Chronic lymphoplasmacytic leukemia (often called Waldenström macroglobulinemia) is a slow-growing cancer of B-cells that behave like a mix of small lymphocytes and plasma cells. These cells live in the bone marrow and make too much of one antibody called IgM. Thick IgM can slow blood flow and cause “hyperviscosity,” nerve damage, tiredness, night sweats, weight loss, big spleen or nodes, and repeated infections. Many people have no symptoms at first and can be safely watched until problems appear. When treatment is needed, doctors use anti-CD20 antibodies, BTK inhibitors, alkylating chemotherapy, and proteasome inhibitors, with urgent plasmapheresis for hyperviscosity. The choice depends on symptoms, age, other illnesses, and mutation profile. WM is usually controllable long-term, but not cured with drugs; transplant is rarely used. ASH Publications+2PubMed+2
Chronic lymphoplasmacytic leukemia / lymphoplasmacytic lymphoma (LPL) is a slow-growing cancer of B lymphocytes. These B cells look partly like small lymphocytes and partly like plasma cells under the microscope. In many patients, the tumor cells make a single type of antibody called IgM. When the IgM level is high, the blood can become “thick” and cause symptoms. When LPL produces excess IgM and involves the bone marrow, we call it Waldenström macroglobulinemia (WM). Diagnosis needs a bone-marrow biopsy showing lymphoplasmacytic cells and evidence of a clonal IgM protein. Doctors also use special lab tests (immunophenotyping and genetics) to confirm it and to tell it apart from other small B-cell lymphomas. ScienceDirect+2PMC+2
Many people with WM/LPL have a driver change in a gene called MYD88 (L265P). About one-third also have changes in CXCR4. These changes affect how the cancer grows and how it responds to some medicines. A small group does not have MYD88 mutations; these patients can behave differently. ASH Publications+2PMC+2
WM/LPL is uncommon and usually affects older adults. It often grows slowly. Some people have no symptoms for years and only need regular checks. Others need treatment if there are symptoms, organ swelling, anemia, high IgM-related problems, or other complications. Doctors follow expert guidelines to decide when to treat and how. NCCN+1
Other names
Doctors and articles may use several names for this disease. The main ones are: Lymphoplasmacytic lymphoma (LPL), Waldenström macroglobulinemia (WM) when IgM is high, IgM-secreting lymphoplasmacytic lymphoma, and the historic term immunocytoma (older literature). “Chronic lymphoplasmacytic leukemia” is not a standard modern label, but some people use it informally to describe when the tumor cells spill into the blood. Today’s WHO classification groups it under small B-cell lymphoid neoplasms with lymphoplasmacytic features. Nature+1
Types
Asymptomatic (“smoldering”) WM/LPL. IgM and marrow involvement are present, but there are no symptoms that need therapy. People are monitored. NCCN
Symptomatic WM/LPL. There are symptoms or complications (for example, anemia, organ enlargement, neuropathy, or hyperviscosity), so treatment is considered. JNCCN
IgM MGUS (monoclonal gammopathy of undetermined significance). This is not cancer but a related condition with a small IgM spike and no marrow lymphoma. It can progress to WM over time in some people, so it is followed. Taylor & Francis Online
Genetic subtypes by mutation pattern: MYD88-mutated / CXCR4-wild type, MYD88-mutated / CXCR4-mutated, and MYD88-wild type. These patterns can affect disease behavior and medication choice. PMC
WM/LPL with IgM-related disorders, such as hyperviscosity, cold agglutinin hemolytic anemia, cryoglobulinemia, and IgM-related neuropathy. These complications come from the effects of the IgM protein, not only from the tumor mass. PMC
Transformed disease. Rarely, WM/LPL can change into a faster-growing lymphoma such as diffuse large B-cell lymphoma. PMC
Causes
There is no single lifestyle cause. Most cases are “sporadic,” meaning they arise on their own. But research has found several risk patterns and biological reasons that help explain why it develops:
Age. Risk rises with age; most patients are older adults. Cells collect genetic changes over time. NCCN
Male sex. Men are affected more often than women, for reasons that are not fully known. Cleveland Clinic
Family history. Having close relatives with WM, other B-cell cancers, or MGUS increases risk. This suggests inherited susceptibility. PMC
MYD88 L265P driver mutation. This change activates NF-κB signaling and helps tumor cells survive. It is present in most WM cases. ASH Publications
CXCR4 mutations. These changes can promote cell growth and affect how the tumor responds to BTK inhibitors. PMC+1
Other acquired gene changes (for example, ARID1A, CD79B, and 6q deletions) contribute to cell survival and the WM gene signature. PMC
Clonal B-cell origin. The tumor arises from a post-germinal-center B cell that has features of both lymphocyte and plasma cell. ScienceDirect
Chronic antigen stimulation. Ongoing immune stimulation may play a role in some patients, though the exact triggers vary. Taylor & Francis Online
IgM MGUS. This precursor condition increases risk of later WM, so it is a clinical risk marker. Taylor & Francis Online
Autoimmune conditions. Some studies suggest associations (for example, Sjögren’s or thyroid autoimmunity), likely via chronic B-cell activation. Strength of links varies. Taylor & Francis Online
Certain infections. Links such as hepatitis C have been explored in the past, but data are mixed; any effect is likely small and not universal. Taylor & Francis Online
Ancestry and geography. WM is more common in people of European ancestry; reasons are unclear and likely genetic and environmental. Cleveland Clinic
Immune microenvironment. Support from stromal cells and cytokines in the marrow helps tumor cells stay alive. PMC
BTK pathway signaling. Signaling through BTK helps tumor cells grow; this is also why BTK inhibitors work for many patients. ASH Publications
NF-κB pathway activation. MYD88 and 6q loss can increase NF-κB activity, driving survival signals. PMC
Epigenetic changes. Changes that affect how genes are turned on and off (beyond DNA sequence) are reported in WM and may support tumor behavior. PMC
Bone-marrow niche signals. CXCR4/CXCL12 interactions keep cells in protective niches, aiding resistance. PMC
Clonal evolution over time. New mutations can appear, sometimes leading to more aggressive disease. PMC
Environmental exposures. Some studies explored pesticides or solvents; evidence is not definitive. Any effect is likely small compared to genetic drivers. Taylor & Francis Online
MYD88-wild-type biology. When MYD88 is absent, the disease may rely on other pathways and can have a worse outlook and higher risk of transformation. PMC
Symptoms
Tiredness and low energy. This often comes from anemia, which happens when the marrow is crowded by tumor cells and makes fewer red blood cells. Cleveland Clinic
Shortness of breath on exertion. This can also be due to anemia or to thick blood when IgM is very high. Cleveland Clinic
Dizziness, headaches, blurred vision. Very high IgM can make the blood thick (hyperviscosity). This slows blood flow in small vessels, including the retina and brain. PMC
Nosebleeds or gum bleeding. Thick blood and effects on platelets can make bleeding easier in some patients. Cleveland Clinic
Numbness, tingling, or burning pain in the feet and hands. IgM can attack nerves (IgM-related neuropathy), causing peripheral neuropathy. PMC
Fevers, night sweats, weight loss. These “B symptoms” may appear as the disease becomes more active. Cleveland Clinic
Enlarged lymph nodes. Painless swelling in the neck, armpit, or groin can occur when lymphoma cells collect in nodes. Cleveland Clinic
Enlarged liver or spleen. These organs may swell when tumor cells collect there. Some people feel fullness or discomfort. Cleveland Clinic
Cold-triggered problems such as color change or pain in fingers and toes. This can be due to cold agglutinin disease or cryoglobulinemia caused by the IgM protein. iwmf.com
Dark urine or jaundice. These can happen if red blood cells break down (hemolysis) from cold agglutinins. iwmf.com
Confusion or vision changes. Severe hyperviscosity can reduce blood flow to the brain and eyes; this is urgent and needs fast treatment (often plasmapheresis). PMC
Frequent infections. Low normal antibodies and marrow crowding can raise infection risk. Cleveland Clinic
Skin findings. Livedo, purpura, or ulcers may appear with cryoglobulinemia or hyperviscosity. PMC
Bone pain is uncommon. If there is new focal bone pain, doctors think about other causes or rare transformation. JNCCN
No symptoms at all. Many people are found because of a routine blood test showing high protein or anemia. They may only need watchful waiting. NCCN
Diagnostic tests
A) Physical examination (bedside checks)
General exam for lymph nodes, liver, and spleen. The doctor feels for swelling in the neck, underarms, groin, and checks the belly for organ enlargement. This helps stage the illness and track change over time. JNCCN
Eye (fundus) check for hyperviscosity signs. Looking at retinal veins can show sluggish flow or bleeding when IgM is very high. This supports the diagnosis of thick blood and guides urgent care. PMC
Neurologic exam. The doctor tests sensation, reflexes, and strength to look for neuropathy linked to the IgM protein. PMC
Skin exam in cold weather. The clinician checks for color changes, purpura, or ulcers that suggest cryoglobulinemia or cold agglutinin disease. iwmf.com
B) Manual or bedside tests (simple office procedures)
Postural vital signs (orthostatic BP and pulse). Dizziness from anemia or hyperviscosity can show up as changes when standing. This is a quick way to assess impact on circulation. JNCCN
Capillary refill and nail-bed check. Slow refill or bluish tips in the cold can hint at poor microcirculation from cryoglobulins or hyperviscosity. PMC
Bedside vision assessment (visual acuity/fields). Worsening vision may point to hyperviscosity and need fast action. PMC
Temperature-provoked symptom review (“cold challenge” history). Asking patients to gently expose fingers to cool air (not harmful cold) during the visit can reproduce color change or pain, supporting cold-reactive IgM problems. iwmf.com
C) Lab and pathologic tests (the core of diagnosis)
Complete blood count (CBC) with differential. This shows anemia, sometimes low platelets or white cells, and gives a baseline to follow. JNCCN
Comprehensive metabolic panel. Doctors check kidney and liver function, calcium, and total protein to look for organ effects and other causes of symptoms. JNCCN
Serum protein electrophoresis (SPEP) and immunofixation. These tests detect and type the monoclonal IgM protein made by the tumor. They help confirm WM/LPL and measure the IgM level over time. ScienceDirect
Serum free light chains. These help further characterize the monoclonal protein and the balance of kappa vs lambda chains. JNCCN
Serum viscosity level. When patients have headaches, blurred vision, or bleeding, this test helps confirm hyperviscosity and the need for urgent plasma exchange. JNCCN
Cold agglutinin titer and hemolysis labs (bilirubin, LDH, haptoglobin, Coombs test). These check for IgM-mediated red cell destruction. PMC
Cryoglobulin testing (done with warm handling of samples). This detects proteins that gel in the cold and can block small vessels. Proper sample handling is essential for accuracy. PMC
Bone-marrow aspirate and biopsy with immunohistochemistry. This is the key test. It shows lymphoplasmacytic cells in the marrow and confirms LPL/WM. Pathologists also stain for markers to separate WM from look-alike diseases. ScienceDirect
Flow cytometry on marrow or blood. This identifies a clonal B-cell population with a typical immunophenotype and helps distinguish WM from other B-cell disorders. PMC+1
Molecular testing for MYD88 and CXCR4 (PCR or next-generation sequencing). These results support the diagnosis and can influence therapy choice, especially with BTK inhibitors. ASH Publications+1
D) Electrodiagnostic tests
Nerve conduction studies (NCS). If there is numbness or tingling, NCS can confirm a demyelinating pattern typical of IgM-related neuropathy. This helps decide treatment and track recovery. PMC
Electromyography (EMG). EMG, along with NCS, evaluates the type and severity of nerve damage to guide care. PMC
E) Imaging tests (often used when symptoms suggest organ involvement or to check for other lymphomas)
CT scan of chest/abdomen/pelvis. This looks for enlarged lymph nodes, liver, or spleen. It helps when exam findings are unclear or when symptoms suggest deeper disease. JNCCN
MRI of the spine or brain (selected patients). MRI helps if there is severe neuropathy, suspicion of Bing-Neel syndrome (rare CNS involvement), or other neurologic signs. JNCCN
Non-pharmacological treatments (therapies & others)
Notes: These are supportive measures you can use alongside medical care. They do not replace anti-cancer treatment. Each item includes description (~150 words), purpose, and mechanism.
Watchful waiting (active surveillance)
Many people with WM feel well and have stable blood counts. In these cases, treatment can wait. With active surveillance, your team checks symptoms, exam, blood counts, IgM level, and sometimes viscosity on a schedule. You start therapy only if problems arise, such as anemia, hyperviscosity symptoms (blurry vision, headaches, bleeding), organ damage, bulky nodes, or neuropathy. This avoids drug side effects when there is no proven benefit to treating early. Purpose: spare toxicity until treatment is truly needed. Mechanism: slow cancers like WM can stay quiet for years; by monitoring closely, doctors time therapy to when benefit is clear. Evidence from expert guidelines supports observation until “treatment criteria” are met. PubMed+1Therapeutic plasma exchange (plasmapheresis)
Plasmapheresis is an emergency procedure for hyperviscosity. A machine removes plasma that contains IgM and replaces it with clean fluid. Symptoms such as blurred vision, headaches, nosebleeds, confusion, and shortness of breath often improve within hours to days. Purpose: quickly lower serum viscosity and relieve life-threatening symptoms, especially when IgM is very high. Mechanism: physical removal of IgM-rich plasma reduces thickness of the blood; it does not kill cancer cells, so drug therapy must follow to keep IgM down. Evidence shows plasma exchange rapidly reduces viscosity and is first-line for hyperviscosity in WM. ACEP+2American Cancer Society+2Vaccination planning
Infections are a major problem in WM, and many treatments weaken immunity. Getting up-to-date inactivated vaccines (influenza, pneumococcal, COVID-19, hepatitis per risk) before starting therapy improves protection. Live vaccines are avoided during and shortly after immunosuppression. After anti-CD20 drugs (rituximab), vaccine responses are lower for months; when possible, give vaccines beforehand or at the least-immunosuppressed point. Purpose: reduce severe infections and hospitalizations. Mechanism: priming the immune system while B-cell function is intact yields better antibody responses; spacing reduces interference from therapy. CDC+2OUP Academic+2Immunoglobulin replacement (IVIG/SCIG) for recurrent infections
Some patients have low IgG/IgA and frequent sinus or chest infections. IVIG or SCIG can lower infection rates when low antibodies and recurrent bacterial infections persist despite routine prevention. Purpose: cut down the number and severity of infections. Mechanism: passive transfer of pooled antibodies supports humoral immunity while your own B-cells are suppressed. Use is individualized and usually reserved for clear infection patterns. Frontiers+2PMC+2Infection-prevention bundle (hygiene & exposure control)
Simple steps matter: hand hygiene, masks during peak respiratory seasons, quick evaluation of fevers, dental care to reduce gum infections, safe food handling, and avoiding sick contacts when possible. Purpose: break common pathways of viral and bacterial spread. Mechanism: lowers inoculum and exposure time; earlier care prevents complications. Guidance for immunocompromised patients emphasizes these basics year-round. CDCNeuropathy protection
WM and some drugs (e.g., bortezomib) can worsen nerve pain, numbness, or tingling. Using protective footwear, foot checks, balance training, physical therapy, and avoidance of prolonged pressure on nerves can reduce falls and injuries. Purpose: preserve function and safety. Mechanism: risk-based modifications decrease nerve stress and improve proprioception; physical therapy builds compensatory strength. ASH PublicationsAnemia & fatigue strategies
Light to moderate activity, energy conservation, treatment of iron or B12 deficiency when present, and sleep hygiene can ease fatigue from anemia or inflammation. Purpose: improve daily function until disease control raises hemoglobin. Mechanism: graded exercise improves mitochondrial efficiency; correcting deficiencies addresses reversible contributors. National Cancer InstituteNutrition for strength (not a cancer cure)
Aim for balanced meals with protein, whole grains, fruits, and vegetables. Maintain weight and muscle mass, and discuss any supplements with your team to avoid drug interactions (especially with proteasome inhibitors). Purpose: support recovery, immune function, and tolerance of therapy. Mechanism: adequate protein and micronutrients aid tissue repair and hematopoiesis; safe supplement use prevents harmful interactions. ods.od.nih.gov+2ods.od.nih.gov+2Exercise & physical therapy
Regular walking and resistance training (as tolerated) maintain muscle, bone health, and mood. Supervised programs can be tailored if you have neuropathy or anemia. Purpose: improve quality of life and lower deconditioning. Mechanism: exercise stimulates neuromuscular adaptation and reduces inflammatory cytokines. National Cancer InstitutePsychosocial support & stress reduction
Counseling, peer groups, mindfulness, and relaxation techniques help with uncertainty and long follow-up. Purpose: reduce anxiety and improve sleep. Mechanism: stress-hormone control benefits immune function and pain perception. National Cancer InstituteFall-prevention & home safety
Check for hazards, use assistive devices if balance is poor, and review medications that cause dizziness. Purpose: prevent fractures and head injuries, especially if anemic or neuropathic. Mechanism: removes environmental risks and compensates for sensory loss. National Cancer InstituteSunlight and vitamin D (within safe limits)
Vitamin D is important for bone and immune health. Testing and supplementing when low is reasonable; avoid very high doses. Purpose: maintain normal levels to support bones during steroids or inactivity. Mechanism: vitamin D regulates calcium and bone remodeling. Follow NIH upper-intake limits to avoid toxicity. ods.od.nih.govThrombosis and bleeding awareness
Very high IgM can affect clotting; some drugs raise bleeding or clot risk. Learn warning signs and when to seek urgent care. Purpose: early detection saves lives. Mechanism: patient education shortens time to evaluation and treatment. ASH PublicationsCold-exposure precautions (cryoglobulins/cold agglutinins)
Some WM patients have proteins that clump in the cold. Keep warm, protect hands/feet, and warm IV fluids when needed. Purpose: prevent pain, skin changes, and vascular issues. Mechanism: warmth reduces protein precipitation and vessel spasm. ASH PublicationsEye safety for hyperviscosity symptoms
Report new floaters, vision changes, or retinal bleeding signs promptly; ophthalmology can help while systemic care proceeds. Purpose: protect vision. Mechanism: viscosity-related retinal issues respond to rapid IgM lowering. American Cancer SocietyBone health during steroids or inactivity
Calcium, vitamin D within safe limits, weight-bearing exercise, and fall prevention protect bones if steroid pulses are used. Purpose: reduce fracture risk. Mechanism: offsets steroid-induced bone loss. ods.od.nih.govFertility and family planning counseling
Some treatments affect fertility or pregnancy safety. Discuss contraception and planning before therapy. Purpose: informed decisions and timing. Mechanism: aligns life goals with treatment windows. National Cancer InstituteTravel health planning
Immunizations, medication lists, and infection-prevention steps are important when traveling. Purpose: reduce risk in new environments. Mechanism: pre-travel vaccines and precautions lower exposure. CDCOral care program
Regular dental visits and daily care reduce mouth infections during therapy. Purpose: prevent bacteremia sources. Mechanism: lowers biofilm and gum inflammation. CDCMedication interaction checks (especially supplements)
Some botanicals interact with chemo. Green tea extracts (EGCG) can blunt bortezomib activity; always clear supplements with your team. Purpose: avoid reduced efficacy or toxicity. Mechanism: biochemical binding or metabolic interactions can neutralize drugs. PMC+1
Drug treatments
Important: Only two agents carry FDA indications specifically for WM: ibrutinib and zanubrutinib. Many other drugs are used off-label in WM based on guidelines and expert practice. FDA labels below confirm each drug’s class/mechanism and approved uses (even if not WM), while clinical guidance shows their roles in WM. Always individualize dosing and timing with your hematology team.
Zanubrutinib (Brukinsa) – BTK inhibitor (FDA-approved for WM)
Description (≈150 words): Zanubrutinib is a next-generation Bruton’s tyrosine kinase (BTK) blocker designed for deep and sustained BTK occupancy. It treats symptomatic WM, including patients who are older or have other conditions. Compared with first-generation BTK inhibitors, it often shows high response rates and favorable tolerability, though it can still cause low blood counts, bruising, infections, and atrial fibrillation (less often than ibrutinib in head-to-head trials). Dose: Commonly 160 mg twice daily or 320 mg once daily, continuous until progression or intolerance. Timing: Continuous oral therapy. Purpose: Control symptoms, shrink marrow disease, lower IgM, and prevent organ damage. Mechanism: Blocks BTK signaling in malignant B-cells, halting survival and trafficking signals. Side effects: Neutropenia, bruising, bleeding, infections, rash, diarrhea, and atrial fibrillation; monitor for hypertension and hepatic labs. (Always follow the current label.) FDA Access Data+2FDA Access Data+2Ibrutinib (Imbruvica) – BTK inhibitor (FDA-approved for WM)
Description: Ibrutinib was the first BTK inhibitor approved for WM and remains a key option. It is very effective at reducing IgM and improving anemia, often within weeks. Dose: 420 mg orally once daily, continuous. Timing: Continuous therapy; dose adjustments for interactions or toxicity. Purpose: Rapid symptom control, durable remission in many patients. Mechanism: Irreversible BTK blockade disrupts B-cell receptor signaling and malignant cell survival. Side effects: Atrial fibrillation, bleeding, hypertension, diarrhea, rash, arthralgia, infections; watch for drug interactions (CYP3A). Monitor blood pressure and rhythm. FDA Access Data+1Rituximab – anti-CD20 monoclonal antibody (used off-label in WM; FDA-approved for B-cell NHL)
Description: Rituximab is the backbone of many WM regimens (alone or with bendamustine, cyclophosphamide, bortezomib). It clears CD20-positive B-cells, lowers IgM, and improves anemia. Dose: 375 mg/m² IV weekly ×4 (with or without repeat courses) or as part of combinations. Timing: Cycles per protocol. Purpose: Debulk disease and enhance chemo/targeted therapy. Mechanism: Antibody-dependent cell death and complement activation against CD20-positive cells. Side effects: Infusion reactions, infections, late hypogammaglobulinemia; “IgM flare” can occur—monitor viscosity and consider plasmapheresis if symptomatic. ASH Publications+1Bendamustine (often with rituximab) – alkylating agent (FDA-approved for indolent NHL/CLL; used in WM)
Description: Bendamustine plus rituximab (BR) is a preferred induction option in many centers. It yields deep responses with time-limited therapy, which some patients prefer to continuous BTK inhibition. Dose: Commonly 90 mg/m² days 1–2 every 28 days × 4–6 cycles (with rituximab). Timing: Time-limited chemo-immunotherapy. Purpose: Durable remission, especially when rapid debulking is desired. Mechanism: DNA crosslinking → apoptosis of malignant cells. Side effects: Cytopenias, infections, nausea, rash, fatigue; infection prophylaxis may be needed. PubMedCyclophosphamide (with rituximab ± dexamethasone) – alkylator
Description: The DRC regimen (dexamethasone-rituximab-cyclophosphamide) is a gentler option for frailer adults and can control IgM and anemia. Dose: Per DRC cycles (e.g., cyclophosphamide 100 mg/m² orally days 1–5; protocols vary). Timing: Time-limited cycles. Purpose: Disease control with modest toxicity. Mechanism: DNA alkylation injures dividing lymphoma cells. Side effects: Cytopenias, nausea, hair thinning, infection risk. ASH PublicationsBortezomib (± rituximab, dexamethasone) – proteasome inhibitor (FDA-approved for myeloma/MCL; used in WM)
Description: Bortezomib is highly active in WM combos and lowers IgM quickly. Dose: Weekly subcutaneous schedules reduce neuropathy risk (e.g., days 1, 8, 15 every 28 days). Timing: Several cycles. Purpose: Rapid IgM drop, cytoreduction. Mechanism: Proteasome inhibition triggers apoptosis in plasma-like malignant cells. Side effects: Peripheral neuropathy, shingles reactivation, cytopenias; consider antiviral prophylaxis. Interaction caution: Concentrated green tea extracts (EGCG) can chemically interfere with bortezomib activity—avoid unless your team approves. ASH Publications+1Ixazomib (± rituximab/dexamethasone) – oral proteasome inhibitor (FDA-approved for myeloma; used in WM)
Description: An oral option when proteasome inhibition is desired without injections. Dose: 4 mg orally on days 1, 8, 15 of 28-day cycles (regimen-specific). Purpose/Mechanism: Same class effect as bortezomib. Side effects: Thrombocytopenia, rash, GI upset, peripheral neuropathy (less frequent than bortezomib). ASH PublicationsCarfilzomib (with rituximab/dexamethasone) – proteasome inhibitor (FDA-approved for myeloma; used in WM)
Description: IV proteasome inhibitor used in relapsed WM when other options fail. Dose: Per protocol; given on two days per week within 28-day cycles. Purpose: Salvage therapy. Mechanism: Irreversible proteasome blockade induces apoptosis. Side effects: Infusion reactions, cardiac events, hypertension; careful selection needed. ASH PublicationsVenetoclax – BCL-2 inhibitor (FDA-approved for CLL/AML; studied off-label in WM)
Description: Active in relapsed WM in studies; often used when BTK inhibitors or chemo are not options. Dose: Oral ramp-up to reduce tumor lysis risk; cycles vary. Purpose: Deep responses in select patients. Mechanism: Frees pro-apoptotic proteins by blocking BCL-2. Side effects: Neutropenia, infections, tumor lysis precautions. The ASCO PostAcalabrutinib – BTK inhibitor (FDA-approved for CLL/MCL; sometimes used off-label in WM)
Description: An alternative BTK inhibitor for patients intolerant of others; evidence in WM is growing though not FDA-labeled for WM. Dose: 100 mg twice daily. Purpose: Continuous BTK blockade. Mechanism/Side effects: Similar to class; may have less atrial fibrillation. The ASCO PostObinutuzumab – anti-CD20 antibody (FDA-approved for CLL/FL; off-label in WM)
Description: Used when rituximab intolerance occurs or in trials; can be paired with chemo. Dose/Timing: Per protocol. Mechanism: Glycoengineered CD20 targeting enhances antibody-dependent cytotoxicity. Side effects: Infusion reactions, infections. National Cancer InstituteOfatumumab – anti-CD20 antibody (FDA-approved for CLL; off-label in WM)
Description: Alternative anti-CD20 when rituximab cannot be used. Dose/Timing: Protocol-specific. Mechanism/Side effects: Similar class effects. National Cancer InstituteChlorambucil – alkylator (older agent; rarely used now)
Description: Historically used in indolent B-cell lymphomas; largely replaced by bendamustine/cyclophosphamide. Mechanism/Side effects: DNA alkylation; myelosuppression. NCBIFludarabine – purine analog (infrequent now due to toxicity)
Description: Active but immunosuppressive; reserved for selected relapses. Mechanism/Side effects: Inhibits DNA synthesis; profound cytopenias and infection risk. NCBIDexamethasone – corticosteroid (often in combinations)
Description: Reduces inflammation, shrinks nodes transiently, part of DRC/VRD-like regimens. Side effects: Hyperglycemia, insomnia, mood changes, osteoporosis. ASH PublicationsLenalidomide – immunomodulatory (myeloma label; limited in WM)
Description: Can provoke anemia (“flare”) in WM; not routine but sometimes used in trials or selected cases. Mechanism: Immune modulation and anti-angiogenesis. Side effects: Cytopenias, thrombosis; requires prophylaxis. ASH PublicationsPomalidomide – immunomodulatory (myeloma label; investigational in WM)
Description: Considered only in clinical trials or special circumstances. Side effects: Cytopenias, clot risk. ASH PublicationsTemsirolimus/Everolimus – mTOR inhibitors (off-label)
Description: Sometimes used in refractory WM; mTOR pathway targeting can produce responses. Side effects: Mouth sores, hyperglycemia, lipids, infections. ASH PublicationsPirtobrutinib (non-covalent BTK inhibitor; FDA-approved for MCL/CLL R/R)
Description: Used off-label in BTK-pretreated WM within trials or select cases; activity seen across BTK-resistance mutations. Mechanism: Reversibly inhibits BTK including C481S mutants. Side effects: Fatigue, diarrhea; monitor bleeding/infection risk. The ASCO PostZanubrutinib + rituximab or Ibrutinib + rituximab (combinations)
Description: Combinations can deepen responses in some settings; choice individualized. Caution: Anti-CD20 may cause “IgM flare”; consider timing/bridging strategies. ASH Publications+1
Dietary molecular supplements
Safety first: Always clear supplements with your hematologist to avoid drug interactions (especially with proteasome inhibitors). Doses here are general adult ranges; personalize with your team.
Vitamin D
Description (~150 words): Vitamin D supports bone and immune health. Levels often fall during indoor recovery or steroid use. A simple blood test (25-OH vitamin D) guides dosing. Typical maintenance is 600–800 IU/day, but people with low levels may need higher, short-term replacement directed by clinicians. Avoid very high chronic doses because toxicity can cause high calcium and kidney problems. Dosage: Common maintenance 600–800 IU/day; do not exceed the NIH Tolerable Upper Intake Level (4,000 IU/day) without supervision. Function/Mechanism: Regulates calcium balance and immune signaling via the vitamin D receptor. ods.od.nih.govZinc
Description: Zinc is essential for white-blood-cell function and wound healing. Deficiency can impair immunity and taste. Dosage: Usual RDA is 8–11 mg/day; long-term intake above ~40 mg/day can cause copper deficiency and anemia. Function/Mechanism: Cofactor for hundreds of enzymes involved in DNA synthesis and immune signaling. ods.od.nih.govSelenium
Description: Selenium is part of antioxidant enzymes (glutathione peroxidases) and supports immune defense. Dosage: RDA ~55 mcg/day; avoid >400 mcg/day to prevent selenosis. Function/Mechanism: Redox regulation and protection from oxidative stress through selenoproteins. ods.od.nih.govOmega-3 fatty acids (EPA/DHA)
Description: May help triglycerides and inflammation; can be useful if steroids raise lipids. Dosage: 1–2 g/day of combined EPA/DHA commonly used; discuss bleeding risk with BTK inhibitors. Function/Mechanism: Competes with arachidonic acid pathways to reduce pro-inflammatory eicosanoids. ods.od.nih.govCurcumin (turmeric extract)
Description: Lab and early clinical data show anti-inflammatory and pro-apoptotic effects across blood cancers, but it is not a substitute for therapy and bioavailability varies. Dosage: 500–1,000 mg/day of standardized extract commonly used in studies; review interactions. Function/Mechanism: Inhibits NF-κB and multiple survival pathways; antioxidant actions. PMC+1Probiotics (strain-specific)
Description: May lower antibiotic-associated diarrhea risk; choose products with defined strains and CFUs; avoid if profoundly immunocompromised or during central line bacteremia. Dosage: Per product; often 10^9–10^10 CFU/day. Function/Mechanism: Modulates gut microbiota and barrier function. ods.od.nih.govVitamin B12 (if deficient)
Description: Correcting B12 deficiency helps anemia and neuropathy symptoms. Dosage: Oral 1,000 mcg/day or intermittent injections per labs. Function/Mechanism: Cofactor in DNA synthesis and myelin integrity. National Cancer InstituteFolate (if deficient)
Description: Treat documented folate deficiency to support red-cell production. Dosage: 400–1,000 mcg/day per clinician. Function/Mechanism: One-carbon metabolism for DNA synthesis. National Cancer InstituteMagnesium (if low)
Description: Helpful for muscle cramps and arrhythmia risk; some drugs alter Mg levels. Dosage: Typically 200–400 mg/day elemental Mg; adjust for kidneys. Function/Mechanism: Cofactor in ATP-dependent reactions and cardiac conduction. ods.od.nih.govN-acetylcysteine (NAC)
Description: Antioxidant precursor that replenishes glutathione; sometimes used for mucus thinning in chronic bronchitis symptoms. Dosage: 600–1,200 mg/day commonly used; confirm with your team. Function/Mechanism: Provides cysteine for glutathione synthesis; mucolytic effect. ods.od.nih.gov
Important interaction warning: Avoid concentrated green tea extract (EGCG) if you receive bortezomib, because it can blunt the drug’s activity in preclinical and translational studies. Always disclose supplements to your oncologist. PMC+1
Drugs for immunity booster / regenerative / stem-cell
Filgrastim (G-CSF)
Description (~100 words): Filgrastim stimulates the bone marrow to make neutrophils. It’s used during/after chemo if neutropenia raises infection risk, or to help collect stem cells before transplant. Dose: Commonly 5 mcg/kg/day subcutaneously, schedule varies. Function/Mechanism: G-CSF binds marrow receptors to speed neutrophil production and release. National Cancer InstitutePegfilgrastim (long-acting G-CSF)
Description: A single injection per cycle can prevent febrile neutropenia after chemo. Dose: 6 mg SC once per cycle (timing per regimen). Function/Mechanism: Same as G-CSF with pegylation for longer half-life. National Cancer InstitutePlerixafor
Description: Used with G-CSF to mobilize stem cells from marrow to blood for collection before autologous transplant. Dose: 0.24 mg/kg SC evening before collection. Function/Mechanism: CXCR4 antagonist releases CD34+ cells into circulation. National Cancer InstituteEltrombopag (TPO-receptor agonist)
Description: Sometimes used off-label for severe, persistent thrombocytopenia not due to marrow infiltration alone. Dose: 25–75 mg/day adjusted by platelets. Function/Mechanism: Activates thrombopoietin pathways to raise platelets. National Cancer InstituteRomiplostim (TPO-RA)
Description: Weekly injection to stimulate platelet production in select cases. Dose: 1–10 mcg/kg SC weekly titrated. Function/Mechanism: Thrombopoietin-mimetic activation of megakaryopoiesis. National Cancer InstituteIVIG (Immunoglobulin)
Description: Replacement antibodies for patients with low IgG and recurrent infections. Dose: Common 0.3–0.4 g/kg every 3–4 weeks (or SCIG split weekly). Function/Mechanism: Passive antibodies help prevent bacterial infections while endogenous B-cells are suppressed. Frontiers
Procedures/surgeries
Autologous peripheral blood stem-cell transplant (ASCT)
Procedure: Your own stem cells are collected, stored, then returned after high-dose chemotherapy. Why: Considered for very selected relapsed WM to extend remission when other options are exhausted; not routine frontline. National Cancer InstituteAllogeneic stem-cell transplant
Procedure: Stem cells come from a donor; requires strong conditioning and carries graft-versus-host risk. Why: Rarely used; potential for long-term disease control but with higher risks—consider only in clinical trials or very select young patients. National Cancer InstituteSplenectomy
Procedure: Surgical removal of the spleen. Why: Very uncommon today; may be used for painful massive spleen or refractory cytopenias from hypersplenism when other treatments fail. Vaccinations are required before/after. National Cancer InstituteCentral venous port placement
Procedure: A small device under the skin to allow repeated safe IV treatments and blood draws. Why: Reduces vein damage and improves comfort during multi-cycle therapy. National Cancer InstituteTherapeutic plasma exchange (via catheter)
Procedure: Large-bore catheter placement allows rapid plasma exchange to treat hyperviscosity. Why: Life-saving, fast IgM reduction while systemic therapy begins. American Cancer Society
Preventions
Keep vaccinations up to date before therapy; use inactivated vaccines during treatment when needed. CDC
Wash hands, wear masks in crowded indoor spaces during outbreaks, and seek early care for fever. CDC
Plan supplements with your team; avoid EGCG (green tea extracts) with bortezomib. PMC
Prevent falls: good lighting, remove tripping hazards, supportive shoes. National Cancer Institute
Protect from cold if cryoglobulins/cold agglutinins are present. ASH Publications
Dental checkups and daily oral care to reduce infections. CDC
Safe food handling and travel vaccines before trips. CDC
Exercise within limits to fight fatigue and maintain strength. National Cancer Institute
Maintain vitamin D and bone health under clinician guidance. ods.od.nih.gov
Keep a current medication/supplement list to avoid dangerous interactions. PMC
When to see doctors
- Immediately: New vision changes, severe headaches, nosebleeds, confusion, chest pain, or stroke-like symptoms—possible hyperviscosity. Urgent plasma exchange can be life-saving. ACEP
- Soon (within 24–48 h): Fever ≥38.0 °C, shaking chills, shortness of breath, painful rash (shingles), or rapidly worsening fatigue or bruising—possible infection or cytopenias. CDC
- Prompt appointment: New or worsening neuropathy, night sweats, weight loss, swollen nodes, or anemia symptoms (light-headedness). ASH Publications
What to eat and what to avoid
Eat: balanced meals with protein, legumes, whole grains, colorful vegetables, fruits, and healthy fats to maintain weight and muscle. Avoid: severe dieting that causes weight loss during treatment. ods.od.nih.gov
Eat: foods rich in vitamin D and calcium (fortified dairy/alternatives, fish) if levels are low. Avoid: exceeding safe vitamin D limits without labs. ods.od.nih.gov
Eat: zinc/selenium from food (seafood, meats, nuts) when possible. Avoid: long-term high-dose supplements that can harm (e.g., excess zinc causes copper deficiency). ods.od.nih.gov+1
Eat: fiber and fermented foods if tolerated to support gut health. Avoid: unpasteurized products and high-risk undercooked meats during neutropenia. ods.od.nih.gov
Hydrate well; this can help with headaches and viscosity symptoms. Avoid: alcohol excess, which worsens dehydration and bleeding risk. ASH Publications
Eat: omega-3-rich fish (e.g., salmon) in normal portions. Avoid: high-dose fish-oil pills without approval if you’re on BTK inhibitors (bleeding risk). ods.od.nih.gov
Eat: spice with turmeric/ginger in cooking. Avoid: concentrated green tea extracts if receiving bortezomib. PMC
Choose: small, frequent meals if nauseated. Avoid: raw sprouts and salad bars during bouts of neutropenia. ods.od.nih.gov
Limit: very salty, highly processed foods, which can worsen blood pressure on BTK inhibitors. Prefer: fresh meals cooked at home. FDA Access Data
Discuss: any herbal/botanical with your doctor before starting. Avoid: assuming “natural” equals “safe” during chemo. ods.od.nih.gov
Frequently asked questions
Do all patients need treatment right away?
No. Many start with “watchful waiting” until symptoms or organ problems appear. This is safe and avoids side effects when there’s no immediate benefit to treating. PubMedWhat symptoms mean it’s time to treat?
Anemia, hyperviscosity symptoms, organ or nerve damage, bulky disease, or B-symptoms (fevers/night sweats/weight loss). ASH PublicationsWhat is the fastest way to fix hyperviscosity?
Therapeutic plasma exchange lowers IgM quickly; it is a bridge until drug therapy controls the disease. ACEP+1Which drugs are FDA-approved specifically for WM?
Ibrutinib and zanubrutinib are FDA-approved for adult patients with WM. FDA Access Data+1Is chemo still used?
Yes. Regimens like bendamustine-rituximab (BR) or DRC are time-limited and effective; choice depends on goals and health status. PubMedCan treatment be continuous or time-limited?
BTK inhibitors are continuous; chemo-immunotherapy is usually given for fixed cycles. Your team will match the plan to your needs. The ASCO PostDo vaccines work during therapy?
They work better before anti-CD20 therapy and during the least immunosuppressed times. Inactivated vaccines are recommended; live vaccines are avoided during/after immunosuppression. CDCWhat about IVIG?
If you have low IgG and repeated bacterial infections, IVIG can reduce infections. It’s not for everyone and is individualized. FrontiersCan supplements cure WM?
No. Supplements may support general health but do not replace WM therapy. Some can interact with drugs (e.g., EGCG with bortezomib). Always clear with your team. PMCWhat lab marker is key?
Serum IgM and serum viscosity are important, together with full blood count and clinical symptoms. ASH PublicationsIs transplant common?
No. Autologous transplant is reserved for very selected relapses; allogeneic transplant is rare due to higher risks. National Cancer InstituteWill treatment fix neuropathy?
It may stop progression, and some symptoms improve over time, but recovery can be slow—physical therapy helps. ASH PublicationsCan rituximab make IgM go up at first?
Yes—“IgM flare” can occur. Doctors watch viscosity and sometimes use plasmapheresis around treatment if symptoms appear. ASH PublicationsHow long do responses last?
Many patients enjoy multi-year control. Durability depends on regimen, tolerance, genetics, and prior therapies. PubMedWhere can I read trusted updates?
NCI PDQ professional and patient summaries and major hematology guidelines are reliable and frequently updated. National Cancer Institute+1
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: October 15, 2025.
