (11.1%) had bone marrow involvement; two (22.2%) had received intrathecal chemoprophylaxis; and 3 (33.3%) had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. ...

Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoietic stem cell transplantation.

BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who we resubmitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count < 0.3 x 10(9)/L on Day +30 post-transplant was considered to be inadequate lymphocyte recovery and counts ≥ 0.3 x 10(9)/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9)/Land ≤ 0.75 x 10(9)/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count < 0.3 x 10(9)/L on Day +30 post-transplant was considered to be inadequate lymphocyte recovery and counts > 0.3 x 10(9)/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9)/Land < 0.75 x 10(9)/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

Transplante de células-tronco hematopoéticas em crianças e adolescentes com leucemia aguda: experiência de duas instituições brasileiras / Hematopoietic stem cell transplantation in children and adolescents with acute leukemia: experience of two Brazilian institutions

O transplante de células-tronco hematopoéticas (TCTH) é o tratamento de escolha para leucemias agudas de alto risco. Apesar da melhora na sobrevida destes pacientes, a recidiva continua sendo a maior causa de óbito pós-transplante de células-tronco hematopoéticas. O objetivo deste trabalho foi analisar os resultados dos transplantes realizados em crianças com leucemia aguda em duas instituições brasileiras. Realizou-se estudo retrospectivo de 208 pacientes transplantados entre 1990-2007. Mediana de idade: 9 anos; 119 pacientes com leucemia linfoide aguda (LLA) e 89 com leucemia mieloide aguda (LMA). Doença precoce: CR1 e CR2. ... 14/195 pacientes tiveram falha primária de pega (8 por cento). Não houve diferença na sobrevida global e sobrevida livre de recaída entre pacientes com leucemia linfoide aguda e leucemia mieloide aguda, entre transplantes aparentados e não aparentados, tampouco entre as fontes de células utilizadas. O desenvolvimento da doença do enxerto contra hospedeiro (DECH) aguda ou crônica também não influenciou a sobrevida global e sobrevida livre de recaída. Pacientes com leucemia linfoide aguda condicionados com irradiação corporal total (TBI) apresentaram melhor sobrevida global e sobrevida livre de recaída (p<0,001). Cento e dezoito pacientes morreram entre 1-1.654 dias pós-transplante de células-tronco hematopoéticas (M:160). Mortalidade relacionada a transplante (MRT) (dia+100): 16 por cento. Incidência cumulativa de recaída: 40 por cento (3 anos). Pacientes com doença avançada tiveram menor sobrevida global e sobrevida livre de recaída (três anos)(p<0,001). Na análise multivariada, o status da doença foi o principal fator associado ao aumento da sobrevida global e sobrevida livre de recaída. Nossos resultados mostram que é possível se atingir uma boa sobrevida para pacientes com doença precoce e também mostram a baixa eficácia naqueles com doença avançada.

Hematopoietic Stem Cell transplantation (HSCT) is the treatment of choice for patients with high-risk leukemia. In spite of this, relapse remains a major cause of death of these patients. Our objective was to analyze the outcomes of patients with acute leukemia submitted to hematopoietic stem cell transplantation in two Brazilian institutions... There were no differences in the overall survival and event free survival between patients with acute lymphocytic leukemia and acute myeloid leukemia, between sources of cells used or between those who developed acute or chronic graft-versus-host disease (GVHD). When comparing transplants from related and unrelated donors, there was no difference in the overall survival. Patients with acute lymphocytic leukemia receiving the total body irradiation (TBI) conditioning regimen had better overall survival and event free survival (p<0.001). One hundred and eighteen patients died between 0 and 1654 days after hematopoietic stem cell transplantation (M: 160 days). Transplantation-related-mortality (TRM) at D+100 was 16 percent and cumulative incidence of relapse was 40 percent (3 years). Patients with advanced disease had lower 3-year overall survival and event free survival (p<0.001). Multivariate analysis showed that disease status was the most significant factor associated with higher event free survival and overall survival . Our results show that children and adolescents transplanted with early disease can achieve considerable overall survival and also highlights the inefficacy of hematopoietic stem cell transplantation for patients with advanced disease.