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La leucemia linfoblástica aguda constituye la neoplasia infantil más frecuente. Los tratamientos actuales posibilitan más del 80% de supervivencia libre de enfermedad por cinco años. En el 2000, se probó un protocolo de quimioterapia llamado leucemia linfoblástica intercontinental Berlín-Frankfurt-Münster (ALLIC BFM). El proceso investigativo se realizó mediante la metodología PRISMA, con el propósito de sistematizar la información acerca de la supervivencia de los pacientes pediátricos con leucemia linfoblástica aguda tratados con el uso del protocolo de quimioterapia ALLIC BFM en sus versiones de 2002 o 2009. La supervivencia global en pacientes donde se utilizó el protocolo de 2002 fue del 52% al 91,7% y la libre de enfermedad fue del 45% a 83,3%; mientras que, con el uso del protocolo 2009 se reportó una supervivencia global del 71,1% al 90% y la libre de enfermedad fue del 69,4% al 90,3%. Los principales factores que afectaron la supervivencia fueron las complicaciones relacionadas con el tratamiento, los pacientes de alto riesgo y la medicación insuficiente.
Acute lymphoblastic leukemia is the most common childhood neoplasia. Current treatments allow more than 80% disease-free survival for five years. In 2000, a chemotherapy protocol called Berlin-Frankfurt-Münster intercontinental lymphoblastic leukemia (ALLIC BFM) was tested. The investigative process was carried out using the PRISMA methodology. This study aimed to systematize the information about the survival of pediatric patients with acute lympho-blastic leukemia treated with the ALLIC BFM chemotherapy protocol in its 2002 or 2009 versions. 52% to 91.7% of patients showed an overall survival in patients where the 2002 proto-col was used, and disease-free was from 45% to 83.3%; while, with the use of the 2009 protocol, an overall survival of 71.1% to 90% was reported, and disease-free survival was 69.4% to 90.3%. The main factors affecting survival were treatment-related complications, high-risk patients, and insufficient medication.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Population , Survival , Leukemia , Patients , Therapeutics , Drug TherapyABSTRACT
La leucemia es una patología neoplásica maligna que constituye un problema de salud que afecta fundamentalmente a la población infantil. Así, se realizó un proceso investigativo con el objetivo de describir la calidad de vida en pacientes pediátricos de LLA con edades entre 2 y 18 años, atendidos en 2019, en el Hospital Pediátrico Baca Ortiz y en el Hospital de Solca - Núcleo Quito, Ecuador; para lo cual se hizo un estudio observacional, transversal, descriptivo, con enfoque cuantitativo. Los datos fueron recopilados mediante la revisión de las historias clínicas de los 60 pacientes en el contexto de investigación. El 66,7% correspondió al sexo masculino, el 43,3% tenía edades entre 2 y 4 años, el 38,3% tuvo fiebre como síntoma inicial. El síndrome de Down resultó la comorbilidad más frecuente (6,7%). En 54 pacientes se diagnosticó LLA tipo B. El 66,7% recibía terapia psicológica, 22 de los enfermos estaban en la fase de inducción y mantenimiento. El 65% abandonó la escuela mientras se le administraba quimioterapia. Predomina-ron los que consideraron su calidad de vida como buena, seguido de los que tuvieron severa afectación. Las mayores afectaciones en los participantes fueron: dificultades con la alimentación, presencia de dolor, falta de comunicación, existencia de ansiedad y presencia de estrés por la preocupación debido a la posible infectividad del tratamiento.
Leukemia is a malignant neoplastic disease that constitutes a health problem that mainly affects children. Thus, this research aimed to describe the quality of life in pediatric ALL patients between 2 and 18 years of age, treated in 2019, at the Baca Ortiz Pediatric Hospital and at the Solca Hospital - Núcleo Quito, Ecuador. A cross-sectional, descriptive, and observational study with a quantitative approach. Data were collected by reviewing the medical records of the 60 patients in the research context. 66.7% were male, 43.3% were between 2 and 4 years old, 38.3% had fever as the initial symptom. Down syndrome was the most frequent comorbidity (6.7%). Type B ALL was diagnosed in 54 patients. 66.7% received psychological therapy. 22 of the patients were in the induction and maintenance phase. 65% dropped out of school while recei-ving chemotherapy. Those ones who considered their quality of life as good predominated, followed by those ones who were severely affected. The greatest effects on the participants were: difficulties with feeding, presence of pain, lack of communication, existence of anxiety and presence of stress due to worry due to the possible infectivity of the treatment.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Quality of Life , Drug Therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Pediatrics , Therapeutics , LeukemiaABSTRACT
Objective:To investigate the relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL).Methods:Fifty-eight children diagnosed with ALL in Shanxi Children's Hospital from January 2019 to December 2020 were recruited. All of them were treated with CCLG-ALL2018 chemotherapy regimen and the bone marrow showed complete remission. They received 6-MP oral treatment during maintenance treatment. Single nucleotide polymorphism of NUDT15 gene was detected by real-time fluorescence quantitative polymerase chain reaction. The bone marrow suppression after 6-MP treatment and 6-MP tolerance dose in patients with different NUDT15 genotypes were analyzed.Results:Among 58 patients, 3 patients had NUDT15 TT genotype, 46 patients had CC genotype and 9 patients had TC genotype. During maintenance treatment with 6-MP, the differences in leukocyte count, hemoglobin and platelet count among the three groups of patients with different NUDT15 genotypes were statistically significant (all P < 0.05). Among 58 patients, 23 (39.66%) patients had varying degrees of neutropenia after medication, including 16 cases of NUDT15 CC genotype, 5 cases of TC genotype and 2 cases of TT genotype. There was a statistically significant difference in bone marrow suppression among the three groups ( H = 29.10, P < 0.05). The dosages of 6-MP used in patients with TT, CC and TC genotypes were (10.4±8.8) mg·m -2·d -1, (41.5±1.3) mg·m -2·d -1 and (36.7±2.4) mg·m -2·d -1, respectively, and the difference was statistically significant ( F = 16.95, P < 0.05). Conclusions:Children with different NUDT15 genotypes have different tolerance to 6-MP, and NUDT15 gene polymorphism is associated with 6-MP intolerance during maintenance treatment in children with ALL, which may affect the treatment of the disease.
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Objective:To investigate the influencing factors of delayed methotrexate (MTX) elimination after high-dose methotrexate (HD-MTX) treatment in children with acute lymphoblastic leukemia (ALL) and the effects of delayed MTX elimination and HD-MTX reduction on the prognosis of children with ALL.Methods:The clinical data of 242 children with ALL diagnosed and treated in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2015 to June 2020 in accordance with the Chinese Children's Cancer Group study ALL 2015 (CCCG-ALL 2015) were retrospectively analyzed. Low risk and intermediate/high risk children respectively received 3 g/m 2 and 5 g/m 2 HD-MTX for 4 times, and the serum MTX concentration was monitored. The serum MTX concentration > 1 μmol/L at 44 h of administration was considered as the delayed elimination, which was divided into mild (> 1 μmol/L and ≤ 5 μmol/L), moderate (> 5 μmol/L and ≤ 10 μmol/L) and severe (> 10 μmol/L) delayed elimination. Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of delayed MTX elimination, and univariate Cox proportional hazards model was used to analyze the related factors of ALL relapse. Results:The 242 children with ALL completed 962 times of HD-MTX chemotherapy. The median serum MTX concentration [ M ( Q1, Q3)] at 44 h of administration was 0.45 μmol/L (0.33 μmol/L, 0.72 μmol/L). The total incidence of delayed MTX elimination was 17.7% (170/962). The incidence of mild, moderate and severe delayed elimination was 13.8% (133/962), 2.6% (25/962) and 1.2% (12/962), respectively. Logistic regression analysis showed that age ≥ 7 years old ( OR = 1.68, 95% CI 1.17-2.41, P = 0.005), MTX dose >3 g/m 2 at each course ( OR = 2.14, 95% CI 1.52-3.03, P < 0.001) and the first course of HD-MTX chemotherapy ( OR = 2.05, 95% CI 1.43-2.93, P < 0.001) were independent risk factors for delayed MTX elimination. The median follow-up time was 50 months (34 months, 68 months), 12.8% (31/242) of the children relapsed, and the median relapse time was 30 months (30 months, 39 months). Univariate Cox regression analysis showed that there were no significant differences in the relapse rates among children with different gender, immunophenotype, risk, the number of delayed MTX elimination, and the completion of HD-MTX chemotherapy (the ratio of MTX average dose to initial planned dose) (all P > 0.05). Conclusions:The independent risk factors of delayed elimination of MTX in children with ALL are age ≥ 7 years old, MTX dose > 3 g/m 2 at each course and the first course of HD-MTX chemotherapy. Delayed elimination of MTX and reduction of HD-MTX have no significant effect on ALL relapse.
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Objective:To explore the expression levels, clinical significances and prognostic evaluation value of T-cell immunoglobulin mucin-3 (Tim-3) and galectin-9 (Gal-9) in bone marrow cells of patients with newly diagnosed acute lymphocytic leukemia (ALL).Methods:Bone marrow samples from 30 newly diagnosed ALL patients admitted to First Affiliated Hospital of Xinjiang Medical University from September 2016 to September 2018 were selected, and peripheral blood samples from 20 healthy volunteers during the same period in the First Affiliated Hospital of Xinjiang Medical University were treated as the controls. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect mRNA relative expression levels of Tim-3 and Gal-9. Differences in mRNA expression of Tim-3 and Gal-9 among ALL patients with varied clinicopathological characteristics were compared. Overall survival (OS) analysis was performed by using the Kaplan-Meier method, Cox proportional hazards model was used to make univariate and multivariate survival analysis.Results:mRNA relative expression levels of Tim-3 and Gal-9 in 30 newly diagnosed ALL patients were higher than those in the healthy control group (2.86±0.47 vs. 0.45±0.05, t = 21.65, P<0.05; 9.79±0.58 vs. 0.96±0.23, t = 63.24, P<0.05). mRNA relative expression level of Tim-3 had statistically significant differences in patients with different ages, France-America-Britain (FAB) Cooperative Group classification, hazard grades and central nervous system invasion (all P<0.01). There were statistically significant differences in mRNA relative expression level of Gal-9 for patients with different ages, FAB Cooperative Group classification, white blood cell count (WBC), central nervous system invasion and NOTCH1 mutation (all P<0.01). All patients were grouped by mRNA relative expression levels of Tim-3 and Gal-9, and patients in high Tim-3 expression group (≥2.86) had worse overall survival (OS) compared with that for patients in low Tim-3 expression group (<2.86) ( P = 0.048). Patients in high Gal-9 expression group (≥9.79) had worse OS compared with that for patients in low Gal-9 expression group (<9.79) ( P = 0.031). Moreover, the OS in Tim-3 and Gal-9 both high expression group was worse than that in Tim-3 and Gal-9 both low expression group and in the low expression group of either of them (all P<0.05). There was no statistically significant difference in OS between the high Tim-3 expression with low Gal-9 expression group and the high Gal-9 expression with low Tim-3 expression group ( P > 0.05). Multivariate Cox regression analysis revealed that peripheral blood WBC≥11.4×10 9/L, BCR-ABL gene mutation, central nervous system invasion, and high expression of Tim-3 and Gal-9 were independent risk prognostic factors of OS for newly diagnosed ALL patients (all P<0.05) . There was a positive correlation between the expression levels of Tim-3 and Gal-9 ( r = 0.788, P<0.01). Conclusions:The high expression of Tim-3 and its ligand Gal-9 are independent effecting factors of poor prognosis in newly diagnosed ALL patients. The expression levels of Tim-3 and Gal-9 can be served as a potential prognostic indicator for ALL patients.
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Adult T- lymphocyte leukemia/ lymphoma (ATLL), described by Uchiyama et al. in 1977, is a distinct neoplasia of peripheral T-lymphocytes caused by human T-cell lymphotropic virus type 1 (HTLV-1). The authors describe the case of a 75-year-old female patient who presented with fever, chills, and altered mental status. The peripheral blood morphology showed large atypical lymphocytes with multilobed nuclei and flow cytometry consistent with ATLL. The authors discuss the pathophysiology, differential diagnosis, and subtypes of ATLL in addition to the diagnostic approach using flow cytometry when bone marrow biopsy is not available and modalities of treatment.
Subject(s)
Humans , Female , Aged , Human T-lymphotropic virus 1 , Leukemia-Lymphoma, Adult T-Cell , Diagnosis, Differential , Flow CytometryABSTRACT
B-cell prolymphocytic leukemia (B-PLL) is an extremely rare disease, accounting for approximately 1% of the lymphocytic leukemias. B-PLL generally occurs in older people. It is characterized by the presence of more than 55% prolymphocytes in the peripheral blood (PB), no or minimal lymphadenopathy, massive splenomegaly, and very high white blood cell counts. The prognosis of B-PLL patients is generally poor, with a median survival of 3 years, although a subset of patients may show a prolonged survival. Herein, we report a case of a 70-year-old male with weakness, generalized lymphadenopathy, and moderate splenomegaly at the initial presentation. Hematologic examination revealed lymphocytic leukocytosis, favoring a chronic lymphoproliferative disorder (CLPD). The key to decoding the precise CLPD was a combination of the clinical profile, morphologic findings on the peripheral blood and the bone marrow, immunophenotypic analysis, and cytogenetic study. The best diagnosis proffered was a de novo chronic lymphocytic leukemia/prolymphocytic leukemia. There was no prior history of lymphoproliferative disorder or lymphocytic leukocytosis. Discriminating this entity from other lymphoproliferative disorders is crucial as the treatment and prognosis are varied compared to the other lymphoproliferative disorders. The diagnostic conundrum encountered and the incredible utility of ancillary studies in such a scenario are highlighted in this study.
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Humans , Male , Aged , Leukemia, Lymphocytic, Chronic, B-Cell , Leukemia, Prolymphocytic , Leukemia, Lymphoid , Leukemia, Prolymphocytic, B-Cell , Rare Diseases , LymphadenopathyABSTRACT
Objective@#To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors.@*Methods@#Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis.@*Results@#No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ2=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors.@*Conclusion@#The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.
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Objective@#To analyze the clinical efficacy and safety of fludarabine combined with cyclophosphamide (FC) and fludarabine and cyclophosphamide combined with rituximab (FCR) in the treatment of chronic lymphocytic leukemia (CLL).@*Methods@#FCR regimen was selected as the experimental group, and FC regimen was selected as the control group. The studies were retrieved from PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP databases by computer and the references listed in these studies were further searched. The randomized controlled trials (RCT) meeting inclusive criteria were extracted, and the quality was evaluated and cross-checked independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then the Meta-analysis was conducted by using StataMP 14.0 software.@*Results@#A total of 7 studies and 1 985 patients were included. The complete remission rate and overall response rate of FCR regimen were better than those of FC regimen, and the differences were statistically significant (RR = 1.89, 95% CI 1.64-2.18, P < 0.01; RR = 1.15, 95% CI 1.10-1.21, P < 0.01). In terms of grade Ⅲ-Ⅳ adverse reactions, the neutropenia of FCR regimen was more severe than that of FC regimen, and the difference was statistically significant (RR = 1.25, 95% CI 1.01-1.55, P = 0.004).@*Conclusion@#The FCR regimen has a better clinical outcome and prognosis than the FC regimen, and is accompanied by more severe grade Ⅲ-Ⅳ neutropenia.
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Objective To analyze the clinical efficacy and safety of fludarabine combined with cyclophosphamide (FC) and fludarabine and cyclophosphamide combined with rituximab (FCR) in the treatment of chronic lymphocytic leukemia (CLL). Methods FCR regimen was selected as the experimental group, and FC regimen was selected as the control group. The studies were retrieved from PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP databases by computer and the references listed in these studies were further searched. The randomized controlled trials (RCT) meeting inclusive criteria were extracted, and the quality was evaluated and cross-checked independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then the Meta-analysis was conducted by using StataMP 14.0 software. Results A total of 7 studies and 1 985 patients were included. The complete remission rate and overall response rate of FCR regimen were better than those of FC regimen, and the differences were statistically significant ( RR＝1.89, 95% CI 1.64-2.18, P<0.01; RR＝1.15, 95% CI 1.10-1.21, P<0.01). In terms of gradeⅢ-Ⅳadverse reactions, the neutropenia of FCR regimen was more severe than that of FC regimen, and the difference was statistically significant ( RR＝1.25, 95% CI 1.01-1.55, P＝0.004). Conclusion The FCR regimen has a better clinical outcome and prognosis than the FC regimen, and is accompanied by more severe grade Ⅲ-Ⅳneutropenia.
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Objective To analyze the clinical and biological characteristics of adult acute T-lymphocytic leukemia (T-ALL) patients carrying SET-NUP214 fusion gene,and the prognostic value of SET-NUP214 molecular marker monitoring.Methods The clinical and laboratory data of 4 adult T-ALL patients with SET-NUP214 fusion gene in the Third People's Hospital of Chengdu from January 2009 to December 2014 were analyzed retrospectively,and T cell receptor (TCR) gene rearrangement was detected to judge the differentiation and developmental stages of tumor cells in these patients.Minimal residual disease (MRD) was detected in 2 patients with follow-up specimens through detection of SET-NUP214 gene by using polymerase chain reaction.Results Four patients expressed T cell immune markers CD5,CD7,and cytoplasmic CD3 (cyCD3),and also expressed some myeloid-specific antigens.All 4 patients had the same SET-NUP214 fusion site.In the tumor cells of 4 patients,5 TCRB gene rearrangements were detected,all of which were incomplete rearrangement of DB-JB;4 patients were detected with TCRG and TCRD gene rearrangements,and all were completely rearranged.The result of MRD monitoring through SET-NUP214 fusion gene was consistent with clinical treatment outcome.Conclusions The T-ALL patients with SET-NUP214 fusion gene have some unique cell biological characteristics.SET-NUP214 fusion gene could be used as a molecular marker for MRD monitoring,and which can be used for the follow-up in the course of treatment.
Subject(s)
Humans , Female , Middle Aged , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Lymphoma, B-Cell/diagnosis , Heart Atria/pathology , Heart Neoplasms/diagnosis , Biopsy , Leukemia, Lymphocytic, Chronic, B-Cell/surgery , Lymphoma, B-Cell/surgery , Coronary Angiography , Incidental Findings , Computed Tomography Angiography , Heart Neoplasms/surgeryABSTRACT
Resumen Introducción. Las enfermedades huérfanas caracterizadas por su baja prevalencia, comúnmente son de origen genético y degenerativo, y amenazan la vida. Objetivo. Describir la mortalidad por enfermedades huérfanas y analizar la tendencia en Colombia entre 2008 y 2013. Materiales y métodos. Se trata de un estudio descriptivo. Se analizó la tendencia de las tasas de mortalidad a partir de los certificados de defunción entre el 2008 y el 2013. Se calcularon las tasas específicas de mortalidad y las ajustadas por edad y sexo. Resultados. Se atribuyeron 7.135 defunciones a enfermedades huérfanas; 51,4 % ocurrieron en hombres de todas las edades. La tasa media de mortalidad fue de 2,53 muertes por 100.000 personas. La tendencia mostró un patrón de ascenso, aunque muy heterogéneo, en el territorio nacional. Las mayores tasas de mortalidad por 100.000 habitantes se registraron en Bogotá (20,0), la región Andina (5,3) y la Caribe (3,7). Las principales causas de muerte en hombres fueron: leucemia linfoblástica aguda, distrofia muscular, displasia broncopulmonar originada en el periodo perinatal, esclerosis múltiple, síndrome de Guillain-Barréy gastrosquisis, y en mujeres, esclerosis múltiple, leucemia linfoide aguda, gastrosquisis, displasia broncopulmonar originada en el periodo perinatal, síndrome de Guillain-Barré y leucemia mieloide aguda. La tasa media de mortalidad por leucemia linfoblástica aguda fue de 0,17 por 100.000 hombres menores de 15 años, y la de mortalidad por esclerosis múltiple fue de 0,16 en mujeres mayores de 40 años. Conclusiones. Las causas de muerte mostraron un comportamiento similar en ambos sexos; sin embargo, la mayor carga de mortalidad se registró en la población masculina de todas edades en Bogotá.
Abstract Introduction: Rare diseases are characterized by their low prevalence, often of genetic origin, degenerative and life threatening. Objective: To describe mortality by orphan diseases and to analyze its trends in Colombia from 2008 to 2013. Materials and methods: We conducted a descriptive study to analyze mortality rate trends from the death certificates between 2008 and 2013. We calculated specific mortality rates and adjusted by age and sex. Results: Seven thousand one hundred and thirty five deaths were attributed to orphan diseases, and 51.4 % of them occurred among men of all ages. The mean mortality rate during the study period was 2.53 deaths per 100,000 people. Overall, the trend showed an increasing pattern of mortality although very heterogeneous across the country. Mortality rates were higher in Bogotá (20), and the Andes and the Caribbean regions (5.3 and 3.7 deaths per 100,000 population). The five most important causes of mortality among men were: Acute lymphoblastic leukemia, muscular dystrophy, bronchopulmonary dysplasia originating in the perinatal period, multiple sclerosis, Guillain-Barré syndrome and gastroschisis, and among women: Multiple sclerosis, acute lymphoblastic leukemia, gastroschisis, bronchopulmonary dysplasia originating in the perinatal period, Guillain-Barré syndrome and acute myeloid leukemia. The mean mortality rate by acute lymphoblastic leukemia was 0.17 deaths per 100,000 men younger than 15 years and that of multiple sclerosis was 0.16 in women over 40 years of age. Conclusion: The causes of death showed a similar pattern in both sexes. However, the burden of mortality was higher among men of all ages in Bogota.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Rare Diseases/mortality , Time Factors , Mortality/trends , Colombia/epidemiologyABSTRACT
@#Recently, much gene mutations have been detected in patients with acute leukemia or myelodysplastic syndrome (MDS) using next-generation sequencing (NSG) technology. Some of them are proved to be important prognostic markers. It has been showed that TP53, TET2 or DNMT3A gene mutations are associated with poor prognosis in acute leukemia or MDS patients. The prognosis of these patients is poor with short remission and survival. Allogeneic hematopoietic stem cell transplantation is the only way to cure these patients. However, the outcomes after transplantation are inferior to those in patients without these mutations. The hypomethylating agents or immune targeting therapy might improve their prognosis when combined with the present strategies. Here, the impact of TP53, TET2 and DNMT3A gene mutations on the prognosis after chemotherapy or transplantation is reviewed.
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The prognosis of acute lymphoblastic leukemia (ALL) is affected by multiple factors.As a simple and inexpensive prognostic indicator,the peripheral blood absolute lymphocyte count (ALC) is more and more concerned.Relevant studies show that ALC values of different time points during induction therapy and its ratio show important value in the assessment of ALL prognosis,which is expected to provide a basis for subsequent individualized treatment.
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Objective@#To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children.@*Methods@#The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model.@*Results@#In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ2=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ2=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ2=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor.@*Conclusions@#Pediatric Ph+ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.
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Objective@#To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) treated by hematopoietic stem cell transplantation (HSCT).@*Methods@#Clinical features and prognoses of 63 newly diagnosed Ph+ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed.@*Results@#Of 63 Ph+ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ2=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ2=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ2=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ2=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS.@*Conclusions@#First-line administration of generic dasatinib could improve EFS for Ph+ALL patients treated by HSCT when compered with imatinib.
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Objective@#To summarize the adverse effects of pegaspargase in the treatment of lymphoid malignancies and management experience.@*Methods@#Clinical data of patients who received chemotherapy including pegaspargase in the Department of Hematology of Beijing Tongren hospital during August 2011 to December 2015 were retrospective analyzed, and the adverse effects of pegaspargase and the management experience was summarized.@*Results@#A total of 129 patients with 443 times of pegaspargase used during this period. The common adverse reactions included allergic reactions in 2 cases (1.6%), acute pancreatitis in 19 (14.7%) including 6 acute symptomatic pancreatitis and 13 chemical pancreatitis with elevated pancreatin, hypertriglyceridemia in 15 cases(11.6%), hyperglycemia in 85 (65.9%), hypoglycemia in 7 (5.4%), elevated aminotransferase in 25 (19.4%), hyperbilirubinemia in 21 (15.5%), hypoalbuminemia in 62 (48.1%), prolonged APTT in 61 (47.3%), prolonged PT in 22 (17.1%), prolonged TT in 15 (11.6%), hypofibrinogen in 75 (58.1%), thrombus in 11 (8.5%) and bleeding in 3 (2.3%). The above adverse reactions were improved by symptomatic treatment of anti allergy, inhibition of secretion of pancreatic juice, lipid lowering, hypoglycemic, liver preservation, supplementation of plasma and hemostasis, respectively. Some serious adverse reactions affected the application of pegaspargase, even lead to discontinuation of the aspartate.@*Conclusion@#Though adverse effects associated with pegaspargase are extensive, most patients can successfully complete the chemotherapy containing the pegaspargase with close monitoring and timely treatment.
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Objective@#To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) .@*Methods@#Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph+ ALL patients with p16 deletion.@*Results@#Of 80 adult Ph+ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×109/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) .@*Conclusion@#This study indicated that deletion of p16 was associated with poor prognosis in adult Ph+ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph+ ALL for predicting prognosis and guiding therapy decision-making.
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Objective@#To analyze the clinical features and prognosis of acute lymphoblastic leukemia patients with immunophenotype of CD10-pre-B (CD10- pre B-ALL) .@*Methods@#6 adult cases with CD10- pre B-ALL immunophenotypes were analyzed retrospectively, related literatures were reviewed to clarify these kind of patients’ clinical features and prognosis.@*Results@#CD10- pre B-ALL occurred in 1.5% of ALL, 1.8% of B-ALL and 11.5% of pre B-ALL respectively. All the 6 patients were male with the median age as 33.5 years old, the median white blood cells was 101.78×109/L, MLL-AF4 fusion transcripts were evident in all cases. Complete remission (CR) was achieved in 5 patients after first induction chemotherapy, 1 patient failed to respond to induction therapy, and got CR after 3 courses of chemotherapy. 2 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, 1 patient relapsed in the short term and underwent allo-HSCT in CR2. 1 patient was still waiting for allo-HSCT. Of the 2 patients who didn’t receive transplantation, 1 died following a relapse, the other remained to be in CR.@*Conclusions@#CD10- pre B-ALL was a rare but distinct subtype in adult ALL characterized by male dominance, high onset white blood cells and MLL rearrangement rate. Conventional chemotherapy produced a high response rate but more likely relapse, allo-HSCT may have the potential to improve the prognosis of these patients.