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Mikkael A . Sekeres , MD , MS , is director of the Leukemia Program at Cleveland Clinic in Cleveland , OH .
ASH Clinical News
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Letters to the Editor
Impatient Practicum
In his April 2017 Editor ’ s Corner , Editor-in-Chief Mikkael Sekeres issued his annual missive to the American Board of Internal Medicine (“ Letter from a Cleveland Jail to the ABIM : Patient Practicum ”). The ABIM ’ s Maintenance of Certification examination is a hotly debated topic , so it was not surprising to receive strong reactions from our readers . Below are a couple of responses we received in the ACNEditor @ hematology . org inbox .
Have a comment about an article ? Let us know what you think ; we welcome your feedback . Email the editor at ACNEditor @ hematology . org .
Editor ’ s Corner
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The content of the Editor ’ s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated .
Letter From a Cleveland Jail to the ABIM : Patient Practicum
EAR AMERICAN BOARD OF INTERNAL MEDICINE ( ABIM ):
Writing to you , as usual , from behind the bars of emotional turmoil , political dissonance , and unresolved neuroses regarding K-type questions , hematology reprobate that I am . Like Henry David Thoreau and Martin Luther King Jr ., both of whom penned meaningful essays while held captive , I beseech you with my keyboard to hear my tales of woe .
First , my kudos for offering internal medicine doctors more choice in how to recertify . Your regular emails have given me hope , particularly in how you write that you are “ working on ” implementing open-book assessments . I noticed , though , that you haven ’ t mentioned much about specialty exams . I had the most curious day at work recently , and I wonder if this story might prompt you to reveal more specifics about your plans as you “ explore ” ( your word ) other changes .
I walked into my clinic room in our cancer center and was greeted by a woman sitting on the examination table . “ Good afternoon , Ms . Pearson ,” I said , flashing her a winning smile . “ Hi ,” she answered back , flatly . “ How are you today ?” I asked , taking a seat . “ Are you ready to begin ?” she responded . Wow , no beating around the bush for her , I thought .
“ Sure ,” I answered . “ I was just hoping to get to know you as a person a bit before we discussed your medical history . I ’ ll be a better doctor for you if I understand your background , what kind of support structure you have at home , and how you like to make decisions .”
She looked at me as if I had three heads and then started speaking . “ A 22-year-old woman presents with lymphadenopathy of her axilla and groin bilaterally . She has been having night sweats for the past month and has lost 10 percent of her body weight . Recent laboratory tests show the following : a white blood cell count of 13,000 / μL with 80 percent lymphocytes – 20 percent of which are atypical . Which diagnostic procedure is best to perform ?” I was a bit taken aback . She hadn ’ t brought along any medical reports and her electronic medical record was bare , except for her name : Pearson , V . So I appreciated the information she provided , despite the odd delivery . But , more importantly , as a hematologist / oncologist at a referral center , I see patients who have a diagnosis already established . And , even more importantly than that , in my practice I see exclusively patients with myeloid malignancies ; Ms . Pearson had what sounded like lymphoma , or a bad infection !
“ Um , a core needle biopsy ?” I answered , hesitantly . She looked at me with disgust . “ I mean , I would excise a lymph node ! No , wait – I ’ d send your blood for flow cytometry ! That ’ s it ! Uh … on second thought , maybe a bone marrow biopsy ?” I was starting to sweat . “ What ’ s the right answer ?” I almost shouted . She stared at me , her lips pursed tightly . I would never find out . I pulled out my phone to check the time . What kind of reality was this ? Was the world standing still ? But the seconds kept ticking away , almost too fast . “ WHAT ARE YOU DOING ?” a voice shouted at me , almost making me drop my phone . “ Checking the time !” I answered . “ Just checking the time !” “ YOU CAN ’ T HAVE THAT IN HERE ! GIVE IT TO ME !” I quickly handed it over to her … no , him . My patient was now an old man . He confiscated my phone and started speaking . “ A 75-year-old man presents with fatigue , recent weight loss , and epistaxis ,” he said . “ He has pancytopenia with a hemoglobin of 8.2 g / dL , a white blood cell count of 2,100 / μL , and a platelet count of 8,000 / μL . A bone marrow biopsy is performed , which shows acute myeloid leukemia ( AML ) with 29 percent myeloblasts in his bone marrow . Cytogenetics reveal a complex karyotype , including a deletion in chromosome 7 . What treatment do you recommend ?”
Well , at least this was more up my alley . But this decision of how to treat an older adult with AML is far from straightforward and largely dependent on individual goals .
April 2017 Editor ’ s Corner
“ Well , can we talk first about your aspirations and what you want to do with the rest of your life ?” I asked .
He looked at me , incredulous . “ I mean , if you want to be really aggressive about treating your leukemia , we could talk about the risks and benefits of 7 + 3 .” His eyes widened . I hesitated . “ There ’ s a population study from Sweden that shows a survival advantage in older adults with this type of induction therapy . Here , let me show you the results .” I swiveled my chair toward the computer on the desk in the clinic room and started accessing PubMed .
“ STOP !” he shouted . “ YOU ’ RE NOT ALLOWED ON THE INTERNET !”
I quickly pulled my hands off the keyboard . “ Why not ? I access it all the time with my patients so we can review laboratory results together . I also use it to check publications to see how their eligibility requirements and results can be applied to my own patients .”
“ BECAUSE IT ’ S NOT ALLOWED !” he said , indignant . “ JUST TELL ME WHAT TREATMENT YOU RECOMMEND !”
“ It ’ s not an easy answer .” I said . “ The studies aren ’ t conclusive . Do you want me to tell you what the National Comprehensive Cancer Network recommends or go into more depth about the level of evidence ? It ’ s nuanced .”
He gave me a withering look , clearly not open to the subject of nuance . I continued , now withered . “ Well , I guess with your presentation , I ’ m supposed to answer that you should be treated with a hypomethylating agent . Is that right ?”
“ For my lung cancer ?” he asked , surprised . He seemed younger all of a sudden . “ No …” I hesitated again . “ Don ’ t you have leukemia ?” He sighed , exasperated . “ I am a 63-year-old man and have a 4 cm mass in the right lower lobe of my lung and ipsilateral hilar lymph nodes . I also have a pleural effusion . What stage am I ?”
“ I have no idea – I ’ m a leukemia doctor !” I said , equally exasperated . “ I haven ’ t treated someone with lung cancer in 15 years !”
He shook his head slowly . “ Sad . Don ’ t you consider yourself a hematologist / oncologist ?” “ Well , yes ,” I answered . “ Then what test would you order to determine my stage ?” I tried to stall . “ I guess I would order a lot of tests all at the same time : computed tomography , positron emission tomography , mediastinoscopy …”
“ But which would you order first ?” he repeated . I didn ’ t answer as we stared at each other for a solid minute .
“ Time ’ s up ,” he said . He handed my phone back and I looked at the time . Eight hours had passed .
“ That ’ s it ?” I asked , as he stood up to leave . “ But , when should I schedule a follow-up appointment ?”
“ Oh , I ’ ll let you know in about 10 to 12 weeks ,” he said . “ If all goes well , I ’ ll explore whether to see you back every couple of years or every 10 years . If not …” he shrugged his shoulders and walked out the door .
How absurd , I thought to myself . Seeing one patient after another with disorders unlike any I regularly see , each requiring answers to questions a patient wouldn ’ t ordinarily ask , and all in the absence of information about their medical histories or goals of care and without the usual computer access I have come to depend on to provide adequate care .
Wouldn ’ t you agree ?
Sincerely , Mikkael A . Sekeres , MD , MS Board certified through 2022
Kudos to Dr . Sekeres for vividly demonstrating the frustration many of us experience in being asked by our credentialing overlords to exhibit expertise across the entire field , as we become more concentrated in our treatment and research practices , and as we rely more on colleagues and specialists in the field to optimally deal with these patients . However , his most poignant message is to first understand the patient – who “ has ” the disease , and “ isn ’ t ” the disease – allowing us as physicians to be able to adequately and personally treat them . Questions on a timed exam do not evaluate , as he stated , “ nuances .”
— Sandra Silberman , MD , PhD SLSOncology , LLC
Durham , NC
I ’ d like to commend you on voicing the thoughts of a very large group of hematologists / oncologists out there ! The message has been out there for a while now , but you have clearly demonstrated the ridiculousness and uselessness of computerized testing with your clever editorial . I hope it impacts the folks at ABIM !
— Caroline Hwang-Gerecs , MD New York , NY
Recertifying for Oncology in November 2017
The Challenge of Cytomegalovirus
CMV seropositivity is common in the United States
Cytomegalovirus ( CMV ) is a highly transmissible and prevalent herpesvirus that remains in the body after primary infection . 1 Data from the National Health and Nutrition Examination Survey ( NHANES ) III ( 1988 – 1994 ), a population-based survey meant to be representative of the US population , established that 66.7 % of the adult population aged ≥25 years were CMV seropositive . 1 CMV seroprevalence increases with age , as a study representative of the US population ( 1999 – 2004 ) revealed a CMV seroprevalence of 49.5 % among 20- to 29-year-old patients and 58.0 % among 40- to 49-year-old patients . 2
Hematopoietic stem cell transplant ( HSCT ), solid organ transplant ( SOT ), intensive care unit ( ICU ), and human immunodeficiency virus ( HIV ) - infected patient populations are most frequently affected by CMV infection . The risk of CMV infection and reactivation varies among these patients , with a 50 % to 90 % incidence in HSCT patients , 30 % to 75 % in SOT patients , 25.7 % in HIV-infected patients with a diagnosis of AIDS , and 15 % to 20 % in ICU patients . 3 – 6
The relationship between CMV and the immune response
A bidirectional relationship exists between CMV and the immune system . Impaired immune defenses allow CMV replication and could lead to CMV disease and associated complications . 6 On the other hand , CMV infection can also alter immune defenses against infections and could increase the likelihood of secondary infections , including bacterial and fungal infections , as well as potentially enhance the proinflammatory response . 6 , 7
Risk factors for CMV infection and reactivation
CMV serostatus is a significant risk factor for CMV infection and reactivation and poor prognosis , especially in immunosuppressed patients . In addition , there are multiple risk factors , such as high-dose corticosteroids , acute and chronic GVHD , ICU admission , mechanical ventilation , and sepsis . These risk factors contribute to the overall state of immunosuppression , which can lead to CMV infection and reactivation . 6 , 8 – 12
CMV disease has serious clinical consequences
The development of CMV disease can have serious consequences , including end-organ damage , increased risk of secondary infections ,
6 , 7 , 13 – 16 and mortality .
The clinical impact of CMV can vary significantly by patient type . HSCT patients most commonly manifest CMV disease as pneumonia or gastrointestinal disease . 8 For SOT patients , the transplanted allograft is typically involved if end-organ damage occurs . This has serious clinical consequences as CMV disease has been associated with an increased
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risk of acute allograft rejection and mortality . 17 In HIV-infected patients with advanced immunosuppression ( CD4 +, < 50 cells / μL ), CMV retinitis is the most common CMV end-organ disease , but since the advance of HAART , CMV end-organ disease has declined by ≥95 %. 14
In addition to end-organ damage , there is an increased risk of secondary opportunistic infections , including bacterial and fungal infections . 7 ICU patients with CMV infection , specifically , were observed to have an increased risk for nosocomial infections . 6 Secondary infections can also have serious clinical consequences , even contributing toward mortality . 16
CMV viremia has also been identified as an independent risk factor for mortality . This was established in a study of 14,153 subjects aged ≥25 years who were tested for CMV and eligible for mortality follow-up on December 31 , 2006 , after being interviewed in NHANES III ( 1988 – 1994 ). CMV seropositivity was associated with all-cause mortality even after adjusting for age , gender , race / ethnicity , country of origin , education level , BMI , smoking status , and diabetes status . 1
Challenges of monitoring CMV
CMV viral load threshold for CMV reactivation or viremia has been difficult to establish due to variability in assay performance with respect to quantitative measurement . 7 , 8 The typical testing methods of DNA PCR , pp65 antigenemia assay , and pp67 mRNA assay perform well , but assay variability is concerning in immunocompromised patients where the viral load can increase rapidly . 8
The optimal strategy for CMV surveillance in posttransplant and severely immunocompromised patients is not well defined . 18 This is particularly important as the significance and role of monitoring varies depending on preventative measures typically used across patient populations . Different CMV monitoring practices are used depending on the current standard of care or guideline recommendations for various patient types . CMV in HSCT and some SOT patients may rely heavily on monitoring for CMV viremia to determine whether preventative measures should be initiated . Weekly monitoring is recommended for HSCT and SOT recipients with either quantitative PCR or detection of CMV RNA . Recommended monitoring is even more rigorous and should continue beyond day 100 posttransplant for HSCT patients who develop acute or chronic GVHD , had an earlier CMV reactivation , or were mismatched or unrelated donor transplants . 7 , 8 , 19 , 20 HIV-infected patients should maintain their CD4 + count in order to prevent CMV disease . 18 Finally , only ICU patients considered at high risk , meaning those with impaired immune systems , are monitored for CMV reactivation . 6
References : 1 . Simanek AM et al . PLoS One . 2011 ; 6 ( 2 ): e16103 . doi : 10.1371 / journal . pone . 0016103 . 2 . Bate SL et al . Clin Infect Dis . 2010 ; 50 ( 11 ): 1439 – 1447 . 3 . Peres RMB et al . BMC Infect Dis . 2010 ; 10:147 . doi : 10.1186 / 1471-2334-10-147 . 4 . van der Bij W , Speich R . Clin Infect Dis . 2001 ; 33 ( suppl 1 ): S32 – S37 . 5 . Wohl DA et al . J Acquir Immune Defic Syndr . 2005 ; 38 ( 5 ): 538 – 544 . 6 . Papazian L et al . Intensive Care Med . 2016 ; 42 ( 1 ): 28 – 37 . 7 . Kotton CN et al . Transplantation . 2013 ; 96 ( 4 ): 333 – 360 . 8 . Boeckh M et al . Biol Blood Marrow Transplant . 2003 ; 9 ( 9 ): 543 – 558 . 9 . Piñana JL et al . Bone Marrow Transplant . 2010 ; 45 ( 3 ): 534 – 542 . 10 . Cohen L et al . Transpl Infect Dis . 2015 ; 17 ( 4 ): 510 – 517 . 11 . Razonable RR , Humar A . Am J Transplant . 2013 ; 13 ( suppl 4 ): 93 – 106 . 12 . Schwarcz L et al . AIDS . 2013 ; 27 ( 4 ): 597 – 605 . 13 . Ljungman P et al . Clin Infect Dis . 2017 ; 64 ( 1 ): 87 – 91 . 14 . Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents . Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents : recommendations from the Centers for Disease Control and Prevention , the National Institutes of Health , and the HIV Medicine Association of the Infectious Diseases Society of America . AIDSinfo website . http :// aidsinfo . nih . gov / contentfiles / lvguidelines / adult _ oi . pdf . Revised November 10 , 2016 . Accessed February 16 , 2017 . 15 . Jabs DA et al . Ophthalmology . 2005 ; 112 ( 5 ): 771 – 779 . 16 . Nichols WG et al . J Infect Dis . 2002 ; 185 ( 3 ): 273 – 282 . 17 . Beam E , Razonable RR . Curr Infect Dis Rep . 2012 ; 14 ( 6 ): 633 – 641 . 18 . Bieniek R et al . Lab Med . 2011 ; 42 ( 6 ): 339 – 343 . 19 . NCCN clinical practical guidelines on oncology ( NCCN Guidelines ® ). https :// www . nccn . org / professionals / physician _ gls / PDF / infections . pdf . Accessed February 16 , 2017 . 20 . Ljungman P et al . https :// www . ebmt . org / Contents / Resources / Library / ECIL / Documents / ECIL % 204 % 20 % 20Update % 202011 % 20CMV . pdf . Accessed February 16 , 2017 .
Learn more about CMV at www . aboutcmv . com .
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