You Make the Call : Readers ’ Response
You Make the Call
Each month in “ You Make the Call ,” we ’ ll pick a challenging clinical question submitted through ASH ’ s Consult a Colleague program and post the expert ’ s response , but we also want to know what you would do . Send in your responses to next month ’ s clinical dilemma and see how your answer matches up to the experts ’ in the next print issue .
This month , Michael W . Deininger , MD , PhD , discusses myelosuppression in a patient with chronic myeloid leukemia .
Clinical Dilemma :
An 82-year-old female with chronic myeloid leukemia ( CML ) presented 8 years ago in chronic phase , without any particular high-risk factors . She went into major molecular response ( MMR ) on imatinib and remains in this state . Her complete blood count has been normal except for mild anemia . However , over the last 2 months , her white blood cell count dropped from normal to 1,400 / μL , with an absolute neutrophil count ( ANC ) of 300 / μL . Her hemoglobin dropped from 10.9 g / dL to 8.9 g / dL and platelets dropped from normal to 98,000 / μL . She remains in MMR by polymerase chain reaction . She has no symptoms except mild fatigue , and her spleen is not palpable . She is on no new medications . She has been on ezetimibe for high cholesterol , lisinopril / hydrochlorothiazide , and metoprolol for years . Her metoprolol dose was increased 6 months ago . I held the imatinib and will probably consider dose reduction after the ANC goes back up . However , is there anything else I should worry about ? It seems odd that her counts went down after so many years .
Expert Opinion
Michael W . Deininger , MD , PhD Professor and Chief of Hematology and Hematologic Malignancies Department of Internal Medicine and the Huntsman Cancer Institute University of Utah
Myelosuppression is common in patients with CML on indicate that achieving a Ph – state does not equal normal , imatinib and other tyrosine kinase inhibitors ( TKIs ). and there may be co-existent age-related clonal hematopoiesis . Fortunately , the prognosis of these CML patients
However , in most patients , myelosuppression is transient after initiation of therapy and reflects suppression of the is generally good and dictated by the TKI response of their CML clone , while residual normal hematopoietic stem cells CML , as long as – and this is critical – there is no evidence ( HSC ) gear up to repopulate the marrow . Consequently , for dysplasia and blood counts are normal . The exception blood counts return to normal once a complete cytogenetic or equivalent molecular response is achieved . Some gression to MDS and acute myeloid leukemia and require
is patients with – 7 or del7q , who have a high risk of pro-
patients fail to normalize blood counts and require dose bone marrow ( BM ) monitoring on a regular basis . However , MDS can develop in any CML patient and is a major reduction . In extreme cases , hematologic toxicity prevents sufficient dose intensity , a difficult clinical situation thought consideration in the current case . My recommendation to indicate the absence of sufficient normal HSCs . Clinically , patients requiring dose reduction due to hematologic and biopsy , with cytogenetics and NGS for myeloid muta-
therefore is to pause imatinib and perform a BM aspirate
toxicity identify themselves during the first few months of tions . If MDS is diagnosed , then management needs to therapy . Once the TKI dose is calibrated to the individual cover both CML and MDS , taking into account that MDS patient , it tends to be stable . With this in mind , your is the prognosis-driving hematologic disorder . It may be 82-year-old patient with her 8-year CML history and MMR tempting to take a pragmatic approach to patients who is clearly deviating from the norm , and her pancytopenia develop cytopenias after years on a TKI and simply reduce requires careful consideration . the dose . While this may be reasonable in certain circumstances ( such as mild cytopenias in older individuals ), my
An inexpensive and noninvasive first step is a thortion reconciliation , as polypharmacy and recommendation is to exclude MDS before committing to ortunities for drug a strategy of dose reduction and increased vigilance . Once MDS has been excluded and other treatable causes seem o blame the TKI for the myelosuppresless myelosup-
TRAINING and EDUCATION
Consult a Colleague Through ASH
Consult a Colleague is a service for ASH members that helps facilitate the exchange of information between hematologists and their peers . ASH members can seek consultation on clinical cases from qualified experts in 11 categories :
• Anemias
• Hematopoietic cell transplantation
• Hemoglobinopathies
• Hemostasis / thrombosis
• Lymphomas
• Lymphoproliferative disorders
• Leukemias
• Multiple myeloma & Waldenström macroglobulinemia
• Myeloproliferative disorders
• Myelodysplastic syndromes
• Thrombocytopenias
Assigned volunteers (“ colleagues ”) will respond to inquiries within two business days ( either by email or phone ).
Have a puzzling clinical dilemma ? Submit a question , and read more about Consult a Colleague volunteers at hematology . org / Clinicians / Consult . aspx or scan the QR code .
We asked , and you answered ! Here are a few responses from this month ’ s “ You Make the Call .”
R o s
For the full description of the clinical dilemma , and to see how the expert responded , turn to page 28 .
Clinical Dilemma :
An 82-year-old female with chronic myeloid leukemia ( CML ) presented 8 years ago in chronic phase , without any particular high-risk factors . She went into major molecular response on imatinib and remains in this state . Her complete blood count has been normal except for mild anemia . However , over the last 2 months , her white blood cell ( WBC ) count dropped from normal to 1,400 / μL , with an absolute neutrophil count ( ANC ) of 300 / μL . She has no symptoms except mild fatigue , and her spleen is not palpable . I held the imatinib and will probably consider dose reduction after the ANC goes back up . However , is there anything else I should worry about ? It seems odd that her counts went down after so many years .
Did you test the vitamin B12 , folate , and ferritin levels ? Did you perform a bone marrow biopsy to test for myelofibrosis ? I would lower the imatinib dose or even pause the medication .
Daniel Mardi , MD St . Bernhard-Hospital
Brake , Germany
Ask the hematopathologist to obtain a bone marrow exam with BCR-ABL by rtPCR , karyotype , and BCR-ABL mutational analysis .
John Maddox , MD Riverside Regional Medical Center
Newport News , VA
We have to rule out transformation to AML phase . I recommend bone marrow biopsy and aspiration .
Takao Ohnuma , MD , PhD Mount Sinai Hospital
New York , NY
I would check methylmalonic acid as well . Vitamin B12 levels are high due to elevated B12 binding protein . I would consider a bone marrow biopsy as well . I am not aware of any drug interactions . No additional changes from the outlined plan .
Shaily Lakhanpal , MD Alabama Oncology
Birmingham , AL
No adverse medication side effects would explain her new onset cytopenia . It would be reasonable to consider obtaining a bone marrow biopsy to rule out myelodysplastic changes , which , given her age and the myelodysplastic / myeloproliferative neoplasms spectrum association , is a possible cause .
See more reader responses at bit . ly / 2qfvELC .
Karrar Elhussein , MD King Fahad Medical City
Riyadh , Saudi Arabia
Autoimmune causes of low platelets and red blood cell and WBC counts rule out blood loss as a separate entity . Was the drug dose consistent ? Are there circulating blasts on thin and thick smears ? I would review the literature on other medications causing problems if there is no recovery in 3 weeks . Conduct a bone marrow biopsy if sepsis occurs and culture everything , including marrow . Ask patient to take temperature twice daily if bruises appear . Conduct a complete blood count every 7-10 days as an outpatient . Rule out vitamin B12 and folic acid deficiencies .
John P . Hanson , MD John P . Hanson Cancer and Cellular Research Foundation , Inc .
Milwaukee , WI
2017 ASH ® MEETING ON HEMATOLOGIC MALIGNANCIES
SEPTEMBER 8-9 , 2017 • FAIRMONT CHICAGO , MILLENNIUM PARK , CHICAGO , IL
Join us in Chicago to learn how the world ’ s top experts treat their patients and ask questions about your own challenging cases .
Program Planning Committee :
Jonathan Friedberg , MD ( Program Co-Chair ) University of Rochester Ruben Mesa , MD ( Program Co-Chair ) Mayo Clinic Wendy Stock , MD ( Program Co-Chair ) University of Chicago
Registration is now open !
Anjali Advani , MD Cleveland Clinic
John Leonard , MD Weill Cornell Medical College
Vincent Rajkumar , MD Mayo Clinic
David Steensma , MD Dana-Farber Cancer Institute
Review the latest program schedule at www . hematology . org / malignancies .