Chronic Myeloid Leukemia, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome resulting from a reciprocal translocation between chromosomes 9 and 22 [t9;22] that gives rise to a BCR::ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase in developed countries. Tyrosine kinase inhibitor (TKI) therapy is a highly effective treatment option for patients with chronic phase-CML. The primary goal of TKI therapy in patients with chronic phase-CML is to prevent disease progression to accelerated phase-CML or blast phase-CML. Discontinuation of TKI therapy with careful monitoring is feasible in selected patients. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase-CML.

Epithelioid neoplasm of the spinal cord in a child with spinal muscular atrophy treated with onasemnogene abeparvovec.

Spinal muscular atrophy is an autosomal recessive disease resulting in motor neuron degeneration and progressive life-limiting motor deficits when untreated. Onasemnogene abeparvovec is an adeno-associated virus serotype 9-based gene therapy that improves survival, motor function, and motor milestone achievement in symptomatic and presymptomatic patients. Although the adeno-associated virus genome is maintained as an episome, theoretical risk of tumorigenicity persists should genomic insertion occur. We present the case of a 16-month-old male with spinal muscular atrophy who was diagnosed with an epithelioid neoplasm of the spinal cord approximately 14 months after receiving onasemnogene abeparvovec. In situ hybridization analysis detected an onasemnogene abeparvovec nucleic acid signal broadly distributed in many but not all tumor cells. Integration site analysis on patient formalin-fixed, paraffin-embedded tumor samples failed to detect high-confidence integration sites of onasemnogene abeparvovec. The finding was considered inconclusive because of limited remaining tissue/DNA input. The improved life expectancy resulting from innovative spinal muscular atrophy therapies, including onasemnogene abeparvovec, has created an opportunity to analyze the long-term adverse events and durability of these therapies as well as identify potential disease associations that were previously unrecognized because of the premature death of these patients.

Prenatal diagnosis of Poland-Möbius syndrome by multimodality fetal imaging.

We describe prenatal diagnosis of Poland-Möbius syndrome using a combination of ultrasound and MRI. Poland syndrome was diagnosed based on absence of the pectoralis muscles associated with dextroposition of the fetal heart and elevation of the left diaphragm. Associated brain anomalies that led to the diagnosis of Poland-Möbius syndrome, included ventriculomegaly, hypoplastic cerebellum, tectal beaking, and a peculiar flattening of the posterior aspect of the pons and medulla oblongata, which has been reported by postnatal diffusion tensor imaging studies as a reliable neuroimaging marker for Möbius syndrome. Since abnormalities of cranial nerves VI and VII may be difficult to detect prenatally, careful attention to the appearance of the brain stem as illustrated in the current report may aid in the prenatal diagnosis of Möbius syndrome.

Data Quality Assessment for Super-Resolution Fetal Brain MR Imaging: A Retrospective 1.5 T Study.

BACKGROUND: Super-resolution is a promising technique to create isotropic image volumes from stacks of two-dimensional (2D) motion-corrupted images in fetal magnetic resonance imaging (MRI). PURPOSE: To determine an acquisition quality metric and correlate that metric with radiologist perception of three-dimensional (3D) image quality. STUDY TYPE: Retrospective. SUBJECTS: Eighty-seven patients, mean gestational age 29 ± 6 weeks. FIELD STRENGTH/SEQUENCE: 1.5 T/2D fast spin-echo. ASSESSMENT: Four radiologists (L.G., D.M.E.B., P.C., and J.V.; 31, 21, 7, and 7 years' experience, respectively) graded reconstructions on a 0 to 4 scale for overall appearance and visibility of specific anatomy. During reconstruction, slices were labeled as inliers based on correlation between a simulated vs. actual acquisition. The fraction of brain voxels in inlier slicers vs. total brain voxels was measured for each acquisition. STATISTICAL TESTS: Paired sample t test, Pearson's correlation, intra-class correlation. RESULTS: The average brain mask inlier fraction for all acquisitions was 0.8. There was a statistically significant correlation (0.71) between overall reconstruction appearance and number of acquisitions with inlier fraction above 0.73. There was low correlation (0.21, P = 0.05) between the number of acquisitions used in the reconstruction and overall score when no data quality measure was considered. Similar results were found for ratings of specific anatomy. Statistically significant differences in overall perception of image quality were found when using three vs. four, four vs. five, and three vs. five high-quality acquisitions in the reconstruction. Five high-quality acquisitions were sufficient to yield an average radiologist rating of 3.59 out of 4.0 for overall image quality. DATA CONCLUSION: Reconstruction quality can be reliably predicted using the brain mask inlier fraction. Real-time super-resolution protocols could exploit this to terminate acquisition when enough high-quality acquisitions have been collected. To achieve consistent 3D image quality it may be necessary to acquire more than five scans to compensate for severely motion-corrupted acquisitions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: 1.

Relating anthropometric indicators to brain structure in 2-month-old Bangladeshi infants growing up in poverty: A pilot study.

Anthropometric indicators, including stunting, underweight, and wasting, have previously been associated with poor neurocognitive outcomes. This link may exist because malnutrition and infection, which are known to affect height and weight, also impact brain structure according to animal models. However, a relationship between anthropometric indicators and brain structural measures has not been tested yet, perhaps because stunting, underweight, and wasting are uncommon in higher-resource settings. Further, with diminished anthropometric growth prevalent in low-resource settings, where biological and psychosocial hazards are most severe, one might expect additional links between measures of poverty, anthropometry, and brain structure. To begin to examine these relationships, we conducted an MRI study in 2-3-month-old infants growing up in the extremely impoverished urban setting of Dhaka, Bangladesh. The sample size was relatively small because the challenges of investigating infant brain structure in a low-resource setting needed to be realized and resolved before introducing a larger cohort. Initially, fifty-four infants underwent T1 sequences using 3T MRI, and resulting structural images were segmented into gray and white matter maps, which were carefully evaluated for accurate tissue labeling by a pediatric neuroradiologist. Gray and white matter volumes from 29 infants (79 â€‹± â€‹10 days-of-age; F/M â€‹= â€‹12/17), whose segmentations were of relatively high quality, were submitted to semi-partial correlation analyses with stunting, underweight, and wasting, which were measured using height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) scores. Positive semi-partial correlations (after adjusting for chronological age and sex and correcting for multiple comparisons) were observed between white matter volume and HAZ and WAZ; however, WHZ was not correlated with any measure of brain volume. No associations were observed between income-to-needs or maternal education and brain volumetric measures, suggesting that measures of poverty were not associated with total brain tissue volume in this sample. Overall, these results provide the first link between diminished anthropometric growth and white matter volume in infancy. Challenges of conducting a developmental neuroimaging study in a low-resource country are also described.

Imaging of fetal brain tumors.

Congenital brain tumors, defined as those diagnosed prenatally or within the first 2 months of age, represent less than 2% of pediatric brain tumors. Their location, prevalence and pathophysiology differ from those of tumors that develop later in life. Imaging plays a crucial role in diagnosis, tumor characterization and treatment planning. The most common lesions diagnosed in utero are teratomas, followed by gliomas, choroid plexus papillomas and craniopharyngiomas. In this review, we summarize the pathogenesis, diagnosis, management and prognosis of the most frequent fetal brain tumors.

Predictors of a drainable suppurative adenitis among children presenting with cervical adenopathy.

OBJECTIVES: We sought to identify predictors for a drainable suppurative adenitis [DSA] among patients presenting with acute cervical lymphadenitis. METHODS: A retrospective cross sectional study of all patients admitted to an urban pediatric tertiary care emergency department over a 15 year period. Otherwise healthy patients who underwent imaging for an evaluation of cervical lymphadenitis were included. Cases were identified using a text-search module followed by manual review. We excluded immunocompromised patients and those with lymphadenopathy felt to be not directly infected (i.e. reactive) or that was not acute (symptom duration >28 days). Data collected included: age, gender, duration of symptoms, highest recorded temperature, physical exam findings, laboratory and imaging results, and surgical findings. A DSA was defined as >1.5 cm in diameter on imaging. We performed binary logistic regression to determine independent clinical predictors of a DSA. RESULTS: Three hundred sixty-one patients met inclusion criteria. Three hundred six patients (85%) had a CT scan, 55 (15%) had an ultrasound and 33 (9%) had both. DSA was identified in 71 (20%) patients. Clinical features independently associated with a DSA included absence of clinical pharyngitis, WBC >15,000/mm3, age ≤3 years, anterior cervical chain location, largest palpable diameter on exam >3 cm and prior antibiotic treatment of >24 h. The presence of fever, skin erythema, or fluctuance on examination, was not found to be predictive of DSA. CONCLUSIONS: We identified independent predictors of DSA among children presenting with cervical adenitis. Risk can be stratified into risk groups based on these clinical features.

Pediatric NUT-midline carcinoma: Therapeutic success employing a sarcoma based multimodal approach.

A subset of poorly differentiated squamous cell carcinomas, NUT midline carcinomas (NMC) are characterized by a translocation t(15;19)(q13;p13) [ 1 ]. The prognosis is generally dismal [ 2 ] and therapeutic success has been limited to exceptional cases [ 3 ]. We present two cases of pediatric NMC from two different institutions treated according to a multimodal sarcoma approach involving surgery, chemotherapy, and focal radiotherapy. One patient has remained in complete continuous remission for over 6 years, while the other is in CR in early follow-up off therapy. Our proposed multimodal strategy apparently meets the aggressive biologic nature of NMC and should be considered for further evaluation in this context potentially in the setting of a clinical trial.

Comorbidities, Alcohol Use Disorder, and Age Predict Outcomes after Autologous Hematopoietic Cell Transplantation for Lymphoma.

Autologous hematopoietic cell transplantation (HCT) is a treatment option for many patients diagnosed with lymphoma. The effects of patient-specific factors on outcomes after autologous HCT are not well characterized. Here, we studied a sequential cohort of 754 patients with lymphoma treated with autologous HCT between 2000 and 2010. In multivariate analysis, patient-specific factors that were statistically significantly associated with nonrelapse mortality (NRM) included HCT-specific comorbidity index (HCT-CI) scores ≥ 3 (HR, 1.94; P = .05), a history of alcohol use disorder (AUD) (HR, 2.17; P = .004), and older age stratified by decade (HR, 1.29; P = .02). HCT-CI ≥ 3, a history of AUD, and age > 50 were combined into a composite risk model: NRM and overall mortality rates at 5 years increased from 6% to 30% and 32% to 58%, respectively, in patients with 0 versus all 3 risk factors. The HCT-CI is a valid tool in predicting mortality risks after autologous HCT for lymphoma. AUD and older age exert independent prognostic impact on outcomes. Whether AUD indicates additional organ dysfunction or sociobehavioral abnormality warrants further investigation. The composite model may improve risk stratification before autologous HCT.

Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation.

Pretransplant values of serum ferritin, albumin, and peripheral blood counts were previously suggested to provide prognostic information about hematopoietic cell transplantation (HCT) outcomes. Whether these "biomarkers" have prognostic value independent of each other and the HCT-comorbidity index (HCT-CI) is unknown. We analyzed data from 3917 allogeneic HCT recipients at multiple sites in the United States and Italy using multivariate models including each biomarker and the HCT-CI. Data from all sites were then randomly divided into a training set (n = 2352) to develop weights for the relevant biomarkers to be added to the HCT-CI scores and a validation set (n = 1407) to validate an augmented HCT-CI compared with the original index. Multivariate analysis with data from one site showed that ferritin, albumin, and platelets-not neutrophils or hemoglobin-were independently associated with increased nonrelapse mortality (NRM) and decreased overall survival. Findings were validated in data from the other sites. Subsequently, in a training set from all sites, ferritin >2500 mg/dL (hazard ratio [HR], 1.69); albumin 3 to 3.5 g/dL (HR, 1.61) and <3.0 g/dL (HR, 2.27); and platelets 50 to <100,000 (HR, 1.28), 20 to <50,000 (HR, 1.29), and <20,000 (HR, 1.55) were statistically significantly associated with NRM. Weights were assigned to these laboratory values following the same equation used to design the original index. In the validation set, the addition of the biomarkers to the original index to develop an augmented HCT-CI resulted in a statistically significant increase in a higher c-statistic estimate for prediction of NRM (P = .0007). Ferritin, albumin, and platelet counts are important prognostic markers that further refine the discriminative power of the HCT-CI for transplant outcomes.

Long-term sustained disease control in patients with mantle cell lymphoma with or without active disease after treatment with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

BACKGROUND: Previously, early results were reported for allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with 2 Gy of total body irradiation with or without fludarabine and/or rituximab in 33 patients with mantle cell lymphoma (MCL). METHODS: This study examined the outcomes of 70 patients with MCL and included extended follow-up (median, 10 years) for the 33 initial patients. Grafts were obtained from human leukocyte antigen (HLA)-matched, related donors (47%), unrelated donors (41%), and HLA antigen-mismatched donors (11%). RESULTS: The 5-year incidence of nonrelapse mortality was 28%. The relapse rate was 26%. The 5-year rates of overall survival (OS) and progression-free survival (PFS) were 55% and 46%, respectively. The 10-year rates of OS and PFS were 44% and 41%, respectively. Eighty percent of surviving patients were off immunosuppression at the last follow-up. The presence of relapsed or refractory disease at the time of HCT predicted a higher rate of relapse (hazard ratio [HR], 2.94; P = .05). Despite this, OS rates at 5 (51% vs 58%) and 10 years (43% vs 45%) were comparable between those with relapsed/refractory disease and those undergoing transplantation with partial or complete remission. A high-risk cytomegalovirus (CMV) status was the only independent predictor of worse OS (HR, 2.32; P = .02). A high-risk CMV status and a low CD3 dose predicted PFS (HR, 2.22; P = .03). CONCLUSIONS: Nonmyeloablative allogeneic HCT provides a long-term survival benefit for patients with relapsed MCL, including those with refractory disease or multiple relapses.

Pre-transplant comorbidity burden and post-transplant chronic graft-versus-host disease.

The Haematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) was designed as a predictor of non-relapse mortality after HCT. Chronic graft-versus-host disease (GVHD) contributes to mortality after HCT. Here, we investigated whether the HCT-CI could predict development of chronic GVHD or post-chronic GVHD mortality. We retrospectively analysed data from 2909 patients treated with allogeneic HCT for malignant and non-malignant haematological conditions at four institutions. In Cox regression models adjusted for potential confounders, increasing HCT-CI was not statistically significantly associated with the development of chronic GVHD [hazard ratio (HR) = 1·02, P = 0·34]. Yet, the index was associated with an increased risk of non-relapse mortality (HR = 1·29, P < 0·0001) as well as overall mortality (HR = 1·25, P < 0·001) following the development of chronic GVHD. The association between HCT-CI and post-chronic GVHD mortality was similar regardless of donor type or stem cell source. HCT-CI scores could be incorporated in the design of clinical trials for treatment of chronic GVHD.

As good as it gets? Managing risks of cardiovascular disease in California's top-performing physician organizations.

BACKGROUND: The California Right Care Initiative (RCI) accelerates the adoption of evidence-based guidelines and improved care management practices for conditions for which the gap between science and practice is significant, resulting in preventable disability and death. METHODS: Medical directors and quality improvement leaders from 11 of the 12 physician organizations that met the 2010 national 90th percentile performance benchmarks for control of hyperlipidemia and glycated hemoglobin in 2011 were interviewed in 2012. Interviews, as well as surveys, assessed performance reporting and feedback to individual physicians; medication management protocols; team-based care management; primary care team huddles; coordination of care between primary care clinicians and specialists; implementation of shared medical appointments; and telephone visits for high-risk patients. RESULTS: All but 1 of 11 organizations implemented electronic health records. Electronic information exchange between primary care physicians and specialists, however, was uncommon. Few organizations routinely used interdisciplinary team approaches, shared medical appointments, or telephonic strategies for managing cardiovascular risks among patients. Implementation barriers included physicians' resistance to change, limited resources and reimbursement for team approaches, and limited organizational capacity for change. Implementation facilitators included routine use of reliable data to guide improvement, leadership facilitation of change, physician buy-in, health information technology use, and financial incentives. CONCLUSION: To accelerate improvements in managing cardiovascular risks, physician organizations may need to implement strategies involving extensive practice reorganization and work flow redesign.

Incidence and geographic distribution of adult acute leukemia in the state of Georgia.

OBJECTIVE: We investigated an apparent increase in acute lymphoblastic leukemia (ALL) referrals from northern Georgia to a tertiary care center located in Atlanta. METHODS: Cases reported to the Georgia Comprehensive Cancer Registry and the national Surveillance Epidemiology and End Results cancer registry between 1999 and 2008 were analyzed. Age-adjusted incidence rates were calculated for all of the counties and public health regions and were compared with national rates calculated using Surveillance Epidemiology and End Results 17 data. Cases of adult acute myeloid leukemia served as controls. RESULTS: Age-adjusted incidence rates of adult ALL (0.8/100,000) and acute myeloid leukemia (4.6/100,000) were comparable to the national rates (0.9 and 5.2, respectively). The age-adjusted incidence rate of ALL in northern Georgia was 1.1 (95% confidence interval 0.8-1.5) and was not affected by race. CONCLUSIONS: The observed increase in cases of ALL at our tertiary center results from a referral pattern rather than heterogeneous distribution of adult ALL across Georgia.

Transplantation for myelodysplastic syndromes 2013.

PURPOSE OF REVIEW: The only current treatment capable of curing patients with myelodysplastic syndromes (MDS) is allogeneic haematopoietic stem cell transplantation (HCT). However, many MDS patients are older, often with substantial comorbid conditions, and the disease is heterogeneous. As a consequence, results of HCT vary considerably, and the practices of HCT for MDS are evolving. RECENT FINDINGS: The newly published modified International Prognostic Scoring System (IPSS-R), developed for nontransplanted patients, also correlates with post-HCT outcome, with the patient's karyotype having the strongest impact. The presence of monosomal karyotype and various genetic and molecular markers have also been shown to have a prognostic value. The use of hypomethylating agents, before or after HCT, may reduce the post-HCT relapse risk or delay relapse. Low and reduced-intensity conditioning regimens have allowed to transplant growing numbers of older patients with MDS, and the development of novel regimens may lead to improved relapse-free survival even in patients with high-risk cytogenetics. The optimal stem cell source may differ for different patient populations and different disease risk categories. SUMMARY: Transplant results for MDS have improved in recent years. Some patients even in the eighth decade of life have been transplanted successfully. Ongoing studies are aimed at further reducing transplant-related toxicity, graft-versus-host disease and post-HCT relapse.

The Sensitivity of Limited-Sequence MRI in Identifying Pediatric Cervical Spine Injury: A Western Pediatric Surgery Research Consortium Multicenter Retrospective Cohort Study.

INTRODUCTION: Clinical clearance of a child's cervical spine after trauma is often challenging due to impaired mental status or an unreliable neurologic examination. Magnetic resonance imaging (MRI) is the gold standard for excluding ligamentous injury in children but is constrained by long image acquisition times and frequent need for anesthesia. Limited-sequence MRI (LSMRI) is used in evaluating the evolution of traumatic brain injury and may also be useful for cervical spine clearance while potentially avoiding the need for anesthesia. The purpose of this study was to assess the sensitivity and negative predictive value of LSMRI as compared to gold standard full-sequence MRI as a screening tool to rule out clinically significant ligamentous cervical spine injury. METHODS: We conducted a ten-center, five-year retrospective cohort study (2017-2021) of all children (0-18y) with a cervical spine MRI after blunt trauma. MRI images were re-reviewed by a study pediatric radiologist at each site to determine if the presence of an injury could be identified on limited sequences alone. Unstable cervical spine injury was determined by study neurosurgeon review at each site. RESULTS: We identified 2,663 children less than 18 years of age who underwent an MRI of the cervical spine with 1,008 injuries detected on full-sequence studies. The sensitivity and negative predictive value of LSMRI were both >99% for detecting any injury and 100% for detecting any unstable injury. Young children (age < 5 years) were more likely to be electively intubated or sedated for cervical spine MRI. CONCLUSION: LSMRI is reliably detects clinically significant ligamentous injury in children after blunt trauma. To decrease anesthesia use and minimize MRI time, trauma centers should develop LSMRI screening protocols for children without a reliable neurologic exam. LEVEL OF EVIDENCE: 2 (Diagnostic Tests or Criteria).

Outpatient management following intensive induction or salvage chemotherapy for acute myeloid leukemia.

Adults with newly diagnosed or relapsed acute myeloid leukemia (AML) commonly receive intensive chemotherapy to achieve disease remission. In the United States and many other countries, it is standard practice that these patients remain hospitalized "preemptively" until blood count recovery, owing to the risk for overwhelming infections and bleeding during pancytopenia. This care policy requires hospitalization for an average of 3 to 4 weeks after completion of chemotherapy. However, highly effective oral prophylactic antimicrobials are now available, and transfusion support of outpatients has become routine in recent years. As a result, the care of patients with hematologic malignancies treated with intensive modalities is increasingly shifting from inpatient to outpatient settings. Benefits of this shift could include the reduced need for medical resources (eg, transfusions or intravenous antimicrobial therapy), improved quality of life (QOL), decreased rates of nosocomial infections, and lower costs. Increasing evidence indicates that select AML patients undergoing intensive remission induction or salvage chemotherapy can be discharged early after completion of chemotherapy and followed closely in a well-equipped outpatient facility in a safe and costeffective manner. Further demonstration that the current approach of preemptive hospitalization is medically unjustified, economically more burdensome, and adversely affects health-related QOL would very likely change the management of these patients throughout this country and elsewhere, resulting in the establishment of a new standard practice that improves cancer care.

Imaging of Pediatric Cervical Lymphadenopathy.

There is a wide variety of disease entities in children, which can present with cervical adenopathy. The spectrum of pathology and imaging appearance differs in many cases from that seen in adults. This review aims to compare the strengths and limitations of the various imaging modalities available to image pediatric patients presenting with cervical adenopathy, provide guidance on when to image, and highlight the imaging appearance of both common and uncommon disorders affecting the cervical nodes in children to aid the radiologist in their clinical practice.