INDICATIONS
Indications
  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.Read More
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.Close
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KYPROLIS® (carfilzomibz) for injection logo
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Help your patients start and stay on KYPROLIS®

Dose according to Prescribing Information for proven results.1

Dose according to Prescribing Information for proven results.1

To determine your patients’ KYPROLIS® priming and therapeutic dose amount, download the quick start dosing guide.

DKd

Dosing summary for KYPROLIS® (carfilzomib) combinations DKd, Isa-Kd, KRd, and Kd

Isa-Kd

Dosing summary for KYPROLIS® (carfilzomib) combinations DKd, Isa-Kd, KRd, and Kd

KRd

Dosing summary for KYPROLIS® (carfilzomib) combinations DKd, Isa-Kd, KRd, and Kd

Kd

Dosing summary for KYPROLIS® (carfilzomib) combinations DKd, Isa-Kd, KRd, and Kd

KYPROLIS® is approved in combination with both daratumumab for intravenous infusion and daratumumab and hyaluronidase-fihj for subcutaneous injection.

m2 = meters squared; mg = milligrams; DKd = carfilzomib + daratumumab + dexamethasone; Isa-Kd = carfilzomib + isatuximab-irfc + dexamethasone; KRd = carfilzomib + lenalidomide + dexamethasone; Kd = carfilzomib + dexamethasone; mg/m2 = milligrams per meter squared body surface area.

Calculating the priming & therapeutic dose

For patients with a body surface area (BSA) of 2.2 m2 or less, calculate the dose using actual BSA:

  • Patients with a BSA greater than 2.2 m2 should receive a dose based upon a BSA of 2.2 m2
  • Dose adjustments do not need to be calculated for weight changes of less than or equal to 20%

To calculate the priming and therapeutic doses, multiply the patient’s BSA by the KYPROLIS® dose for the specific treatment regimen:

  • Patient’s body surface area (BSA; m2) x dose (mg/m2)
  • Example: Calculate the correct Kd once-weekly dose for a patient with a BSA of 1.8 m2

Priming dose: 1.8 m2 x 20 mg/m2 = 36 mg

Therapeutic dose: 1.8 m2 x 70 mg/m2 = 126 mg

Using the patient’s total dose calculated, refer to the full Prescribing Information to determine the appropriate number of vials required for administration. KYPROLIS® is supplied in 60-mg, 30-mg, and 10-mg single-dose vials for reconstitution.

Read the complete preparation instructions prior to reconstitution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Administration & Storage

Precautions for administration of KYPROLIS®

The quantity of KYPROLIS® (carfilzomib) contained in one single-dose vial (30 mg or 60 mg) may exceed the recommended dose. Caution should be used in calculating the quantity delivered to prevent overdosing.

  • KYPROLIS® 70 mg/m2 is infused intravenously over 30 minutes
  • KYPROLIS® 56 mg/m2 is infused intravenously over 30 minutes
  • KYPROLIS® 27 mg/m2 is infused intravenously for 10 minutes

Administer as an intravenous infusion.

Storage

KYPROLIS® vials contain no antimicrobial preservatives and are intended for single dose only. Unopened vials of KYPROLIS® are stable until the date indicated on the package when stored in the original package at 2°C to 8°C (36°F to 46°F). Retain in original package to protect from light. The reconstituted solution contains carfilzomib at a concentration of 2 mg/mL.

Stability of reconstituted KYPROLIS®
Stability of reconstituted KYPROLIS® (carfilzomib) table
Stability of reconstituted KYPROLIS® (carfilzomib) table

*Total time from reconstitution to administration should not exceed 24 hours.

†5% Dextrose Injection, USP.

mg = milligram; mg/m2 = milligrams per meter squared body surface area; mg/mL = milligrams per milliliter.

Managing hydration throughout treatment

Adequate hydration is required prior to KYPROLIS® dosing in Cycle 1—especially in patients at high risk of tumor lysis syndrome or renal toxicity.1

IMAGE 1

During cycle 1

If needed, give an additional 250-500 mL of IV fluids following KYPROLIS® administration

IMAGE 2

In subsequent cycles

Continue oral and/or IV hydration, as needed

Image 3

Throughout treatment

Monitor patients for evidence of volume overload and adjust hydration to individual patient needs, especially in patients with, or at risk for, cardiac failure

Consider hydration with both oral and IV fluids

oral fluids

30 mL/kg

at least 48 hours before Cycle 1, Day 1

Oral fluids
IV fluids

IV fluids

250-500 mL

prior to each dose in Cycle 1

mL = milliliter; IV = intravenous; mL/kg = milliliters per kilogram.

  • Additional Dosing Considerations

    Managing the cardiovascular health of your patients

    The risk of cardiovascular events may be mitigated with basic management strategies, including proper fluid management and appropriate monitoring.2

    BEFORE Identify & Plan2

    Identify and assess patients at risk for cardiac ARs

    Control hypertension and active heart failure and optimize blood pressure prior to initiating treatment

    Consider cardiology consult before initiating treatment

    Plan for fluid management during treatment

    DURING Monitor2

    Measure blood pressure regularly in all patients

    Check for signs and symptoms of cardiac ARs

    Monitor volume status in all patients and adjust fluids

    AFTER Stop & Assess2

    Withhold for Grade 3 or 4 cardiac ARs until recovery

    Consider reinitiating with one dose-level reduction based on a benefit-risk assessment†

    *KYPROLIS® is approved in combination with both daratumumab for intravenous infusion and daratumumab and hyaluronidase-fihj for subcutaneous injection.

    †Consultation with a cardiologist is warranted at the time of AR and upon reinitiation of treatment.

    AR = adverse reaction.

Dose modifications for adverse reactions

  • Hematologic toxicity

    Recommended action

    Absolute neutrophil count (ANC) less than 0.5 x 109/L

    Withhold dose

    • If recovered to greater than or equal to 0.5 x 109/L, continue at the same dose level

    For subsequent drops to less than 0.5 x 109/L, follow the same recommendations as above and consider one dose level reduction when restarting KYPROLIS®*

    Febrile neutropenia (ANC less than 0.5 x 109/L and an oral temperature more than 38.5°C or two consecutive readings of more than 38.0°C for 2 hours)

    Withhold dose

    • If ANC returns to baseline grade and fever resolves, resume at the same dose level

    Platelets less than 10 x 109/L or evidence of bleeding with thrombocytopenia

    Withhold dose

    • If recovered to greater than or equal to 10 x 109/L and/or bleeding is controlled, continue at the same dose level

    For subsequent drops to less than 10 x 109/L, follow the same recommendations as above and consider one dose level reduction when restarting KYPROLIS®*

  • Renal toxicity

    Recommended action

    Serum creatinine greater than or equal to 2 × baseline, or

    Creatinine clearance less than 15 mL/min, or creatinine clearance decreases to less than or equal to 50% of baseline, or need for hemodialysis

    Withhold dose and continue monitoring renal function (serum creatinine or creatinine clearance)

    • If attributable to KYPROLIS®, resume when renal function has recovered to within 25% of baseline; start at one dose level reduction*

    If not attributable to KYPROLIS®, dosing may be resumed at the discretion of the healthcare provider

    For patients on hemodialysis receiving KYPROLIS®, the dose is to be administered after the hemodialysis procedure

  • Other non-hematologic toxicity

    Recommended action

    All other severe or life-threatening (Grade 3 or 4) non-hematological toxicities

    Withhold until resolved or returned to baseline

    Consider restarting the next scheduled treatment at one dose level reduction (see table below for dose level reductions)*

  • Dose modifications for use in hepatic impairment1

    For patients with mild or moderate hepatic impairment, reduce the dose of KYPROLIS® by 25%.

  • Dosing in patients with end stage renal disease1

    For patients with end stage renal disease who are on dialysis, administer KYPROLIS® after the hemodialysis procedure.

Note: Infusion times remain unchanged during dose reduction(s).

*If toxicity persists, discontinue KYPROLIS® treatment.

mL/min = milliliter per minute; mg/m2 = milligrams per meter squared body surface area; ANC = absolute neutrophil count; L = liter; mg/min = milligrams per minute.

Help patients continue treatment with dose level reductions when needed

Dose modification for AE KYPROLIS® (carfilzomib) datatable

Infusion times remain unchanged during dose reduction(s).

*If toxicity persists, discontinue KYPROLIS® treatment.

mg/m2 = milligrams per meter squared body surface area.

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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), 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 reactions until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/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 fluid 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 fluid management.

Acute Renal Failure

  • Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency (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 infiltrative 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 benefit/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 benefit/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 benefit/risk assessment.

Venous Thrombosis

  • Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Provide thromboprophylaxis for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
  • For patients using hormonal contraception associated with a risk of thrombosis, consider an alternative method of effective contraception during treatment.

Infusion-Related Reactions

  • Infusion-related reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal 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-related reactions.

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.

Progressive Multifocal Leukoencephalopathy (PML)

  • Cases of PML, including fatal cases, have occurred. In addition to KYPROLIS, other contributary factors may include prior or concurrent use of immunosuppressive therapy. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, discontinue and initiate evaluation for PML including neurology consultation.

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 reactions 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.
  • Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment with KYPROLIS and for 6 months following the final dose. Males of reproductive potential should use effective contraception during treatment with KYPROLIS and for 3 months following the final dose.

Adverse Reactions

  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS in the combination therapy trials: anemia, diarrhea, hypertension, fatigue, upper respiratory tract infection, thrombocytopenia, pyrexia, cough, dyspnea, and insomnia.
  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see accompanying full Prescribing Information.

INDICATIONS

  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more 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), 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 reactions until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/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 fluid 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 fluid management.

Acute Renal Failure

  • Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency (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 infiltrative 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 benefit/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 benefit/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 benefit/risk assessment.

Venous Thrombosis

  • Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Provide thromboprophylaxis for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
  • For patients using hormonal contraception associated with a risk of thrombosis, consider an alternative method of effective contraception during treatment.

Infusion-Related Reactions

  • Infusion-related reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal 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-related reactions.

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.

Progressive Multifocal Leukoencephalopathy (PML)

  • Cases of PML, including fatal cases, have occurred. In addition to KYPROLIS, other contributary factors may include prior or concurrent use of immunosuppressive therapy. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, discontinue and initiate evaluation for PML including neurology consultation.

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 reactions 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.
  • Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment with KYPROLIS and for 6 months following the final dose. Males of reproductive potential should use effective contraception during treatment with KYPROLIS and for 3 months following the final dose.

Adverse Reactions

  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS in the combination therapy trials: anemia, diarrhea, hypertension, fatigue, upper respiratory tract infection, thrombocytopenia, pyrexia, cough, dyspnea, and insomnia.
  • The most common adverse reactions occurring in at least 20% of patients taking KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see accompanying full Prescribing Information.

INDICATIONS

  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
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References: 1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Jakubowiak AJ, DeCara JM, Mezzi K. Cardiovascular events during carfilzomib therapy for relapsed myeloma: practical management aspects from two case studies. Hematology. 2017;22(10):585-591.