Investigation of MHC gamma block C4A and C4B polymorphisms in unrelated hematopoietic stem cell transplantation

ABSTRACT Background: Immunological life-threatening complications frequently occur in post-hematopoietic stem cell transplantation (HSCT), despite matching recipient and donor (R/D) pairs for classical human leukocyte antigens (HLA). Studies have shown that R/D non-HLA disparities within the major histocompatibility complex (MHC) are associated with adverse effects post-HSCT. Methods: We investigated the impact of mismatches of single-nucleotide polymorphisms (SNPs) in C4A/C4B genes, for showing the highest diversity in the MHC gamma block, on 238 patients who underwent HLA 10/10 unrelated donor (URD) HSCT. The endpoints were acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD) and mortality. One hundred and twenty-nine R/D pairs had 23 C4-SNPs typed by PCR-SSP (Gamma-Type™v.1.0), and 109 R/D pairs had these 23 SNPs identified by next-generation sequencing (NGS) using the Illumina platform. Results: The percentage of patients who received HSC from HLA 10/10 donors with 1-7 mismatches was 42.9%. The R/D pairs were considered C4 mismatched when bearing at least one disparity. These mismatches were not found to be risk factors for aGVHD, cGVHD or mortality after unrelated HSCT when SNPs were analyzed together (matched or mm ≥ 1), independently or according to the percentage of incompatibilities (full match for 23 SNPs; 1-3 mm and >3 mm). An exception was the association between 1-3 mismatches at the composite of SNPs C13193/T14952/T19588 with the development of aGVHD (P = 0.012) and with grades III-IV of this disease (P = 0.004). Conclusion: Our data are not consistent with the hypothesis that disparities in C4A/C4B SNPs increase the risks of post-HSCT adverse effects for the endpoints investigated in this study.

A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort

Abstract Introduction Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib. Methods JUMP is a single-arm, open-label, phase IIIb, expanded-access study. The primary endpoint was to evaluate the safety and tolerability (frequency, duration, and severity of adverse events [AEs]) of ruxolitinib. Results All of the 104 patients received the treatment. Median duration of exposure was 35.8 months. The most common hematologic AEs were anemia (57.7), thrombocytopenia (38.5%), neutropenia (11.5%), and leukopenia (9.6%). Second malignancies (all grades) occurred in 19.2% of patients (n = 20). Serious AEs were reported in 62.5% of patients (n = 65). The proportions of patients with ≥50% reduction from baseline in palpable spleen length at weeks 24 and 48 were 62.7% and 69.2%, respectively. The mean change from the baseline in the Functional Assessment of Cancer Therapy (FACT)-Lymphoma total score was 10.8 [15.6%] at week 4, 12.6 [14.1%] at week 24, and 12.2 [14.3%] at week 48. The mean change from the baseline for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale was 3.9 [42.8%] at week 4, 4.9 [29.9%] at week 24, and 4.7 [28%] at week 48. At week 48, the estimated progression-free survival, leukemia-free survival, and overall survival probabilities were 91%, 91% and 93%, respectively Overall, 21 deaths were observed in the present study. Conclusion Findings from this study suggest that ruxolitinib could be evaluated as a standard-of-care treatment for the MF population in need of a viable treatment option. NCT01493414

Conhecimento de enfermeiros de hospital universitário sobre bactérias multirresistentes / Nurses knowledge about multidrug resistant bacteria in a teaching hospital

Objetivo identificar o conhecimento de enfermeiros de hospital de ensino universitário sobre bactérias multirresistentes. Métodos estudo transversal e prospectivo, com participação de 109 enfermeiros. Coleta de dados por meio de questionário com questões abertas e fechadas. A análise estatística, seu deu por meio do programa Statistical Package for the Social Sciences. Resultados 67,0% dos participantes consideraram o conhecimento adquirido na graduação relativo a bactérias multirresistentes insuficiente para o enfrentamento destas, com predomínio dos formados anterior ao ano de 2005; do processo de transmissão, predominaram os profissionais mais jovens. Conclusão o conhecimento sobre bactérias multirresistentes foi maior entre profissionais mais jovens, de formação mais recente, com iniciativa individual para expandir o conhecimento sobre o tema e participação em treinamentos em serviço. O Serviço de Controle de Infecção Hospitalar foi a principal fonte provedora de conhecimentos para os enfermeiros participantes do estudo.

Objective to identify the knowledge of nurses of a teaching hospital about multidrug resistant bacteria. Methods cross-sectional and prospective study with the participation of 109 nurses. Data collection used a questionnaire with open and objective questions. Statistical analysis used the Statistical Package for the Social Sciences software. Results 67.0% of the participants considered the knowledge acquired in the graduation regarding multi-resistant bacteria insufficient to deal with them, with a predominance of professionals graduated before the year 2005; in the transmission process, younger professionals predominated. Conclusion knowledge about multidrug-resistant bacteria was higher among younger, more recently graduated professionals, with proactive enough to expand knowledge about the subject and to participate in in-service training. The Hospital Infection Control Service was the main source of knowledge for nurses participating in the study.

Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene in Brazilian patients with chronic myeloid leukemia

ABSTRACT Introduction: Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene are the leading cause of resistance to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients. Mutations have been detected throughout the extension of the kinase domain of this gene and it is important to investigate their positions because there may be a difference in clinical relevance. Objective: To evaluate mutations in the transcripts of the BCR-ABL1 gene in Brazilian patients with chronic myeloid leukemia under tyrosine kinase inhibitor treatment in the Hospital de Clínicas of the Universidade Federal do Paraná. Methods: This retrospective observational cross-sectional study analyzed mutation data of BCR-ABL1 gene transcripts. Three hundred and thirty peripheral blood samples from 193 patients were evaluated with the search for mutations being achieved by Sanger sequencing. Results: Sixteen mutation types were identified in 48/193 (24.87%) patients with T315I (20.83%) being the most common. Furthermore, four polymorphisms (T240T, K247R, E275E and Y275Y) were identified. The highest incidence of mutations (19/53: 35.85%) occurred in the P-loop of the tyrosine kinase domain, whereas no mutation was found in the A-loop. In 43/48 (89.58%) patients only one mutation was found and more than one mutation was found in 5/48 (10.42%). The simultaneous presence of two mutations (E189G/V299L and E255K/T315I) was observed in 2/5 patients while the different mutations were seen in sequential samples of the other three patients (Y253Y/T315I, T315I/E255K and E255K/T315I). Conclusions: This molecular characterization contributed to the identification of the resistance profile to tyrosine kinase inhibitors in Brazilian patients, thus enabling the use of adequate therapeutic strategies in a timely manner.

THPO gene variants in patients with acquired aplastic anemia

ABSTRACT Background: Human aplastic anemia is a hematologic disease characterized by low peripheral blood cell counts associated with reduced numbers of hematopoietic stem and progenitor cells and a hypocellular bone marrow. Thrombopoietin (THPO) regulates megakaryocytes, but it also stimulates hematopoietic stem and progenitor cells. Biallelic mutations in the THPO gene have been reported in a family with recessive inherited aplastic anemia. Methods: This study screened 83 patients diagnosed with acquired aplastic anemia and 92 paired healthy controls for germline variants in the THPO gene using Sanger sequencing. Results: Three common single nucleotide polymorphisms were identified in patients and controls at comparable allele frequencies. There was no correlation between the single nucleotide polymorphism carrier status and platelet counts at diagnosis. Conclusion: The presence of THPO polymorphisms is comparable between patients with acquired aplastic anemia and healthy individuals.

Late chimerical status after bone marrow transplantation in severe aplastic anemia according to two different preparatory regimens

ABSTRACT Background: This study investigated the influence of two conditioning regimens on the chimerical status of 104 patients with acquired severe aplastic anemia. Methods: Patients were monitored for at least 18 months after related bone marrow transplantation and reaching partial or complete hematologic recovery. Group I patients (n = 55) received 200 mg/kg cyclophosphamide alone and Group II (n = 49) received 120 mg/kg cyclophosphamide associated with 12 mg/kg busulfan. Patients were classified in three chimerism levels according to the percentage of donor cells in the peripheral blood. Results: Chimerism ≤50% occurred in 36.4% of Group I and none of Group II; chimerism 51-90% was found in 20.0% of Group I and 10.2% of Group II; and chimerism >90% was found in 43.6% of Group I versus 89.8% of Group II. A significant association (p-value < 0.001) was found between conditioning type and chimerism levels. A higher number of infused cells was associated with higher levels of chimerism only in Group I (p-value = 0.013). Multivariate analysis showed that chimerism >90% is associated with the cyclophosphamide plus busulfan conditioning (p-value < 0.001) and higher number of infused cells (p-value = 0.009), suggesting that these factors are predictive of graft outcome. Regarding hematological recovery, higher chimerism levels were associated with higher neutrophil (p-value = 0.003) and platelet counts (p-value < 0.001) in Group I only. These results show that myeloablative conditioning favors full donor chimerism and non-myeloablative conditioning predisposes to mixed chimerism or autologous recovery of hematopoiesis. Conclusion: These data show that autologous recovery depends on the intensity of immunosuppression and that the immunosuppressive function of cyclophosphamide alone can induce this type of hematopoietic recovery.

Evaluation of criteria of manual blood smear review following automated complete blood counts in a large university hospital

Abstract Background: There is great interest in reducing the number of automated complete blood counts requiring manual blood smear reviews without sacrificing the quality of patient care. This study was aimed at evaluating and establishing appropriate screening criteria for manual blood smear reviews to improve the performance in a hematology laboratory. Method: A total of 1977 consecutive samples from the daily workload were used to evaluate four sets of screening criteria for manual blood smear reviews to identify samples with positive smear findings. Three sets of screening criteria were arbitrarily proposed in this study: Group 1 (narrow ranges), Group 2 (intermediate ranges), and Group 3 (wide limits) and one set (Group 4) was adapted from the International Society for Laboratory Hematology. All samples were run on Sysmex hematology analyzers and were investigated using manual blood smear reviews. Diagnostic accuracy and agreement were performed for each set of screening criteria, including an investigation of microscopic review rate and efficiency. Results: The microscopic review rates for Groups 1, 2, 3 and 4 were 73.85%, 54.52%, 46.33% and 46.38%, respectively; the false-negative rates were 0.50%, 1.97%, 2.73% and 3.95%, respectively. The efficiency and negative predictive values of Group 3 were 73.04% and 4.91%, respectively. Conclusions: Group 3 had the best relationship between safety (false-negative rate: ≤3%) and efficiency to estimate the limits of automation in performing complete blood counts. This study strengthens the importance of establishing screening criteria for manual blood smear reviews, which account for the different contexts in which hematological determinations are performed. Each laboratory should optimize the screening criteria for manual blood smear reviews in order to maximize their efficiency and safety.

Molecular response to imatinib mesylate of Brazilian patients with chronic myeloid leukemia

Abstract Background Imatinib mesylate has revolutionized the treatment of chronic myeloid leukemia leading to significant reductions of BCR-ABL1 transcript levels in peripheral blood. Objective To evaluate the response to imatinib mesylate treatment (400 mg/day) in Brazilian patients in the chronic phase of chronic myeloid leukemia monitored by quantitative real time polymerase chain reaction. Methods Between October 2002 and October 2010, 3169 peripheral blood samples were collected from 1403 patients from 3 to 5 months, 6 to 11 months, 12 to 17 months, 18 to 23 months and ≥24 months after beginning imatinib treatment. Eighty-two patients had samples available and analyzed for all time intervals. BCR-ABL1 quantification was performed by quantitative real time polymerase chain reaction using the ABL1 gene as the control. Results of the BCR-ABL1 ratio as a percentage were reported by the international scale (IS) using the laboratory conversion factor (0.51). Results In the first interval, 80.8% of patients achieved the optimal response (BCR-ABL1 IS ≤ 10%). In the second period, 69.1% achieved optimal response (BCR-ABL1 IS ≤ 1%) and, between 12 and 17 months, 47.3% achieved major molecular response (BCR-ABL1 IS ≤ 0.1%). Conclusions The results of this retrospective study show that the response to imatinib treatment (400 mg/day) of Brazilian patients in the chronic phase of chronic myeloid leukemia is within the expected profile when compared to patients reported in international prospective randomized studies.

Patients' perceptions about diagnosis and treatment of chronic myeloid leukemia: a cross-sectional study among Brazilian patients / Percepções dos pacientes sobre diagnóstico e tratamento da leucemia mieloide crônica: estudo transversal entre pacientes brasileiros

CONTEXT AND OBJECTIVES: Chronic myeloid leukemia (CML) requires strict daily compliance with oral medication and regular blood and bone marrow control tests. The objective was to evaluate CML patients' perceptions about the disease, their access to information regarding the diagnosis, monitoring and treatment, adverse effects and associations of these variables with patients' demographics, region and healthcare access. DESIGN AND SETTING: Prospective cross-sectional study among CML patients registered with the Brazilian Lymphoma and Leukemia Association (ABRALE). METHODS: CML patients receiving treatment through the public healthcare system were interviewed by telephone. RESULTS: Among 1,102 patients interviewed, the symptoms most frequently leading them to seek medical care were weakness or fatigue. One third were diagnosed by means of routine tests. The time that elapsed between first symptoms and seeking medical care was 42.28 ± 154.21 days. Most patients had been tested at least once for Philadelphia chromosome, but 43.2% did not know the results. 64.8% had had polymerase chain reaction testing for the BCR/ABL gene every three months. 47% believed that CML could be controlled, but 33.1% believed that there was no treatment. About 24% reported occasionally stopping their medication. Imatinib was associated with nausea, cramps and muscle pain. Self-reported treatment adherence was significantly associated with normalized blood count, and positively associated with imatinib. CONCLUSIONS: There is a lack of information or understanding about disease monitoring tools among Brazilian CML patients; they are diagnosed quickly and have good access to treatment. Correct comprehension of CML control tools is impaired in Brazilian patients.

CONTEXTO E OBJETIVOS: Leucemia mieloide crônica (CML) exige estrita adesão à medicação oral e ao monitoramento do sangue e da medula. O objetivo foi avaliar percepções de pacientes com leucemia mieloide crônica (LMC) sobre a doença, seu acesso à informação sobre diagnóstico, monitoramento e tratamento, efeitos adversos e a associação destes com dados demográficos, geográficos e de acesso a tratamento. DESENHO E LOCAL: Estudo prospectivo transversal realizado com pacientes de LMC cadastrados na Associação Brasileira de Leucemia e Linfoma (Abrale). MÉTODOS: Pacientes com LMC recebendo tratamento do sistema público de saúde foram entrevistados por telefone. RESULTADOS: Entre os 1.102 pacientes entrevistados, os sintomas mais frequentemente levando à busca de consulta foram fraqueza e fadiga. Um terço foi diagnosticado por exames de rotina. O tempo entre sintoma inicial e procura por ajuda foi de 42,28 ± 154,21 dias. A maioria foi testada pelo menos uma vez para o cromossomo Filadélfia, mas 43,2% não sabiam os resultados. 64,8% fizeram exame de reação em cadeia da polimerase para o gene BCR/ABL a cada três meses. 47% acreditavam que LMC pode ser controlada, mas 33,1% acham que não há tratamento. Cerca de 24% disseram que ocasionalmente interrompem o tratamento. Imatinibe associou-se com náusea, câimbra e dor muscular. Aderência auto-reportada associou-se significativamente com hemograma normal e positivamente com uso de imatinibe. CONCLUSÕES: Falta informação ou compreensão sobre monitoramento entre pacientes com LMC; eles recebem diagnóstico rapidamente e têm bom acesso ao tratamento. A correta compreensão das ferramentas de controle em LMC está prejudicada entre eles.

Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase

BACKGROUND: Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.METHODS: This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils ≥ 20%, platelets > 1 × 106/µL or <1 × 105/µL and white blood cells > 1 × 105/µL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin < 10 g/dL, time between diagnosis of chronic myeloid leukemia and imatinib treatment, and hematologic toxicity.RESULTS: Risk factors for poor survival in multivariate analysis were Grades 3-4 hematologic toxicity (p-value = 0.001), blasts 10-29% (p-value = 0.023), and hemoglobin < 10 g/dL (p-value = 0.04). Risk factors for not achieving major cytogenetic response were blasts 10-29% (p-value = 0.007), hemoglobin < 10 g/dL (p-value = 0.001), and previous use of interferon (p-value = 0.032). Risk factors for progression to the blast phase were hemoglobin < 10 g/dL (p-value = 0.005), basophils ≥ 20% (p-value = 0.023), and time from diagnosis of chronic myeloid leukemia to imatinib treatment > 12 months (p-value = 0.030).CONCLUSION: These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

Paroxysmal nocturnal hemoglobinuria clone in 103 Brazilian patients: diagnosis and classification

Background: Paroxysmal nocturnal hemoglobinuria is an acquired chronic hemolytic ane- mia, which often manifests as peripheral blood cytopenias and thrombosis. Objective: The aim of this study is to describe a Brazilian population of paroxysmal nocturnal hemoglobinuria patients. Methods: One hundred and three paroxysmal nocturnal hemoglobinuria cases were retrospectively reviewed and the clinical presentation, thrombosis, survival, and clone size were assessed. Diagnosis was established by flow cytometry. Results: Fifty-two male and 51 female patients with a median age of 24.1 years (5.5-62 years) were studied. Clinical symptoms included hemoglobinuria (18.4%), infection (46.6%) and thrombosis (16.5%), and 80.6% had pancytopenia. Patients were classified as classic parox- ysmal nocturnal hemoglobinuria (10), paroxysmal nocturnal hemoglobinuria with aplastic anemia (39), and paroxysmal nocturnal hemoglobinuria with subclinical features and aplas- tic anemia (54). There were significant differences in terms of median age, size of clone, clinical symptoms, and peripheral blood cell counts between the three subcategories. The clone size in erythrocytes and granulocytes were respectively 0.04% (range: 0-18%) and 7.3% (range: 0.3-68.7%) in patients with subclinical features and aplastic anemia, 15.8% (range: 0-99.7%) and 63.0% (range: 1.7-99.8%) in patients with aplastic anemia alone, and 82.2% (range: 0-99.85%) and 98.0% (81.3-100.0%) in Classic disease. Statistical differences were identified for platelets (p-value = 0.001), lactate dehydrogenase (p-value = 0.002) and the clone size (p-value < 0.001) in patients who suffered thrombotic events compared to those who did not. Overall survival was 81.7%, with patients with subclinical features and aplastic anemia having lower overall survival (76.5%). Conclusion: This retrospective review of 103 patients over an 11-year period represents the largest collection of paroxysmal...

Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy / Transplante Autólogo de Células-Tronco Adultas para Tratamento da Cardiomiopatia Dilatada Idiopática

Background: Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective: Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods: We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results: During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion: Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. .

Fundamento: Pacientes portadores de cardiomiopatia dilatada idiopática apresentam alta morbimortalidade, mesmo em tratamento clínico otimizado. A infusão autóloga de células-tronco adultas da medula óssea mostrou resultados clínicos preliminares promissores nesses pacientes. Objetivo: Determinar a eficácia do transplante autólogo de células-tronco adultas da medula óssea sobre as funções sistólica e diastólica, e o grau de insuficiência mitral em pacientes portadores de cardiomiopatia dilatada idiopática em classes funcionais NYHA II e III. Métodos: Infundiram-se 4,54 x 108 ± 0,89 x 108 células-tronco adultas da medula óssea nas artérias coronárias de 24 pacientes com cardiomiopatia dilatada idiopática em classes funcionais NYHA II e III. Após 3 meses, 6 meses e 1 ano, avaliaram-se as mudanças de classe funcional, das funções ventricular esquerda sistólica e diastólica, e do grau da insuficiência mitral. Resultados: No seguimento, seis (25%) pacientes melhoraram sua classe funcional e oito (33,3%) mantiveram sua classe funcional inicial. A fração de ejeção ventricular esquerda aumentou 8,9%, 9,7% e 13,6%, após 3 e 6 meses e 1 ano (p = 0,024; p = 0,017 e p = 0,018), respectivamente. A função diastólica ventricular esquerda e o grau de insuficiência mitral não demonstraram mudanças significativas. Dois pacientes (8,3%) receberam cardioversor e ressincronizador implantável. Ocorreram quatro (16,6%) mortes súbitas e quatro (16,6%) mortes por insuficiência cardíaca terminal. A sobrevida média desses oitos pacientes foi de 2,6 anos. Conclusão: A infusão intracoronariana de células-tronco adultas da medula óssea em pacientes com cardiomiopatia dilatada idiopática promoveu melhora ...

Are the review criteria for automated complete blood counts of the International Society of Laboratory Hematology suitable for all hematology laboratories?

OBJECTIVE: to verify whether the review criteria for automated blood counts suggested by the International Consensus Group for Hematology Review of the International Society for Laboratory Hematology are suitable for the Hematology Laboratory of Hospital de Clinicas, Universidade Federal do Paraná. METHODS: initially, the review criteria of the International Society for Laboratory Hematology were adapted due to limitations in the Institution's electronic hospital records and interfacing systems. The adapted review criteria were tested using 1977 samples. After this first assessment, an additional 180 inpatient samples were analyzed to evaluate the screening criteria of the review criteria in conjunction with positive smear findings established by the institution. The performance of the review criteria was verified by determining false positive, false negative, true positive and true negative rates, sensitivity, specificity, positive predictive value, negative predictive value, microscopic review rate and efficiency. RESULTS: initial analysis showed false negatives = 6.73%, false positives = 23.27%, microscopic review rate = 46.03% and efficiency = 70.0%. An evaluation of the screening criteria adapted from the review criteria together with the positive smear findings of the institution showed false negatives = 15.5%, false positives = 10.5%, microscopic review rate = 37.3% and efficiency = 73.8%. In both situations the safety limit (false negative <5%) recommended by the review criteria was exceeded. CONCLUSIONS: the review criteria adapted from the International Society for Laboratory Hematology are neither suitable nor safe for use in the hematology laboratory of the Hospital de Clinicas. This implies a need to develop and validate institution-specific review criteria in order to decrease false negative results to an acceptable and safe rate for patients. .

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.

Anemia aplásica adquirida e anemia de fanconi: diretrizes brasileiras em transplante de células-tronco hematopoéticas / Acquired aplastic anemia and fanconi anemia: Brazilian guidelines in hematopoietic stem cell transplantation

As diretrizes apresentadas neste trabalho foram elaboradas e aprovadas na I Reunião de Diretrizes Brasileiras em Transplante de Células-Tronco Hematopoéticas (TCTH) realizada no Rio de Janeiro, entre os dias 19 e 21 de julho de 2009. O evento foi promovido pela SBTMO (Sociedade Brasileira de Transplante de Medula Óssea). Neste artigo, tratamos da anemia aplásica severa (AAS), considerada uma urgência hematológica, que, identificada e manejada de forma precoce, apresenta grande possibilidade de recuperação da hematopoese seja através de transplante de medula óssea ou terapia imunossupressora. Objetiva-se nortear o manejo terapêutico no contexto do transplante e indicar formas de condicionamento, de acordo com as características clínicas dos pacientes, como o número de transfusões, com intuito de minimizar a rejeição primária e secundária, garantindo a melhora da sobrevida global e livre de doença (observadas pela literatura e já validadas por resultados na população brasileira). No que concerne à anemia de Fanconi, o transplante é a única modalidade curativa para o componente aplásico de medula óssea; embora não modificando as outras características da síndrome também demanda perícia e agilidade na busca de um doador com resultados expressivos de sobrevida.

The guidelines presented in this article have been prepared and approved in the I Meeting of Brazilian Guidelines in Hematopoietic Stem Cell Transplantation (HSCT) - Rio de Janeiro, July 19-21, 2009. The event was sponsored by SBTMO (Brazilian Society of Bone Marrow Transplantation). In this paper, we treat the severe aplastic anemia (SAA), considered a hematological emergency, that when identified and medically treated early, shows a great chance of recovery of the hematopoiesis, either through bone marrow transplantation or immunosuppressive therapy. Its objective is to guide the management of the transplantation, and indicate methods of conditioning, according to clinical characteristics of each patient, including the number of transfusions, in order to minimize the primary and secondary rejection, ensuring better overall and disease-free survival observed in literature and already validated by the results in our population. In the Fanconi Anemia, transplantation is the only curative option for the aplastic bone marrow component, although insignificant for the other components of the syndrome, it also requires skill and agility in finding a donor with important results.

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.

Invasive aspergillosis in hematopoietic stem cell transplant recipients: a retrospective analysis

Invasive aspergillosis (IA) currently is an important cause of mortality in subjects undergoing hematopoietic stem cell transplants (HSCT) and is also an important cause of opportunistic respiratory and disseminated infections in other types of immunocompromised patients. We examined the medical records of 24 cases of proven and probable invasive aspergillosis (IA) at the Hospital de Clinicas of the Federal University of Parana, Brazil, from January 1996 to October 2006. During this period occurred a mean of 2.2 cases per year or 3.0 cases per 100 HSTC transplants. There was a significant relationship between structural changes in the bone marrow transplant (BMT) Unit and the occurrence of IA cases (p=0.034, relative risk (RR) = 2.47). Approximately 83 percent of the patients died due to invasive fungal infection within 60 days of follow up. Some factors tended to be associated with mortality, but these associations were not significant. These included corticosteroid use, neutropenia (<100 cells/mm³) at diagnosis, patients that needed to change antifungal therapy because of toxicity of the initial first-line regimen and disseminated disease. These factors should be monitored in BMT units to help prevent IA. Physicians should be aware of the risk factors for developing invasive fungal infections and try to reduce or eliminate them. However, once this invasive disease begins, appropriate diagnostic and treatment measures must be implemented as soon as possible in order to prevent the high mortality rates associated with this condition.

Neurological complications of hematopoietic stem cell transplantation (HSCT): a retrospective study in a HSCT center in Brazil / Complicações neurológicas do transplante de células tronco hematopoiéticas (TCTH): estudo retrospectivo em um centro de TCTH no Brasil

We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (HSCT). Central nervous system (CNS) neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and CNS infections. An unusual neurological complication was Wernicke's encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. The most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.

Apresentamos as complicações neurológicas avaliadas em uma série de 1000 pacientes submetidos ao transplante de células tronco hematopoiéticas (TCTH). As complicações neurológicas do sistema nervoso central foram as mais encontradas, particularmente as hemorragias encefálicas, seguidas por crises convulsivas e por infecções. Uma complicação peculiar foi a encefalopatia de Wernicke. Menos freqüentemente foram encontrados casos de encefalopatia metabólica, síndrome maligna neuroléptica, leucoencefalopatia posterior reversível, infarto cerebral e os distúrbios do movimento. Entre as complicações neurológicas do sistema nervoso periférico a mais encontrada foi a radiculopatia pelo herpes zoster, enquanto que raramente se observaram casos de polineuropatias periféricas, miopatia inflamatória e de miotonia.