Hematologic Disorders - Comprehensive Overview

Hematologic disorders encompass conditions affecting red blood cells, white blood cells, platelets, and the coagulation system. They range from common nutritional anemias to complex hematologic malignancies and coagulation disorders. This article provides comprehensive coverage of major hematologic conditions.

Anemia

Parameter	Detail
Definition	Decrease in red blood cell (RBC) mass, hemoglobin concentration (Hb), or hematocrit (Hct) below reference range for age, sex, and altitude
WHO criteria for anemia	Men: Hb <13 g/dL; Women (non-pregnant): <12 g/dL; Pregnancy: <11 g/dL

Classification of Anemia by MCV

Type	MCV (fL)	Differential Diagnosis
Microcytic	<80	Iron deficiency (most common), thalassemia, anemia of chronic disease (microcytic subset), sideroblastic anemia (some), lead poisoning
Normocytic	80-100	Anemia of chronic disease (most common normocytic), acute blood loss, hemolytic anemia, mixed deficiencies, CKD, bone marrow failure, endocrine disorders
Macrocytic	>100	Megaloblastic (B12/folate deficiency), non-megaloblastic (alcohol, liver disease, hypothyroidism, MDS, drugs, reticulocytosis)

Iron Deficiency Anemia (IDA)

Parameter	Detail
Prevalence	Most common anemia worldwide; affects 33% of population globally
Causes	Blood loss (GI: colon cancer, peptic ulcer, angiodysplasia; women: menorrhagia), decreased absorption (gastrectomy, celiac, H. pylori, PPI use), increased demands (pregnancy, growth, lactation), inadequate intake (vegetarian/vegan diet)

Iron Studies Interpretation

Parameter	Iron Deficiency	Anemia of Chronic Disease	Thalassemia (Trait)
Serum iron	Low	Low	Normal
TIBC	High	Low	Normal
Transferrin saturation	<20%	10-20%	Normal
Serum ferritin	Low (<30 ng/mL)	Normal or high (>100 ng/mL)	Normal
Soluble transferrin receptor (sTfR)	High	Normal	Normal
Hb electrophoresis	Normal	Normal	Elevated HbA2 (beta thal trait) or HbF
RDW	High	Normal or high	Normal

IDA Treatment

Severity	Hb (g/dL)	Treatment	Expected Response
Mild	10-12 (F) / 10-13 (M)	Oral iron: ferrous sulfate 325 mg (65 mg elemental iron) daily to TID	Reticulocytosis in 3-7 days; Hb rise of 1 g/dL in 2-3 weeks; continue 3-6 months to replenish stores
Moderate	7-10	Oral iron (as above); consider IV iron if intolerant/non-absorbing	Same as above
Severe	<7	Oral or IV iron; consider RBC transfusion if unstable or symptomatic	Same
IV iron options	Iron sucrose, ferric carboxymaltose, iron dextran, ferumoxytol, ferric derisomaltose	For intolerance, malabsorption, CKD, IBD, severe deficiency, post-bariatric surgery	IV iron corrects faster and replenishes stores more reliably

Vitamin B12 (Cobalamin) Deficiency

Parameter	Detail
Causes	Pernicious anemia (autoimmune destruction of gastric parietal cells -> lack of intrinsic factor, most common in adults), malabsorption (gastrectomy, Crohn, celiac, atrophic gastritis), dietary (vegans, vegetarians), pancreatic insufficiency, bacterial overgrowth, Diphyllobothrium latum (fish tapeworm), metformin, PPI
Neurologic symptoms	Peripheral neuropathy, subacute combined degeneration of spinal cord (dorsal columns -> vibratory/proprioception loss, spasticity, ataxia), cognitive impairment (memory loss, confusion), autonomic dysfunction
Hematologic findings	Macrocytic anemia (MCV >100), hypersegmented neutrophils (>5 lobes), pancytopenia (severe), megaloblastic bone marrow

B12 vs Folate Deficiency

Feature	B12 Deficiency	Folate Deficiency
Methylmalonic acid (MMA)	Elevated	Normal
Homocysteine	Elevated	Elevated
Neurologic symptoms	Yes (neuropathy, subacute combined degeneration)	No (except depression)
Response to treatment	Reticulocytosis + improvement in anemia and neurology	Reticulocytosis + improvement in anemia
Treatment	B12: IM (1000 mcg daily x1 week, then weekly x4 weeks, then monthly) or high-dose oral (1000-2000 mcg daily)	Folic acid 1-5 mg PO daily (correct before B12 if both deficient to avoid precipitating neurologic symptoms with isolated folate)

Anemia of Chronic Disease (ACD)

Parameter	Detail
Pathophysiology	Inflammatory cytokines (IL-6, TNF-alpha, hepcidin) -> decreased erythropoiesis (impaired EPO response), shortened RBC survival, impaired iron utilization (hepcidin blocks ferroportin -> iron sequestration in macrophages)
Common causes	Chronic infections (TB, HIV, osteomyelitis), autoimmune diseases (RA, SLE, IBD), malignancy, CKD, chronic rejection
Diagnosis	Normocytic anemia (may be microcytic), low serum iron, low TIBC, elevated ferritin, normal/elevated hepcidin
Treatment	Treat underlying condition; ESAs for selected cases (CKD, MDS, chemotherapy); iron supplementation only if concomitant iron deficiency confirmed

Sickle Cell Disease (SCD)

Parameter	Detail
Definition	Autosomal recessive hemoglobinopathy caused by point mutation in beta-globin gene (GAG->GTG, Glu->Val at position 6) -> hemoglobin S (HbS)
Genotypes	HbSS (sickle cell anemia, most severe), HbSC (milder), HbS-beta-thal (variable), HbS trait (AS, asymptomatic)
Pathophysiology	HbS polymerizes under hypoxia -> RBC sickling -> hemolysis -> vaso-occlusion -> tissue ischemia/reperfusion injury -> chronic organ damage

Sickle Cell Disease Complications

Complication	Age	Pathophysiology	Treatment/Prevention
Vaso-occlusive crisis (painful crisis)	Any age	Sickling -> vascular occlusion -> tissue ischemia	Hydration, analgesia (NSAIDs + opioids), O2 (if hypoxic), incentive spirometry
Acute chest syndrome (ACS)	Any age (peak children)	Pulmonary vaso-occlusion +/- infection	Antibiotics (levofloxacin/ceftriaxone/azithromycin), bronchodilators, transfusion (simple or exchange), O2
Stroke	Children (peak 2-9)	Large vessel vasculopathy (ICA, MCA)	Chronic transfusion program (to keep HbS <30%); TCD screening (start at 2 years)
Splenic sequestration	Children (peak 6 mo-5 years)	RBC trapping in spleen	Transfusion, splenectomy after first severe episode
Aplastic crisis	Children	Parvovirus B19 infection -> temporary arrest of erythropoiesis	Transfusion (usually self-limited within 1-2 weeks)
Priapism	Males	Vaso-occlusion of penile vessels	Hydration, analgesia, aspiration/irrigation, exchange transfusion
Chronic organ damage	Adults	Cumulative vaso-occlusion	Pulmonary HTN, renal insufficiency, retinopathy, AVN of femoral heads, leg ulcers, gallstones (hemolysis), iron overload (transfusions)
Pregnancy complications	Women	Increased sickling	High-risk obstetrics, prophylactic transfusion (controversial)

SCD Disease-Modifying Therapies

Drug	Mechanism	Effect	Side Effects
Hydroxyurea	Increases HbF (fetal hemoglobin), decreases sickling	Reduces VOC by 50%, decreases ACS, improves survival	Myelosuppression, teratogenic; requires monitoring CBC
L-glutamine (Endari)	Reduces oxidative stress	Reduces VOC by 25%	Minimal (GI)
Crizanlizumab (Adakveo)	Anti-P-selectin monoclonal antibody	Reduces VOC by 45%	Nausea, arthralgia, infusion reactions
Voxelotor (Oxbryta)	HbS polymerization inhibitor	Increases Hb by 1-1.5 g/dL, decreases hemolysis	Headache, diarrhea, nausea
Hematopoietic stem cell transplant (HSCT)	Curative	–	Treatment-related mortality 5-10%; limited by donor availability
Gene therapy (Casgevy, Lyfgenia)	CRISPR or lentiviral editing of HbF or HbS	Curative potential	Emerging; very high cost; limited availability

Hemolytic Anemia

Type	Mechanism	Examples	Lab Findings	Treatment
Intrinsic (intracorpuscular)	Defect within RBC	Sickle cell, thalassemia, hereditary spherocytosis, G6PD deficiency, pyruvate kinase deficiency	Increased reticulocytes, elevated LDH, decreased haptoglobin, elevated unconjugated bilirubin, increased AST, spherocytes/fragments on smear	Specific to disorder: splenectomy (spherocytosis), folic acid, avoid triggers (G6PD), transfusion, HSCT
Extrinsic (extracorpuscular)	External factor destroys normal RBC	Autoimmune hemolytic anemia (warm AIHA most common: IgG, 70%; cold agglutinin disease: IgM), microangiopathic hemolytic anemia (TTP, HUS, DIC), drug-induced, mechanical (heart valves), infection, hypersplenism	Same hemolytic labs + Coombs test positive (direct antiglobulin test)	Corticosteroids (warm AIHA first-line), rituximab, splenectomy, immunosuppression; treat underlying cause

G6PD Deficiency

Parameter	Detail
Definition	X-linked recessive disorder; most common RBC enzyme defect; deficiency of glucose-6-phosphate dehydrogenase leading to inability to handle oxidative stress
Prevalence	400 million people worldwide; more common in African, Mediterranean, Middle Eastern, Southeast Asian populations
Triggers for hemolysis	Oxidative stress: certain drugs (dapsone, sulfonamides, nitrofurantoin, primaquine, rasburicase, methylene blue), infections (viral hepatitis, typhoid), fava beans, metabolic acidosis
Acute hemolytic anemia	Onset 1-3 days after exposure; pallor, jaundice, dark urine (hemoglobinuria), back pain; self-limited (2-4 weeks, as young RBCs with normal G6PD emerge)
Diagnosis	G6PD enzyme assay (may be false normal during acute hemolysis due to reticulocytosis with higher G6PD activity; repeat in 2-3 months)
Treatment	Discontinue trigger, supportive care (IV fluids, transfusion if severe), avoid oxidative drugs lifelong

Coagulation Disorders

Hemophilia

Parameter	Hemophilia A	Hemophilia B
Deficient factor	Factor VIII	Factor IX
Inheritance	X-linked recessive	X-linked recessive
Prevalence	1:5,000 males	1:30,000 males
Severity by factor level	Severe (<1%), Moderate (1-5%), Mild (6-40%)	Same

Hemophilia Severity and Bleeding Pattern

Severity	Factor Level	Bleeding Pattern	Prophylaxis
Severe	<1%	Spontaneous bleeding (joints, muscles, soft tissue) into joints (hemarthrosis) without trauma	Primary prophylaxis: factor replacement 2-3x/week (A) or 2x/week (B) starting at age 1-2
Moderate	1-5%	Bleeding with mild-moderate trauma; occasional spontaneous bleeding	Secondary prophylaxis (after first significant bleed) or on-demand
Mild	6-40%	Bleeding only with significant trauma or surgery	On-demand treatment

Hemophilia Treatment

Product/Intervention	Hemophilia A	Hemophilia B
Plasma-derived factors	Factor VIII concentrates	Factor IX concentrates
Recombinant factors	Standard half-life (SHL), Extended half-life (EHL: Fc-fusion, PEGylated)	Standard and extended half-life products
Desmopressin (DDAVP)	Mild-moderate A (raises vWF and FVIII)	Not effective
Antifibrinolytics	Tranexamic acid, aminocaproic acid (mucosal bleeding, dental procedures)	Same
Emicizumab (Hemlibra)	Bispecific monoclonal antibody (mimics FVIII function); SC prophylaxis q1-4 weeks; for hemophilia A with/without inhibitors	Not effective (FVIII mimic)
Gene therapy	Valoctocogene roxaparvovec (AAV-mediated FVIII gene transfer)	Approved (eti…)
Inhibitors (alloantibodies)	20-30% of severe A (more common); treated with bypassing agents (rFVIIa, aPCC), emicizumab	1-3% of B (more common with large deletions; risk of anaphylaxis)

von Willebrand Disease (VWD)

Type	Defect	Inheritance	Frequency	Features	Treatment
Type 1	Partial quantitative deficiency of vWF	AD (variable penetrance)	70-80%	Mild-moderate mucocutaneous bleeding, epistaxis, menorrhagia, easy bruising	DDAVP (stimulates vWF release from endothelium), tranexamic acid
Type 2	Qualitative defect (2A: loss of high-molecular-weight multimers; 2B: increased binding to platelets; 2M: decreased platelet binding; 2N: decreased FVIII binding)	AD (except 2N: AR)	15-20%	Variable bleeding severity	DDAVP (variable response in 2A, 2M; contraindicated in 2B - can cause thrombocytopenia); vWF-containing factor concentrates (Humate-P, Wilate)
Type 3	Severe quantitative deficiency (near absent vWF)	AR	1-5%	Severe bleeding, hemarthrosis, similar to moderate hemophilia A	vWF-containing factor concentrates; DDAVP ineffective

Thrombocytopenia

Severity	Platelet Count (x 10^9/L)	Bleeding Risk	Management Threshold
Mild	100-150	Minimal	No specific treatment
Moderate	50-99	Mild: easy bruising, petechiae	Treat if actively bleeding or pre-procedure
Moderate-Severe	30-49	Increased bruising, prolonged bleeding from cuts	Pre-procedure transfusion often indicated
Severe	10-29	Spontaneous bleeding possible	Pre-procedure transfusion typically indicated
Very severe	<10	High risk of spontaneous intracranial hemorrhage	Prophylactic platelet transfusion (in hospitalized patients)

Immune Thrombocytopenia (ITP)

Parameter	Detail
Definition	Acquired autoimmune disorder characterized by isolated thrombocytopenia due to autoantibody-mediated platelet destruction and impaired platelet production
Prevalence	5-10 per 100,000; children (acute, post-infectious) and adults (chronic)
Pathophysiology	Anti-platelet antibodies (mostly IgG against GPIIb/IIIa) -> platelet destruction in spleen; impaired megakaryopoiesis in bone marrow
Presentation	Cutaneous bleeding (petechiae, purpura, ecchymoses), mucosal bleeding (epistaxis, gingival, menorrhagia), intracranial hemorrhage (rare, <1%)

ITP Treatment

Line	Adult (Newly Diagnosed)	Children
First-line	Corticosteroids (prednisone 1 mg/kg/day x2-4 weeks with taper; or dexamethasone 40 mg/day x4 days); IVIG (1 g/kg x1-2 days) if bleeding/refractory	Observation (if mild, as 80% remit within 6 months); IVIG (0.8-1 g/kg) or prednisone (2-4 mg/kg/day x5-7 days) for moderate-severe
Second-line	TPO-receptor agonists (eltrombopag PO, romiplostim SC, avatrombopag PO, lusutrombopag PO) - highly effective; rituximab (anti-CD20); splenectomy (definitive but irreversible)	TPO-RAs (eltrombopag approved), rituximab, splenectomy (avoid before age 5-6)
Third-line	Immunosuppression (mycophenolate mofetil, azathioprine, cyclosporine), combination therapy	Clinical trials
Emergency	Platelet transfusion + IVIG + high-dose methylprednisolone; recombinant factor VIIa (rFVIIa) for life-threatening bleeding	Same

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Parameter	Detail
Definition	Formation of thrombus in deep veins (usually lower extremities) with potential embolization to lungs
Risk factors	Virchow triad: stasis (immobility, travel, obesity, surgery), hypercoagulability (cancer, pregnancy, OCP/HRT, thrombophilia, antiphospholipid syndrome, nephrotic syndrome), endothelial injury (surgery, trauma, central line, vasculitis)

Wells Criteria for DVT

Clinical Sign	Points
Active cancer (treatment within 6 months or palliative)	1
Paralysis, paresis, or recent plaster immobilization of lower extremity	1
Bed rest >3 days or surgery within 12 weeks	1
Localized tenderness along distribution of deep veins	1
Entire leg swollen	1
Calf swelling >3 cm compared to asymptomatic leg	1
Pitting edema (symptomatic leg only)	1
Collateral superficial veins (non-varicose)	1
Previously documented DVT	1
Alternative diagnosis as likely or more likely than DVT	-2

Interpretation: Likely (>=2 points): proceed to ultrasound; Unlikely (<=1): perform D-dimer.

Anticoagulation for VTE

Phase	Duration	DOACs	VKA (Warfarin)
Acute (first 5-21 days)	–	Rivaroxaban 15 mg BID x21d, then 20 mg daily; Apixaban 10 mg BID x7d, then 5 mg BID; Edoxaban (after 5 days parenteral); Dabigatran (after 5 days parenteral)	Start warfarin + LMWH bridge; stop LMWH when INR 2-3 for 2 consecutive days
Long-term (3-6 months)	3 months (provoked, reversible risk factor), 3-6 months (unprovoked), indefinite (recurrent, cancer, high-risk thrombophilia, unprovoked with low bleeding risk)	Rivaroxaban 20 mg daily; Apixaban 5 mg BID; Edoxaban 60 mg daily; Dabigatran 150 mg BID	INR target 2-3; frequent monitoring
Extended (>6 months)	Indefinite if high recurrence risk	Same as above (reduced dose apixaban 2.5 mg BID or rivaroxaban 10 mg daily may be considered for extended secondary prevention)	Same INR target

Direct Oral Anticoagulants (DOACs) vs Warfarin

Feature	DOACs (Apixaban, Rivaroxaban, Edoxaban, Dabigatran)	Warfarin
Mechanism	Direct factor Xa (apixaban, rivaroxaban, edoxaban) or thrombin (dabigatran) inhibition	Vitamin K antagonist (factors II, VII, IX, X, protein C, S)
Onset	Rapid (1-4 hours)	Slow (3-5 days)
Half-life	5-17 hours	40 hours
Dosing	Fixed dose	Variable dose (INR-adjusted)
Monitoring	Not required	INR required (frequency: daily to monthly)
Drug interactions	Fewer (P-gp, CYP3A4)	Many (CYP system, diet, alcohol, many drugs)
Food interactions	No	Yes (vitamin K)
Reversal agents	Andexanet alfa (factor Xa), idarucizumab (dabigatran)	Vitamin K, PCC, FFP
Clinical trial data	Non-inferior or superior to warfarin for VTE treatment and AFib stroke prevention	Historical gold standard
Major bleeding risk	Lower (especially intracranial hemorrhage)	Higher (especially intracranial hemorrhage)

Hematologic Malignancies

Leukemia Classification

Type	Cell Line	Age Group	Frequency	Key Features
ALL (Acute Lymphoblastic Leukemia)	Lymphoid (B-cell 85%, T-cell 15%)	Children (peak 2-5), adults (peak >50)	Most common childhood cancer	L1/L2/L3 morphology; Philadelphia chromosome (t(9;22)) in 25% of adult ALL; good prognosis in children (90% cure), guarded in adults
AML (Acute Myeloid Leukemia)	Myeloid	Adults (median 68)	Most common acute leukemia in adults	Auer rods, myeloperoxidase positive; subtypes (M0-M7 by FAB); APL (M3) with t(15;17) -> treat with ATRA + arsenic; poor prognosis in older adults
CLL (Chronic Lymphocytic Leukemia)	Lymphoid (B-cell)	Older adults (median 70)	Most common leukemia in Western adults	Smudge cells on smear; CD5+, CD19+, CD23+; Rai/Binet staging; indolent (many asymptomatic, watch and wait); treat with BTK inhibitors (ibrutinib, acalabrutinib) or venetoclax + obinutuzumab
CML (Chronic Myeloid Leukemia)	Myeloid	Adults (median 55)	–	Philadelphia chromosome t(9;22) BCR-ABL1 (100%); triphasic: chronic -> accelerated -> blast crisis; treat with TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib); excellent prognosis (10-year survival >90% on TKI)

Lymphoma Classification

Type	Frequency	Cell of Origin	Key Features	Treatment
Hodgkin lymphoma (HL)	10%	Reed-Sternberg cells (germinal center B-cell origin)	Nodular sclerosis (most common), mixed cellularity, lymphocyte-rich, lymphocyte-depleted, nodular lymphocyte predominant; B symptoms (fever, night sweats, weight loss); good prognosis	Chemotherapy (ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine or escalated BEACOPP) + radiation; 90% cure rate (early stage)
Diffuse large B-cell lymphoma (DLBCL)	30-35%	Mature B-cell	Most common NHL; can present at any nodal or extranodal site; fast-growing, symptomatic	R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) x6 cycles; 60-70% cure rate
Follicular lymphoma	20-25%	Germinal center B-cell	Indolent; t(14;18) BCL-2 rearrangement; slow-growing, wax-waning; advanced stage at diagnosis; not curable (except early stage)	Watchful waiting; rituximab +/- chemotherapy (bendamustine, CHOP, CVP); rituximab maintenance; CAR-T in relapsed; median survival >10 years
Mantle cell lymphoma	5-7%	Mantle zone B-cell	t(11;14) CCND1 -> cyclin D1; aggressive but incurable	Immunochemotherapy + stem cell transplant; BTK inhibitors; CAR-T
Marginal zone lymphoma	5-10%	Post-germinal center B-cell	MALT (gastric: H. pylori-associated, antibiotic responsive), nodal, splenic; indolent	Treat underlying cause (H. pylori eradication for gastric MALT); rituximab; watchful waiting
Burkitt lymphoma	<5%	Germinal center B-cell	Sporadic, endemic (EBV+ in Africa), immunodeficiency-associated; t(8;14) MYC; very aggressive, highly proliferative	Intensive chemotherapy (CODOX-M/IVAC, hyper-CVAD); curable

Multiple Myeloma

Parameter	Detail
Definition	Clonal plasma cell malignancy characterized by production of monoclonal immunoglobulin (M-protein), lytic bone lesions, renal impairment, anemia, and hypercalcemia (CRAB criteria)
Prevalence	1-2% of all cancers; 15% of hematologic malignancies; median age 69
Pathophysiology	Plasma cell proliferation driven by genetic events (IgH translocations, hyperdiploidy, del(13q), del(17p), MYC, RAS mutations, mutations in NF-kB pathway) -> monoclonal Ig production (IgG 55%, IgA 20%, light chain only 20%, IgD/IgM/IgE rare)

Multiple Myeloma: CRAB Criteria and Complications

Complication	Definition	Mechanism	Management
Hypercalcemia	Corrected Ca >11.5 mg/dL	Osteoclast activation (RANKL, MIP-1alpha, IL-6) -> bone resorption	Hydration, bisphosphonates (zoledronic acid, pamidronate), denosumab, calcitonin, glucocorticoids
Renal insufficiency	Cr >2 mg/dL or CrCl <40 mL/min	Light chain cast nephropathy (most common), hypercalcemia, hyperuricemia, amyloidosis, bisphosphonates, NSAIDs	Hydration, treat hypercalcemia, discontinue nephrotoxins; plasma exchange (limited evidence), dialysis if needed
Anemia	Hb <10 g/dL	Marrow infiltration, anemia of chronic disease, renal insufficiency, chemotherapy	Transfusions, ESAs, treat underlying disease
Bone disease (lytic lesions)	One or more osteolytic lesions on X-ray, CT, PET/CT	Osteoclast activation	Bisphosphonates (zoledronic acid monthly), denosumab; radiation for painful lesions/pathologic fracture; orthopedics for impending/actual fracture
Infections	Recurrent bacterial infections (encapsulated organisms: S. pneumoniae, H. influenzae, N. meningitidis)	Hypogammaglobulinemia, impaired neutrophil function, immunoparesis	Vaccinations (pneumococcal, influenza, H. influenzae type b, meningococcal); IVIG if recurrent/recalcitrant
Hyperviscosity	Symptoms: nosebleeds, visual changes, headache, confusion	High M-protein levels (usually IgA or IgG3)	Plasmapheresis

Multiple Myeloma Treatment

Regimen	Anti-myeloma Agents	Corticosteroid	Notes
Induction (transplant-eligible)	VRd: Bortezomib (Velcade) + Lenalidomide (Revlimid) + Dexamethasone	Dexamethasone	Standard of care; followed by stem cell collection and autologous stem cell transplant (ASCT)
Induction (transplant-eligible alternative)	Dara-VRd: Daratumumab + VRd	Dexamethasone	Quadruplet therapy; emerging standard
Maintenance (post-ASCT)	Lenalidomide	–	Prolongs PFS and OS (phase 3 trial data)
Non-transplant candidates	DRd: Daratumumab + Lenalidomide + Dex; RVd (if lenalidomide tolerant)	Dexamethasone	Continuous therapy
Relapsed/refractory	Carfilzomib, pomalidomide, elotuzumab, isatuximab, selinexor, teclistamab, idecabtagene vicleucel (CAR-T), belantamab mafodotin	Dexamethasone	Multiple options; sequential therapy

Multiple Myeloma Staging (R-ISS)

Stage	Criteria	5-Year Survival
I	Beta-2 microglobulin <3.5 mg/L + albumin >=3.5 g/dL + normal LDH + standard-risk cytogenetics	80%
II	Not stage I or III	60%
III	Beta-2 microglobulin >=5.5 mg/L + either high-risk cytogenetics [t(4;14), t(14;16), del(17p)] or elevated LDH	40%