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S0629, Observation or Combination Chemotherapy, Bortezomib, Thalidomide, and Rituximab Followed By Two Autologous Peripheral Blood Stem Cell Transplants in Treating Patients With Waldenstrom Macroglobulinemia

Primary Purpose

Lymphoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
bortezomib
carmustine
cisplatin
cyclophosphamide
cytarabine
dexamethasone
doxorubicin hydrochloride
etoposide
melphalan
thalidomide
autologous-autologous tandem hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
Sponsored by
SWOG Cancer Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring Waldenström macroglobulinemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Diagnosis of Waldenstrom macroglobulinemia (WM)
  • Measurable disease as determined by IgM protein quantification
  • Must be registered to the treatment portion of the study within 28 days of experiencing disease-related symptoms* AND must present with ≥ 1 of the following disease-related symptoms:

    • Hemoglobin ≤ 11 g/dL
    • Platelet count ≤ 100,000/mm³
    • Marked tumor mass, defined as lymphadenopathy > 2 cm, palpable hepatomegaly, splenomegaly, or significant marrow involvement (> 50%)
    • Serum albumin < 2.5 g/dL
    • Persistently elevated beta-2-microglobulin > 3.0 mg/L in the absence of renal impairment or active infections
    • Presence of B symptoms (i.e., fever, night sweats, or weight loss of > 10% from baseline)
    • Appearance of new or worsening neuropathy manifested by numbness and tingling or pain
    • Symptomatic cryoglobulinemia (i.e., Raynaud phenomenon, skin ulcers, cold urticaria, or skin necrosis)
    • Symptoms of hyperviscosity, if measured viscosity > 4 cp (i.e., new headaches, vertigo, ataxia, dizziness with or without evident causes of changes in funduscopic exam, including retinal vein engorgement, hemorrhages, or exudates)
  • NOTE: *Appearance of any of the above symptoms caused by WM with no other obvious cause is a trigger for treatment initiation. Symptoms need not persist for any specified time frame.

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2 (Zubrod performance status 3 allowed provided it is based solely on morbidity due to WM)
  • ANC > 1,500/mm³ (unless more marked cytopenias can be explained by marked marrow involvement or autoimmune myelosuppression)
  • Serum creatinine < 3 mg/dL
  • Creatinine clearance > 30 mL/min
  • SGOT/SGPT < 2 times upper limit of normal
  • Direct bilirubin < 2.0 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception according to the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.®) program
  • Ejection fraction ≥ 50% by ECHO or MUGA scan

    • Patients with evidence of amyloidosis (i.e., periorbital perforation, proteinuria not attributable to Bence-Jones protein, unexplained arrhythmias, increased liver function tests, peripheral neuropathy, carpal tunnel syndrome, and/or macroglossia) must have an ECHO, rather than MUGA, performed to evaluate for cardiac amyloidosis (septal thickness, diastolic dysfunction, granular sparkling, or low-voltage QRS complexes)
  • No myocardial infarction within the past 6 months
  • No unstable angina
  • No difficult-to-control congestive heart failure or cardiac arrhythmias
  • No uncontrolled hypertension
  • No peripheral neuropathy ≥ grade 2
  • No history of multi-infarced dementia or multiple strokes
  • No known hypersensitivity to boron or mannitol
  • No hepatitis B or C positivity
  • No HIV positivity
  • No other prior malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

  • At least 28 days since prior chemotherapy and/or radiotherapy and recovered
  • No prior bortezomib
  • No concurrent glucocorticoids unless used to control autoimmune disease associated with WM
  • Concurrent participation in the Myeloma Specimen Repository study allowed

Sites / Locations

  • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
  • St. Francis Hospital and Health Centers - Beech Grove Campus
  • Reid Hospital & Health Care Services
  • Lawrence Memorial Hospital
  • Wesley Medical Center
  • Saint Joseph Mercy Cancer Center
  • CCOP - Michigan Cancer Research Consortium
  • Oakwood Cancer Center at Oakwood Hospital and Medical Center
  • Barbara Ann Karmanos Cancer Institute
  • Genesys Hurley Cancer Institute
  • Hurley Medical Center
  • Van Elslander Cancer Center at St. John Hospital and Medical Center
  • Foote Memorial Hospital
  • Sparrow Regional Cancer Center
  • St. Mary Mercy Hospital
  • St. Joseph Mercy Oakland
  • Mercy Regional Cancer Center at Mercy Hospital
  • Seton Cancer Institute at Saint Mary's - Saginaw
  • St. John Macomb Hospital
  • Grandview Hospital
  • Good Samaritan Hospital
  • David L. Rike Cancer Center at Miami Valley Hospital
  • CCOP - Dayton
  • Blanchard Valley Medical Associates
  • Middletown Regional Hospital
  • Charles F. Kettering Memorial Hospital
  • UVMC Cancer Care Center at Upper Valley Medical Center
  • Clinton Memorial Hospital
  • Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Observation

Treatment

Arm Description

Non-symptomatic patients are monitored monthly for 3 months, then every 3 months thereafter.

Symptomatic pts: 2 cycles VTDPACE+R: dex 40 mg PO D1-4 thalid 200 mg PO D1-4 cisplatin 10 mg/m2 IV D1-4 dox 10 mg/m2 IV D1-4 cyclophos 400 mg/m2 IV D1-4 etoposide 40 mg/m2 IV D1-4 bortezomib 1.0 mg/m2 IV D1,4,8,11 ritux 375 mg/m2 IV D1,8,15 lovenox 40 mg/d SQ D1-platelets >50,000/mcl GCSF 10 mcg/kg/d IV D9-WBC <2,000/mcl apheresis >/= 20x10^6 when WBC and CD34 within normal range, up to 4 cycles st Trans: mel 200 mg/m2 IV D-1 bortezomib 1.3 mg/m2 IV D-4, -1 PBSC >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 500 ml IV D-1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1 nd Trans: BCNU 300 mg/m2 IV D-5 etoposide 200 mg/m2 IV D-5 to -2 AraC 400 mg/m2 IV D-5 to -2 mel 140 mg/m2 IV D-1 PBSC infusion >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 150 ml/hr IV D-5 to -1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1

Outcomes

Primary Outcome Measures

Progression-free survival at 3 years

Secondary Outcome Measures

Overall survival
Response rate (complete response, very good partial response, and partial response)
Standard prognostic factors and other potential correlates that may relate to progression, symptomatic disease, and/or survival
Toxicity

Full Information

First Posted
July 26, 2008
Last Updated
March 5, 2015
Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00723658
Brief Title
S0629, Observation or Combination Chemotherapy, Bortezomib, Thalidomide, and Rituximab Followed By Two Autologous Peripheral Blood Stem Cell Transplants in Treating Patients With Waldenstrom Macroglobulinemia
Official Title
S0629, Observational Study of Asymptomatic Waldenstrom's Macroglobulinemia and Phase II Study of Tandem Autologous Transplant and Maintenance Treatment for Patients With Symptomatic Disease
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Withdrawn
Why Stopped
lack of accrual
Study Start Date
September 2008 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. Giving combination chemotherapy together with bortezomib, thalidomide, and rituximab before an autologous peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. PURPOSE: This observational and phase II trial is studying how well giving combination chemotherapy together with bortezomib, thalidomide, and rituximab followed by two autologous peripheral blood stem cell transplants works in treating patients with Waldenstrom macroglobulinemia.
Detailed Description
OBJECTIVES: Primary To assess the progression-free and overall survival of patients with symptomatic Waldenstrom macroglobulinemia treated with bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin hydrochloride, cyclophosphamide, and etoposide (VDT-PACE) in combination with rituximab, followed by single or tandem autologous peripheral blood stem cell transplantation and maintenance therapy. To assess the confirmed and unconfirmed response in patients treated with this regimen. Secondary To evaluate the feasibility and toxicity of this regimen in these patients. To correlate the time to symptom development and overall survival with standard prognostic factors and cytopenias. To examine the natural history of Waldenstrom macroglobulinemia. To identify, in a preliminary fashion, biological correlates that may relate to progression or to symptomatic disease. OUTLINE: This is a multicenter study. Patients with asymptomatic disease at study entry proceed directly to observation. Patients with symptomatic disease at study entry proceed directly to induction therapy. Observation: Patients with asymptomatic disease undergo observation monthly for 3 months and then every 3 months for up to 3 years. Patients who develop symptomatic disease proceed to induction therapy within 28 days of onset of disease symptoms. Patients who continue to have asymptomatic disease after 3 years of observation are removed from the study. Induction therapy: Patients receive oral dexamethasone and oral thalidomide on days 1-4; cisplatin IV, doxorubicin hydrochloride IV, cyclophosphamide IV, and etoposide IV continuously on days 1-4; bortezomib IV on days 1, 4, 8, and 11; and rituximab IV on days 1, 8, and 15. Treatment repeats every 6-8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Peripheral blood stem cell (PBSC) collection: Patients receive filgrastim (G-CSF) IV beginning on day 9 of course 1 of induction therapy and continuing until WBC counts are adequate for apheresis. Patients also receive G-CSF IV beginning on day 6 of course 2 of induction therapy and continuing until apheresis is complete. First autologous PBSC transplantation*: Beginning approximately 4-6 weeks after the completion of induction therapy, patients receive conditioning therapy comprising high-dose melphalan IV and bortezomib IV on days -4 and -1. Patients undergo autologous PBSC transplantation on day 0 NOTE: *Patients who will receive a single transplant (for medical, insurance, or other reasons) will not receive melphalan and bortezomib, but will receive conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM) and will proceed to Maintenance Therapy. Second autologous PBSC transplantation: Beginning approximately 56-90 days after the first transplant, patients receive conditioning therapy comprising carmustine IV over 2 hours on day -5; etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to -2; and melphalan IV on day -1. Patients undergo autologous PBSC transplantation on day 0. Maintenance therapy: Beginning after platelet counts recover, patients receive bortezomib IV on days 1, 4, 8, and 11 and rituximab IV over 2 hours on day 11. Treatment repeats every 3 months for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
Waldenström macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Observation
Arm Type
No Intervention
Arm Description
Non-symptomatic patients are monitored monthly for 3 months, then every 3 months thereafter.
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Symptomatic pts: 2 cycles VTDPACE+R: dex 40 mg PO D1-4 thalid 200 mg PO D1-4 cisplatin 10 mg/m2 IV D1-4 dox 10 mg/m2 IV D1-4 cyclophos 400 mg/m2 IV D1-4 etoposide 40 mg/m2 IV D1-4 bortezomib 1.0 mg/m2 IV D1,4,8,11 ritux 375 mg/m2 IV D1,8,15 lovenox 40 mg/d SQ D1-platelets >50,000/mcl GCSF 10 mcg/kg/d IV D9-WBC <2,000/mcl apheresis >/= 20x10^6 when WBC and CD34 within normal range, up to 4 cycles st Trans: mel 200 mg/m2 IV D-1 bortezomib 1.3 mg/m2 IV D-4, -1 PBSC >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 500 ml IV D-1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1 nd Trans: BCNU 300 mg/m2 IV D-5 etoposide 200 mg/m2 IV D-5 to -2 AraC 400 mg/m2 IV D-5 to -2 mel 140 mg/m2 IV D-1 PBSC infusion >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 150 ml/hr IV D-5 to -1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Drug
Intervention Name(s)
carmustine
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
thalidomide
Intervention Type
Procedure
Intervention Name(s)
autologous-autologous tandem hematopoietic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Primary Outcome Measure Information:
Title
Progression-free survival at 3 years
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
3 years
Title
Response rate (complete response, very good partial response, and partial response)
Time Frame
3 years
Title
Standard prognostic factors and other potential correlates that may relate to progression, symptomatic disease, and/or survival
Time Frame
3 years
Title
Toxicity
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of Waldenstrom macroglobulinemia (WM) Measurable disease as determined by IgM protein quantification Must be registered to the treatment portion of the study within 28 days of experiencing disease-related symptoms* AND must present with ≥ 1 of the following disease-related symptoms: Hemoglobin ≤ 11 g/dL Platelet count ≤ 100,000/mm³ Marked tumor mass, defined as lymphadenopathy > 2 cm, palpable hepatomegaly, splenomegaly, or significant marrow involvement (> 50%) Serum albumin < 2.5 g/dL Persistently elevated beta-2-microglobulin > 3.0 mg/L in the absence of renal impairment or active infections Presence of B symptoms (i.e., fever, night sweats, or weight loss of > 10% from baseline) Appearance of new or worsening neuropathy manifested by numbness and tingling or pain Symptomatic cryoglobulinemia (i.e., Raynaud phenomenon, skin ulcers, cold urticaria, or skin necrosis) Symptoms of hyperviscosity, if measured viscosity > 4 cp (i.e., new headaches, vertigo, ataxia, dizziness with or without evident causes of changes in funduscopic exam, including retinal vein engorgement, hemorrhages, or exudates) NOTE: *Appearance of any of the above symptoms caused by WM with no other obvious cause is a trigger for treatment initiation. Symptoms need not persist for any specified time frame. PATIENT CHARACTERISTICS: Zubrod performance status 0-2 (Zubrod performance status 3 allowed provided it is based solely on morbidity due to WM) ANC > 1,500/mm³ (unless more marked cytopenias can be explained by marked marrow involvement or autoimmune myelosuppression) Serum creatinine < 3 mg/dL Creatinine clearance > 30 mL/min SGOT/SGPT < 2 times upper limit of normal Direct bilirubin < 2.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception according to the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.®) program Ejection fraction ≥ 50% by ECHO or MUGA scan Patients with evidence of amyloidosis (i.e., periorbital perforation, proteinuria not attributable to Bence-Jones protein, unexplained arrhythmias, increased liver function tests, peripheral neuropathy, carpal tunnel syndrome, and/or macroglossia) must have an ECHO, rather than MUGA, performed to evaluate for cardiac amyloidosis (septal thickness, diastolic dysfunction, granular sparkling, or low-voltage QRS complexes) No myocardial infarction within the past 6 months No unstable angina No difficult-to-control congestive heart failure or cardiac arrhythmias No uncontrolled hypertension No peripheral neuropathy ≥ grade 2 No history of multi-infarced dementia or multiple strokes No known hypersensitivity to boron or mannitol No hepatitis B or C positivity No HIV positivity No other prior malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: At least 28 days since prior chemotherapy and/or radiotherapy and recovered No prior bortezomib No concurrent glucocorticoids unless used to control autoimmune disease associated with WM Concurrent participation in the Myeloma Specimen Repository study allowed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordan Srkalovic, MD, PhD
Organizational Affiliation
Sparrow Regional Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06105
Country
United States
Facility Name
St. Francis Hospital and Health Centers - Beech Grove Campus
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
Reid Hospital & Health Care Services
City
Richmond
State/Province
Indiana
ZIP/Postal Code
47374
Country
United States
Facility Name
Lawrence Memorial Hospital
City
Lawrence
State/Province
Kansas
ZIP/Postal Code
66044
Country
United States
Facility Name
Wesley Medical Center
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Saint Joseph Mercy Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106-0995
Country
United States
Facility Name
CCOP - Michigan Cancer Research Consortium
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Oakwood Cancer Center at Oakwood Hospital and Medical Center
City
Dearborn
State/Province
Michigan
ZIP/Postal Code
48123-2500
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-1379
Country
United States
Facility Name
Genesys Hurley Cancer Institute
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
Hurley Medical Center
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
Van Elslander Cancer Center at St. John Hospital and Medical Center
City
Grosse Pointe Woods
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
Facility Name
Foote Memorial Hospital
City
Jackson
State/Province
Michigan
ZIP/Postal Code
49201
Country
United States
Facility Name
Sparrow Regional Cancer Center
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48912-1811
Country
United States
Facility Name
St. Mary Mercy Hospital
City
Livonia
State/Province
Michigan
ZIP/Postal Code
48154
Country
United States
Facility Name
St. Joseph Mercy Oakland
City
Pontiac
State/Province
Michigan
ZIP/Postal Code
48341-2985
Country
United States
Facility Name
Mercy Regional Cancer Center at Mercy Hospital
City
Port Huron
State/Province
Michigan
ZIP/Postal Code
48060
Country
United States
Facility Name
Seton Cancer Institute at Saint Mary's - Saginaw
City
Saginaw
State/Province
Michigan
ZIP/Postal Code
48601
Country
United States
Facility Name
St. John Macomb Hospital
City
Warren
State/Province
Michigan
ZIP/Postal Code
48093
Country
United States
Facility Name
Grandview Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45405
Country
United States
Facility Name
Good Samaritan Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45406
Country
United States
Facility Name
David L. Rike Cancer Center at Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
CCOP - Dayton
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45420
Country
United States
Facility Name
Blanchard Valley Medical Associates
City
Findlay
State/Province
Ohio
ZIP/Postal Code
45840
Country
United States
Facility Name
Middletown Regional Hospital
City
Franklin
State/Province
Ohio
ZIP/Postal Code
45005-1066
Country
United States
Facility Name
Charles F. Kettering Memorial Hospital
City
Kettering
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
UVMC Cancer Care Center at Upper Valley Medical Center
City
Troy
State/Province
Ohio
ZIP/Postal Code
45373-1300
Country
United States
Facility Name
Clinton Memorial Hospital
City
Wilmington
State/Province
Ohio
ZIP/Postal Code
45177
Country
United States
Facility Name
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
City
Xenia
State/Province
Ohio
ZIP/Postal Code
45385
Country
United States

12. IPD Sharing Statement

Learn more about this trial

S0629, Observation or Combination Chemotherapy, Bortezomib, Thalidomide, and Rituximab Followed By Two Autologous Peripheral Blood Stem Cell Transplants in Treating Patients With Waldenstrom Macroglobulinemia

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