Publications by authors named "Natasha Archer"

24 Publications

  • Page 1 of 1

A call to start hydroxyurea by 6 months of age and before the advent of sickle cell disease complications.

Pediatr Blood Cancer 2021 Nov 24:e29423. Epub 2021 Nov 24.

Pediatric Hematology and Oncology, Boston Children's Hospital, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1002/pbc.29423DOI Listing
November 2021

Will the changing therapeutic landscape meet the needs of patients with sickle cell disease?

Lancet Haematol 2021 05 7;8(5):e306-e307. Epub 2021 Apr 7.

Department of Pediatric Hematology and Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1016/S2352-3026(21)00098-3DOI Listing
May 2021

A systematic review of ketamine for the management of vaso-occlusive pain in sickle cell disease.

Pediatr Blood Cancer 2021 07 31;68(7):e28989. Epub 2021 Mar 31.

Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.

Vaso-occlusive episodes (VOEs) are a common complication of sickle cell disease (SCD) and a significant cause of morbidity. Managing VOE pain can be difficult and complex. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been used to manage VOE pain. This systematic literature review synthesizes research published from 2010 to 2020 on the use of ketamine infusion to decrease VOE pain. The review demonstrates that ketamine, a safe and effective treatment for VOE pain, could be considered more widely. However, the significant variability among published clinical studies with regard to dosing, timing of initiation, duration of infusion, and timing of discontinuation highlights the need for standardized ketamine infusion protocols for the management of VOE pain. We conclude with a brief discussion of key components of a potential standardized protocol supported by the literature reviewed as well as areas for future investigation.
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http://dx.doi.org/10.1002/pbc.28989DOI Listing
July 2021

Autoimmune hemolytic anemia complicated by parvovirus infection.

Blood 2021 02;137(8):1130

Dana-Farber/Boston Children's Hospital Blood Disorders and Cancer Center.

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http://dx.doi.org/10.1182/blood.2020009849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907726PMC
February 2021

End the pain: Start with antiracism.

Am J Hematol 2021 01 11;96(1):4-6. Epub 2020 Nov 11.

Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts.

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http://dx.doi.org/10.1002/ajh.26032DOI Listing
January 2021

Association of Blood Type With Postsurgical Mucosal Bleeding in Pediatric Patients Undergoing Tonsillectomy With or Without Adenoidectomy.

JAMA Netw Open 2020 03 2;3(3):e201804. Epub 2020 Mar 2.

Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts.

Importance: Blood type (BT) O has been identified as a risk factor for bleeding complications, while non-O BTs may increase risk for thromboembolic events. Limited data are available in children undergoing tonsillectomy with or without adenoidectomy.

Objective: To determine whether BT O is associated with hemorrhage after tonsillectomy with or without adenoidectomy.

Design, Setting, And Participants: Retrospective cohort study of patients younger than 22 years who underwent tonsillectomy with or without adenoidectomy at a single institution between January 1, 2008, and August 7, 2017. Statistical analysis was performed from November 2017 to January 2019.

Main Outcomes And Measures: Prevalence of hemorrhage following surgery was defined as any bleeding requiring cauterization up to 1 month after the procedure. Data on sex, age, von Willebrand disease (VWD) status, BT, white blood cell counts, and platelet counts closest to date of surgery were collected from an electronic medical record system, and the association of these factors with hemorrhage following surgery was investigated.

Results: A total of 14 951 pediatric patients (median [range] age, 5.6 [0.8-21.9] years; 6956 [46.5%] female) underwent tonsillectomy with or without adenoidectomy. Prevalence of hemorrhage following the procedure was 3.9% (578 patients) for the full cohort and 2.8% (362 of 13 065) for patients with no BT identified or preprocedure VWD panel results at baseline. Children who had a BT identified and/or a VWD panel before surgery had higher bleeding rates (BT only, 14.9% [172 of 1156]; preprocedure VWD panel only, 4.6% [28 of 607]; and BT and preprocedure VWD panel, 13.0% [16 of 123]), all of which were significantly different from the baseline bleeding rate (P < .001). While the bleeding rates in children with BT O were not statistically different from those with non-O BT (14.8% and 14.6%, respectively; P > .99), mean von Willebrand factor values were statistically different (mean [SD] von Willebrand factor antigen level in O group, 86.9 [42.4] IU/dL in the O group vs 118.0 [53.8] IU/dL in the non-O group; P = .002; and mean [SD] von Willebrand factor ristocetin-cofactor in the O group, 72.2 [44.3] IU/dL vs 112.6 [68.0] IU/dL in the non-O group; P = .001). In addition, children older than 12 years had increased bleeding rates in the full cohort (8.3% vs 3.2%), in the testing-naive cohort (6.5% vs 2.3%), and in those with a preprocedure VWD panel only (13.5% vs 3.1%) compared with children aged 12 years or younger.

Conclusions And Relevance: Type O blood was not a risk factor associated with hemorrhage after tonsillectomy with or without adenoidectomy despite lower baseline von Willebrand factor antigen and von Willebrand factor ristocetin-cofactor values in children with BT O vs those with non-O BT in our study cohort. No association was found between VWD status and bleeding, and there was no difference in VWD panel values in those who experienced hemorrhage vs those who did not within BT groups. Further studies elucidating the utility of von Willebrand factor values for children undergoing tonsillectomy with or without adenoidectomy are needed.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.1804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109594PMC
March 2020

Fetal hemoglobin does not inhibit growth.

Blood Adv 2019 07;3(14):2149-2152

Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA.

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http://dx.doi.org/10.1182/bloodadvances.2019000399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650726PMC
July 2019

Erythrocyte ion content and dehydration modulate maximal Gardos channel activity in KCNN4 V282M/+ hereditary xerocytosis red cells.

Am J Physiol Cell Physiol 2019 08 15;317(2):C287-C302. Epub 2019 May 15.

Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.

Hereditary xerocytosis (HX) is caused by missense mutations in either the mechanosensitive cation channel PIEZO1 or the Ca-activated K channel KCNN4. All HX-associated KCNN4 mutants studied to date have revealed increased current magnitude and red cell dehydration. Baseline KCNN4 activity was increased in HX red cells heterozygous for KCNN4 mutant V282M. However, HX red cells maximally stimulated by Ca ionophore A23187 or by PMCA Ca-ATPase inhibitor orthovanadate displayed paradoxically reduced KCNN4 activity. This reduced Ca-stimulated mutant KCNN4 activity in HX red cells was associated with unchanged sensitivity to KCNN4 inhibitor senicapoc and KCNN4 activator Ca, with slightly elevated Ca uptake and reduced PMCA activity, and with decreased KCNN4 activation by calpain inhibitor PD150606. The altered intracellular monovalent cation content of HX red cells prompted experimental nystatin manipulation of red cell Na and K contents. Nystatin-mediated reduction of intracellular K with corresponding increase in intracellular Na in wild-type cells to mimic conditions of HX greatly suppressed vanadate-stimulated and A23187-stimulated KCNN4 activity in those wild-type cells. However, conferral of wild-type cation contents on HX red cells failed to restore wild-type-stimulated KCNN4 activity to those HX cells. The phenotype of reduced, maximally stimulated KCNN4 activity was shared by HX erythrocytes expressing heterozygous PIEZO1 mutants R2488Q and V598M, but not by HX erythrocytes expressing heterozygous KCNN4 mutant R352H or PIEZO1 mutant R2456H. Our data suggest that chronic KCNN4-driven red cell dehydration and intracellular cation imbalance can lead to reduced KCNN4 activity in HX and wild-type red cells.
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http://dx.doi.org/10.1152/ajpcell.00074.2019DOI Listing
August 2019

Resistance to in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition.

Proc Natl Acad Sci U S A 2018 07 26;115(28):7350-7355. Epub 2018 Jun 26.

Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115;

Sickle cell trait (AS) confers partial protection against lethal malaria. Multiple mechanisms for this have been proposed, with a recent focus on aberrant cytoadherence of parasite-infected red blood cells (RBCs). Here we investigate the mechanistic basis of AS protection through detailed temporal mapping. We find that parasites in AS RBCs maintained at low oxygen concentrations stall at a specific stage in the middle of intracellular growth before DNA replication. We demonstrate that polymerization of sickle hemoglobin (HbS) is responsible for this growth arrest of intraerythrocytic parasites, with normal hemoglobin digestion and growth restored in the presence of carbon monoxide, a gaseous antisickling agent. Modeling of growth inhibition and sequestration revealed that HbS polymerization-induced growth inhibition following cytoadherence is the critical driver of the reduced parasite densities observed in malaria infections of individuals with AS. We conclude that the protective effect of AS derives largely from effective sequestration of infected RBCs into the hypoxic microcirculation.
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http://dx.doi.org/10.1073/pnas.1804388115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048551PMC
July 2018

Knowledge of Blood Group Decreases von Willebrand Factor Panel Testing in Children.

Hemasphere 2017 12 20;1(1):e3. Epub 2017 Dec 20.

Laboratory Medicine, Boston Children's Hospital, Boston, MA.

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http://dx.doi.org/10.1097/HS9.0000000000000003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745975PMC
December 2017

Pediatric sialoblastoma: Evaluation and management.

Int J Pediatr Otorhinolaryngol 2016 Aug 29;87:44-9. Epub 2016 Apr 29.

Department of Otolaryngology and Communication Enhancement, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Otolaryngology, Harvard School of Medicine, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address:

Objectives: Sialoblastoma is a rare congenital salivary gland tumor of epithelial origin. The objectives of this study are to review the literature regarding clinical presentation of sialoblastoma, evaluate the effectiveness of various treatment methods, and present guidelines for evaluation and management in the pediatric population.

Data Sources: Case presentation and literature review.

Review Methods: A comprehensive search was conducted to identify cases of pediatric sialoblastoma in the English-language literature. The presentation, evaluation, and management of reported cases were analyzed. We also report an invasive and recurrent case in a pediatric patient to highlight the aggressive nature of these lesions.

Results: Sixty-two cases of pediatric sialoblastoma were reviewed. The age at initial presentation ranged from before birth to 15 years. The parotid gland was the most common location (n = 47). Surgical excision was the primary treatment in all patients. Nine patients developed metastatic disease of the lung, lymph nodes, or bone. Almost a third of patients had recurrence and over two thirds of patients were tumor-free for at least 1 year following their last treatment intervention.

Conclusion: Prompt and complete surgical excision should be recommended to prevent local and systemic recurrence of pediatric sialoblastoma. Chemotherapy has also shown promise in several cases, and clinical genomics may shed light on more therapy options. Patients should be closely followed for at least 12 months following diagnosis, or longer depending on the histopathological staging of the tumor.
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http://dx.doi.org/10.1016/j.ijporl.2016.04.037DOI Listing
August 2016

Diagnosis of iron-deficient states.

Crit Rev Clin Lab Sci 2015 14;52(5):256-72. Epub 2015 Aug 14.

a Hematology Division and.

The diagnosis of iron deficiency anemia is typically straightforward, especially when classic biochemical and hematological changes are present in a subject at risk. It can be challenging in the presence of diseases or when it is due to inherited defects of iron metabolism. The identification of iron deficiency prior to anemia development is also difficult. New hematological parameters such as reticulocyte Hb content have expanded the classic ones such as MCV, MCH and MCHC. A variety of hematology analyzers now provide novel parameters to assess cellular hypochromia and microcytosis in both reticulocytes and mature red blood cells. The repertoire of biochemical markers has also been expanded, with iron, transferrin and ferritin being supplemented by circulating transferrin receptor and hepcidin. Molecular identification of functional variants of key iron metabolism determinants has provided explanations for the heritability of some iron metabolism biomarkers. Genetic defects in some of these molecules are responsible for hereditary microcytic anemias, also called atypical microcytic anemias. In this review, we examine the most significant hematological and biochemical markers for iron metabolism, as well as relevant genetic polymorphisms and defects affecting iron handling.
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http://dx.doi.org/10.3109/10408363.2015.1038744DOI Listing
May 2016

An Increased Risk of Second Malignant Neoplasms After Rhabdomyosarcoma: Population-Based Evidence for a Cancer Predisposition Syndrome?

Pediatr Blood Cancer 2016 Feb 20;63(2):196-201. Epub 2015 Jul 20.

Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.

Background: Rhabdomyosarcoma survivors have an increased risk of developing second malignant neoplasms (SMN); this risk is traditionally attributed to the effects of multidisciplinary management required for cure. However, the impact of constitutional predisposition has not been properly analyzed.

Methods: We analyzed the risk of SMN among 1,151 children diagnosed with rhabdomyosarcoma and reported to the Surveillance, Epidemiology, and End Results registries (SEER-9) from 1973 to 2010. Standardized incidence ratios (SIR) and corresponding 95% confidence intervals (CI) were calculated using SEERStat 8.1.2.

Results: Children with pleomorphic and embryonal rhabdomyosarcoma had an increased risk of developing a SMN (SIR = 15.77, 95%CI 1.91-56.96 and SIR = 5.6, 95%CI 3.32-8.85, respectively). The risk was age-dependent; the highest was among children <2 years (SIR = 13.38, 95%CI 4.34-31.22) and the lowest was in children >10 years (SIR = 3.35, 95%CI 1.53-6.35). The risk for the youngest patients was higher for those with embryonal rhabdomyosarcoma (SIR = 14.72, 95%CI 4.01-37.70) compared to other histiotypes. Additionally, the risk of SMN was independent of the use of radiation to the primary (SIR = 6.50, 95%CI 3.97-10.03 and SIR = 4.57, 95%CI 2.09-8.68, for children receiving and not receiving radiation, respectively). The pattern of SMN observed was consistent with the Li-Fraumeni spectrum.

Conclusions: Children with rhabdomyosarcoma are at high risk of developing SMN. This risk is higher for a subgroup of young children with pleomorphic and embryonal histologies, and is independent of the use of radiation. This suggests that a subgroup of children with pleomorphic and embryonal rhabdomyosarcoma may have a constitutional cancer predisposition.
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http://dx.doi.org/10.1002/pbc.25678DOI Listing
February 2016

2015 Clinical trials update in sickle cell anemia.

Am J Hematol 2015 Oct;90(10):934-50

Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts.

Polymerization of HbS and cell sickling are the prime pathophysiological events in sickle cell disease (SCD). Over the last 30 years, a substantial understanding at the molecular level has been acquired on how a single amino acid change in the structure of the beta chain of hemoglobin leads to the explosive growth of the HbS polymer and the associated changes in red cell morphology. O2 tension and intracellular HbS concentration are the primary molecular drivers of this process, and are obvious targets for developing new therapies. However, polymerization and sickling are driving a complex network of associated cellular changes inside and outside of the erythrocyte, which become essential components of the inflammatory vasculopathy and result in a large range of potential acute and chronic organ damages. In these areas, a multitude of new targets for therapeutic developments have emerged, with several ongoing or planned new therapeutic interventions. This review outlines the key points of SCD pathophysiology as they relate to the development of new therapies, both at the pre-clinical and clinical levels.
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http://dx.doi.org/10.1002/ajh.24116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752136PMC
October 2015

The utility of the DDAVP challenge test in children with low von Willebrand factor.

Br J Haematol 2015 Sep 2;170(6):884-6. Epub 2015 Mar 2.

Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1111/bjh.13331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558249PMC
September 2015

A diagnostic role for dense cells in sickle cell disease.

Authors:
Natasha M Archer

Proc Natl Acad Sci U S A 2014 Oct 22;111(41):14647-8. Epub 2014 Sep 22.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215

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http://dx.doi.org/10.1073/pnas.1416147111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205654PMC
October 2014

Hereditary xerocytosis revisited.

Am J Hematol 2014 Dec 21;89(12):1142-6. Epub 2014 Jul 21.

Division of Hematology and Oncology, Boston Children's Hospital, Boston, Massachusetts; Dana-Farber Cancer Center, Boston, Massachusetts.

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http://dx.doi.org/10.1002/ajh.23799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237618PMC
December 2014

Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers.

Cancer 2014 Apr 30;120(7):1068-75. Epub 2013 Dec 30.

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/ Oncology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Howard Hughes Medical Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, Massachusetts; Joslin Diabetes Center, Boston, Massachusetts.

Background: Rhabdomyosarcoma (RMS) represents a diverse category of myogenic malignancies with marked differences in molecular alterations and histology. This study examines the question if RMS predisposition due to germline TP53 mutations correlates with certain RMS histologies.

Methods: The histology of RMS tumors diagnosed in 8 consecutive children with TP53 germline mutations was reviewed retrospectively. In addition, germline TP53 mutation analysis was performed in 7 children with anaplastic RMS (anRMS) and previously unknown TP53 status.

Results: RMS tumors diagnosed in 11 TP53 germline mutation carriers all exhibited nonalveolar, anaplastic histology as evidenced by the presence of enlarged hyperchromatic nuclei with or without atypical mitotic figures. Anaplastic RMS was the first malignant diagnosis for all TP53 germline mutation carriers in this cohort, and median age at diagnosis was 40 months (mean, 40 months ± 15 months; range, 19-67 months). The overall frequency of TP53 germline mutations was 73% (11 of 15 children) in pediatric patients with anRMS. The frequency of TP53 germline mutations in children with anRMS was 100% (5 of 5 children) for those with a family cancer history consistent with Li-Fraumeni syndrome (LFS), and 80% (4 of 5 children) for those without an LFS cancer phenotype.

Conclusions: Individuals harboring germline TP53 mutations are predisposed to develop anRMS at a young age. If future studies in larger anRMS cohorts confirm the findings of this study, the current Chompret criteria for LFS should be extended to include children with anRMS irrespective of family history.
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http://dx.doi.org/10.1002/cncr.28507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173134PMC
April 2014

Perspective: postearthquake haiti renews the call for global health training in medical education.

Acad Med 2011 Jul;86(7):889-91

Internal Medicine, Pediatrics, and Global Health Equity, Harvard Medical School, Boston, Massachusetts, USA.

On January 12, 2010, Haiti experienced one of the worst disasters in human history, a magnitude 7.0 earthquake, resulting in the deaths of approximately 222,000 Haitians and grievous injury to hundreds of thousands more. International agencies, academic institutions, nongovernmental organizations, and associations responded by sending thousands of medical professionals, including nurses, doctors, medics, and physical therapists, to support the underresourced Haitian health system. The volunteers who came to provide medical care to disaster victims worked tirelessly under extremely challenging conditions, but in many cases they had no previous work experience in resource-limited settings, minimal training in tropical disease, and no knowledge of the historical background that contributed to the catastrophe. Often, this lack of preparedness hindered their ability to care adequately for their patients. The authors of this perspective argue that the academic medicine community must prepare medical trainees not only to treat the illnesses of patients in resource-limited settings but also to fight the injustice that fosters disease and allows such catastrophes to unfold. The authors advocate purposeful attention to building global health curricula; providing adequate time, funding, and opportunity to work in resource-limited international settings; and ensuring sufficient supervision for trainees to work safely. They also call for an interdisciplinary approach to global health that both affirms health care as a fundamental human right and explores the historical, economic, and political causes of inequitable health care.
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http://dx.doi.org/10.1097/ACM.0b013e31821b3e14DOI Listing
July 2011
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