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Although it is absolutely clear that postremission therapy is currently necessary to obtain disease-free long-term survivorship for patients with acute myeloid leukemia (AML) in first complete remission (CR), it is not entirely cl...
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Although it is absolutely clear that postremission therapy is currently necessary to obtain disease-free long-term survivorship for patients with acute myeloid leukemia (AML) in first complete remission (CR), it is not entirely clear what form that treatment should take. High-dose cytarabine is clearly effective and there definitely is a dose-response relationship for cytarabine and remission duration. High-dose cytarabine is effective for younger patients but not elderly patients. It is effective for patients with favorable cytogenetics but it is not clear whether it is effective for patients with intermediate or unfavorable cytogenetics. Furthermore, it is not clear what the most effective and least toxic dose and schedule of high-dose cytarabine is.
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摘要 :
Although it is absolutely clear that postremission therapy is currently necessary to obtain disease-free long-term survivorship for patients with acute myeloid leukemia (AML) in first complete remission (CR), it is not entirely cl...
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Although it is absolutely clear that postremission therapy is currently necessary to obtain disease-free long-term survivorship for patients with acute myeloid leukemia (AML) in first complete remission (CR), it is not entirely clear what form that treatment should take. High-dose cytarabine is clearly effective and there definitely is a dose-response relationship for cytarabine and remission duration. High-dose cytarabine is effective for younger patients but not elderly patients. It is effective for patients with favorable cytogenetics but it is not clear whether it is effective for patients with intermediate or unfavorable cytogenetics. Furthermore, it is not clear what the most effective and least toxic dose and schedule of high-dose cytarabine is.
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Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome...
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Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues. This resulted in deregulated EPOR expression, hypersensitivity to erythropoietin stimulation, and heightened JAK-STAT activation. Expression of truncated EPOR in mouse B cell progenitors induced ALL in vivo. Human leukemic cells with EPOR rearrangements were sensitive to JAK-STAT inhibition, suggesting a therapeutic option in high-risk ALL.
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Objective: To determine long-term survival of visceral pleural invasion (VPI) and parenchymal invasion (PAI) (angiolymphatic and/or vascular) on survival of NSCLCs less than 30 mm in maximum diameter.
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Despite some claims to the contrary, I believe substantial progress has been made in the last half century toward cure of acute myeloid leukemia in children and adults. The tried and true mechanism for this progress has been clini...
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Despite some claims to the contrary, I believe substantial progress has been made in the last half century toward cure of acute myeloid leukemia in children and adults. The tried and true mechanism for this progress has been clinical trial and error. This method has been supplemented with an ever-increasing amount of work at the clinical laboratory interface that is beginning to allow us to develop specific therapy for afflicted individuals. This review details where we stand today and how we got here.
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Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patient...
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Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1(-) B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-isk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-ypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-isk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non-risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.
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The relationship between renal cell cancer (RCC) and hematologic malignancy (HM) in the same individual has been reported for more than 20 years, and is noted in SEER database studies. Family histories suggest a familial associati...
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The relationship between renal cell cancer (RCC) and hematologic malignancy (HM) in the same individual has been reported for more than 20 years, and is noted in SEER database studies. Family histories suggest a familial association as well. This study evaluates the occurrence of renal cell cancer and hematologic malignancies in individual patients and families, and the occurrence of age-of-onset anticipation among generations. Family history data from our familial patient registry, including more than 700 pedigrees of familial hematologic malignancies, and 700 patients with renal cell cancer, were reviewed. Twenty-six patients with a personal history of both RCC and HM are reported. Seventy four patients with RCC are noted to have 95 family members with HM. Consistent with past reports, there was male predominance among the patients with both diseases (71 %), and among the RCC patients' relatives with HM (57 %). Also consistent was a predominance of lymphoid malignancies in those with both diseases (92 %) and in the HMs among family members of RCC patients (79 %). The majority (95 %) of HM relatives were first or second degree relatives of the patient with RCC. Thirty of 34 parent/child pairs demonstrated age of onset anticipation in which the child developed either disease at a younger age than the parent. The co-occurrence of RCC and HM in the same patient has been shown to be significantly greater than expected. Families also appear to have an increased association. The appearance of anticipation suggests that genetic factors may be significant in this association of RCC and HM.
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Familial leukemia has been described for more than 50 years but only recently have modern genetic techniques allowed for the investigation of the genome. Genome-wide association studies have identified a number of genetic sites th...
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Familial leukemia has been described for more than 50 years but only recently have modern genetic techniques allowed for the investigation of the genome. Genome-wide association studies have identified a number of genetic sites that appear to relate to susceptibility to leukemia in certain families and occasionally to susceptibility to a specific leukemia in general. Many questions remain, including susceptibility to what? An oncogenic virus? An environmental chemical? Mutation of another gene induced by a heritable mutation-promoting gene?. Clinically important facts have been learned. Chronic lymphocytic leukemia (CLL) is by far the most common familial leukemia. Patients with CLL have approximately a 10 % chance of a first-degree relative developing CLL, and even a greater chance of one developing monoclonal B-cell lymphocytosis which may be an asymptomatic forme fruste of the neoplasm. Furthermore, there may be an increased incidence of breast cancer in familial CLL pedigrees which raises the question of a common etiology for neoplasms in general, or at least a previously unrecognized relationship among them.
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