eMedicine Specialties > Hematology > Plasma Cell Disorders

Waldenstrom Hypergammaglobulinemia: Treatment & Medication

Author: Doris Ponce, MD, Fellow, Department of Hematology/Oncology, New York Medical College
Coauthor(s): Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College; Vijay Ramu, MBBS, Staff Physician, Department of Internal Medicine, East Tennessee State University; Harsha Vyas, MD, Fellow, Section of Hematology and Oncology, Wake Forest University School of Medicine; Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Contributor Information and Disclosures

Updated: Aug 29, 2009

Treatment

Medical Care

Patients who meet criteria for Waldenström macroglobulinemia (serum IgM monoclonal protein, bone marrow lymphoplasmacytic infiltration, or both) without end-organ damage are considered to have indolent disease or smoldering Waldenström macroglobulinemia. No treatment is indicated for asymptomatic disease. Patients can be observed carefully with periodic measurement of the M component, immunoglobulin, and serum viscosity. Therapeutic intervention of Waldenström macroglobulinemia can be divided into treatment of IgM paraprotein complications and treatment of the disease per se. Current therapy available include plasmapheresis, alkylating agents, interferon alfa, purine nucleoside analogues, high-dose chemotherapy, splenectomy, rituximab (anti-CD20 antibody), thalidomide, bone marrow transplantation, and other new agents.

  • Emergent treatment
    • Hyperviscosity syndrome manifestations should be treated promptly, and emergent care is paramount.
    • The treatment of choice for symptoms related to hyperviscosity is urgent plasmapheresis.9 The principle behind management is that 80% of all IgM is confined to the intravascular space. Most often, half of the volume or more should be removed to significantly lower the serum viscosity.
    • Viscosity should be measured before and after plasmapheresis. Approximately 2-4 U of plasma must be removed every 1-2 weeks because the effects produced are not permanent and plasma is replaced with albumin and saline.
    • Chemotherapy should be considered soon after stabilization to reduce the production of the paraprotein by the malignant lymphocytes.
    • Macroglobulinemia can cause complications similar to peripheral neuropathy; cryoglobulinemia or amyloidosis can occur in the absence of high IgM concentrations and manifestations of the lymphomatous process.
    • These symptoms largely result from certain physicochemical properties of the monoclonal IgM protein and can be treated by repeated plasmapheresis followed by systemic therapy. However, evidence supporting plasma exchange for the treatment of peripheral neuropathy associated with IgM paraprotein is weak (grade of recommendation C).
  • Current therapy for Waldenström macroglobulinemia
    • Front line therapy consists of alkylator agents, nucleoside analogues,10 monoclonal antibody, and combination therapy. Currently, no randomized data determine the best option. Therapy is decided based on patient age, performance status, aggressiveness of disease, and paraprotein manifestations.
    • Single agent alkylating agent therapy has been traditionally used for over 40 years. Oral chlorambucil with or without prednisone is frequently used as initial therapy, especially in elderly patients. The response rate is approximately 60%, and the median survival 60 months. Kyle et al conducted a prospective study comparing daily with intermittent oral chlorambucil, and demonstrated no significant difference in response rate or survival.11 The optimal duration of treatment is unknown.
    • Cyclophosphamide alone or in combination is also effective, but no comparative data with chlorambucil exist.
    • Purine nucleoside analogues, fludarabine or cladribine, have demonstrated activity against Waldenström macroglobulinemia. They are effective therapy for patients who are primarily resistant or who relapse after alkylating agents. In 2001, Dhodapkar et al published results of the United States intergroup trial, evaluating fludarabine response in previously untreated and previously treated patients.12 The overall response rate was 36%, with 3% complete remissions, and the overall survival was 84 months. Fludarabine has also demonstrated activity for patients resistant to cladribine.
    • Cladribine is another nucleoside analogue used as initial therapy. Cladribine provides excellent response rates with minimal therapy. The M.D. Anderson Cancer Center published data from 90 patients treated with either cladribine alone or in combination with prednisone, cyclophosphamide, or rituximab. The overall response was 94% for cladribine alone, 60% for cladribine and prednisone, 84% for cladribine and cyclophosphamide, and 94% for cladribine, cyclophosphamide, and rituximab.13 The median overall survival was 73 months.
    • The anti-CD20 monoclonal antibody, rituximab, produces response rates of 20-50% irrespective of prior exposure to chemotherapy. Response to rituximab may be affected by polymorphisms in the Fc-gamma RIIIA (CD16) receptor gene.8 Time to response is slow and exceeds 3 months on average. The flare phenomenon (abrupt increase of IgM paraprotein level) has been described, which may result in hyperviscosity syndrome and indication for plasmapheresis.
    • Combination chemotherapy approaches have been explored, with response rates of more than 75%. Combinations include fludarabine plus rituximab, fludarabine plus cyclophosphamide, cladribine plus cyclophosphamide, cladribine plus cyclophosphamide and rituximab, and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone).14 The German Low Grade Lymphoma Study Group reported results from 72 patients treated with either CHOP or R-CHOP. The response rates were 69% and 94%, respectively.
    • A phase III study of chlorambucil versus fludarabine as initial therapy is ongoing. Results from this trial will help to determine the best initial therapeutic approach and management of Waldenström macroglobulinemia.
    • Salvage therapy for patients with resistant disease or relapse includes reuse or alternative use of front line agent, combination therapy, thalidomide with or without steroids, autologous transplantation, monoclonal antibody (alemtuzumab).
    • There is only one randomized trial in patients with relapsed or refractory disease. Leblond et al15 compared fludarabine with the combination of cyclophosphamide, doxorubicin, and prednisone (CAP) in 92 patients with Waldenström macroglobulinemia who had previously received alkylating agent based therapy. Partial responses were observed in 30% of patients receiving fludarabine compared to 11% of those receiving CAP (P =.019). Responses were more durable in patients receiving fludarabine compared to CAP (19 mo vs 3 mo, respectively). There was no difference in overall survival between the 2 groups.
    • Thalidomide has demonstrated activity against Waldenström macroglobulinemia. Coleman et al16 reported the use of clarithromycin, thalidomide, and dexamethasone in 12 patients previously treated with a purine analogue or alkylating agent; 10 patients responded (3 near complete, 3 major, and 4 partial responses). This combination can be useful in heavily pretreated patients.
    • High-dose chemotherapy with autologous peripheral blood cell transplantation is reserved for selected younger patients with primary refractory or relapsed disease. Desikan et al17 reported 6 patients that received autologous transplant. All 6 achieved a partial response, 5 of the 6 are alive, and 4 are event-free from 2-52 months. Long-term disease control can be achieved, even in those with refractory disease.
    • Other agents are currently under way investigation to evaluate efficacy and tolerability. Interferon alpha, administered for 6 months in untreated and pretreated patients, showed a response rate of 50% with a median duration of response of 27 months. Sildenafil, a phosphodiesterase inhibitor used to treat erectile dysfunction, has demonstrated apoptosis activity against tumor cells in Waldenström macroglobulinemia. Clinical activity in 5 patients has been reported (1 complete response, 4 partial response). The Bcl-2 antisense oligonucleotide (oblimersen sodium) has apoptosis modulating activity in Waldenström macroglobulinemia. Of 16 patients evaluated (untreated and previously treated), all expressed Bcl-2. Phase I and II trials are ongoing to evaluate increased cell death and potential synergy with chemotherapeutic agents; bortezomib, a proteasome inhibitor, has demonstrated 6 partial responses of 16 patients evaluated.18
  • Asymptomatic Waldenström macroglobulinemia
    • Patients with Waldenström macroglobulinemia may not need any treatment apart from close observation.
    • Indications for initiating active treatment include clinical evidence of adverse effects of the paraprotein (hyperviscosity with neurological or ocular disturbance, peripheral neuropathy, amyloidosis, symptomatic cryoglobulinemia, cytopenias), disease progression, or development of constitutional symptoms.
  • Remission and monitoring
    • The effectiveness of chemotherapy is monitored with serum monoclonal IgM concentration on protein electrophoresis and evaluation for signs or symptoms of active disease.
    • Response criteria from the Third International Workshop on Waldenström's Macroglobulinemia include the following19 :
      • Complete response - Disappearance of monoclonal protein by serum electrophoresis, no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly, or signs or symptoms attributable to Waldenström macroglobulinemia
      • Partial response - At least 50% reduction of serum monoclonal IgM concentration on protein electrophoresis and at least 50% decrease in adenopathy/organomegaly; no new symptoms or signs of active disease
      • Minor response - At least 25% but less than 50% reduction of serum monoclonal IgM by protein electrophoresis; no new symptoms or signs of active disease
      • Stable disease - A less than 25% reduction and less than 25% increase of serum monoclonal IgM by electrophoresis without progression of adenopathy/organomegaly, cytopenias, or clinically significant symptoms due to disease and/or signs of Waldenström macroglobulinemia
      • Progressive disease - At least 25% increase in serum monoclonal IgM by protein electrophoresis confirmed by second measurement or progression of clinically significant findings due to disease or symptoms attributable to Waldenström macroglobulinemia

Surgical Care

Splenectomy has been shown to be effective in some patients in whom chemotherapy has failed. Surgical removal of the spleen removes a major source of cells that produce IgM. This surgery is rarely indicated with current treatment options.

Medication

Various drugs, including corticosteroids (eg, prednisone), alkylating agents (eg, chlorambucil, melphalan, cyclophosphamide), biological response modifiers (eg, interferon alfa, interferon gamma), and purine analogues (eg, fludarabine, 2-chlorodeoxyadenosine), are used in the treatment of Waldenström macroglobulinemia.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.


Prednisone (Deltasone, Orasone, Sterapred)

Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Adult

40 mg/m2/d PO for 4 d; repeat cycle q21d

Pediatric

Not established

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; concomitant NSAID use can increase risk of GI bleed

Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in patients with leukopenia or thrombocytopenia (can cause lowering of blood counts, with a prolonged recovery phase); abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Antineoplastic agents

Many combinations of chemotherapeutic agents have been tried, with no evidence of clear superiority over single-agent chemotherapy with chlorambucil and considerably more toxicity.


Chlorambucil (Leukeran)

Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.
Important drug in the treatment of WM. Usually administered when extreme bone marrow infiltration, anemia, splenomegaly, lymphadenopathy, and bleeding are present.

Adult

0.3 mg/kg PO on days 1-5; repeat cycle q4-6wk; adjust dose based on blood counts

Pediatric

4.5 mg/m2/d PO; adjust dose based on blood counts

Documented hypersensitivity; previous resistance to medication

Pregnancy

D - Unsafe in pregnancy

Precautions

Caution in patients with a history of seizure disorders; nephrotic syndrome or bone marrow suppression; use in pregnancy only under life-threatening conditions; narrow therapeutic index, and adverse effects are common; monitor hematologic status regularly


Melphalan (Alkeran)

Inhibits mitosis by cross-linking DNA strands and ultimately disrupts nucleic acid function.

Adult

8 mg/m2/d PO on days 1-4 with prednisone 40 mg/m2/d PO

Pediatric

Not established

Concurrent administration with cyclosporine increases nephrotoxicity; cimetidine and H2 antagonists increase gastric pH, decreasing effects; cisplatin decreases clearance; concomitant use of nalidixic acid can cause severe hemorrhagic necrotizing enterocolitis

Documented hypersensitivity, severe bone marrow suppression, resistance to prior therapy

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Amenorrhea may occur; caution in patients previously diagnosed with myelosuppression; narrow therapeutic index (notify physician if fever, sore throat, rash, vasculitis, unusual lumps, or bleeding occurs); hematological monitoring is essential


Cyclophosphamide (Cytoxan)

Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Adult

125 mg/m2 PO with prednisone 40 mg/m2 PO for 7 d; repeat cycle q4-6wk depending on blood count results

Pediatric

Not established

Allopurinol may increase risk of bleeding or infection and enhances myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity; mesna chemically interacts with the metabolites of drug in bladder and decreases incidence of bladder toxicity; can prolong activity of succinylcholine

Documented hypersensitivity; severely depressed bone marrow function

Pregnancy

D - Unsafe in pregnancy

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; narrow therapeutic index (use judiciously); notify physician if bleeding, sore throat, or fever occurs


Cladribine (Leustatin)

Synthetic antineoplastic agent for continuous IV infusion. The enzyme deoxycytidine kinase phosphorylates this compound into active 5+-triphosphate derivative, which, in turn, breaks DNA strands and inhibits DNA synthesis. Disrupts cell metabolism, causing death to resting and dividing cells.

Adult

0.1 mg/kg/d IV continuous infusion on days 1-7 only or 0.12 mg/kg/d by 2-h continuous infusion for 5 consecutive d every mo

Pediatric

Not established

Pregnancy

D - Unsafe in pregnancy

Precautions

Caution in patients with history of hematologic or immunologic dysfunction; neurotoxicity may occur; allopurinol can be used prophylactically to prevent hyperuricemia secondary to tumor lysis; discontinue if renal or neurotoxicities develop; narrow therapeutic index (use judiciously); notify physician if bleeding, sore throat, or fever occurs; tumor lysis syndrome can occur in patients with high tumor burden (monitor metabolic panel)


Fludarabine (Fludara)

Nucleotide analog of vidarabine converted to 2-fluoro-ara-A that enters the cell and is phosphorylated to form active metabolite 2-fluoro-ara-ATP, which inhibits DNA synthesis.

Adult

25 mg/m2/d IV for 5 d; repeat 5-d course q28d for as many as 6 cycles; adjust dose based on hematologic or nonhematologic toxicity

Pediatric

Not established

Causes fatal pulmonary toxicity when used with pentostatin; cytarabine decreases antineoplastic effect when used prior to a dose of fludarabine

Documented hypersensitivity; breastfeeding; bone marrow suppression

Pregnancy

D - Unsafe in pregnancy

Precautions

Perform frequent peripheral blood counts to detect development of anemia, thrombocytopenia, and neutropenia; monitor for tumor lysis syndrome; adjust dose for renal impairment, severe bone marrow suppression, severe neurological effects, or life-threatening and fatal autoimmune hemolytic anemia; narrow therapeutic index (use judiciously); notify physician if bleeding, sore throat, or fever occurs; monitor closely in pediatric and elderly populations; increased risk of opportunistic infections (eg, Pneumocystis carinii pneumonia and Listeria infections), prophylaxis with TMP-SMZ (160 mg TMP/800 mg SMZ PO q12h) for course of the fludarabine therapy and for at least 6 mo thereafter


Doxorubicin (Adriamycin)

Inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. Combination of these 2 events can, in turn, inhibit growth of neoplastic cells. May be effective in chlorambucil-refractory WM.

Adult

60-75 mg/m2 IV as a single dose; repeat q21d
Alternatively, 20-30 mg/m2/d for 2-3 d; repeat in 4 wk

Pediatric

35-75 mg/m2 IV as single dose; repeat q21d
Alternatively, 20-30 mg/m2 once a week

May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity

Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression

Pregnancy

D - Unsafe in pregnancy

Precautions

Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function

Biological response modifiers

These agents immunomodulate response against malignant cells.


Rituximab (Rituxan)

Genetically engineered human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.

Adult

375 mg/m2 IV qwk for 4 doses

Pediatric

Not established

Coadministration with cisplatin is known to cause severe renal toxicity including acute renal failure; may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 months of vaccine)

Documented hypersensitivity; IgE mediated reaction to murine proteins

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use with caution in patients with dormant infections such as hepatitis B, hepatitis C, or CMV due to risk of reactivation; hypotension, bronchospasm, and angioedema may occur, premedication with acetaminophen and diphenhydramine may decrease incidence; discontinue treatment if life-threatening cardiac arrhythmias occur; must administer by slow IV infusion, do not administer IV push or bolus


Interferon alfa (Intron, Roferon)

Protein product manufactured by recombinant DNA technology. Possesses complex antiviral, antineoplastic, and immunomodulating activities.

Adult

3 million U SC qd for 30 d followed by 3 million U SC 3 times/wk for at least 5 mo; alternatively, 1 million U SC 3 times per wk

Pediatric

Not established

Theophylline may increase toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity; can potentiate neurotoxicity of vidarabine; can enhance antiviral effect of acyclovir; can potentiate bone marrow suppression when used with other myelosuppressive drugs; antipyretics may decrease fever and attenuate myalgia when used before administering interferons

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in patients with brain metastases, debilitating cardiac and pulmonary conditions (perform baseline chest x-ray and ECG), severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or compromised CNS; baseline ophthalmologic evaluation necessary in patients with diabetes and hypertension; elevation of triglycerides is potential adverse effect (monitor lipid panel)


Interferon gamma-1b (Actimmune)

Single-chain polypeptide containing 140 amino acids. Produced by fermentation of genetically engineered Escherichia coli bacterium containing DNA that encodes for the human protein.

Adult

0.125-0.5 mg/m2/d IM

Pediatric

Not established

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in patients with myelosuppression, cardiac disease, and compromised CNS; regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression


Thalidomide (Thalomid)

A derivative of glutethimide; mode of action for immunosuppression is unclear; inhibition of neutrophil chemotaxis and decreased monocyte phagocytosis may occur; may cause 50-80% reduction of tumor necrosis factor–alpha

Adult

50 mg PO; 200 mg/d maximum

Pediatric

Not established

May be associated with increased risk of serious infection when used in combination with anakinra; may enhance sedative activity of other drugs such as ethanol, barbiturates, reserpine, and chlorpromazine;
may decrease serum concentrations and/or efficacy of hormonal contraceptives

Documented hypersensitivity to thalidomide or any component of the formulation; neuropathy (peripheral); pregnancy or women in childbearing years unless alternative therapies are inappropriate and adequate precautions are taken to avoid pregnancy

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Effective contraception must be used for at least 4 weeks before initiating therapy, during therapy, and for 4 weeks following discontinuation of thalidomide
May cause sedation; patients must be warned to use caution when performing tasks which require alertness
Caution in patients with renal or hepatic impairment, neurological disorders, cardiovascular disease, or constipation; has been associated with the development of peripheral neuropathy, which may be irreversible; consider immediate discontinuation (if clinically appropriate) in patients who develop neuropathy; use caution in patients with a history of seizures, concurrent therapy with drugs which alter seizure threshold, or conditions which predispose to seizures; may cause neutropenia; discontinue therapy if absolute neutrophil count decreases to <750/mm3; caution in patients with HIV infection; has been associated with increased viral loads; may cause orthostasis and/or bradycardia; caution in patients with cardiovascular disease or in patients who would not tolerate transient hypotensive episodes ; thrombotic events reported (generally in patients with other risk factors for thrombosis [neoplastic disease, inflammatory disease, or concurrent therapy with other drugs which may cause thrombosis])


Bortezomib (Velcade)

First drug approved of anticancer agents known as proteasome inhibitors. The proteasome pathway is an enzyme complex existing in all cells. This complex degrades ubiquitinated proteins that control the cell cycle and cellular processes and maintains cellular homeostasis. Reversible proteasome inhibition disrupts pathways supporting cell growth, thus decreases cancer cell survival.

Adult

Not established; 1.3 mg/m2 IV on d 1, 4, 8, and 11 of a 3-wk cycle suggested

Pediatric

Not established

Substrate of CYP450 isoenzymes1A2, 2C9, 2C19, 2D6, and 3A4; may inhibit CYP450 2C19, therefore caution with coadministration of isoenzyme 2C19 substrates (eg, barbiturates, phenytoin, valproic acid, imipramine, lansoprazole, warfarin)

Documented hypersensitivity to bortezomib, boron, mannitol, or any component of the formulation; pregnancy

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause peripheral neuropathy (usually sensory but may be mixed sensorimotor; risk may be increased with previous use of neurotoxic agents or pre-existing peripheral neuropathy; adjustment of dose and schedule may be required)
May cause orthostatic/postural hypotension; use caution with dehydration, history of syncope or medications associated with hypotension
Has been associated with the development or exacerbation of congestive heart failure; use caution in patients with risk factors or existing heart disease
May cause tumor lysis syndrome; risk is increased in patients with large tumor burden prior to treatment; hematologic toxicity with severe thrombocytopenia may occur (risk is increased in patients with pretreatment platelet counts <75,000 µL (frequent monitoring is required throughout treatment); use caution with hepatic or renal impairment

More on Waldenstrom Hypergammaglobulinemia

Overview: Waldenstrom Hypergammaglobulinemia
Differential Diagnoses & Workup: Waldenstrom Hypergammaglobulinemia
Treatment & Medication: Waldenstrom Hypergammaglobulinemia
Follow-up: Waldenstrom Hypergammaglobulinemia
References
Further Reading
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References

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Keywords

Waldenström hypergammaglobulinemia, macroglobulinemia, Waldenström's hypergammaglobulinemia, malignant lymphoproliferative disease, monoclonal gammopathy, malignant monoclonal gammopathies, Waldenström macroglobulinemia, Waldenström's macroglobulinemia, Waldenstrom macroglobulinemia, WM,

lymphoproliferative disorder, clonal disorder, B-lymphocyte disorder, blood malignancy, hematologic malignancy, blood cell cancer, plasmacytoid lymphocytic lymphoma, lymphoplasmacytoid lymphoma, primary macroglobulinemia, plasma cell neoplasms hemostatic disorders, paraproteinemias

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Contributor Information and Disclosures

Author

Doris Ponce, MD, Fellow, Department of Hematology/Oncology, New York Medical College
Doris Ponce, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, and American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College
Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology
Disclosure: Novartis Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching

Vijay Ramu, MBBS, Staff Physician, Department of Internal Medicine, East Tennessee State University
Vijay Ramu, MBBS is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Harsha Vyas, MD, Fellow, Section of Hematology and Oncology, Wake Forest University School of Medicine
Harsha Vyas, MD is a member of the following medical societies: American College of Physicians
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, Program Director, Hematology-Oncology Fellowship, 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.

Medical Editor

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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