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You Make the Call: Readers’ Response TRAINING through the ON and EDUCATI e program Consult a Colleagu clinical month’s We asked, and you answered! Here are a few responses from this month’s “You Make the Call.” ed to next question submitt in your response e the Call we pick a challenging clinical do. Send You Mak omatosis. what you would print issue. the Call,” want to know next history of hemochr “You Make in in the a family , but we also Each month mutation and up to the expert’s expert’s response the C282Y answer matches and post the a patient with see how your s managing dilemma and , MD, discusse Susan F. Leitman This month, in the showed ferritin le for . The results . history is remarkab ma: by her primary-c liver function. Family for the C282Y mutation performed Clinical Dilem red meat. and normal homozygous had iron studies and eats no 38 percent, that she is are physician of ld woman shows method mg/dL, n saturation A 19-year-o iron of 208 genetic testing her oral contraceptive range, transferri of matosis, and showed a serum ng/mL. Would you 250 ng/mL hemochro 301 iron studies menses because use aunt with and ferritin She has no however, her told me to a maternal been pregnant. liver function; n saturation of 78 percent, One hematologist She has never labs showed normal therapy? mcg/dL, transferri on frequency of Her most recent ing capacity of 268 decide women. you use to pre-menopausal total iron-bind y? And what would as a goal in start phlebotom below 50 percent saturation transferrin inion Expert Op Colleague Consult a ASH Through is a service for ASH Consult a Colleague facilitate the exchange helps members that between hematologists on can seek of informati ASH members and their peers. clinical cases from qualified on consultation : 11 categories experts in MD Susan F. Leitman, Research Scholars Director, Medical Program of Health National Institutes Bethesda, MD for the HFE homozygosity frequent matosis with of the most . Genetic hemochro mutation is one population (C282Y) in the Caucasian starts in p.Cys282Tyr recessive disorders ed iron absorption autosomal serum fer- due to dysregulat by an elevated Iron loading manifested in this patient. and may be the teens, as childhood saturation in in target organs, 30. ritin and transferrin significant iron burden levels. until after age use of is below targeted However, clinically generally occur women liver, does not in men than when the ferritin level, to maximize effective ence, I would 19, such as the a faster pace e that at age On a practical proceeds at and inconveni and Iron loading minimize costs diet. It is remarkabl already has bio- . The U.S. Food affected by resources and for treatment this patient and can be ng/mL iron, blood collection 301 a blood center heme of a listing of low in y ref er her to with a ferritin phlebotom despite a diet ation maintains of excess iron, Drug Administr deliver hemochromatosis meets blood in women). of chemical evidence that 150 ng/mL 1 the patient with quality of normal is establishments patient. If (upper limit made available symptom interfering charge to the occurring removed are care without find that The most common matosis is arthritis, be aggres- the blood units delighted to can with hemochro donor criteria, are usually The arthritis life in patients n. Patients with the than discarded. percent of subjects. severity is correlated for transfusio others rather help to in 10 to 30 its is used to avoid alcohol g; since that early initiation their blood counseled sive and debilitatin it is assumed should be be vaccinated The patient at diagnosis, She should Elevated alanine s, strongly of her life. arthropathy. ferritin value done) and for the rest of individual y can prevent to excess already percent her 40 not to (if phlebotom B of expose in less occurs in 10 n, occurring against hepatitis behaviors that might be ad- aminotransferase disease is uncommo disease to avoid siblings should liver y prevents liver counseled addition, all but advanced Phlebotom C virus. In testing. of patients. cancer. hepatitis ular percent genotype 5 HFE than the risk of hepatocell when the ferritin vised to undergo d treatment and mitigates a signif- recommen already has for a Variance Most experts a. Granted Approval Since this patient age, female sex, and REFERENCE “List of Establishments 20, 2018, from https://www.fd 300 ng/mL. ariances/ her young rapid rises above and Drug Administration. Accessed on March eBloodSupply/V 1. U.S. Food elevation despite to load iron at a more I /Regulationofth and 21CFR640.3(f).” dBloodProducts to 21CFR640.3(d) icant ferritin odVaccines/Bloo diet, she appears hemochromatosis, and gov/BiologicsBlo . low heme-iron one 500-mL patient with ucm164649.htm typical remove the pace than y now. I would phlebotom until the ferritin a: would initiate to four months ce ferritin every three a maintenan com- ’s Clinical Dilemm unit of blood and then target this to prevent Next Month ld patient who presented had with 150 ng/mL, a few atypi- I would do falls below liver months. He and 200 ng/mL. arthropathy, as well as (BM) I have a 40-year-o between 150 lasting three and his bone marrow sociated control at this plaints of fever l smear aim for tighter of acute pro- hemochromatosis-as e to reserves periphera his iron reason in suggestiv with is no cal cells gically to leave her to injury. There was not detected was morpholo and it is reasonable aspiration of bleeds necessary PML-RAR alpha on all-trans retinoic early stage, leukemia. . The frequency weight, diet, and was started myelocytic after for future pregnancy will depend on her six to l blood. He cytopenia bleeds every range from periphera trioxide. He developed this patient? be maintenance maintain this level should I suspect that PML- acid plus arsenic ea. How should I manage Her ferritin other factors. aspirate for are would be sufficient. bleeds. and sent the starting hydroxyur 12 months for a BM aspiration situ hybridization results to any scheduled sensitive test I repeated in sample reassessed prior saturation is a highly its use Fluorescence cyte count in the BM variant, but RAR alpha. ? ● The transferrin low promyelo an HFE C282Y that, it has no transcript detection presence of After pending. Does alpha e detecting the diagnosis. PML-RAR It is susceptibl screening and influence the to therapy. is limited to even g response be quite high utility in monitorin variation and can dietary to diurnal and • Anemias oietic cell • Hematop transplantation inopathies • Hemoglob sis/thrombosis • Hemosta as • Lymphom disorders roliferative • Lymphop s • Leukemia Waldenström myeloma & • Multiple macroglobulinemia s liferative neoplasm • Myelopro s plastic syndrome • Myelodys cytopenias • Thrombo es”) will s (“colleagu Assigned volunteer within two business inquiries respond to phone). by email or days (either dilemma? clinical Have a puzzling and read more s at volunteer Submit a question, a Colleague px about Consult nicians/ QR code. or scan the to a a request related here, listed *If you have c disorder not ation to  hematologi your recommend it can be .org so please email hematology ashconsult@ addition in the future. for considered For the full description of the clinical dilemma, and to see how the expert responded, turn to page 32. 32 ASH Clinical d not recommen , : ASH does tests, physicians any specific and or endorse s, or opinions, or products, procedure tion, warranty, representa any disclaims any Reliance on to the same. is solely guaranty as in this article n provided informatio risk. at your own DISCLAIMER Why not wait until the ferritin level increases? Any data to support venesec- tion (phlebotomy) just based on rising transferrin saturation? Glenn J. Shamdas, MD Veterans Affairs Medical Center Fargo, ND April 2018 News I would use quantitative phlebotomy to assess mobilizable iron stores, then decide on a course of action. Some patients with that level of ferritin and classical hemochromatosis can have significantly increased iron stores. With normal liver function, no hepatomegaly, and ferritin less than 1,000 ng/mL, there is no risk of occult cirrhosis. Pradyumna D. Phatak, MBBS Rochester Regional Health Rochester, NY I recommend periodic phlebotomy to main- tain transferrin saturation below 50 percent. Donald H. Mahoney Jr., MD Texas Children’s Hospital Cancer and Hematology Centers Houston, TX See more reader responses at you-make-the-call. CMYK Clinical Dilemma: A 19-year-old woman’s iron studies results showed ferritin in the 250 ng/mL range, transferrin saturation of 38 per- cent, and normal liver function. Family history includes a maternal aunt with hemochromatosis, and genetic test- ing shows that she is homozygous for the C282Y mutation. She has never been pregnant. She has no menses because of her ora l contraceptive method and eats no red meat. Her most recent labs showed normal liver function; however, her iron studies showed a serum iron of 208 mg/dL, total iron-binding capacity of 268 mcg/dL, transferrin saturation of 78 percent, and ferritin 301 ng/mL. Would you start phlebotomy? And what would you use to decide on frequency of therapy? Start phlebotomy, initially once every two months, to keep transfer- rin saturation below 50 percent. Monitor iron parameters once every three months. Javid Gaziev, MD, PhD Mediterranean Institute of Hematology Rome, Italy I would consider bringing her ferritin below 50 ng/mL with weekly phle- botomy, then check ferritin every two to three months. Nagesh H. Jayaram, MD Southeastern Medical Oncology Center Jacksonville, NC We have had similar findings with heterozygotes at our pediatric center and have sent those with elevated saturations to get liver imaging for iron levels. If they have evidence of liver iron overload, we start inter- mittent phlebotomy. Depending on the levels and whether the patient is female and premenarchal, we sometimes wait until menarche to decide whether phlebotomy is necessary. Our understanding of multiple myeloma is evolving. Learn how new techniques are helping to fi ght relapse. MULTIPLE MYELOMA: KEY STATISTICS RELAPSE AND HETEROGENEITY THE ROLE OF THE PROTEASOME Second most common blood cancer, with a global yearly incidence of almost 114,000 cases 1,2 Although outcomes have improved, most patients with multiple myeloma inevitably relapse 3 In multiple myeloma, normal function of the proteasome likely contributes to survival and proliferation of malignant cells 4,5 Discover more at References: 1. American Cancer Society. Cancer Facts and Figures 2017. -cancer-facts-and-fi gures/2017/cancer-facts-and-fi gures-2017.pdf. Accessed December 21, 2017. 2. International Agency for Research on Cancer. GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. Accessed December 8, 2017. 3. Paiva B, van Dongen JJM, Orfao A. Blood. 2015;125:3059-3068. 4. Crawford LJ, Walker B, Irvine AE. J Cell Commun Signal. 2011;5:101-110. 5. Fribley A, Wang CY. Cancer Biol Ther. 2006;5:745-748. 6. Terpos E, Moulopoulos LA, Dimopoulos MA. J Clin Oncol. 2011;29:1907-1915. Tiffany F. Lin, MD University of California, San Francisco BONE DISEASE A common complication, bone disease develops in up to 90% of patients over the course of the disease 6 © 2018 Amgen Inc. All rights reserved. 01/18 USA-171-058302 Printed in USA