• Anemias
ASH Clinical News 27
You Make the Call : Readers ’ Response
You Make the Call
Each month in “ You Make the Call ,” we pick a challenging clinical question submitted through the Consult a Colleague program and post the expert ’ s response , but we also want to know what you would do . Send in your response to next month ’ s clinical dilemma and see how your answer matches up to the expert ’ s in the next print issue .
This month , Spero Cataland , MD , discusses whether a patient with thrombocytopenia has hypersplenism , immune thrombocytopenia , or both .
Clinical Dilemma :
I have a 22-year-old Vietnamese female patient who moved to the U . S . at around age 10 . She has no pertinent family history . She presented two years ago to an outside hospital with epistaxis and was found to have a platelet count of zero . She was also noted to have abnormal liver function tests . The workup , including a liver biopsy , revealed autoimmune hepatitis with grade 4 cirrhosis . She responded to immune thrombocytopenia purpura ( ITP )– directed therapy ( steroids , intravenous immunoglobin [ IVIG ] therapy , and platelet transfusion ). She did not follow up regularly , but had at least two subsequent bone marrow biopsies , the second of which showed megakaryocyte hyperplasia . More recently , she presented in a similar way to how she did initially ( 2 years ago ) and was treated the same – steroids , IVIG , and prednisone . She was also given one dose of rituximab . Her platelet count increased to 99 × 10 9 / L , but is dropping to 77 × 10 9 / L . What is the best approach to obtain remission ? Is splenectomy the next step ? She is also being referred for possible liver transplantation , so how does ITP treatment factor into the question of liver transplant ? She has no history of alcohol use .
Expert Opinion
Spero Cataland , MD Professor of Internal Medicine Division of Hematology Wexner Medical Center The Ohio State University
This is certainly a very challenging case that you have on your hands . When I heard cirrhosis and thrombocytopenia , my first thought was splenic sequestration instead of ITP , but her previous complete blood count with a platelet count of 1 × 10 9 / L would fit with a diagnosis of ITP . Given the recent platelet count of 70 to 90 × 10 9 / L , I would consider reimaging now to make sure that progressive spleno-megaly and sequestration have not developed since her last acute ITP event . If that is the case , then what you are seeing now may be more consistent with hypersplenism as the cause of her thrombocytopenia .
If hypersplenism doesn ’ t explain the picture , it may be a recurrence of her ITP that likely is secondary to her autoimmune disease ( hepatitis ). The rituximab she already received may still be helping , but it may take more time . Her platelet count is not too bad at 70 to 90 × 10 9 / L , so if there are no issues with bleeding I would consider watching her ( as the goals of therapy are to maintain a safe platelet count of 30 to 40 × 10 9 / L with as little treatment as possible ). If she needs treatment to maintain a safe platelet count , I might consider the use of the thrombopoietin ( TPO ) agents eltrombopag or romiplostim . In many patients with liver disease , the thrombocytopenia may also be a function I have a patient who is a Jehovah ’ s Witness with stage of TPO deficiency as it is produced in the liver . Splenectomy is typically a very good choice for patients with hospital with a uterine abscess . Her hemoglobin is low
IV uterine cancer who was admitted to a community
ITP , but I would not proceed with this in the context of and I am giving her epoetin alfa and intravenous iron . portal hypertension / sequestration from liver disease , if Are there any other options for treatment of anemia for present . This can lead to an increased risk for portal and patients who refuse packed red blood cell transfusions ? splenic vein thromboses postoperatively . In addition , if Her son suggested PolyHeme ( a human hemoglobinbased red cell substitute ). Is it U . S . Food and Drug a liver transplant could be in her future , I might want to avoid a splenectomy and first try to manage her ITP ( if Administration – approved ? treatment is needed ) with the TPO agents .
How would you respond ? Email us at ashclinicalnews @ hematology . org . ●
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Next Month ’ s Clinical Dilemma :
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 :
• Hematopoietic cell transplantation
• Hemoglobinopathies
• Hemostasis / thrombosis
• Lymphomas
• Lymphoproliferative disorders
• Leukemias
• Multiple myeloma & Waldenström macroglobulinemia
• Myeloproliferative neoplasms
• 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 .
* If you have a request related to a hematologic disorder not listed here , please email your recommendation to ashconsult @ hematology . org so it can be considered for addition in the future .
DISCLAIMER : ASH does not recommend or endorse any specific tests , physicians , products , procedures , or opinions , and disclaims any representation , warranty , or guaranty as to the same . Reliance on any information provided in this article is solely at your own risk .
Clinical Dilemma :
A 22-year-old woman presented two years ago to an outside hospital with epistaxis and was found to have a platelet count of zero . She was also noted to have abnormal liver function tests . The workup revealed autoimmune hepatitis with grade 4 cirrhosis . She responded to immune thrombocytopenia purpura ( ITP )– directed therapy , but did not follow up regularly . More recently , she presented in a similar way and was treated the same , but also given one dose of rituximab . Her platelet count increased initially to 99 × 10 9 / L , but is dropping to 77 × 10 9 / L . What is the best approach to obtain remission ? Is splenectomy the next step ? She is also being referred for possible liver transplantation , so how does ITP treatment factor into the question of liver transplant ?
Yes , liver transplant is an option . I guess that she has been screened for other autoimmune antibodies already . The platelet count of approximately 30 × 10 9 / L should be enough for survival . She will need a platelet transfusion if going for surgery . It is better to keep her on a minimum dose of steroids if she is comfortable . Splenectomy should be a last option in my opinion .
Mala Tudawe , MD Durdans Hospital
Colombo , Sri Lanka
Continue rituximab or eltrombopag .
Anastasia Skandali , MD Hygeia Hospital Athens , Greece
First of all , if she is being considered for liver transplantation , it is possible that the patient has portal hypertension , so the splenectomy is a very risky alternative ( because of post-surgery bleeding ).
I would prefer maintaining the prednisone in 1 mg / kg daily for at least one month , then initiate a slow , six-month taper . If the platelet count drops below 30 × 10 9 / L , I would give another dose of rituximab ( or IVIg depending on the clinical scenario ).
We asked , and you answered ! Here are a few responses from this month ’ s “ You Make the Call .”
For the full description of the clinical dilemma , and to see how the expert responded , turn to page 27 .
If the patient is already waiting for a liver donor , I would prefer adding eltrombopag to the steroid therapy , with the aim of inducing a complete response .
After the transplant , I would continue with eltrombopag ( added to the immunosuppressive therapy used with the transplant ), trying to reduce the dose , very carefully , keeping the patient in complete response .
José Luis Viñuela Cox Hospital del Salvador
Santiago , Chile
INDICATION AND IMPORTANT SAFETY INFORMATION FOR KYPROLIS
INDICATION
KYPROLIS ® ( carfi lzomib ) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy .
IMPORTANT SAFETY INFORMATION FOR KYPROLIS Cardiac Toxicities :
• New onset or worsening of pre-existing cardiac failure ( e . g ., congestive heart failure , pulmonary edema , decreased ejection fraction ), restrictive cardiomyopathy , myocardial ischemia , and myocardial infarction including fatalities have occurred following administration of KYPROLIS . Some events occurred in patients with normal baseline ventricular function . Death due to cardiac arrest has occurred within one day of administration .
• Monitor patients for signs or symptoms of cardiac failure or ischemia . Evaluate promptly if cardiac toxicity is suspected . Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery , and consider whether to restart at 1 dose level reduction based on a benefi t / risk assessment .
• While adequate hydration is required prior to each dose in Cycle 1 , monitor all patients for evidence of volume overload , especially patients at risk for cardiac failure . Adjust total fl uid intake as clinically appropriate .
• For patients ≥ 75 years , the risk of cardiac failure is increased . Patients with New York Heart Association Class III and IV heart failure , recent myocardial infarction , conduction abnormalities , angina , or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment prior to starting treatment with KYPROLIS and remain under close follow-up with fl uid management .
Acute Renal Failure :
• Cases of acute renal failure , including some fatal renal failure events , and renal insuffi ciency adverse events ( including renal failure ) have occurred . Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy . Monitor renal function with regular measurement of the serum creatinine and / or estimated creatinine clearance . Reduce or withhold dose as appropriate .
Tumor Lysis Syndrome :
• Cases of Tumor Lysis Syndrome ( TLS ), including fatal outcomes , have occurred . Patients with a high tumor burden should be considered at greater risk for TLS . Adequate hydration is required prior to each dose in Cycle 1 , and in subsequent cycles as needed . Consider uric acid lowering drugs in patients at risk for TLS . Monitor for evidence of TLS during treatment and manage promptly , and withhold until resolved .
Pulmonary Toxicity :
• Acute Respiratory Distress Syndrome ( ARDS ), acute respiratory failure , and acute diffuse infi ltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred . Some events have been fatal . In the event of drug-induced pulmonary toxicity , discontinue KYPROLIS .
Pulmonary Hypertension :
• Pulmonary arterial hypertension ( PAH ) was reported . Evaluate with cardiac imaging and / or other tests as indicated . Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart based on a benefi t / risk assessment .
Dyspnea :
• Dyspnea was reported in patients treated with KYPROLIS . Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes . Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline . Consider whether to restart based on a benefi t / risk assessment .
Hypertension :
• Hypertension , including hypertensive crisis and hypertensive emergency , has been observed , some fatal . Control hypertension prior to starting KYPROLIS . Monitor blood pressure regularly in all patients . If hypertension cannot be adequately controlled , withhold KYPROLIS and evaluate . Consider whether to restart based on a benefi t / risk assessment .
Thrombopoietin receptor agonists .
Splenectomy is my advice .
Mixalis Mixail , MD Nicosia General Hospital
Nicosia , Cyprus
David M . Baer , MD Kaiser Permanente Oakland Medical Center
Oakland , CA
Venous Thrombosis :
• Venous thromboembolic events ( including deep venous thrombosis and pulmonary embolism ) have been observed . Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone . The thromboprophylaxis regimen should be based on an assessment of the patient ’ s underlying risks .
• Patients using hormonal contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment .
Infusion Reactions :
• Infusion reactions , including life-threatening reactions , have occurred . Symptoms include fever , chills , arthralgia , myalgia , facial fl ushing , facial edema , vomiting , weakness , shortness of breath , hypotension , syncope , chest tightness , or angina . These reactions can occur immediately following or up to 24 hours after administration . Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions . Inform patients of the risk and of symptoms and seek immediate medical attention if they occur .
Hemorrhage :
• Fatal or serious cases of hemorrhage have been reported . Hemorrhagic events have included gastrointestinal , pulmonary , and intracranial hemorrhage and epistaxis . Promptly evaluate signs and symptoms of blood loss . Reduce or withhold dose as appropriate .
Thrombocytopenia :
• KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle . Monitor platelet counts frequently during treatment . Reduce or withhold dose as appropriate .
Hepatic Toxicity and Hepatic Failure :
• Cases of hepatic failure , including fatal cases , have occurred . KYPROLIS can cause increased serum transaminases . Monitor liver enzymes regularly regardless of baseline values . Reduce or withhold dose as appropriate .
Thrombotic Microangiopathy :
• Cases of thrombotic microangiopathy , including thrombotic thrombocytopenic purpura / hemolytic uremic syndrome ( TTP / HUS ), including fatal outcome , have occurred . Monitor for signs and symptoms of TTP / HUS . Discontinue if diagnosis is suspected . If the diagnosis of TTP / HUS is excluded , KYPROLIS may be restarted . The safety of reinitiating KYPROLIS is not known .
Posterior Reversible Encephalopathy Syndrome ( PRES ):
• Cases of PRES have occurred in patients receiving KYPROLIS . If PRES is suspected , discontinue and evaluate with appropriate imaging . The safety of reinitiating KYPROLIS is not known .
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients :
• In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS , melphalan , and prednisone ( KMP ) vs bortezomib , melphalan , and prednisone ( VMP ), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm . KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma .
Embryo-fetal Toxicity :
• KYPROLIS can cause fetal harm when administered to a pregnant woman .
• Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS . Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS . If this drug is used during pregnancy , or if pregnancy occurs while taking this drug , the patient should be apprised of the potential hazard to the fetus .
ADVERSE REACTIONS
The most common adverse reactions in the combination therapy trials : anemia , neutropenia , diarrhea , dyspnea , fatigue , thrombocytopenia , pyrexia , insomnia , muscle spasm , cough , upper respiratory tract infection , hypokalemia .
Please see Brief Summary of full Prescribing Information on adjacent pages .
6 ASH Clinical News
Learn more at KYPROLIS-HCP . com