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3.
Article in Chinese | WPRIM | ID: wpr-939672

ABSTRACT

OBJECTIVE@#To establish the droplet digital PCR (ddPCR) assay for the detection of NPM1 type A mutation in patients with acute myeloid leukemia (AML), and to evaluate its specificity, sensitivity and its value in clinical application.@*METHODS@#NPM1 mutant and wildtype plasmids were used to verify the performance of ddPCR. Both ddPCR and Sanger sequencing were used to detect the bone marrow samples of 87 AML patients, which were confirmed by next generation sequencing (NGS). Moreover, NPM1 mutation burden was dynamically monitored in five patients by ddPCR.@*RESULTS@#The limit of blank (LOB) of ddPCR established for NPM1 mutation detection was 1.1 copies/μl, and the limit of detection (LOD) was 2.43 copies/μl, which had good linearity. Among the 87 newly diagnosed AML patients, ddPCR identified seventeen cases positive for NPM1 mutation (19.5%), which was consistent with Sanger sequencing. NGS confirmed 12 positive cases, including 8 of type A mutations, 2 of type D mutations, and 2 of rare type mutations. The results of dynamic monitoring of NPM1 mutation burden in 5 patients showed that the NPM1 mutation burden decreased obviously even close to 0, when patients achieve complete remission after chemotherapy. However, the mutation burden was increased again at the time of relapse.@*CONCLUSION@#In this study, we established a ddPCR method for detection of NPM1 mutation with good sensitivity and repeatability, which can be used for screening NPM1 mutation in newly diagnosed AML patients and for minimal residual disease monitoring after remission in positive AML patients to guide treatment.


Subject(s)
Humans , Leukemia, Myeloid, Acute/therapy , Mutation , Nuclear Proteins/genetics , Nucleophosmin , Polymerase Chain Reaction , Prognosis
4.
Article in Chinese | WPRIM | ID: wpr-928721

ABSTRACT

OBJECTIVE@#To analyze and compare the effects of leukapheresis on hemostatic function in patients with hyperleukocytic leukemia.@*METHODS@#A total of 139 patients with AML, ALL and CML who underwent leukapheresis from June 2009 to February 2020 and did coagulation test before and after operation were included in this study. The clearance efficiency of each group and the difference among three groups were evaluated, as well as hemostatic function including platelet counts, coagulation indicators, CDSS score and incidence of adverse events. The difference of hemostatic function caused by leukapheresis in different leukemia patients were compared.@*RESULTS@#After leukapheresis, the WBC counts were decreased significantly in the three groups of patients (P<0.001), and the clearance efficiency was highest in ALL patients. However, the platelet counts also were decreased significantly (AML:P<0.001, ALL: P<0.001, CML: P<0.01) in the three groups of patients, particularly for acute leukemia patients with a positive correlation with WBC clearance efficiency(r=0.284). After leukapheresis, fibrinogen decreased, PT and APTT prolonged. For acute leukemia patients, higher CDSS score was related to an elevated incidence of bleeding events (P<0.05).@*CONCLUSION@#Leukapheresis is an effective method to decrease the leukemic burden, but it is necessary to monitor the impact on hemostatic function. It is recommended to assess the CDSS socre for acute leukemia patients, in order to identify the predictive value for bleedings.


Subject(s)
Acute Disease , Blood Coagulation , Blood Coagulation Tests , Hemorrhage , Hemostatics , Humans , Leukapheresis/methods , Leukemia, Myeloid, Acute/therapy
5.
Article in Chinese | WPRIM | ID: wpr-928671

ABSTRACT

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.


Subject(s)
Busulfan , Cladribine , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/therapy , Retrospective Studies , Transplantation Conditioning
6.
Article in Chinese | WPRIM | ID: wpr-880135

ABSTRACT

OBJECTIVE@#To observe the clinical efficacy of allogeneic peripheral blood stem cell transplantation(allo-HSCT) on the treatment of adult acute leukemia patients, moreover, to establish and evaluate a Logistic model to predict the risk of relapse in adult acute leukemia patients after allo-HSCT.@*METHODS@#The clinical data of 145 adult acute leukemia patients treated by peripheral blood stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 was enrolled and analyzed retrospectively. Complications and survival of patients were observed. The relationship between patients' age, diagnosis, leukocyte count at onset, risk stratification, time of diagnosis to transplantation, HCT-CI, minimal residual disease pre-transplantation, donor-recipient sex relationship, HLA match degree, prophylaxis of graft versus host disease(GVHD), donor age, number of transfused mononuclear cells, CD34 positive cells, engraftment time, acute and chronic GVHD, CMV, EBV infection, and hemorrhagic cystitis and recurrence after transplantation were analyzed by logistic regression. Relapse prediction model was established and evaluated according to the results.@*RESULTS@#Among 145 acute leukemia patients, 81 with acute myeloid leukemia, 64 with acute lymphocytic leukemia, 18 with EBV infection, 2 with post-transplant lymphoproliferative disorder(PTLD), 85 with CMV, 26 with hemorrhagic cystitis, 65 patients developed acute GVHD, 51 patients developed chronic GVHD and 45 patients relapsed. The overall survival (OS) rates in one and three years were 86.4% and 61.8%, and the progress-free survival (PFS) rates in one and three years were 67.5% and 62.4%, respectively. There were significant differences in OS and PFS between relapsed and non-relapsed patients, as well as AML and ALL patients. Univariate analysis revealed that patient's age, risk stratification, time to transplantation, HCT-CI index, ATG based GVHD prophylaxis, minimal residual disease pre-transplantation, GVHD prophylaxis, and acute and chronic GVHD were associated with the relapse of disease, multivariate logistic regression analysis showed that pre-transplantation minimal residual disease showed positively correlation with relapse of the disease, while chronic GVHD showed negatively correlation.@*CONCLUSION@#The relapse rate of adult acute leukemia patients treated with allo-HSCT in our hospital is 31.0%, and OS of AML patients is better than ALL patients'. OS of relapsed patients is significantly lower than non-relapsed patients'. Pre-transplantation minimal residual disease is a risk factor of relapse. The risk of relapse is reduced in patients with chronic GVHD.


Subject(s)
Adult , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/therapy , Peripheral Blood Stem Cell Transplantation , Recurrence , Retrospective Studies , Transplantation Conditioning
7.
Article in Chinese | WPRIM | ID: wpr-879845

ABSTRACT

OBJECTIVE@#To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).@*METHODS@#A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis.@*RESULTS@#Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×10@*CONCLUSIONS@#Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.


Subject(s)
Adolescent , Child , Child, Preschool , Female , Hematopoietic Stem Cell Transplantation , Humans , Infant , Leukemia, Myeloid, Acute/therapy , Male , Myelodysplastic Syndromes/therapy , Prognosis , Retrospective Studies
8.
Frontiers of Medicine ; (4): 728-739, 2021.
Article in English | WPRIM | ID: wpr-922506

ABSTRACT

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo + m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo + m-DLI in our center. With a median follow-up of 918 (457-1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1% ± 4.9% and 25.0% ± 8.4%. The cumulative incidences of relapse were 50.0% ± 9.8% and 53.5% ± 9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo + m-DLI.


Subject(s)
Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/therapy , Lymphocytes , Recurrence , Retrospective Studies , Transplantation, Homologous
9.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(3): 252-254, July-Sept. 2020.
Article in English | LILACS | ID: biblio-1134035

ABSTRACT

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


Subject(s)
Humans , Brazil , Leukemia, Myeloid, Acute/therapy , Surveys and Questionnaires , Bone Marrow Transplantation , Idarubicin/therapeutic use , Daunorubicin/therapeutic use , Anthracyclines/therapeutic use , Cytarabine/therapeutic use
10.
Frontiers of Medicine ; (4): 701-710, 2020.
Article in English | WPRIM | ID: wpr-880968

ABSTRACT

Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.


Subject(s)
Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive , Leukemia, Myeloid, Acute/therapy , Receptors, Chimeric Antigen , T-Lymphocytes
11.
Journal of Experimental Hematology ; (6): 2089-2092, 2020.
Article in Chinese | WPRIM | ID: wpr-880020

ABSTRACT

Acute myeloid leukemia (AML) is a malignant tumor with abnormal myelocyte differentiation. With the development of immunological technology, great importance has been attached to the immunotherapy of AML patients, which may become an effective treatment strategy for AML, and providing a new means for the prognosis and survival. In this review, the advanced research of immunotherapy for AML, such as antibody-dependent drugs, chimeric antigen receptor T cell therapy, and checkpoint inhibitors, the bastest reaserch advanves of clinical experiment for immunotherapy was summarized briefly.


Subject(s)
Humans , Immunologic Factors , Immunotherapy , Immunotherapy, Adoptive , Leukemia, Myeloid, Acute/therapy , T-Lymphocytes
12.
Rev. chil. obstet. ginecol. (En línea) ; 84(4): 332-336, 2019. graf, ilus
Article in Spanish | LILACS | ID: biblio-1058156

ABSTRACT

RESUMEN Introducción y objetivos: El sarcoma mieloide puede ser la primera manifestación de la leucemia mieloide aguda (LMA), presentarse simultáneamente o constituir una forma de recaída. Material y métodos: Presentamos el caso de una paciente con sarcoma mieloide uterino, como forma de recaída de LMA. Resultados: El diagnóstico se basa en los hallazgos histopatológicos, la inmunohistoquímica y el inmunofenotipo. El tratamiento y el pronóstico son similares a LMA. Conclusión: La afectación uterina por leucemia mieloide extramedular es rara pero debe tenerse en cuenta en el diagnostico diferencial de una masa uterina en aquellas pacientes con antecedentes de LMA.


ABSTRACT Introduction and objectives: Myeloid Sarcoma can present as a first MLA sign, concurrently with or at relapse form. Materials and methods: We present the case of a patient with uterine myeloid sarcoma, as a form of relapse of MLA. Results: The diagnostic is based on the histopathology findings along with immunohistochemistry and immunophenotyping. Conclusion: Uterine involvement due to extramedullary myeloid leukemia is rare but it should be taken into account in the differential diagnosis of a uterine mass in those patients with a history of MLA.


Subject(s)
Humans , Female , Aged , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Sarcoma, Myeloid/diagnostic imaging , Thrombosis , Immunohistochemistry , Magnetic Resonance Spectroscopy , Leukemia, Myeloid, Acute/pathology
13.
Actual. SIDA. infectol ; 26(97 Suplemento 1): 2-25, 20180000. tab, graf
Article in Spanish | LILACS, BINACIS | ID: biblio-1355025

ABSTRACT

La leucemia aguda ha sido reconocida como una enfermedad compleja y rápidamente fatal desde su primera descripción hace 150 años. Librada a su historia natural, la leucemia mieloide aguda lleva a la muerte en pocos meses. Las infecciones son la principal causa de muerte, siendo la bacteriemia y la neumonía las más frecuentes.Los avances ocurridos en los últimos 50 años, como el advenimiento de quimioterapias efectivas, la mejor comprensión de la patogénesis de las complicaciones infecciosas en el paciente neutropénico, la disponibilidad de agentes anti infecciosos de amplio espectro y la mejoría en los cuidados de soporte contribuyeron a mejorar esta situación. En relación a otras enfermedades oncohematológicas, la leucemia mieloide aguda registra la mayor incidencia de eventos febriles, siendo el período de mayor riesgo el de la inducción a la remisión.La fiebre de origen desconocido, la multirresistencia bacteriana y las infecciones fúngicas invasivas constituyen un desafío para el equipo de trabajo.El uso de profilaxis antibacteriana y antifúngica no reemplaza a las medidas de prevención de carácter institucional


Acute leukemias have been recognized as complex and radiply fatal diseases since its first description 150 years ago. Delivered to its natural history, acute myeloid leukemia leads to death in a few months. Infections are the main cause of death, being bacteremia and pneumonia the most frequent. Advances in the last 50 years, such as the advent of effective chemotherapy, a best understanding of the pathogenesis of infectious complications in the neutropenic patient, the availability of broad-spectrum anti-infective agents and better supportive care helped improve this situation. Among other oncological diseases, acute myeloid leukemia has the highest incidence of febrile events, being induction to remission the period of greatest risk. Fever of unknown origin, bacterial multidrug resistance and invasive fungal infections are a challenge for the medical team. The use of antibacterial and antifungal prophylaxis does not replace institutional preventive measures


Subject(s)
Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Antibiotic Prophylaxis , Drug Therapy , Febrile Neutropenia/therapy
15.
Ciênc. Saúde Colet. (Impr.) ; 23(2): 399-408, Fev. 2018. tab
Article in Portuguese | LILACS | ID: biblio-890531

ABSTRACT

Resumo O presente artigo analisa os impactos materiais e imateriais imersos na experiência de adultos jovens com um adoecimento de longa duração - Leucemia Mieloide Aguda. Decorre de pesquisa mais ampla, inspirada na Fenomenologia de Alfred Schutz. Os dados foram obtidos por entrevistas em profundidade com quatro jovens, de 20 a 28 anos, em fase de manutenção no tratamento oncológico, entre novembro de 2013 a janeiro de 2014, em Mato Grosso. Os resultados enfocam aspectos marcantes dos impactos na experiência como o processo de descoberta da enfermidade em que o diagnóstico provocou sentimentos mobilizados por ideias sobre uma doença grave. Seguem-se os impactos na aparência devidos ao tratamento, sobressaindo a queda de cabelo e as estratégias cotidianas de enfrentamento, bem como o aumento ou a perda de peso. Por fim, é marcante o impacto da iminência da morte diante da letalidade da doença e o testemunho da ocorrência em pessoas conhecidas, colocando-a como possibilidade concreta para si, mas também como sobreviventes. Os impactos são os efeitos e as transformações na vida das pessoas e seu entorno e evocam (re) ações, contudo, diluem-se na experiência compondo-a, e não sendo homogênea, sua abordagem privilegia a singularidade inscrita em biografias contextualizadas.


Abstract This article analyzes the tangible and intangible impacts involved in the experience of young adults diagnosed with a long-term illness, namely Acute Myeloid Leukemia. It follows on from broader research, inspired by the Phenomenology of Alfred Schutz. The data were obtained through in-depth interviews with four young adults, aged between 20 and 28, who were in the maintenance phase of cancer treatment between November 2013 and January 2014 in the State of Mato Grosso. The results focus on striking aspects of the impacts of the experience during the process of becoming aware of the illness in which the diagnosis provoked feelings mobilized by ideas regarding a serious illness. This is followed by the impacts on appearance due to the treatment, especially hair loss and day-to-day coping strategies, as well as weight gain or loss. Finally, there is the marked impact of the imminence of death due to the lethality of the disease and the testimony of the occurrence in friends and family, but also for the survivors. The impacts are the effects and transformations in the lives of people and their relations and evoke (re)actions, however, they are diluted in the experience composing it, and not being homogeneous, its approach addresses the singularity encountered in contextualized biographies.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Adaptation, Psychological , Leukemia, Myeloid, Acute/therapy , Alopecia/etiology , Cancer Survivors/psychology , Leukemia, Myeloid, Acute/psychology , Attitude to Death , Family/psychology , Interviews as Topic , Friends/psychology , Alopecia/psychology
16.
Rev. salud pública ; 19(5): 657-663, sep.-oct. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-962053

ABSTRACT

RESUMEN Objetivo Estimar la razón de costo-efectividad de las pruebas para estratificación del riesgo en pacientes pediátricos con Leucemia Mieloide Aguda (LMA). Métodos Se construyó un árbol de decisión con años de vida ganados como medida de efectividad. Los costos fueron estimados desde la perspectiva del sistema de salud colombiano. En los costos de la estratificación se incluyeron los costos del tratamiento consecuente con ella. Los precios de medicamentos fueron tomados del SISMED 2008 y el valor monetario de los procedimientos se extrajo del manual tarifario del ISS 2001 adicionando el 30 %. Todos los costos se expresaron en pesos colombianos del 2010 y el producto interno per-cápita de ese año fue empleado como umbral de costo efectividad. Se condujeron análisis de sensibilidad univariados y probabilísticos. Resultados La razón de costo-efectividad incremental de las pruebas de estratificación a todos los pacientes, fue de $8 559 944. Los resultados son sensibles a las probabilidades de recaída, supervivencia al trasplante y efectos secundarios. Conclusión Las pruebas para estratificación del riesgo en LMA son costo-efectivas dentro del sistema de salud colombiano.(AU)


ABSTRACT Objective To estimate the cost-effectiveness of risk-stratification tests for the treatment of acute myeloid leukemia (AML) in pediatric patients. Methods A decision-tree model was built using Life Years Gained as a measure of effectiveness. Costs were estimated considering the perspective of the Colombian health system. Stratification costs included treatment costs based on said stratification. Drug prices were taken from SISMED (Drug Price Information System) 2008 and the monetary value of the procedures was extracted from the ISS 2001 rate manual, plus 30%. All costs were expressed in Colombian pesos for 2010 and the gross domestic product per capita of the same year was used as a cost-effective threshold. Univariate and probabilistic sensitivity analyzes were performed. Results Risk stratification tests have an incremental cost-effectiveness ratio of COP 8,559,944. These results are sensitive to changes in probabilities of relapse, transplant survival and side effects. Conclusion Risk stratification tests for AML treatment in pediatric patients are cost-effective in the context of the Colombian health care system.(AU)


Subject(s)
Humans , Leukemia, Myeloid, Acute/therapy , Consolidation Chemotherapy , Transplantation, Homologous , Colombia , Risk Assessment , Cost-Effectiveness Evaluation
17.
Einstein (Säo Paulo) ; 15(3): 355-358, July-Sept. 2017.
Article in English | LILACS | ID: biblio-891404

ABSTRACT

ABSTRACT Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials.


RESUMO A leucemia mieloide aguda é uma doença neoplásica de células-tronco hematopoiéticas com alta morbimortalidade. A presença de mutações de duplicação em tandem de FLT3 leva a altas taxas de recorrência e a menor sobrevida global. Os pacientes com duplicação em tandem de FLT3 são normalmente tratados com transplante de células-tronco hematopoiéticas na primeira remissão completa. No entanto, a incidência de recidiva pós-transplante é considerável neste grupo de pacientes, e a conduta, nestes casos, é um desafio. O relato descreve os resultados do tratamento de pacientes com leucemia mieloide aguda positiva e duplicação em tandem de FLT3 que recidivaram depois do transplante alogênico de células-tronco hematopoiéticas e que foram tratados com combinação de quimioterapia de reindução, infusão de linfócitos de doador, sorafenib e azacitidina. São descritos três casos, e todos os pacientes apresentaram remissão completa prolongada com a terapia combinada. A combinação de quimioterapia de indução, seguida de infusão de linfócitos do doador, e a manutenção com azacitidina e sorafenib podem ser abordagens eficazes no tratamento da recorrência pós-transplante em pacientes com leucemia mieloide aguda e duplicação em tandem de FLT3. Essa estratégia deve ser mais explorada no contexto de ensaios clínicos.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Phenylurea Compounds/administration & dosage , Azacitidine/administration & dosage , Leukemia, Myeloid, Acute/therapy , Niacinamide/analogs & derivatives , Lymphocyte Transfusion , fms-Like Tyrosine Kinase 3/genetics , Induction Chemotherapy , Antineoplastic Agents/administration & dosage , Recurrence , Leukemia, Myeloid, Acute/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment Outcome , Niacinamide/administration & dosage , Combined Modality Therapy/methods , Neoplasm Recurrence, Local/therapy
18.
Bol. méd. Hosp. Infant. Méx ; 74(2): 122-133, mar.-abr. 2017. tab
Article in Spanish | LILACS | ID: biblio-888605

ABSTRACT

Resumen: Introducción: Se desconocen las características citopatológicas de las leucemias agudas en pacientes de Chiapas, México, ya que es una población relativamente aislada con alto índice de consanguinidad, lo cual podría afectar la evolución y la respuesta terapéutica. Métodos: Se clasificaron morfológica, inmunofenotípica y genotípicamente 81 casos de leucemia aguda en pacientes atendidos en el Hospital de Especialidades Pediátricas de Chiapas, indicando riesgo al ingreso y situación al momento del estudio. Los resultados se comparan con información nacional e internacional pertinente. Resultados: Se encontró la siguiente proporción de tipos de leucemia aguda: leucemias B, 75.3%; mieloides, 16%; de células T, 3.7%; B-M, 3.7% y de células NK, 1.2%. Las alteraciones genéticas estuvieron presentes en 40.6% de las B y en 69% de las mieloides. La alteración genética se relacionó con la evolución del paciente a corto plazo en las leucemias tipo B; no así en las mieloides. En las B, los casos con el gen MLL alterado fallecieron en menos de un mes, los casos con la translocación t(1;19)(q23;p13) han tenido buena evolución, y aquellos con la t(12;21)(p13;q22) han tenido mala evolución a medio plazo. La hiperdiploidía se presentó en el 20% de los casos B; el 83% de ellos permanecen en remisión de 1 a 12 meses desde el diagnóstico. El 69% de los casos con leucemias mieloides falleció o abandonó el tratamiento en recaída de 15 días a 37 meses del diagnóstico. Conclusiones: La proporción de los diferentes tipos de leucemia aguda atendidas en el HEP es similar a la encontrada en otras partes del país. Su comportamiento y desenlace está relacionado con la presencia o ausencia de alteraciones genéticas específicas y no específicas.


Abstract: Background: Childhood acute leukemia cytological features are unknown in Chiapas, Mexico. Defining these features is important because this is a relatively isolated population with high consanguinity index, and these aspects could determine differences in responses to treatment and outcome. Methods: Eighty-one childhood acute leukemia cases treated at the Hospital de Especialidades Pediátricas in Chiapas were characterized by morphology, immunophenotype, genotype, initial risk assignment and status at the time of the study. Results: The proportion of leukemic cell types found in this study was B cell, 75.3%; myeloid, 16%; T cell, 3.7% and NK 1.2%. In B cell leukemia, genetic alterations were present in 40.6% of cases and had a specific outcome regardless of initial risk assessment. Cases with MLL gene alteration died within a month from diagnosis. Translocations were present in 17.5% B cases; t(1;19) was present in those with a favorable outcome. The t(12;21) translocation was related to initial remission and midterm relapse and dead. Hyperdiploidy was present in 20% of B cell cases with good outcome. In 38.5%of myeloid cases were translocations and karyotypic abnormalities. Short-term outcome in this group has been poor; 69% have died or abandoned treatment in relapse from 15 days to 37 months after diagnosis. Conclusions: Relative frequency of different types of acute leukemia in patients treated at a tertiary level pediatric hospital in Chiapas, Mexico, was similar to the one found in other parts of the country. Patients' outcome, under a standardized treatment, differs according to the group, the subgroup and the presence and type of genetic alterations.


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Translocation, Genetic , Leukemia, Myeloid, Acute/pathology , Diploidy , Recurrence , Time Factors , Remission Induction , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Immunophenotyping , Risk Assessment , Genotype , Hospitals, Pediatric , Mexico
19.
Rev. Assoc. Med. Bras. (1992) ; 62(supl.1): 23-24, Oct. 2016.
Article in English | LILACS | ID: biblio-829560

ABSTRACT

SUMMARY The allogeneic hematopoietic stem cell transplantation (HSCT) can cure intermediate and high-risk acute myeloid leukemia. Even with the development of strategies to reduce HSCT toxicity, this is still a complex treatment with high morbidity and mortality. Knowledge of the graft versus leukemia effect of HSCT has prepared the way for the development of Adoptive Immunotherapy or in vitro expansion of activated lymphocytes without alloreactivity, with subsequent intravenous infusion. The infusion of genetically modified T lymphocytes and haploidentical natural killer cells has been tested as an alternative to HSCT with very interesting results worldwide and in Brazil, as we not only have the technology of in vitro expansion of clinical grade lymphocytes available, but also do it according to the Good Manufacturing Practices that have been determined internationally.


RESUMO O transplante de células-tronco hematopoéticas (TCTH) alogênico é curativo para leucemia mielóide aguda de risco intermediário e alto. Mesmo com o desenvolvimento de estratégias para minorar a toxicidade do TCTH, este ainda é um tratamento complexo com elevada morbi-mortalidade. O conhecimento sobre o efeito enxerto contra leukemia do TCTH pavimentou o caminho para o desenvolvimento da Imunoterapia Adotiva ou expansão in vitro de linfócitos ativados, sem alo-reatividade, com posterior infusão endovenosa. A infusão de Linfócitos T geneticamente modificados e de células Natural Killer haploidenticas tem sido testada como alternativa ao TCTH com resultados bastante interessantes no mundo e no Brazil já que não apenas dominamos a tecnologia de expansão in vitro de linfócitos em grau clínico, como o fazemos segundo as Boas Práticas de Manufatura determinadas internacionalmente.


Subject(s)
Humans , Killer Cells, Natural/immunology , Leukemia, Myeloid, Acute/therapy , Immunotherapy, Adoptive/methods , Brazil , Immunotherapy, Adoptive/trends , Hematopoietic Stem Cell Transplantation/methods , Graft vs Leukemia Effect
20.
Biomédica (Bogotá) ; 35(4): 549-556, oct.-dic. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-768085

ABSTRACT

Introducción. La leucemia mieloide aguda representa alrededor del 20 % de las leucemias en menores de 18 años. Actualmente, solo existen dos alternativas de tratamiento de consolidación: la quimioterapia y el trasplante con progenitores hematopoyéticos. Objeti vo. Evaluar el costo-efectividad del trasplante alogénico con progenitores hematopoyéticos de donantes emparentados o no emparentados, en comparación con la quimioterapia de consolidación en niños de alto riesgo con leucemia mieloide aguda. Materiales y métodos. Se construyó un árbol de decisiones utilizando los años de vida ganados como resultado. Los costos y probabilidades se extrajeron de estudios y reportes que se encuentran en la literatura científica. El umbral de costo-efectividad fue tres veces el producto interno bruto per cápita de 2010. Se hicieron análisis de sensibilidad univariados y probabilísticos, así como una curva de aceptabilidad. Resultados. Al comparar el trasplante de donante emparentado o no emparentado con los ciclos de quimioterapia, se obtuvieron tasas de costo-efectividad incremental de COP$ 9´226.421 (USD$ 4.820) y COP$ 6´544.116 (USD$ 3.419), respectivamente, cifras estas inferiores al producto interno bruto per cápita: COP$ 12´047.418 (USD$ 6.294). El trasplante resultó ser costo-efectivo en 70 % de las simulaciones y con mayor probabilidad de serlo cuando había disposición a pagar cantidades superiores a COP$ 7´200.000 (USD$ 3.762). Conclusión. El trasplante alogénico (emparentado o no) en Colombia resultó ser costo-efectivo frente al tratamiento de consolidación en niños de alto riesgo con leucemia mieloide aguda.


Introduction: Acute myeloid leukemia represents about 20% of leukemias in minors under 18 years old. At present, there are only two consolidation treatment alternatives: Chemotherapy and stem-cell transplantation. Objective: To evaluate the cost-effectiveness of unrelated and related hematopoietic stem cell transplantations, versus chemotherapy consolidation in pediatric patients with high-risk acute myeloid leukemia. Materials and methods: A decision tree was constructed with life-years gained as the outcome. Costs and probabilities were extracted from the literature. Probabilistic sensitivity analyses and acceptability curves were computed. The cost-effectiveness threshold was three times the 2010 per capita gross domestic product. Results: When compared to consolidation chemotherapy cycles, related and unrelated hematopoietic stem-cell transplantation had incremental cost-effectiveness ratios of COP$ 9,226,421 (USD$ 4,820) and COP$ 6,544,116 (USD$ 3,419) respectively, which are lower than the per capita gross domestic product (COP$ 12,047,418, USD$ 6,294). Transplant proved to be cost-effective in 70% of the simulations and had a higher probability of the willingness to pay being over than COP$ 7,200,000 (USD$ 3,762). Conclusion: In Colombia, related and unrelated hematopoietic stem-cell transplants are cost-effective alternatives to consolidation treatment for high-risk acute myeloid leukemia in pediatric patients.


Subject(s)
Adolescent , Child , Child, Preschool , Humans , Leukemia, Myeloid, Acute/economics , Antineoplastic Combined Chemotherapy Protocols/economics , Hematopoietic Stem Cell Transplantation/economics , Consolidation Chemotherapy/economics , Computer Simulation , Decision Trees , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Risk , Cost-Benefit Analysis , Colombia , Combined Modality Therapy , Models, Economic , Allografts/economics
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