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Journal of Medical Economics Sep 2017To evaluate healthcare resource utilization and economic burden of patients with chronic myeloid leukemia (CML) progression to the blast phase.
AIMS
To evaluate healthcare resource utilization and economic burden of patients with chronic myeloid leukemia (CML) progression to the blast phase.
METHODS
Patients (≥ 18 years) with ≥1 inpatient or ≥2 outpatient CML diagnoses were identified from the MarketScan Commercial and Medicare databases (January 1, 2007-June 30, 2015). CML patients were grouped into two study cohorts, those with evidence of disease progression to the blast phase and those without. Patients were required to have continuous medical and prescription coverage during a 12-month baseline period, in which demographics and clinical characteristics were evaluated. All-cause healthcare resource utilization and costs were evaluated during the baseline period, and a variable follow-up period, lasting ≥1 day and up to 1 year. Generalized linear models (GLM) were used to compare the incremental costs of CML patients with vs without progression.
RESULTS
Of the overall study population, 587 (7%) experienced disease progression and 7,504 (93%) did not. On the index date, of patients with progression, ∼ 31% were treated with allogeneic hematopoietic cell transplant and 69% with chemotherapy. During the baseline period, mean total healthcare costs, including costs for hospitalizations and outpatient costs, were significantly greater for CML patients with progression as compared to those without progression ($143,778 vs $53,143, p < .001). During the follow-up, mean total healthcare costs, costs for hospitalizations, and outpatient medical service costs were substantially greater for patients with progression as compared to those without progression; however, costs for outpatient prescriptions were less for patients who progressed. When patient characteristics were controlled for, mean incremental 1-year cost for CML patients with vs without progression was $270,925 (confidence interval = $235,290-$311,958, p < .001).
CONCLUSIONS
The healthcare burden, in terms of healthcare resource utilization and costs, of patients with CML progression is substantial. Healthcare providers and payers should consider various strategies to minimize the rate of CML progression.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Blast Crisis; Costs and Cost Analysis; Disease Progression; Female; Health Resources; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Linear Models; Male; Middle Aged; Retrospective Studies; Socioeconomic Factors; United States; Young Adult
PubMed: 28681664
DOI: 10.1080/13696998.2017.1345750 -
Blood Jan 1990We tested a population of over 60 patients with chronic myelogenous leukemia (CML) for changes in the structure and expression of the p53 gene, which is located on...
We tested a population of over 60 patients with chronic myelogenous leukemia (CML) for changes in the structure and expression of the p53 gene, which is located on chromosome 17. Six of 27 (22%) blast crisis samples and 3 of 5 (60%) accelerated phase samples had rearrangements of chromosome 17, whereas only 3 of 42 (7%) chronic phase patients had cytogenetic changes in chromosome 17. There was no loss of heterozygosity during the transition to blastic crisis among seven individuals who were informative for polymorphic probes for regions in or around the p53 gene on 17p. One patient in the chronic phase and one patient in the blastic phase of the 61 CML patients studied exhibited rearrangements of the p53 gene that were detectable by Southern analysis. One p53 allele was rearranged in the chronic phase patient and both p53 alleles were rearranged in the blastic phase patient. The p53 messenger RNA (mRNA) was of normal size (2.8 kb) in chronic phase and blast crisis, and the expression of the p53 gene was at least as high or higher in blast crisis as in the chronic phase of CML. The high incidence of abnormalities of chromosome 17 in blast-crisis CML found in our studies and the discovery of rearrangements of the p53 gene in two CML patients studied suggest that further study with probes for the p53 gene and anonymous polymorphic sites in chromosome 17 should be conducted in CML.
Topics: Blast Crisis; Blotting, Northern; Blotting, Southern; Chromosomes, Human, Pair 17; Gene Expression Regulation, Neoplastic; Gene Rearrangement; Genes, Neoplasm; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Oncogene Proteins; Phosphoproteins; Polymorphism, Restriction Fragment Length; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-myc; RNA, Messenger; RNA, Neoplasm; Tumor Suppressor Protein p53
PubMed: 1967214
DOI: No ID Found -
The Journal of Clinical Endocrinology... Jan 2021Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome. (Observational Study)
Observational Study
CONTEXT
Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome.
OBJECTIVE
This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases.
DESIGN AND SETTING
A multi-institutional case series is presented from tertiary pediatric oncology centers.
PATIENTS
Patients included children with pituitary blastoma.
INTERVENTIONS
Genetic testing, surgery, oncologic therapy, endocrine support are reported.
OUTCOME MEASURES
Outcome measures included survival, long-term morbidities, and germline and tumor DICER1 genotypes.
RESULTS
Seventeen pituitary blastoma cases were studied (10 girls and 7 boys); median age at diagnosis was 11 months (range, 2-24 months). Cushing syndrome was the most frequent presentation (n = 10). Cushingoid stigmata were absent in 7 children (2 with increased adrenocorticotropin [ACTH]; 5 with normal/unmeasured ACTH). Ophthalmoplegia and increased intracranial pressure were also observed. Surgical procedures included gross/near-total resection (n = 7), subtotal resection (n = 9), and biopsy (n = 1). Six children received adjuvant therapy. At a median follow-up of 6.7 years, 9 patients were alive; 8 patients died of the following causes: early medical/surgical complications (n = 3), sepsis (n = 1), catheter-related complication (n = 1), aneurysmal bleeding (n = 1), second brain tumor (n = 1), and progression (n = 1). Surgery was the only intervention for 5 of 9 survivors. Extent of resection, but neither Ki67 labeling index nor adjuvant therapy, was significantly associated with survival. Chronic complications included neuroendocrine (n = 8), visual (n = 4), and neurodevelopmental (n = 3) deficits. Sixteen pituitary blastomas were attributed to DICER1 abnormalities.
CONCLUSIONS
Pituitary blastoma is a locally destructive tumor associated with high mortality. Surgical resection alone provides long-term disease control for some patients. Quality survival is possible with long-term neuroendocrine management.
Topics: Blast Crisis; Child, Preschool; DEAD-box RNA Helicases; Female; Follow-Up Studies; Germ-Line Mutation; Humans; Infant; Male; Pituitary Neoplasms; Postoperative Complications; Prognosis; Retrospective Studies; Ribonuclease III; Survival Rate
PubMed: 33236116
DOI: 10.1210/clinem/dgaa857 -
Health Technology Assessment... 2012Chronic myeloid leukaemia (CML) is a form of cancer affecting the blood, characterised by excessive proliferation of white blood cells in the bone marrow and circulating... (Review)
Review
BACKGROUND
Chronic myeloid leukaemia (CML) is a form of cancer affecting the blood, characterised by excessive proliferation of white blood cells in the bone marrow and circulating blood. In the UK, an estimated 560 new cases of CML are diagnosed each year.
OBJECTIVES
The purpose of this study was to assess the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in the treatment of people with imatinib-resistant (ImR) and imatinib-intolerant (ImI) CML. A systematic review of the clinical effectiveness literature, a review of manufacturer submissions and a critique and exploration of manufacturer submissions for accelerated phase and blast crisis CML were carried out and a decision-analytic model was developed to estimate the cost-effectiveness of dasatinib and nilotinib in chronic phase CML. SYSTEMATIC REVIEW METHODS: Key databases were searched for relevant studies from their inception to June 2009 [MEDLINE (including MEDLINE In-Process & Other Non-Indexed Citations), EMBASE, (ISI Web of Science) Conference Proceedings Citation Index and four others]. One reviewer assessed titles and abstracts of studies identified by the search strategy, with a sample checked by a second reviewer. The full text of relevant papers was obtained and screened against the full inclusion criteria independently by two reviewers. Data from included studies were extracted by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through narrative review. ECONOMIC EVALUATION METHODS: Cost-effectiveness analyses reported in manufacturer submissions to the National Institute of Health and Clinical Excellence were critically appraised and summarised narratively. In addition, the models for accelerated phase and blast crisis underwent a more detailed critique and exploration. Two separate decision-analytic models were developed for chronic phase CML, one simulating a cohort of individuals who have shown or developed resistance to normal dose imatinib and one representing individuals who have been unable to continue imatinib treatment owing to adverse events. One-way, multiway and probabilistic sensitivity analyses were performed to explore structural and parameter uncertainty.
RESULTS
Fifteen studies were included in the systematic review. Chronic phase: effectiveness data were limited but dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic response and haematological response in both ImR and ImI populations. In terms of cost-effectiveness, it was extremely difficult to reach any conclusions regarding either agent in the ImR population. All three models (Novartis, PenTAG and Bristol-Myers Squibb) were seriously flawed in one way or another, as a consequence of the paucity of data appropriate to construct robust decision-analytic models. Accelerated and blast crisis: all available data originated from observational single-arm studies and there were considerable and potentially important differences in baseline characteristics which seriously undermined any process for making meaningful comparisons between treatments. Owing to a lack of available clinical data, de novo models of accelerated phase and blast crisis have not been developed. The economic evaluations carried out by the manufacturers of nilotinib and dasatinib were seriously undermined by the absence of evidence on high-dose imatinib in these populations.
LIMITATIONS
The study has been necessarily constrained by the paucity of available clinical data, the differences in definitions used in the studies and the subsequent impossibility of undertaking a meaningful cost-effectiveness analyses to inform all policy questions.
CONCLUSIONS
Dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic and haematological responses in both ImR and ImI populations. It was difficult to reach any cost-effectiveness conclusions as a consequence of the paucity of the data. Future research should include a three-way, double-blind, randomised clinical trial of dasatinib, nilotinib and high-dose imatinib.
Topics: Benzamides; Blast Crisis; Clinical Trials as Topic; Cost-Benefit Analysis; Dasatinib; Decision Support Techniques; Disease Progression; Drug Resistance, Neoplasm; Health Care Costs; Humans; Imatinib Mesylate; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Models, Economic; Piperazines; Prognosis; Protein Kinase Inhibitors; Pyrimidines; Quality of Life; Thiazoles
PubMed: 22551803
DOI: 10.3310/hta16220 -
The American Journal of Case Reports Feb 2017BACKGROUND Hypercalcemia associated with chronic myeloid leukemia (CML) is an ominous sign. Although rare, several cases have been reported and multiple pathophysiologic... (Review)
Review
BACKGROUND Hypercalcemia associated with chronic myeloid leukemia (CML) is an ominous sign. Although rare, several cases have been reported and multiple pathophysiologic mechanisms have been independently proposed. We present a patient case and a literature review of the clinical presentation and mechanisms of CML-associated hypercalcemia. CASE REPORT A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia. On physical examination, we observed tachycardia, altered mental status, and dehydration. Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL). His chest CT scan showed diffuse lytic lesions and bone destruction concerning for diffuse bone marrow involvement. The patient was diagnosed with hypercalcemia in the context of a CML blast phase. Treatment with hydration, calcitonin, and zoledronic acid lead to control of his symptoms and normalization of his serum calcium levels. After discharged, the patient was maintained on palliative treatment and zoledronic acid management without new episodes of hypercalcemia. However, eight months later, the patient died. CONCLUSIONS Evidence from the literature demonstrates a highly variable clinical presentation of CML-associated hypercalcemia, commonly occurring during an accelerated or a blast phase, and associated with poor survival. Multiple mechanisms could be involved and are not exclusive of each other. Better understanding of the pathophysiologic mechanisms involved in CML-associated hypercalcemia could lead to improvement in clinical and laboratory evaluation of these patients and be the foundation for the development of better management strategies and possibly target-directed therapy to positively improve prognosis.
Topics: Blast Crisis; Bone Density Conservation Agents; Calcitonin; Diphosphonates; Disease Progression; Drug Therapy, Combination; Fatal Outcome; Humans; Hypercalcemia; Imidazoles; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Zoledronic Acid
PubMed: 28239141
DOI: 10.12659/ajcr.902467 -
Leukemia Research Oct 2018
Topics: Blast Crisis; Central Nervous System Neoplasms; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 30243134
DOI: 10.1016/j.leukres.2018.08.013 -
Cytometry. Part B, Clinical Cytometry May 2021Inconclusive knowledge persists regarding the course of chronic myeloid leukemia-chronic phase (CML-CP) patients with detectable abnormal blasts by flow-cytometry at...
Sudden blast phase in pediatric chronic myeloid leukemia-chronic phase with abnormal lymphoid blasts detected by flow cytometry at diagnosis: Can it be considered a warning sign?
BACKGROUND
Inconclusive knowledge persists regarding the course of chronic myeloid leukemia-chronic phase (CML-CP) patients with detectable abnormal blasts by flow-cytometry at diagnosis. The 2016 WHO classification is not specific regarding sub-classification of CML with <10% abnormal B-lymphoid blasts (ABLB), and suggests these patients often show rapid progression. We report the clinical course of pediatric CML-CP patients who had detectable abnormal blasts by flow-cytometry at baseline.
METHODS
Retrospective audit of all pediatric CML patients between January 2013 and December 2017 were included. Their clinical presentation, demographic profile, and treatment outcomes were extracted from electronic medical records. Some of these patients got flow-cytometry done by default, though it was not a routine part of diagnostic CML marrow studies.
RESULTS
Amongst 65 pediatric CML patients, flow-cytometry at initial diagnosis was available in 15 (CP-12; AP-3). Of the 12 CML-CP patients, 10 (83%) had abnormal flow-cytometric findings-5 (50%) with mixed lineage blasts (4-B/Myeloid, 1-B/T/Myeloid), and myeloid lineage blasts in the remaining 5 (50%). At a median follow-up of 26 months (range: 9-34 months), 3/5 patients with ABLB at diagnosis progressed to frank blast crisis (2 B-cell; 1 Mixed lineage). None among the five patients with diagnostic myeloid-alone aberrant blasts progressed to blast crisis. Imatinib resistant mutation was also found in 3/5 (60%) CML-CP patients with these ABLB at baseline.
CONCLUSIONS
Although a retrospective study with limited sample size, presence of ABLB detected on flow-cytometry in CML-CP patients, had a noticeable early conversion to CML-BC in our cohort. Incorporation of flow-cytometry in diagnostic work-up can provide useful insight regarding the behavior of pediatric CML-CP patients and guide therapy.
Topics: Adolescent; B-Lymphocytes; Blast Crisis; Cell Count; Child; Child, Preschool; Female; Flow Cytometry; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocytes; Lymphocytes; Male; Retrospective Studies
PubMed: 33030302
DOI: 10.1002/cyto.b.21958 -
American Journal of Hematology Nov 2020Treatment of advanced-phase chronic myeloid leukemia (CML) remains unsatisfactory. Single-agent tyrosine kinase inhibitors have modest and short-lived activity in this... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment of advanced-phase chronic myeloid leukemia (CML) remains unsatisfactory. Single-agent tyrosine kinase inhibitors have modest and short-lived activity in this setting. We conducted a phase I/II study to determine safety and efficacy of the combination of dasatinib and decitabine in patients with advanced CML. Two different dose schedules were investigated with a starting decitabine dose of either 10 mg/m or 20 mg/m daily for 10 days plus dasatinib 100 mg daily. The target dose level was decitabine 10 mg/m or 20 mg/m daily for 10 days plus dasatinib 140 mg daily. Thirty patients were enrolled, including seven with accelerated-phase CML, 19 with blast-phase CML, and four with Philadelphia-chromosome positive acute myeloid leukemia. No dose-limiting toxicity was observed at the starting dose level with either schedule. Grade ≥3 treatment emergent hematological adverse events were reported in 28 patients. Thirteen patients (48%) achieved a major hematologic response and six (22%) achieved a minor hematologic response, with 44% of these patients achieving a major cytogenetic response and 33% achieving a major molecular response. Median overall survival (OS) was 13.8 months, with significantly higher OS among patients who achieved a hematologic response compared to non-responders (not reached vs 4.65 months; P < .001). Decitabine plus dasatinib is a safe and active regimen in advanced CML. Further studies using this combination are warranted.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Dasatinib; Decitabine; Disease-Free Survival; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Middle Aged; Survival Rate
PubMed: 32681739
DOI: 10.1002/ajh.25939 -
Indian Journal of Cancer 2014Imatinib is a bcr-abl tyrosine kinase inhibitor which has revolutionized the treatment for chronic myeloid leukemia (CML). Even though there is much data on CML chronic...
INTRODUCTION
Imatinib is a bcr-abl tyrosine kinase inhibitor which has revolutionized the treatment for chronic myeloid leukemia (CML). Even though there is much data on CML chronic phase, there is limited data on imatinib-naοve advanced phase CML.
MATERIALS AND METHODS
We retrospectively analysed 90 patients with advanced phase CML (accelerated phase [AP]: 51 and blast crisis [BC]: 39), patients who received imatinib as frontline therapy.
RESULTS
The median age of presentation in CML-AP and CML-BC were 32 years (12-61) and 39 years (8-59), respectively. Imatinib at 600 mg/day was initiated within 2 weeks of diagnosis. Median time to complete hematological response in both CML-AP and CML-BC was 3 months (CML-AP: 1-9 months and CML-BC: 1-14 months). At 6 months 30 (59%) CML-AP and 15 (38%) CML-BC patients achieved major cytogenetic response (MCyR), of them 24 (47%) and 10 (25.6%) being the complete cytogenetic response, respectively. At a median follow-up of 41 months, the median overall survival in CML-AP was 61 months, but in CML-BC it was 14 months. The median progression-free survival and event-free survival were 30 months and 23 months in CML-AP and 14 and 12 months in CML-BC, respectively. On univariate analysis, performance status (PS), spleen size, and MCyR predicted survival in AP, whereas in BC, platelet count, PS, and early MCyR were predictive. Non-hematologic and hematologic adverse events were observed in 80% and 60% of patients, respectively. Dose was reduced in 10% of patients for grade IV toxicity and interrupted in 30% for grade III toxicity.
CONCLUSION
Front-line imatinib is an option in advanced phases of CML especially in CML-AP in low-resource countries, where stem cell transplantation and alternate TKIs are not available.
Topics: Adolescent; Adult; Antineoplastic Agents; Benzamides; Blast Crisis; Child; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Neoplasm Staging; Piperazines; Prognosis; Pyrimidines; Remission Induction; Retrospective Studies; Survival Rate; Young Adult
PubMed: 24947087
DOI: 10.4103/0019-509X.134598 -
Blood Dec 2009
Topics: Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Female; Humans; Leukapheresis; Leukemia, Myeloid, Acute; Middle Aged
PubMed: 20050125
DOI: 10.1182/blood-2009-03-212936