scholarly journals Pancytopenia in a child with cystic fibrosis and severe copper deficiency: Insight from bone marrow evaluation

2021 ◽  
Author(s):  
Maggie D. Seblani ◽  
Susanna A. McColley ◽  
Shunyou Gong ◽  
Lee M. Bass ◽  
Sherif M. Badawy
Keyword(s):  
Cystic Fibrosis ◽  
Bone Marrow ◽  
Copper Deficiency ◽  
Bone Marrow Evaluation

scholarly journals A rare case of pancytopenia in a child with cystic fibrosis: Can copper cure it all?

2021 ◽  
Author(s):  
Maggie Seblani ◽  
Susanna McColley ◽  
Shawn Gong ◽  
Lee Bass ◽  
Sherif Badawy
Keyword(s):  
Cystic Fibrosis ◽  
Bone Marrow ◽  
Copper Deficiency ◽  
Intestinal Resection ◽  
Serum Copper ◽  
Nutritional Deficiencies ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Copper Supplementation ◽  
Treatment Considerations

Nutritional deficiencies such as iron, vitamin B12 and folate are recognized as etiologies for several cytopenias; although copper’s role in multiple metabolic enzymes is well-established, copper deficiency is often overlooked as a contributing entity. Frequently diagnosis is delayed, patients may undergo bone marrow investigations with findings overlapping a myelodysplastic process, which can lead to further testing and treatment considerations including hematopoietic stem cell transplant referral. We present a case of a young boy with cystic fibrosis with biliary dysplasia corrected with hepato-portoenterostomy and distal intestinal obstruction syndrome resulting in jejunal resection, with severe anemia and thrombocytopenia requiring transfusion support. Initial evaluation had been unremarkable, ongoing pancytopenia prompted bone marrow studies, which revealed vacuolated granulocytic and erythroid precursors and ring sideroblasts, suggestive of copper deficiency. Serum copper and ceruloplasmin were consistent with severe deficiency, attributed to insufficient absorption intestinal resection, chronic parenteral nutrition and prior zinc supplementation. Following enteral copper supplementation, anemia, leukopenia and thrombocytopenia significantly improved, however upon cessation, counts again worsened and has since been maintained on daily copper supplementation without further transfusion needs. Our experience exemplifies the importance of early consideration for copper deficiency in children with cytopenias, especially within context of intestinal malabsorption or inadequate nutritional intake which often occurs in children with cystic fibrosis.

Letter to the Editor

PEDIATRICS ◽  
1969 ◽  
Vol 43 (5) ◽  
pp. 905-906
Author(s):  
Aubrey Milunsky
Keyword(s):  
Cystic Fibrosis ◽  
Bone Marrow ◽  
Clinical Presentation ◽  
Pancreatic Insufficiency ◽  
Chloride Concentration ◽  
Letter To The Editor ◽  
Patient Reported ◽  
Sweat Sample ◽  
Chloride Concentrations

The patient reported in the foregoing letter is of particular interest in view of the recent observations on patients with tnisomy 21 and cystic fibrosis. The multiple possibilities that could explain the clinical presentation have no doubt been considered by the authors. However, the description of "hypoplastic thrombocytopenia" and later pancytopenia in this patient, associated with pancreatic insufficiency, leads to the serious consideration of Shwachman's syndrome (pancreatic insufficiency and bone marrow dysfunction). The wide discrepancy between the sodium and chloride concentrations in the sweat reported in their letter indicates that evaporation of water may have occurred from the sweat sample, leading to an apparently higher sodium and chloride concentration.

scholarly journals Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice

2022 ◽  
pp. ji1901171
Author(s):  
Zhichao Fan ◽  
Elise Pitmon ◽  
Lai Wen ◽  
Jacqueline Miller ◽  
Erik Ehinger ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Monocyte Recruitment

scholarly journals Optimizing Response to Enasidenib with Dose Escalation: Case Series

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-5
Author(s):  
Amany R. Keruakous ◽  
Sarah A. Schmidt ◽  
Marcus T. Autry ◽  
Pragathi Balakrishna ◽  
Julia Ye ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dose Escalation ◽  
Karyotype Analysis ◽  
Standard Dose ◽  
Case Series ◽  
Bone Marrow Evaluation ◽  
Poor Risk ◽  
Daily Dose ◽  
Variant Frequency ◽  
Idh2 Mutation

Background: Isocitrate dehydrogenase enzymes catalyze the conversion of isocitrate to alpha-ketoglutarate. Mutated IDH enzymes generate the "oncometabolite" 2-hydroxyglutarate (2-HG), which inhibits TET2 function. IDH2 mutations have been reported in 9% to 19% of acute myeloid leukemia (AML) cases. Inhibition of the mutant IDH2 enzyme led to decreased 2-HG levels and induced myeloid differentiation in IDH2 mutant AML. Enasidenib, a small-molecule inhibitor of mutant IDH2, was approved in 2017, after a successful phase I/II trial showing an overall response rate (ORR) of 40.3% in relapsed/refractory (R/R) disease, with 19.3% of patients achieving complete remission (CR). A Phase III trial is currently ongoing. It targets the mutant IDH2 variants R140Q, R172S, and R172K; at an approved dose of 100 mg oral daily dose. At higher doses the drug was less tolerated, however, few subjects received dose modification at the 650 mg daily dose group; these events did not qualify as a dose-limiting toxicity (DLT). In this descriptive study, we are reporting a case series of R/R AML, with an IDH2 mutation, that are treated with escalated dose enasidenib. Method: This case series is based on retrospective observations of patients with R/R IDH2 mutant AML since January 2017, who are treated with enasidenib. We are reporting two cases treated with an escalated dose of 200 mg daily. We included patients with intermediate to poor-risk AML, who received at least one prior line of therapy, started on standard dose enasidenib (100 mg daily) for a minimum of 6 months and followed until disease relapse or death. We excluded patients who are primarily resistant to enasidenib (AML risk stratification and response evaluation by ELN-Leukemia NET. IDH2 mutations were identified by a local diagnostic laboratory that is regulated under CLIA through PCR which is validated to detect 10% or more mutant allele frequency. To quantify IDH2 variant frequency, confirmatory testing was performed via ARUP next-generation sequencing panel (NGS). Results: Here we report the descriptive outcomes of 2 cases from a single institution, who were treated with escalated dose enasidenib (200 mg oral daily) for R/R AML with an IDH2 mutation. The first case describes a 65-year-old female diagnosed with poor-risk AML in the setting of pancytopenia with bone marrow evaluation consistent with the background of erythroid and granulocytic dysplasia, with normal karyotype analysis. The patient has treated with induction chemotherapy and 2 cycles consolidation that was complicated with bacterial infections, prolonged hospitalization, and profound deconditioning led to stopping treatment. After 18 months of surveillance, repeat bone marrow evaluation for new-onset pancytopenia revealed relapsed AML with evidence of IDH2 mutation at codon 140, with a variant frequency of 36.9% by NGS. The case was started on enasidenib at 100 mg oral daily dose. After 6 months of therapy, the patient continued to be cytopenic, repeated bone marrow evaluation showed residual AML with IDH2 variant frequency of 27.6%. The decision was made to increase the enasidenib dose to 200 mg daily. With follow up for another 5 months on the escalated dose, the patient achieved hematologic complete response (hCR) with normalization of peripheral platelet count and ANC. [Figures 1-2] The patient maintained hCR for another 5 months on 200 mg enasidenib daily until she died from COVID-19 infection. The second case describes a 59-year-old female with poor-risk AML in the setting of leukocytosis, with bone marrow evaluation consistent with the background of megakaryocytic dysplasia and karyotype analysis positive for monosomy 7. The patient was treated with induction chemotherapy and failed to respond. Repeat bone marrow evaluation showed primary refractory disease with positive IDH2 mutation at codon 140 with a variant frequency of 40.7%. Treatment with 100 mg enasidenib was started. The patient maintained a partial response for 6 months, then peripheral blasts counts started to gradually increase. The decision was made to increase enasidenib dose to 200 mg daily, which improved peripheral blasts within one month of escalated dose therapy. [Figure 3] The patient maintained a response to therapy for another 3 months before she relapsed. Conclusion: Our limited data showed that initial response to standard dose enasidenib could potentially be optimized by dose escalation to 200 mg daily. Disclosures No relevant conflicts of interest to declare.

scholarly journals Limited Restoration of Cystic Fibrosis Lung EpitheliumIn Vivowith Adult Bone Marrow–derived Cells

2006 ◽  
Vol 173 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Roberto Loi ◽  
Travis Beckett ◽  
Kaarin K. Goncz ◽  
Benjamin T. Suratt ◽  
Daniel J. Weiss
Keyword(s):  
Cystic Fibrosis ◽  
Bone Marrow ◽  
Cystic Fibrosis Lung ◽  
Adult Bone Marrow ◽  
Bone Marrow Derived Cells ◽  
Adult Bone

Bone Marrow Evaluation for Lymphoma

2011 ◽  
pp. 887-917 ◽  
Author(s):  
Beverly P. Nelson ◽  
LoAnn C. Peterson
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Evaluation

Laboratory and Bone Marrow Evaluation in Patients with Cancer

1998 ◽  
Vol 5 (2_suppl) ◽  
pp. 12-16 ◽  
Author(s):  
Lynn C. Moscinski
Keyword(s):  
Bone Marrow ◽  
Laboratory Findings ◽  
Patients With Cancer ◽  
Bone Marrow Evaluation ◽  
Bone Marrow Histopathology ◽  
Multiple Causes

Anemia in patients with cancer has multiple causes. Since establishing a diagnosis can be difficult, evaluation via laboratory findings and bone marrow histopathology is often necessary. Cytopenias can result either directly or indirectly from the malignancy, or they occasionally are the result of other causes, such as AIDS or infection.

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