Microcosting analysis of haematopoietic stem cell transplantation and chemotherapy with intermediate doses of cytarabine in the treatment of acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is considered a costly disease. Depending on the risk stratification, the patient may receive consolidation with cycles of intermediate doses of cytarabine, auto-HSCT or allo-HSCT according to availability in each service and the availability of a compatible donor. Literature data indicate that safety and effectiveness do not differ between consolidation therapy with intermediate-dose cytarabine or auto-HSCT, and so the cost can help physicians and health managers in their choice. METHOD: The cost of the second consolidation was compared in 18 to 60-year-old patients with de novo AML who were included in the International Consortium of Acute Myeloid Leukaemia (ICAML) protocol. Patients treated with auto-HSCT or intermediate doses of cytarabine (IDAC) were analysed during four years using the microcosting methodology. RESULTS: The mean costs for auto-HSCT and IDAC were BRL$ 34,900.95 (range: 23,611.36-41,229.59) and 15,231.64 (range: 6,546.36-23,253.53), respectively. The mean duration of in-hospital stay was 88.4 (93-133) and 94 (50-153) days, respectively. The mean cost of the four cycles of treatment was BRL$ 114.212,78 for auto-HSCT and BRL$ 121.980,93 for the chemotherapy group. Regardless of the type of treatment, the input that had the greatest economic impact was hospital admission, mainly due to infections. CONCLUSION: Auto-HSCT had a lower average cost per patient and hospitalization rate than chemotherapy.

Analytical study of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1p210 , and KMT2-MLLT3 in Mexican children with acute myeloid leukemia: A multicenter study of the Mexican interinstitutional group for the identification of the causes of childhood leukemia (MIGICCL).

Background: The distribution of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1p210 , and KMT2A-MLLT3 in the pediatric population with acute myeloid leukemia (AML) in many countries of Latin America is largely unknown. Therefore, we aimed to investigate the frequency of these fusion genes in children with de novo AML from Mexico City, which has one of the highest incidence rates of acute leukemia in the world. Additionally, we explored their impact in mortality during the first year of treatment. Methods: We retrospectively analyzed the presence of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1p210 , and KMT2A-MLLT3 by RT-PCR among 77 patients (<18 years) diagnosed with de novo AML between 2019 and 2021 in nine Mexico City hospitals. Results: The overall frequency of the fusion genes was 50.7%; RUNX1-RUNXT1 (22.1%) and PML-RARA (20.8%) were the most prevalent, followed by CBFB-MYH11 (5.2%) and BCR-ABL1p210 (2.4%). KMT2A-MLLT3 was not detected. Patients with PML-RARA showed the lowest survival with high early mortality events. However, more studies are required to evaluate the impact of analyzed fusion genes on the overall survival of the Mexican child population with AML. Conclusion: The pediatric population of Mexico City with AML had frequencies of AML1-ETO, PML-RARA, CBFB-MYH11, and BCR-ABL1p210 similar to those of other populations around the world. Patients with BCR-ABL1p210 and CBFB-MYH11 were few or did not die, while those with MLL-AF9 was not detected. Although patients with PML-RARA had a low survival and a high early mortality rate, further studies are needed to determine the long-term impacts of these fusion genes on this Latino population.

Reduced Osteogenic Differentiation Potential In Vivo in Acute Myeloid Leukaemia Patients Correlates with Decreased BMP4 Expression in Mesenchymal Stromal Cells.

The osteogenic differentiation potential of mesenchymal stromal cells (hMSCs) is an essential process for the haematopoiesis and the maintenance of haematopoietic stem cells (HSCs). Therefore, the aim of this work was to evaluate this potential in hMSCs from AML patients (hMSCs-AML) and whether it is associated with BMP4 expression. The results showed that bone formation potential in vivo was reduced in hMSCs-AML compared to hMSCs from healthy donors (hMSCs-HD). Moreover, the fact that hMSCs-AML were not able to develop supportive haematopoietic cells or to differentiate into osteocytes suggests possible changes in the bone marrow microenvironment. Furthermore, the expression of BMP4 was decreased, indicating a lack of gene expression committed to the osteogenic lineage. Overall, these alterations could be associated with changes in the maintenance of HSCs, the leukaemic transformation process and the development of AML.

Pathological and immunohistochemical aspects of acute megakaryoblastic leukaemia in a cat - Short communication.

An adult, mixed-breed, feline leukaemia virus (FeLV-) positive female cat was presented with mucosal jaundice and a history of anorexia and constipation for three days. Physical examination revealed splenomegaly, cachexia, and dehydration. Humane euthanasia was conducted, followed by postmortem examination. Grossly, the cat was icteric, and presented hepatomegaly with multifocal white spots and splenomegaly. Histologically, the bone marrow was nearly completely replaced by a proliferation of megakaryocytes and megakaryoblasts, and there was a proliferation of fibrous connective tissue. Similar neoplastic proliferation was observed infiltrating the liver, lymph nodes, spleen, kidney, skeletal muscle, and lungs. Immunohistochemistry was performed for von Willebrand Factor (VWF), CD79α, CD3, feline immunodeficiency virus, FeLV, and CD61. Marked cytoplasmic labelling was observed in the neoplastic cells for FeLV, VWF and CD61, corroborating the diagnosis of acute megakaryoblastic leukaemia.

Epidemiology of invasive fungal disease in haematologic patients.

Invasive fungal disease (IFD) is frequent in patients with haematologic malignancies and in recipients of haematopoietic cell transplantation (HCT). An epidemiologic study conducted in Brazil reported a high incidence of IFD in haematologic patients, and invasive fusariosis was the leading IFD. A limitation of that study was that galactomannan was not available for at least half of the study period. In order to characterise the epidemiology and burden of IFD in three cohorts, HCT, acute myeloid leukaemia (AML) or myelodysplasia (MDS), and acute lymphoid leukaemia (ALL), we conducted a prospective multicentre cohort study in four haematologic Brazilian centres. From August 2015 to July 2016, all patients receiving induction chemotherapy for newly diagnosed or relapsed AML, MDS or ALL, and all HCT recipients receiving conditioning regimen were followed during the period of neutropenia following chemotherapy or the conditioning regimen. During a 1-year period, 192 patients were enrolled: 122 HCT recipients (71 allogeneic, 51 autologous), 46 with AML, and 24 with ALL. The global incidence of IFD was 13.0% (25 cases, 11 proven and 14 probable). Invasive aspergillosis (14 cases) was the leading IFD, followed by candidemia (6 cases) and fusariosis (3 cases). The incidence of IFD was 26.1% in AML/MDS, 16.7% in ALL, 11.3% in allogeneic HCT, and 2.0% in autologous HCT. The burden of IFD in haematologic patients in Brazil is high, with a higher frequency in AML and ALL. Invasive aspergillosis is the leading IFD, followed by invasive candidiasis and fusariosis.

Incidence and mortality of myeloid malignancies in children, adolescents and Young adults in Brazil: A population-based study.

BACKGROUND: Myeloid malignancies (MM) are heterogeneous when it comes to incidence rates and pathogenesis. These variation rates are important to generate hypotheses on causal aetiology. This study aimed to describe incidence and mortality patterns of MM among children, adolescents and young adults (cAYA) in Brazil and to evaluate trends in incidence and mortality rate overtime. METHODS: Data were extracted from a dataset of 15 Population-based Cancer Registries located in five Brazilian geographical regions and calculated by age-specific, crude, and age-standardized incidence (ASR) and mortality rates per million persons. Joinpoint regression analyses were performed for trends evaluations, regionally. Annual Percent Change (APC) and Average Annual Percent Change (AAPC) were also estimated. RESULTS: The overall ASR for incidence and mortality of MM in Brazil was 14.57 and 8.83 per million, respectively. The AML (non-APL AML and APL) incidence rate is 8.18 per million, whereas other MM subtypes altogether have an incidence rate of 2.62 per million, and not otherwise specified (NOS) is 3.70 per million. The analysis of incidence trends (AAPC) showed a significant decline in Manaus (-5.6%) and São Paulo (-4.7%), and a significant increase was observed in Fortaleza (5.8%). Mortality trends steadily declined in all registries, with significant declines occurring in Goiânia (-1.5%), Belo Horizonte (-2.3%), São Paulo (-2.5%), Curitiba (-2.8%) and Porto Alegre (-4.1%). CONCLUSION: Our findings showed differences in the incidence and mortality rates of MM in cAYA in Brazil, geographically. Infants-AML have the highest incidence within the cAYA population (17.42 per million). There was a substantial decrease in mortality rate observed, which was interpreted as an improvement in MM recognition and therapeutic approach.

Longitudinal sequencing of RUNX1 familial platelet disorder: new insights into genetic mechanisms of transformation to myeloid malignancies.

The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully understood. We report the results of targeted next-generation sequencing on three patients with RUNX1 FPDMM who developed acute myeloid leukaemia or myelodysplastic syndromes (AML/MDS). DNA samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an SRSF2 p.P95R variant, prior to his AML diagnosis, when he developed an additional NRAS p.G12D variant. His sister presented to us with MDS, with a TET2 p.S471fs and identical NRAS p.G12D variant. The third patient, from another family, had an additional RUNX1 p.R204X and an NFE2 p.Q139fs variant at AML diagnosis. This constitutes the first report of NFE2 variants in AML without extramedullary disease and NRAS variants in AML/MDS in the setting of FPDMM. A systematic review of the literature including our findings distinguishes two genetic landscapes at AML transformation from FPDMM characterized by either the presence or absence of somatic abnormalities in RUNX1 with or without variants in genes usually associated with MM. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in RUNX1 needs further confirmation.

Evaluation of the impact of single-nucleotide polymorphisms on treatment response, survival and toxicity with cytarabine and anthracyclines in patients with acute myeloid leukaemia: a systematic review protocol.

INTRODUCTION: Acute myeloid leukaemia is the most common type of acute leukaemia in the world. Thus, the study of genetic alterations, such as single-nucleotide polymorphisms (SNPs), has contributed to a better understanding of the mechanisms underlying leukaemogenesis, to improve the prognosis and to increase the survival of these patients. However, there is no synthesis of evidence in the literature evaluating the quality of evidence and the risk of bias in the studies such that the results can be translated. Thus, this systematic review protocol aims to assess the impact of SNPs on genes involved in the metabolism of cytarabine and anthracyclines with respect to survival, treatment response and toxicity in patients with AML. METHODS: This systematic review protocol is based on PRISMA guidelines and includes searches in six electronic databases, contact with authors, repositories of clinical trials, and cancer research. Studies published in peer-reviewed journals will be included if they meet the eligibility criteria: (a) samples composed of individuals of any age, of both sexes, with a diagnosis of AML, regardless of the time of diagnosis of disease; (b) participants who have undergone or are undergoing cytarabine- and anthracycline-associated chemotherapy or cytarabine-only chemotherapy; and (c) in vivo studies. Studies that include patients with promyelocytic leukaemia (Fab type 3) will be excluded because this disease has different treatment. The process of study selection, data extraction, and evaluation/synthesis will be performed in duplicate. Assessment of methodological quality and risk of bias will be performed using the Cochrane Risk of Bias Tool for randomized clinical studies and the Downs-Black Checklist for cohort and case-control studies. The synthesis of evidence will include the level of evidence based on the GRADE protocol. A meta-analysis of the association between SNPs and outcomes may be performed based on Cochrane guidelines. DISCUSSION: It is expected that clinical decisions for AML patients will consider evidence-based practices to contribute to better patient management. In this way, we will be able to define how to treat patients with AML to improve their survival and quality of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018100750.

Up-regulation of SPINT2/HAI-2 by Azacytidine in bone marrow mesenchymal stromal cells affects leukemic stem cell survival and adhesion.

The role of tumour microenvironment in neoplasm initiation and malignant evolution has been increasingly recognized. However, the bone marrow mesenchymal stromal cell (BMMSC) contribution to disease progression remains poorly explored. We previously reported that the expression of serine protease inhibitor kunitz-type2 (SPINT2/HAI-2), an inhibitor of hepatocyte growth factor (HGF) activation, is significantly lower in BMMSC from myelodysplastic syndromes (MDS) patients compared to healthy donors (HD). Thus, to investigate whether this loss of expression was due to SPINT2/HAI-2 methylation, BMMSC from MDS and de novo acute myeloid leukaemia (de novo AML) patients were treated with 5-Azacitidine (Aza), a DNA methyltransferase inhibitor. In MDS- and de novo AML-BMMSC, Aza treatment resulted in a pronounced SPINT2/HAI-2 levels up-regulation. Moreover, Aza treatment of HD-BMMSC did not improve SPINT2/HAI-2 levels. To understand the role of SPINT2/HAI-2 down-regulation in BMMSC physiology, SPINT2/HAI-2 expression was inhibited by lentivirus. SPINT2 underexpression resulted in an increased production of HGF by HS-5 stromal cells and improved survival of CD34+ de novo AML cells. We also observed an increased adhesion of de novo AML hematopoietic cells to SPINT2/HAI-2 silenced cells. Interestingly, BMMSC isolated from MDS and de novo AML patients had increased expression of the integrins CD49b, CD49d, and CD49e. Thus, SPINT2/HAI-2 may contribute to functional and morphological abnormalities of the microenvironment niche and to stem/progenitor cancer cell progression. Hence, down-regulation in SPINT2/HAI-2 gene expression, due to methylation in MDS-BMMSC and de novo AML-BMMSC, provides novel insights into the pathogenic role of the leukemic bone marrow microenvironment.

Acute myeloid leukaemia at an early age: Reviewing the interaction between pesticide exposure and KMT2A-rearrangement.

Acute myeloid leukaemia (AML) in early childhood is characterised by a high frequency of recurrent genomic aberrations associated with distinct myeloid subtypes, clinical outcomes and pathogenesis. Genomic instability is the first step of pathogenic mechanism in early childhood AML. A sum of adverse events is necessary to the development of infant AML (i-AML), which includes latency of biochemical-molecular and cellular effects. Inherited genetic susceptibility associated with exposures to biotransformation substances can modulate the risk of DNA damage and it is a very important piece in the pathogenic puzzle. In this review, we have aimed to explore the chain of events in the time-points of the natural history of i-AML, which includes maternal exposures during pregnancy, the speculations about the formation of somatic mutations during foetal life and the secondary genomic aberrations associated with i-AML. The modulation of risk conferred by xenobiotic metabolism´s genes variants is the bottom line of the pathogenic process. Since we have conducted observational and molecular investigations in early childhood leukaemia, the data focused here is based on Brazilian findings with summarised results of our experience with epidemiological and molecular studies in early-age leukaemia.

Acute promyelocytic leukaemia is highly frequent among acute myeloid leukaemias in Brazil: a hospital-based cancer registry study from 2001 to 2012.

The WHO classification that defines subtypes of acute myeloid leukaemias (AMLs) is relatively unexplored at the population-based level. This study aimed to examine the frequency of acute promyelocytic leukaemia (APL or AML-M3) in Brazil. Data were extracted from 239 cancer centres (2001-2012) and categorized according to the International Classification of Diseases for Oncology (CID-O 3.0) and WHO classification (n = 9116). CID-O3 code 9866 identified 614 APL patients. AML not otherwise specified (NOS) was frequent, and the APL group represented the main subtype specified. The mean age of APL was lower than that of other AMLs (31.5, standard deviation (SD) 18.6 versus 40.9, SD 24.6; p < 0.001); there was a high frequency of APL in the 13-21-year-old (11.8 %) and ≤12.9-year-old (6.4 %) age groups. Time taken to begin treatment (as ≤14 days versus >14 days) and induction death rate were lower in APL than in other AML subtypes (p < 0.001). This report provides additional evidence on the distribution of APL among cases of AML in Brazil.

Cohorte de supervivencia en pacientes menores de 60 años con leucemia mieloide aguda de acuerdo con la citogenética y el tratamiento de consolidación / Survival cohort of patients under 60 years with acute myeloid leukemia according to cytogenetics and consolidation treatment / Coorte de sobrevivência em pacientes menores de 60 anos com leucemia mielóide aguda de acordo com a citogenética e o tratamento de consolidação

Introducción: la supervivencia de pacientes con leucemia mieloide aguda (LMA) puede variar de acuerdo con el cariotipo y el tratamiento recibido. Métodos: en esta cohorte retrospectiva se evaluaron la supervivencia, sus factores pronósticos y su asociación con el cariotipo inicial, en 66 pacientes con LMA menores de 60 años, que recibieron quimioterapia o trasplante alogénico de médula ósea. Resultados: la supervivencia global a 2 años fue del 90 % para el grupo de bajo riesgo, del 61 % para el de riesgo intermedio y del 30 % para el de riesgo alto (p = 0,016). Se hallaron como factores que afectan la supervivencia global el no haber alcanzado la remisión completa (HR: 16,36; IC 95 %: 6,17-43,33) y el no recibir trasplante de progenitores hematopoyéticos (HR: 4,76; IC 95 %: 1,36-16,69). Como factores de riesgo para la recaída de la enfermedad se identificaron el cariotipo de alto riesgo (HR: 9,18; IC 95 %: 1,22- 68,56) y la no realización de trasplante (HR: 3,06; IC 95 %: 1,14-8,18). Conclusión: este estudio sugiere que en Colombia la supervivencia global de los pacientes con LMA con riesgo citogenético intermedio o alto puede mejorar cuando reciben como parte del tratamiento el trasplante de progenitores hematopoyéticos.

Introduction: Survival of patients with acute myeloid leukemia (AML) differs according to karyotype and the treatment they receive. Methods: In this retrospective cohort we evaluated survival, its prognostic factors and its association with the initial karyotype in 66 patients younger than 60 years with AML, who received chemotherapy or allogeneic bone marrow transplantation. Results: Overall survival at 2 years was 90 % in the low risk group, 61 % in the intermediate risk group and 30 % in the high risk group (p = 0.016). The following factors affected overall survival: not having reached complete remission (HR: 16.36; IC 95 %: 6.17-43.33), and not having received haematopoietic stem cell transplantation (HR: 4.76; IC 95 %: 1.36-16.69). As risk factor for relapse we found: High risk karyotype (HR: 9.18; IC 95 %: 1.22- 68.56) and not having performed haematopoietic stem cell transplantation (HR: 3.06; IC 95 %: 1.14-8.18). Conclusion: This study suggests that in Colombia the global survival of young patients with AML with intermediate or high cytogenetic risk at diagnosis may improve when they receive hematopoietic stem cell transplantation as part of the treatment.

Introdução: a sobrevivência de pacientes com leucemia mielóide aguda (LMA) pode variar de acordo com o cariótipo e o tratamento recebido Métodos: nesta coorte retrospectiva se avaliaram a sobrevivência, seus fatores prognósticos e sua associação com o cariótipo inicial, em 66 pacientes com LMA menores de 60 anos, que receberam quimioterapia ou transplante alogênico de medula óssea. Resultados: a sobrevivência global a 2 anos foi do 90 % para o grupo de baixo risco, do 61 % para o de risco intermédio e do 30 % para o de risco alto (p = 0,016). Acharam-se como fatores que afetam a sobrevivência global o não ter atingido a remessa completa (HR: 16,36; IC 95 %: 6,17-43,33) e o não receber transplante de progenitores hematopoiéticos (HR: 4,76; IC 95 %: 1,36-16,69). Como fatores de risco para a recaída da doença se identificaram o cariótipo de alto risco (HR: 9,18; IC 95 %: 1,22- 68,56) e a não realização de transplante (HR: 3,06; IC 95 %: 1,14-8,18). Conclusão: este estudo sugere que na Colômbia a sobrevivência global dos pacientes com LMA com risco citogenético intermédio ou alto pode melhorar quando recebem como parte do tratamento o transplante de progenitores hematopoiéticos.

Conventional and high-dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta-analysis of 7258 patients.

Previous meta-analyses suggested that acute myeloid leukaemia induction regimens containing idarubicin (IDA) or high-dose daunorubicin (HDD) induce higher rates of complete remission (CR) than conventional-dose daunorubicin (CDD), with a possible benefit in overall survival. However, robust comparisons between these regimens are still lacking. We conducted a mixed treatment comparison meta-analysis regarding these three regimens. Mixed treatment comparison is a statistical method of data summarization that aggregates data from both direct and indirect effect estimates. Literature search strategy included MEDLINE, EMBASE, Cochrane, Scielo and LILACS, from inception until August 2013 and resulted in the inclusion of 17 trials enrolling 7258 adult patients. HDD [relative risk (RR) 1.13; 95% credible interval (CrI) 1.02-1.26] and IDA (RR 1.13; 95% CrI 1.05-1.23) showed higher CR rates than CDD. IDA also led to lower long-term overall mortality rates when compared with CDD (RR 0.93, 95% CrI 0.86-0.99), whereas HDD and CDD were no different (RR 0.94, 95% CrI 0.85-1.02). HDD and IDA comparison did not reach statistically significant differences in CR (RR 1.00; 95% CrI 0.89-1.11) and in long-term mortality (RR 1.01, 95% CrI 0.91-1.11). IDA and HDD are consistently superior to CDD in inducing CR, and IDA was associated with lower long-term mortality. On the basis of these findings, we recommend incorporation of IDA and HDD instead of the traditional CDD as standard treatments for acute myeloid leukaemia induction. The lack of HDD benefit on mortality, when compared with CDD in this study, should be cautiously addressed, because it may have been susceptible to underestimation because of statistical power limitations.

Sarcoma granulocítico en una paciente con leucemia mieloide crónica / Granulocytic sarcoma in a female patient with chronic myeloid leukemia

El sarcoma granulocítico es un tumor localizado poco común, compuesto de células granulocíticas inmaduras. Generalmente se presenta en pacientes con leucemia mieloide aguda, síndromes mielodisplásicos o leucemia mieloide crónica. Puede ocurrir en cualquier localización anatómica. Reportamos el caso de una mujer de 41 años con el diagnóstico de leucemia mieloide crónica que presentó edema en brazo derecho que no remitía a pesar de tratamiento antibiótico y fasciotomía. El estudio histológico de la biopsia la lesión tomada mostró un sarcoma granulocítico. En este trabajo se revisa la citogenética, presentación clínica, diagnóstico y pronóstico de este síndrome tumoral.

Granulocytic sarcoma is an uncommon and localized extramedullary tumor composed of immature granulocytic cells. It may present in patiens with acute myeloid leukaemia, myelodysplastic syndrome or chronic myelogenous leukaemia. It may occur in any anatomical site. We report on the case of a 41 year old female diagnosed with chronic myelogenous leukaemia who presented with right arm swelling that did not resolve after antibiotic and surgical fasciotomy. The histological examination showed granulocytic sarcoma. In this report the citogenetics, clinical presentation, diagnosis and outcome of granulocytic sarcoma was reviewed.

The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia / O papel do transplante de célula-tronco hematopoiética em pacientes idosos com leucemia mielóide aguda

Older adults with Acute Myeloid Leukaemia (AML), when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85 percent-95 percent of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older AML patients provides better outcomes than no post-remission therapy. The only studies demonstrating that long-term Disease Free Survival (DFS) is possible in older AML patients have included remission induction and post-remission therapy. For these reasons alternative post-remission strategies, including autologous or allogeneic transplantation have been explored also in people over sixty considered fit for aggressive therapy. Up to now the data available from clinical trials suggest that the stem cell transplant procedure is promising, and can lead to long-term survival, but it is feasible only in a minority of fit elderly patients. The main limits of Autologous Stem Cell Transplantation (ASCT) are represented by the low percentage of patients able to mobilize a sufficient amount of stem cells and by the still high relapse incidence after ASCT, especially in those with poor prognostic factors; for these patients the allogeneic transplant procedure, by using non myeloablative conditioning regimens, could offer a better chance of cure, thanks to the Graft versus Leukemia (GVL) effect, but there are no prospective trials showing the superiority of any transplant approach over conventional treatment in this subset of patients.

Pacientes idosos com leucemia mielóide aguda (LMA), quando comparados com pacientes jovens com a mesma doença, apresentam prognóstico pobre e representam uma população particular em termos biológicos, complicações relacionadas ao tratamento e evolução clínica. Como resultado de tudo isto, o paciente idoso requer manuseio distinto. Para 85 por cento-95 por cento dos pacientes idosos a abordagem terapêutica será finalmente apenas paliativa. Nenhum estudo randomizado demonstrou qualquer vantagem de qualquer terapêutica na fase pós-remissão. Os únicos estudos que mostraram alguma vantagem em termos de sobrevida livre de doença em pacientes idosos portadores de LMA incluíram juntas as fases de indução e consolidação da remissão. Por estas razões, estratégias terapêuticas alternativas pós-remissão, incluindo transplante autólogo ou alogênico, têm sido exploradoras também em pacientes acima de 60 anos com boa performance status para as terapias de alta dose. Até agora, os dados disponíveis dos estudos clínicos sugerem que o procedimento usando célula-tronco é promissor e pode levar a sobrevida de longo prazo, porém factível apenas em uma minoria de pacientes idosos. Os principais limites para o transplante autólogo são representados pela baixa porcentagem de pacientes capazes de mobilizar suficiente quantidade de células-tronco e pela, ainda, alta incidência de recidiva após o transplante, principalmente em pacientes de fatores de mau prognóstico. Para o transplante alogênico, o uso de regimes de intensidade reduzida pode oferecer uma melhor oportunidade de cura graças ao efeito enxerto versus leucemia. Porém, não existem estudos clínicos comprovando a superioridade de qualquer modalidade de transplante em relação à terapia convencional.