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Guidelines

Guidelines Summary

Guidelines contributor: Priyank P Patel, MD Hematology/Oncology Fellow, Roswell Park Cancer Institute, University at Buffalo

Diagnosis

Updated guidelines on the management of Hodgkin lymphoma have been issued by the National Comprehensive Cancer Network (NCCN)^[4]and the European Society for Medical Oncology (ESMO).^[5]The NCCN and ESMO guidelines have very similar recommendations for the diagnostic evaluation.^{[4, 5]}Histological evaluation is required for diagnosis according to the World Health Organization (WHO) classification of either nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) or one of four classical Hodgkin lymphoma (CHL) subtypes, as follows:

Nodular sclerosis CHL (NSCHL)
Mixed cellularity CHL (MCCHL)
Lymphocyte-depleted CHL (LDCHL)
Lymphocyte-rich CHL (LRCHL)

The presence of Hodgkin and Reed-Sternberg (HRS) cells is disease defining for CHL. Detection of lymphocyte-predominant (LP) cells is required for the diagnosis of NLPHL

Biopsy recommendations are as follows:

Excisional biopsy is preferred
Core needle biopsy can be considered if excisional biopsy is not possible
Fine needle aspiration should be avoided

Other recommendations for diagnosis are as follows:

History and physical examination to determine presence of B symptoms (unexplained weight loss >10%, fever, drenching night sweats)
Fatigue, pruritus, and alcohol intolerance should also be noted

Staging

Both the National Comprehensive Cancer Network (NCCN)^[4] and the European Society for Medical Oncology (ESMO)^[5]recommend the Cotswold modified Ann Arbor classification for staging Hodgkin lymphoma.^[122]See Table 1, below.

Table 1. Cotswold Modification of Ann Arbor Staging System (Open Table in a new window)

Stage	Area of Involvement
I	Single lymph node group
II	Multiple lymph node groups on same side of diaphragm
III	Multiple lymph node groups on both sides of diaphragm

The ESMO guidelines for staging and risk assessment include the following recommendations^[5]:

Chest x-ray and a contrast-enhanced CT scan of neck, chest, and abdomen are mandatory
A baseline PET should be conducted, if this is available
A bone marrow biopsy is not indicated in patients undergoing PET-CT evaluation but must be carried out if PET-CT is not available.
Full blood cell count, erythrocyte sedimentation rate (ESR), and blood chemistry analysis are obligatory. Screening for hepatitis B and C viruses and HIV is compulsory.
After staging examinations are completed, HL patients are allocated to distinct risk groups depending on their clinical stage and the presence of clinical risk factors
Cardiac and pulmonary function tests should be performed out before the start of treatment
Reproductive counselling and consideration of sperm banking, oocyte collection, or ovarian tissue cryopreservation should be offered to patients of reproductive age before treatment.

In 2014, the International Conference on Malignant Lymphomas, a multi-disciplinary team of researchers, representing major lymphoma clinical trial groups and cancer centers from North America, Europe, Japan and Australasia, published guidelines for the evaluation, staging, and response assessment. These guidelines were intended to be an update to the 2007 revised guidelines of the International Harmonization Project.^[6]The revised recommendations for staging are as follows^[123]:

PET-CT is preferred for pretreatment assessment and routine staging
Contrast-enhanced CT is more accurate for measurement of nodal size and is also preferred for radiation planning
Chest x-ray is not required
PET-CT is preferred for determining splenic involvement with cutoff for splenomegaly of more than 13 cm
Liver size is not a reliable measure of hepatic involvement; diffusely increased or focal uptake, with or without focal or disseminated nodules, supports liver involvement
Bone marrow aspirate/biopsy is not required for early-stage HL (stage I-IIA) if PET-CT was performed (an exception noted by NCCN is if PET-CT is negative but the patient has unexplained cytopenias^[4])
Bone marrow biopsy and aspirate is required for patients with advanced-stage HL (stage IIB-IV)

In addition, these guidelines offered consensus on further modifications to the Ann Arbor staging classification. See Table 2, below.^[123]

Table 2. International Conference on Malignant Lymphomas Modification of Ann Arbor Staging (Open Table in a new window)

Stage		Area of Involvement	Extranodal (E) Status
I	Single node or adjacent group of nodes		Single extranodal lesions without nodal involvement
II	Multiple lymph node groups on same side of diaphragm		Stage I or II by nodal extent with limited contiguous extranodal involvement
II bulky*	Multiple lymph node groups on same side of diaphragm with bulk >10 cm		N/A
III	Multiple lymph node groups on both sides of diaphragm; nodes above the diaphragm with spleen involvement		N/A
IV	Multiple noncontiguous extranodal sites		N/A
A/B	B symptoms: weight loss >10%, fever, drenching night sweats		N/A
*Stage II bulky disease is defined as limited or advanced on the basis of histology and a number of prognostic factors.

Risk Stratification

Based on the clinical scenario, staging, and degree of end-organ damage, patients with Hodgkin lymphoma are further categorized into the following three groups:

Early-stage favorable
Early-stage unfavorable
Advanced-stage

National Comprehensive Cancer Network (NCCN) guidelines define unfavorable factors for stage I-II as follows^[4]:

Bulky mediastinal disease (mediastinal mass ratio [MMR; maximum width of mass/maximum intrathoracic diameter] greater than 0.33) or bulky disease greater than 10 cm
B symptoms
Erythrocyte sedimentation rate (ESR) >50 mm/hr
More than two-three nodal sites of disease

The European Society for Medical Oncology (ESMO) guidelines recommend the slightly different definitions of risk factors from the European Organization for Research and Treatment of Cancer /Lymphoma Study Association (EORTC/LSA) and the German Hodgkin Study Group (GSHG), as outlined in Table 3, below.^[5]

Table 3. Unfavorable Risk Factors for Stages I and II Hodgkin Lymphoma (Open Table in a new window)

Risk Factor	GSHG	EORTC/LSA
Age	–	≥50 y
Histology	–	MC or LD
ESR or B symptoms	>50 mm/hr if A or >30 if B	>50 mm/hr if A or > 30 if B
Mediastinal mass*	MMR >0.33	MMR >0.35
Number of nodal sites	>2	>3
Extranodal lesions	Any	–
* Mediastinal mass is measured on chest x-ray by the mediastinal mass ratio (MMR), which is the maximum width of the mass/maximum intrathoracic diameter.ESR = erythrocyte sedimentation rate; LD = lymphocyte depletion; MC = mixed cellularity.

Patients with advanced disease are further risk stratified using the International Prognostic Score (IPS), which includes the following risk factors (for scoring, each factor receives 1 point)^[30]:

Albumin < 4 g/dL
Hemoglobin < 0.5 g/dL
Male
Age ≥45 y
Stage IV disease
Leukocytosis: white blood cell count (WBC) >15,000/μL
Lymphopenia: Lymphocyte count < 8% of WBC and/or absolute lymphocyte count < 600 cells/μL

Based on the IPS score, patients with advanced disease can be categorized as follows^[123]:

Good risk (IPS 0-1)
Fair risk (IPS 2-3)
Poor risk (IPS 4-7)

Treatment for Classical Hodgkin Lymphoma

Recommendations for primary treatment of classical Hodgkin lymphoma (cHL) vary by stage and risk stratification. Chemotherapy is followed by restaging with PET-CT.

On the basis of fluorodeoxyglucose (FDG) PET findings, a Deauville score can be assigned. The Deauville score is based on visual interpretation of FDG uptake by FDG-avid (or previously FDG-avid) lesions, compared with two reference points: the mediastinum (which represents the blood pool) and the liver.^[124]Scores are as follows:

No uptake or no residual uptake (when used interim)
Slight uptake, but equal to or less than that of blood pool (mediastinum)
Uptake above mediastinal, but below or equal to uptake in the liver
Uptake slightly to moderately higher than liver
Markedly increased uptake or any new lesion (on response evaluation)

Early-stage favorable disease

Combined modality is the treatment of choice in patients with early-stage cHL. The National Comprehensive Cancer Network (NCCN) guidelines give the ABVD (doxorubicin [Adriamycin]/bleomycin/vinblastine/dacarbazine) regimen a category 1 rating (ie, the recommendation is based on high-level evidence and uniform NCCN consensus that the intervention is appropriate), but also list an 8-week Stanford V regimen (doxorubicin, vinblastine, mechlorethamine [or cyclophosphamide], etoposide, vincristine, bleomycin, and prednisone) as an alternative.^[4]

ABVD is administered in four cycles. However, two cycles are suggested in highly selected patients with very favorable disease characterized by the following^[4]:

No bulky disease
No extralymphatic involvement
Fewer than three sites of disease
Erythrocyte sedimentation rate (ESR) < 30 mm/hr, or < 50 mm/hr in patients without B symptoms

After initial ABVD and interim restaging with PET, the NCCN recommends subsequent management according to the patient’s Deauville score, as follows^[125]:

Deauville score of 1 to 3: A planned course of involved-site radiation therapy (ISRT) (20 Gy) is recommended.
Deauville score of 4: Two additional cycles of ABVD followed by interim PET/CT may be considered prior to ISRT (30 Gy).
Deauville score of 5: Biopsy is recommended. If the biopsy is negative, patients may be treated with two additional cycles of ABVD and ISRT (30 Gy). A repeat PET/CT could be considered before initiation of RT. If the biopsy is positive, patients should be managed as described for refractory disease.
Alternatively, patients with a Deauville score of 1 to 2 can be treated with an additional cycle of ABVD and ISRT (30 Gy). Patients with a Deauville score of 3 can be treated with two additional cycles of ABVD and ISRT (30 Gy).

If there is a preference to use chemotherapy alone, recommended options for subsequent management depend on the patient’s Deauville score, as follows^[125]:

Deauville score of 1 or 2: An additional one to two cycles of ABVD or four cycles of AVD (for initial stage IIB or ≥3 sites)
Deauville score of 3: An additional two cycles of ABVD or 4 cycles of AVD (for initial stage IIB or ≥3 sites).
Deauville score of 4: Two additional cycles of ABVD or two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], procarbazine, prednisone) followed by restaging with PET. If the restaging Deauville score is 1 to 3, the treatment options include an additional two cycles of ABVD (if previously given), or an additional 2 cycles of escalated BEACOPP (if previously given).
Deauville score of 5: Biopsy is warranted; patients with a negative biopsy should be managed as for Deauville 1 to 3. Those with a positive biopsy should be managed as for refractory disease.

The European Society for Medical Oncology (ESMO) guidelines recommend two to three cycles of ABVD followed by ISRT. Alternatively, patients may undergo PET-CT scanning after two cycles of ABVD: PET-postive patients then receive two cycles of BEACOPPesc (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone in escalated dose) followed by 30Gy ISRT; PET-negative patients undergo one cycle of BEACOPPesc followed by 20Gy ISRT.^[5]

ESMO notes that whether RT can be omitted in selected patients with complete metabolic response at interim PET is a matter of debate. However, this approach may be offered to individual patients in whom the late risk of RT is thought to outweigh the short-term benefit of improved disease control.^[5]

Early-stage unfavorable disease

Stage I-II unfavorable, non-bulky disease

According to NCCN guidelines, if the preference is to treat with combined-modality therapy, the preferred regimen, recommended options for subsequent management depend on the patient’s Deauville score, as follows^[125]:

Deauville score of 1 to 2: Two additional cycles of ABVD and ISRT
Deauville score of 3 to 4: Either two additional cycles of ABVD alone (preferred if Deauville 3) or two cycles of escalated BEACOPP (preferred for Deauville 4 or 5). PET restaging may be considered at this point and patients are followed up with ISRT (30 Gy).
Deauville score of 5: Biopsy is recommended. If the biopsy is negative, patients are treated as described for a Deauville score of 3 to 4. All patients with a positive biopsy should be managed as described for refractory disease.

If there is a preference to treat patients with chemotherapy alone, the treatment recommendations are the same as for stage I–II favorable, non-bulky disease.

The ESMO guidelines recommend four cycles of ABVD with involved-field radiation therapy (IFRT). In younger patients (≤60 years) a more intensive treatment can be considered, consisting of two cycles of escalated BEACOPP followed by two cycles of ABVD with IFRT.^[5]

Stage I-II unfavorable, bulky mediastinal disease or adenopathy >10 cm

According to NCCN guidelines, after initial ABVD and interim restaging with PET, subsequent management by the patient’s Deauville score is as follows^[125]:

Deauville score of 1 to 3: Two additional cycles of ABVD plus ISRT or four cycles of AVD with or without ISRT
Deauville score of 4: Two additional cycles of ABVD or two to three cycles of escalated BEACOPP followed by PET and ISRT or an additional cycle of escalated BEACOPP, if they were previously treated with three cycles of escalated BEACOPP.
Deauville score of 5: Biopsy is recommended. If the biopsy is negative, management is as described for patients with a Deauville score of 4. Patients with a positive biopsy should be managed as described for refractory disease. Alternatively, two cycles of escalated BEACOPP may be given, followed by PET and ISRT.

Advanced-stage disease

NCCN guidelines advise that chemotherapy is always used for patients with advanced-stage disease (stage III-IV), but combined-modality therapy is used in some treatment regimens, especially for patients with bulky disease and in those who show a poor response to chemotherapy in other treatment regimens.^[125]

After initial ABVD and interim restaging with PET, subsequent management by the patient’s Deauville score is as follows:

Deauville score of 1 to 3: Four cycles of AVD, then observation or ISRT to initially bulky or selected PET-positive sites.
Deauville score of 4: Two additional cycles of ABVD or two cycles of escalated BEACOPP followed by reassessment of response with PET.
Deauville score of 5: Two cycles of BEACOPP may be considered in select cases, but biopsy is recommended. If a biopsy is negative, treatment is as for a Deauville score of 4; if it is positive, management is as described for refractory disease.

The addition of brentuximab vedotin to AVD is a category 2A option in select patients with no known neuropathy, if the International Prognostic Score (IPS) ≥4 or bleomycin is contraindicated.

The ESMO guidelines recommend the following^[5]:

ABVD for six to eight cycles, followed by localized radiotherapy of residual lymphoma larger than 1.5 cm
Escalated BEACOPP for six cycles, followed by localized radiotherapy of residual lymphoma larger than 2.5 cm

Older patients

The NCCN recommends enrollment in a clinical trial, when available, for patients older than 60 years with classical HL.^[125]Otherwise, the NCCN recommends considering the regimens listed below in order to lessen or minimize toxicity, although they have not been proven to improve disease outcomes in older patients.

Stage I-II favorable disease options are as follows:

ABVD (preferred) or AVD, followed by ISRT
CHOP (cyclophosphamide, doxorubicin [hydroxydaunomycin], vincristine [Oncovin], prednisolone) with ISRT
VEPEMB (vinblastine, cyclophosphamide, procarbazine, prednisone, etoposide, mitoxantrone, bleomycin) with or without ISRT

Stage I–II unfavorable or stage III–IV disease options are as follows:

ABVD plus brentuximab vedotin lead in followed by AVD and brentuximab vedotin maintenance
Brentuximab vedotin plus dacarbazine (DTIC)
CHOP
PVAG (prednisone, vinblastine, doxorubicin, gemcitabine)
VEPEMB with or without ISRT

Refractory or relapsed disease

NCCN guidelines recommend second-line systemic therapy followed by response assessment with PET for all patients with refractory or relapsed disease.^[125]Other options include the following:

Further cytoreduction and high-dose therapy with autologous stem cell rescue (HDT/ASCR), with RT if not previously given
RT or systemic therapy with or without RT
Conventional-dose second-line systemic therapy may precede HDT/ASCR
RT should be strongly considered for selected sites of relapse that have not been previously irradiated. In radiation-naïve patients, total lymphoid irradiation may be an appropriate component of HDT/ASCR.

ESMO guidelines recommend high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for refractory or relapsed disease. The selection of second-line chemotherapy is determined by comparison with the agents previously used.^[5]Brentuximab vedotin is recommended for patients who have a failure of ASCT or failure of at least two prior multi-agent chemotherapy regimens.^[5]

Treatment for NLPHL

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a distinct entity with unique clinical features and a different treatment paradigm. The National Comprehensive Cancer Network (NCCN) prefers involved-site radiation therapy (ISRT) over involved-field radiation therapy (IFRT) for treatment of early-stage favorable NLPHL. (Involved-site fields are generally smaller than classic involved fields.) For early-stage unfavorable or advanced-stage NLPHL, an ABVD regimen (doxorubicin [Adriamycin]/bleomycin/vinblastine/dacarbazine) plus ISRT is recommended. CHOP (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], and prednisone) may also be used.^[4]

Rituximab may be considered in combination with ABVD or CHOP. For refractory disease, maintenance rituximab may be considered. Individualized treatment is recommended. At relapse, patients biopsy should be performed due to the high rate of conversion to aggressive B-cell lymphoma.^[4]

ESMO recommends IFRT for treatment of patients with stage IA NLPHL who have no risk factors. For early-stage unfavorable or advanced stage disease, the treatment recommendation is identical to that for CHL.^[5]

Long-Term Monitoring

Both the National Comprehensive Cancer Network (NCCN)^[4]and the European Society for Medical Oncology (ESMO)^[5]guidelines provide recommendations for the long-term follow-up of treated patients with Hodgkin lymphoma who are in complete remission. The NCCN recommends interim physical exams and blood tests every 3 to 6 months for 1 to 2 years and then every 6 to 12 months for the next 3 years and then annually.^[4]ESMO suggests follow-up every 3 months for the first 6 months, and every 6 months until year 4, then annually.^[5]

Follow-up examination recommendations are similar for both guidelines, but those from the NCCN are more detailed. NCCN recommendation for follow-up in the first 5 years include the following^[4]:

History and physical examination
Complete blood cell count (CBC), serum chemistry panel, and erythrocyte sedimentation rate (ESR)
Thyroid-stimulating hormone (TSH) levels (at least annually if the patient has had neck radiation therapy)
Annual influenza vaccine
Neck/chest/abdomen/pelvis CT scan with contrast, at 6, 12, and 24 mo following completion of therapy, or as clinically indicated, is acceptable
PET/CT is recommended only if last PET was Deauville 4-5, to confirm complete response

Recommendations for annual monitoring for late complications after 5 years include the following^[5]:

CBC, serum chemistry panel, and erythrocyte sedimentation rate (ESR)
TSH levels (at least annually if the patient had neck radiation therapy)
Biannual lipids assay
Annual fasting glucose
Blood pressure monitoring
Management of cardiovascular risk factors; stress test/echocardiogram and carotid ultrasound (if the patient has had neck radiation therapy) every 10 years
Vaccinations against pneumococcus, Haemophilus influenzae, and meningococcus (especially in patients who have had splenectomy), with revaccination every 5-7 years
Annual influenza vaccine
Chest x-ray or low-dose CT scans of the chest in patients with increased risk of lung cancer
In women who have received chest irradiation¸ annual screening with mammography, starting at age 40 years or 8-10 years after radiation therapy; breast magnetic resonance imaging (MRI) in addition to mammography is indicated for patients who received chest radiation therapy between the ages of 10 and 30 years

Medication

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Media Gallery

Micrograph of Hodgkin lymphoma in a fine-needle aspiration lymph node specimen (field stain). Eosinophils, Reed-Sternberg cells, plasma cells, and histocytes can be seen.
Nodular sclerosing Hodgkin lymphoma of the mediastinum. The diagnosis is strongly suggested by the presence of distinct nodules on the cut surface of this lymph node.
A Reed-Sternberg cell in Hodgkin lymphoma. Reed-Sternberg cells are large, abnormal lymphocytes that may contain more than one nucleus. Image courtesy of National Cancer Institute.
Mixed cellularity Hodgkin lymphoma showing both mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells (hematoxylin and eosin, original magnification x200).
Very high magnification micrograph of nodular lymphoctye predominant Hodgkin lymphoma (NLPHL), with a popcorn-shaped Reed-Sternberg cell (hematoxylin and eosin).
A positron emission tomography (PET) scan obtained with fluorodeoxyglucose (FDG) that shows increased FDG uptake in a mediastinal lymph node.
A computed tomography (CT) scan showing bulk disease in a patient with Hodgkin lymphoma.
This computed tomography scan is from a 46-year patient with Hodgkin lymphoma at the level of the neck. Enlarged lymph nodes are visible on the left side of the neck (red-shaded region).
This image depicts a computed tomography (CT) scan, positron-emission tomography (PET) scan, and maximum intensity projection (MIP) PET scan from a patient with histologically proven Hodgkin lymphoma.

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Table 1. Stage Distribution and 5-Year Relative Survival by Stage at Diagnosis for All Races and Both Sexes: 2011-2015

Stage at Diagnosis	Stage Distribution, %	5-year Relative Survival, %
Stage I (only in originating layer of cells)	15	92.3
Stage II (confined to primary site)	40	93.4
Stage III (spread to regional lymph nodes)	21	83.0
Stage IV (cancer has metastasized)	20	72.9
Unstaged	4	82.7
Source: National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at: http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: September 12, 2018

Table 1. Cotswold Modification of Ann Arbor Staging System

Stage	Area of Involvement
I	Single lymph node group
II	Multiple lymph node groups on same side of diaphragm
III	Multiple lymph node groups on both sides of diaphragm

Table 2. International Conference on Malignant Lymphomas Modification of Ann Arbor Staging

Stage		Area of Involvement	Extranodal (E) Status
I	Single node or adjacent group of nodes		Single extranodal lesions without nodal involvement
II	Multiple lymph node groups on same side of diaphragm		Stage I or II by nodal extent with limited contiguous extranodal involvement
II bulky*	Multiple lymph node groups on same side of diaphragm with bulk >10 cm		N/A
III	Multiple lymph node groups on both sides of diaphragm; nodes above the diaphragm with spleen involvement		N/A
IV	Multiple noncontiguous extranodal sites		N/A
A/B	B symptoms: weight loss >10%, fever, drenching night sweats		N/A
*Stage II bulky disease is defined as limited or advanced on the basis of histology and a number of prognostic factors.

Table 3. Unfavorable Risk Factors for Stages I and II Hodgkin Lymphoma

Risk Factor	GSHG	EORTC/LSA
Age	–	≥50 y
Histology	–	MC or LD
ESR or B symptoms	>50 mm/hr if A or >30 if B	>50 mm/hr if A or > 30 if B
Mediastinal mass*	MMR >0.33	MMR >0.35
Number of nodal sites	>2	>3
Extranodal lesions	Any	–
* Mediastinal mass is measured on chest x-ray by the mediastinal mass ratio (MMR), which is the maximum width of the mass/maximum intrathoracic diameter.ESR = erythrocyte sedimentation rate; LD = lymphocyte depletion; MC = mixed cellularity.

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Author

Bradley W Lash, MD Attending Physician, Lehigh Valley Cancer Institute

Bradley W Lash, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Zachary Wolfe, MD Fellow in Hematology/Oncology, Lehigh Valley Health Network

Zachary Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Athanassios Argiris, MD Professor, Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine

Athanassios Argiris, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Scott K Dessain, MD, PhD Associate Professor, Lankenau Institute for Medical Research

Disclosure: Genentech Speaker's bureau.

Virginia Kaklamani, MD, Fellow, Department of Internal Medicine, Division of Hematology-Oncology, Northwestern University Medical School

Disclosure: Nothing to disclose.

Koyamangalath Krishnan, MD, FRCP, FACP Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

James L Spears, MD Consulting Staff, Bux-Mont Hematology Oncology Medical Associates

James L Spears, MD is a member of the following medical societies: American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Christine Wasilewski, MD, MPH, Fellow, Department of Medicine, Division of Hematology-Oncology, Thomas Jefferson University Hospital

Disclosure: Nothing to disclose.