MyelofibrosisMANAGEMENT

HEMATOLOGIC AND ONCOLOGIC PRESENTATIONS · 12 SECTIONS

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729 items

☷ Legend

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Cardiovascular Presentations71▾

Respiratory Presentations52▾

Neurological Presentations83▾

Gastrointestinal Presentations74▾

Genitourinary and Reproductive Presentations48▾

Infectious Disease Presentations148▾

Trauma Presentations89▾

Toxicologic Presentations80▾

Psychiatric Presentations26▾

Musculoskeletal and Rheumatologic Presentations96▾

Dermatology Presentations23▾

Environmental and Exposure Presentations27▾

Hematologic and Oncologic Presentations36▾

Acute chest syndrome Acute Hemolytic Transfusion Reaction Anticoagulant reversal (warfarin, DOAC, heparin)Aplastic Anemia (Crisis)Autoimmune Hemolytic Anemia CAR-T and cytokine release syndrome Coagulopathy Delayed Hemolytic Transfusion Reaction Disseminated Intravascular Coagulation (DIC)Essential Thrombocythemia Febrile Non-hemolytic Transfusion Reaction Graft Versus Host Disease (Acute)Hemolytic Uremic Syndrome (HUS)Hemophilia A (Bleeding Crisis)Heparin-Induced Thrombocytopenia (HIT)Hyperviscosity syndrome Immune checkpoint inhibitor toxicity Immune Thrombocytopenic Purpura (ITP)Leukemoid Reaction Leukostasis Massive transfusion protocol Myelofibrosis Neutropenic enterocolitis (typhlitis)Paroxysmal Nocturnal Hemoglobinuria Polycythemia Vera (Crisis)Pure Red Cell Aplasia Sickle Cell (Acute Chest Syndrome)Sickle Cell (Splenic Sequestration)Sickle cell crisis (vaso-occlusive)Symptomatic anemia Thrombocytopenia (severe)Thrombotic Thrombocytopenic Purpura (TTP)Transfusion-Associated Circulatory Overload (TACO)Transfusion-Related Acute Lung Injury (TRALI)Tumor lysis syndrome Von Willebrand Disease (Bleeding)

Pediatric-Specific Presentations19▾

Endocrine and Metabolic Presentations45▾

ENT and Maxillofacial Presentations27▾

Ophthalmologic Presentations19▾

Obstetric Presentations23▾

Systemic and Miscellaneous Presentations17▾

01Approach to the Critical Patient/attcp49

Immediate priorities

›Life-threatening presentations of myelofibrosis

›Blast crisis (leukemic transformation)

›Peripheral blast count >= 20% defines blast phase

›Occurs in ~15% within 5 years of diagnosis

›Urgent hematology consult and bone marrow evaluation

›Severe anemia with hemodynamic compromise

›Hemoglobin <8 g/dL with symptomatic hypoxia

›Median survival ~2.1 years with Hgb <8 g/dL

›Transfusion threshold individualized to symptoms and cardiopulmonary reserve

›Splenic infarction

›Acute severe LUQ pain with peritoneal signs

›CT abdomen with contrast for confirmation

›Pain management and urgent surgical/hematology consult

›JAK inhibitor withdrawal syndrome

›Fever, respiratory distress, hypotension after abrupt discontinuation

›Multi-organ failure risk

›Reinstate JAK inhibitor and supportive care urgently

Escalation triggers

›Critical thresholds requiring escalation

›Hemodynamic instability

›SBP <90 mmHg

›MAP <65 mmHg

›Tachycardia with hemoglobin <70 g/L

›Respiratory compromise

›Dyspnea at rest with SpO2 <92%

›Pulmonary hypertension from extramedullary hematopoiesis

›Pleural effusion with respiratory embarrassment

02History/hx63

Presenting symptoms

›Cardinal constitutional symptoms

›Fatigue

›Present in ~85% of patients

›Most debilitating and functionally limiting symptom

›Night sweats

›Drenching quality distinguishes MPN-related from infectious

›Unexplained fevers

›Low-grade persistent pattern

›Unintentional weight loss

›>10% body weight in 6 months carries prognostic significance

›Bone pain

›Diffuse extremity pain from extramedullary hematopoiesis

›Abdominal symptoms

›Early satiety

›Mechanical compression from progressive splenomegaly

›Left upper quadrant pain or fullness

›Increasing with progressive splenomegaly

›Diarrhea

›Gastrointestinal involvement

Alarm features

›High-risk presentations

›Acute severe LUQ pain

›Splenic infarction until proven otherwise

›Peritoneal signs suggest rupture risk

›Sudden onset dyspnea

›Pulmonary hypertension from extramedullary hematopoiesis

›Pleural effusion

03Physical Exam/exam56

Vitals and general appearance

›Vital sign assessment

›Temperature

›Low-grade fever from constitutional inflammation

›High fever prompts infection workup in immunocompromised state

›Heart rate

›Tachycardia proportional to anemia severity

›Resting HR >100 suggests hemodynamically significant anemia

›Blood pressure

›Hypotension with severe anemia or bleeding

›Hypertension may reflect prior JAK2-driven PV

›Weight and BMI

›Cachexia and weight loss

›Document against prior recorded weights

Abdominal exam

›Splenomegaly assessment

›Present in nearly all patients with established MF

›Measure distance from left costal margin in cm

›Massive splenomegaly defined as >10 cm below costal margin

›Spleen palpation technique

›Dullness to percussion in Traube's space

›May extend to right iliac fossa in massive cases

›Hepatomegaly

›Extramedullary hematopoiesis in liver

›Document liver span

›Ascites and portal hypertension signs

›Ascites

›Fluid wave and shifting dullness

04Differential Diagnosis/ddx45

Myeloproliferative and myeloid disorders

›BCR-ABL1-positive disorders

›Chronic myeloid leukemia (CML)

›ICD-10 C92.1

›Must exclude with BCR::ABL1 FISH or RT-PCR — mandatory in workup

›Similar splenomegaly and leukocytosis pattern

›Distinguishing features

›CML has BCR::ABL1 fusion; MF does not

›Philadelphia chromosome present in CML

›BCR-ABL1-negative MPNs

›Polycythemia vera

›ICD-10 D45

›Distinguished by erythrocytosis and JAK2 V617F

›Post-PV MF develops after established PV course

›Essential thrombocythemia

›ICD-10 D47.3

›Distinguished by isolated thrombocytosis without fibrosis early

›Post-ET MF distinguished by characteristic bone marrow morphology

Bone marrow failure and malignancy

›Myelodysplastic syndromes

›MDS with fibrosis

›ICD-10 D46.9

›Can have reticulin fibrosis

›Distinguished by dysplastic morphology and cytogenetics

›MDS/MPN overlap syndromes

›Chronic myelomonocytic leukemia (CMML) can develop monocytosis mimicking MF

›ICD-10 C93.1

›Acute leukemia

05Laboratory Tests/lt62

Hematologic core labs

›Complete blood count with differential

›Anemia pattern

›Normocytic or macrocytic anemia typical

›Hemoglobin <100 g/L common at diagnosis

›Hemoglobin <80 g/L indicates high-risk category

›White blood cell count

›Leukocytosis or leukopenia depending on disease phase

›WBC >25 × 10^9/L carries prognostic weight in DIPSS

›Platelet count

›Thrombocytopenia <100 × 10^9/L in ~30% at diagnosis

›Platelets <50 × 10^9/L restricts ruxolitinib; pacritinib indicated

›Peripheral blood smear

›Leukoerythroblastosis

›Nucleated red blood cells (normoblasts) in circulation

›Immature granulocytes (myelocytes, metamyelocytes)

›Hallmark of bone marrow infiltration or fibrosis

›Teardrop cells (dacrocytes)

›Classic finding in myelofibrosis

›Formed as RBCs are forced through fibrotic marrow

›Blast percentage

›>10% suggests accelerated phase

›>= 20% defines blast phase transformation

Biochemical and prognostic labs

›Metabolic panel

›Lactate dehydrogenase (LDH)

›Elevated LDH is a minor diagnostic criterion for MF

›Reflects high cell turnover

06Diagnostic Tests/dt91

Scoring Systems

›Prognostic risk stratification tools

›DIPSS (Dynamic International Prognostic Scoring System)

›Age >65 years (1 point)

›Hemoglobin <100 g/L (2 points)

›WBC >25 × 10^9/L (1 point)

›Circulating blasts >= 1% (1 point)

›Constitutional symptoms (1 point)

›Low risk (0 points): median survival >15 years

›Intermediate-1 (1-2 points): median survival 6.5 years

›Intermediate-2 (3-4 points): median survival 2.9 years

›High risk (5-6 points): median survival 1.3 years

›DIPSS-Plus

›Adds karyotype, platelet count, and transfusion status to DIPSS

›Unfavorable karyotype adds 1 point

›Platelet count <100 × 10^9/L adds 1 point

›Transfusion dependence adds 1 point

›MIPSS70+v2.0

›Integrates molecular mutation data for refined prognostication

›High-molecular-risk mutations worsen score

›More precise than DIPSS for transplant decision-making

›GIPSS (Genetically Inspired Prognostic Scoring System)

›Purely genomic-based: karyotype and driver mutations

›Does not require clinical variables

›MTSS (Myelofibrosis Transplant Scoring System)

›Guides hematopoietic cell transplant candidacy assessment

›Integrates age, comorbidities, and disease variables

›Symptom burden quantification

›MPN-SAF TSS (Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score)

›10-item patient-reported outcome tool

›Scores fatigue, night sweats, itching, abdominal discomfort, early satiety, pain under ribs, bone pain, weight loss, fever, inactivity

›Baseline and monitoring assessment to guide treatment

›Score >44 associated with significantly reduced quality of life

MRI

›MRI indications in myelofibrosis

›Spinal cord compression evaluation

›New neurologic symptoms with MF diagnosis

›Epidural extramedullary hematopoiesis detected on MRI spine

›Gadolinium-enhanced for best characterization

›Bone marrow characterization

›MRI marrow signal reflects cellularity and fibrosis

›T1 hypointense marrow signal with diffuse fibrosis

›Research utility; not required for routine diagnostic workup

›Extramedullary hematopoiesis sites

›Paraspinal and epidural masses

›Intracranial extramedullary hematopoiesis (rare)

›Hepatic and splenic signal assessment

›Limitations

›Not required for routine MF monitoring

›Availability and cost constraints in acute setting

›CT abdomen and pelvis

›Spleen and liver volumetrics

›Quantitative spleen volume measurement

›>= 35% spleen volume reduction is key treatment response endpoint

›Baseline and post-treatment comparison

›Splenic infarction

›CT with IV contrast identifies wedge-shaped perfusion defect

›Indicated for acute severe LUQ pain

›Assess for subcapsular hematoma or splenic rupture

›Portal hypertension complications

›Ascites quantification

›Varices identification (mesenteric, splenic, retroperitoneal)

›Splenoportal axis patency

›CT chest

›Pulmonary hypertension workup

›Main pulmonary artery diameter >29 mm suggests PH

›Right heart enlargement pattern

›Pleural effusion characterization

›Extramedullary hematopoiesis in pleural space

›Volume and complexity assessment

›Extramedullary hematopoiesis in thorax

›Paraspinal masses

›Mediastinal soft tissue deposits

Ultrasound

›Abdominal ultrasound

›Splenomegaly quantification

›Longitudinal splenic diameter >13 cm defines splenomegaly

›Serial measurements for treatment response monitoring

›First-line imaging for routine surveillance

›Hepatomegaly assessment

›Liver span measurement

›Echogenicity changes with infiltration

›Portal vein Doppler

›Portal vein thrombosis detection

›Hepatopetal vs hepatofugal flow

›Reversal of flow indicates severe portal hypertension

›Targeted point-of-care ultrasound

›Pleural effusion

›Identify effusion amenable to thoracentesis

›Real-time guidance for thoracentesis

›Ascites

›Confirm free fluid

›Guide diagnostic paracentesis

›Septations may indicate complicating infection

07Disposition/dispo40

Inpatient admission criteria

›Indications for hospital admission

›Hematologic emergency

›Blast crisis transformation

›Symptomatic anemia requiring transfusion (Hgb <70-80 g/L)

›Severe thrombocytopenia with bleeding (platelets <20 × 10^9/L)

›Febrile neutropenia in setting of immunosuppression

›Complications requiring acute management

›Splenic infarction

›Variceal or gastrointestinal hemorrhage

›Cord compression from extramedullary hematopoiesis

›JAK inhibitor withdrawal syndrome

›Systemic compromise

›Hemodynamic instability

›Respiratory compromise from pleural effusion or pulmonary hypertension

ICU admission criteria

›High-acuity indicators

›Hemorrhagic shock

›Variceal bleeding requiring resuscitation

›Spontaneous splenic rupture

›Blast crisis with multi-organ compromise

›Leukostasis from very high blast count

›DIC from AML transformation

›Respiratory failure

›Pulmonary hypertension with acute decompensation

›Massive pleural effusion with respiratory distress

›SpO2 <90% despite supplemental oxygen

08Treatment/t108

Risk-stratified treatment approach

›Low and intermediate-1 risk disease

›Watch and wait for asymptomatic patients

›Monitoring CBC every 3-6 months

›No proven benefit of early cytoreduction in asymptomatic low-risk

›Symptom-directed therapy

›Symptomatic splenomegaly or constitutional symptoms guide initiation

›Anemia-directed therapy if Hgb <100 g/L and symptomatic

›JAK inhibitor consideration

›Ruxolitinib for symptomatic disease regardless of risk category

›Class I recommendation from NCCN for symptomatic intermediate-1

›Intermediate-2 and high-risk disease

›Allogeneic hematopoietic cell transplant (allo-HCT)

›Only potentially curative therapy for MF

›Transplant referral for eligible patients

›MTSS score guides selection

›Reduced intensity conditioning regimens extend eligibility to older patients

›Bridge to transplant with JAK inhibitor

›Spleen reduction and symptom control prior to HCT

›Pretransplant JAK inhibitor may improve engraftment

JAK inhibitor therapy

›Ruxolitinib (Jakafi)

›First-line for intermediate/high-risk MF

›Approved for MF with platelets >= 50 × 10^9/L

›~42% achieve >= 35% spleen volume reduction at week 24

›Significant improvement in constitutional symptoms and quality of life

›Dosing by platelet count

›Platelets >= 200 × 10^9/L: 20 mg orally twice daily

›Platelets 100-199 × 10^9/L: 15 mg orally twice daily

›Platelets 50-99 × 10^9/L: 5 mg orally twice daily

›Dose adjustments

›Reduce dose with renal impairment (GFR <15 mL/min)

›Titrate based on efficacy and cytopenias

›Do not abruptly discontinue; taper over 1-2 weeks to avoid withdrawal

›Monitoring

›CBC every 2-4 weeks until stable

›Infection surveillance (CMV, HBV reactivation risk)

›Non-melanoma skin cancer annual dermatology exam

›Lipid panel every 6 months

›Fedratinib (Inrebic)

›Second-line after ruxolitinib failure or intolerance

›Approved for intermediate-2 and high-risk MF

›Effective spleen volume reduction in ruxolitinib-refractory patients

›Dosing

›400 mg orally once daily with food

›Thiamine supplementation required (risk of Wernicke encephalopathy)

›CBC and renal function monitoring

›Side effects

›Diarrhea and nausea common (take with food and antiemetics)

›Wernicke encephalopathy risk; check thiamine levels before initiation

›Pacritinib (Vonjo)

›Specifically indicated for MF with platelets <50 × 10^9/L

›Only JAK inhibitor approved for severe thrombocytopenia

›Phase 3 PERSIST-2 and PAC203 trial data

›Dosing

›200 mg orally twice daily

›No dose adjustment required for severe thrombocytopenia

›Cardiac monitoring

›QT prolongation and arrhythmia risk

›Baseline ECG recommended

›Momelotinib (Ojjaara)

›MF with anemia (Hgb <100 g/L)

›Unique dual mechanism: JAK1/2 plus ACVR1 inhibition

›ACVR1 inhibition reduces hepcidin, improving iron-restricted erythropoiesis

›Simultaneously addresses anemia, splenomegaly, and constitutional symptoms

›Dosing

›200 mg orally once daily

›Peripheral neuropathy monitoring required

Anemia-directed therapies

›Erythropoiesis-stimulating agents

›Epoetin alfa or darbepoetin alfa

›Indicated when endogenous EPO <500 mU/mL

›Darbepoetin alfa 150-300 mcg subcutaneously every 1-3 weeks

›Response assessment at 12 weeks

›Avoid if platelets >600 × 10^9/L (thrombosis risk)

›Luspatercept

›Erythroid maturation agent

›1 mg/kg subcutaneously every 3 weeks

›Titrate to maximum 1.75 mg/kg if no response

›Evidence in transfusion-dependent MF patients

›Danazol

›Androgenic agent for anemia

›200 mg orally 2-3 times daily

›Monitor liver function tests (hepatotoxicity risk)

›Prostate cancer screening in males before initiation

›Avoid concurrent statins (rhabdomyolysis risk)

›Red blood cell transfusion

›Threshold individualized

›Symptomatic anemia trigger (not a fixed hemoglobin)

›Pre-transfusion Hgb typically <70-80 g/L in stable patients

›Leukocyte-depleted irradiated blood products for transplant candidates

›Iron chelation therapy if >20 lifetime transfusions (serum ferritin >1000 mcg/L)

Cytoreductive and other therapies

›Hydroxyurea

›Cytoreduction for symptomatic leukocytosis or thrombocytosis

›500-2000 mg orally daily in divided doses

›Titrate to CBC response

›Skin ulcers and macrocytosis as side effects

›Peginterferon alfa-2a

›Early-stage or low-risk disease option

›45-135 mcg subcutaneously weekly

›May reduce JAK2 allele burden

›Autoimmune and mood side effects limit use

›Spleen-directed therapies

›Splenic irradiation

›Symptomatic splenomegaly refractory to systemic therapy

›1-2 Gy in 5-10 fractions

›Temporary benefit; risk of severe cytopenias

›Splenectomy

›Refractory splenomegaly with severe symptoms

›Significant operative risk in MF (infection, thrombosis, portal hypertension)

›Postoperative thrombocytosis and hepatomegaly risk

09Special Populations/sp65

Pregnancy

›Pregnancy in myelofibrosis

›Epidemiology

›MF in reproductive-age females is rare; most diagnoses are post-menopausal

›Reported cases show high fetal and maternal complication rates

›Maternal risks

›Thrombosis and hemorrhage with thrombocytopenia

›Progressive anemia worsening with pregnancy demands

›Portal hypertension and variceal hemorrhage risk from splenomegaly

›Fetal risks

›First trimester loss is increased

›Intrauterine growth restriction from placental thrombosis

›Treatment considerations

›JAK inhibitors contraindicated in pregnancy (teratogenicity)

›Hydroxyurea is teratogenic and contraindicated

›Peginterferon alfa-2a is relatively contraindicated; limited pregnancy data

›Low-dose aspirin and LMWH may be used for thromboprophylaxis

›Red blood cell transfusion for symptomatic anemia (target Hgb >80 g/L)

›Fetal monitoring and high-risk obstetric co-management essential

›Postpartum

›Restart or initiate JAK inhibitor promptly postpartum if needed

›Breastfeeding is contraindicated with JAK inhibitor use

Geriatric

›Older adult considerations in myelofibrosis

›Disease demographics

›Median age at diagnosis 65-70 years

›Most MF patients are in the geriatric age range

›Comorbidity burden is high and affects treatment tolerance

10Background/b81

Epidemiology

›Incidence and prevalence

›Incidence rate approximately 0.5-1.5 per 100,000 persons per year

›Primary MF accounts for the majority of cases

›Post-PV MF and post-ET MF account for secondary MF

›Age distribution

›Median age at diagnosis 65-70 years

›Rare below age 40; more aggressive course when occurring in younger patients

›Sex distribution

›Slight male predominance in primary MF

›Post-ET MF may be more common in females given higher ET prevalence

›Survival heterogeneity

›Low-risk: median survival >15 years

›Intermediate-1: median survival 6.5 years

›Intermediate-2: median survival 2.9 years

›High-risk: median survival 1.3 years

›Leukemic transformation

›Blast crisis occurs in ~15% within 5 years

›Median survival after transformation <6 months with chemotherapy

›High-molecular-risk mutations predict higher transformation rate

›IDH1/2 and SRSF2 mutations particularly associated with transformation

Pathophysiology

›Clonal origin and driver mutations

›Origin in hematopoietic stem cell clone

›BCR-ABL1-negative clonal myeloproliferation

›Driver mutations activate JAK-STAT signaling pathway

›JAK2 V617F mutation (~60% of cases)

›Point mutation in pseudokinase domain of JAK2

›Constitutive activation of JAK-STAT signaling

›Promotes unregulated proliferation of myeloid progenitors

›CALR mutations (~25% of cases)

›Exon 9 frameshift insertions or deletions

›Mutant calreticulin activates MPL (thrombopoietin receptor)

›Predominantly type 1 (del52) and type 2 (ins5) mutations

›MPL mutations (~5% of cases)

›W515L/K point mutations in thrombopoietin receptor

›Also constitutively activate JAK-STAT pathway

›Triple-negative MF (~8-10% of cases)

›No JAK2, CALR, or MPL driver mutation

›Worst prognosis; may harbor non-canonical mutations

›Bone marrow fibrosis mechanism

›Abnormal megakaryocyte proliferation and apoptosis

›Megakaryocytes release TGF-beta, PDGF, and VEGF

›TGF-beta is the primary driver of reticulin and collagen fibrosis

›Progressive fibrosis grades from 0 (absent) to 3 (dense collagen)

›Osteosclerosis in advanced disease

›Trabecular bone thickening

›"Dry tap" on aspirate from sclerotic marrow

›Extramedullary hematopoiesis

›Hematopoietic stem cell egress from fibrotic marrow

›Spleen and liver are primary extramedullary hematopoietic sites

›Progressive splenomegaly and hepatomegaly

›Paraspinal, epidural, pleural, and lymph node sites possible

›Consequences

›Portal hypertension from splenic congestion and hepatic involvement

›Cytopenias from splenic sequestration (hypersplenism)

›Leukoerythroblastosis from marrow space compromise

Therapeutic Considerations

›JAK inhibitor mechanism and rationale

›All three JAK inhibitors target JAK1 and JAK2

›Suppress constitutively active JAK-STAT signaling regardless of driver mutation

›Effective in triple-negative MF as well as mutation-positive disease

›Clinical benefits

›Spleen volume reduction reduces hypersplenism and abdominal symptoms

›Constitutional symptom improvement through cytokine suppression

›Overall survival benefit suggested in landmark COMFORT trials for ruxolitinib

›Disease-modifying debate

›JAK inhibitors do not eliminate the malignant clone

›Allele burden reduction is modest and variable

›Allo-HCT remains the only potentially curative approach

›Transplant principles

›Timing of transplant is critical

›Too early: unnecessary transplant-related mortality in lower-risk disease

›Too late: poor marrow function and performance status at high-risk stage

›Intermediate-2 or high-risk by DIPSS-Plus or MIPSS70+v2.0 triggers referral

›JAK inhibitor before transplant

›Pretransplant ruxolitinib reduces spleen and inflammatory milieu

›May improve transplant outcomes; avoid abrupt discontinuation

›Taper ruxolitinib in days before conditioning, not weeks before

›High-molecular-risk mutation implications

›ASXL1, EZH2, SRSF2, IDH1/2, TP53 mutations

›Associated with shorter survival and higher leukemic transformation

›IDH1/2 mutations may be targetable with enasidenib or ivosidenib

›TP53 mutations predict poor response to standard therapies

11Patient Discharge Instructions/pdi41

copy discharge instructions

›Myelofibrosis home care instructions

›Continue all prescribed medications without stopping suddenly

›Do not stop JAK inhibitors (ruxolitinib, fedratinib, pacritinib, momelotinib) abruptly

›Sudden stopping can cause fever, low blood pressure, and serious illness

›Rest and activity

›Rest when fatigued; anemia makes energy levels low

›Light activity as tolerated; avoid contact sports if platelet count is low

›Diet

›Small frequent meals if your spleen is large and you feel full quickly

›High-protein, high-calorie food to maintain weight

›Stay well hydrated, especially if taking hydroxyurea

›Skin care on JAK inhibitors

›Use sunscreen and check skin regularly for new lesions

›Annual skin check with a dermatologist is recommended

›Warning signs to return to the emergency department

›Sudden severe left-sided abdominal or left shoulder pain

›May indicate splenic infarction or rupture

›Weakness, numbness, or difficulty walking

›May indicate spinal cord compression from the disease

›Significant bleeding

›Blood in stool, urine, or vomiting blood

›Heavy bruising or prolonged bleeding from minor cuts

›Fever above 38.5 C (101.3 F)

›Infection risk is higher with myelofibrosis and its treatments

›Severe shortness of breath or chest pain

›Signs of JAK inhibitor withdrawal if medication was missed or stopped

›High fever, shaking, low blood pressure, confusion

12References/r28

Guidelines and key sources

›Society guidelines

›NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms

›Current version provides diagnostic criteria, risk stratification, and treatment algorithms

›Guides JAK inhibitor selection by platelet count and risk category

›European LeukemiaNet (ELN) recommendations for MF

›Molecular diagnostic standards

›Treatment response criteria

›British Society for Haematology guidelines on myelofibrosis

›Landmark clinical trials

›COMFORT-I and COMFORT-II trials (ruxolitinib vs placebo/best available therapy)

›Established ruxolitinib as standard of care for intermediate/high-risk MF

›~42% of patients achieved >= 35% spleen volume reduction at week 24

›Overall survival benefit observed

›JAKARTA and JAKARTA-2 trials (fedratinib)

›Established fedratinib efficacy post-ruxolitinib

›PERSIST-1, PERSIST-2, PAC203 trials (pacritinib)

›Established pacritinib for platelets <50 × 10^9/L

›SIMPLIFY-1 and MOMENTUM trials (momelotinib)

›Demonstrated anemia benefit via ACVR1 inhibition

›Prognostic tools and scoring references

›Passamonti F et al. DIPSS validation studies

›Gangat N et al. DIPSS-Plus: J Clin Oncol 2011

›Guglielmelli P et al. MIPSS70+ and MIPSS70+v2.0

›Tefferi A et al. GIPSS: Blood 2018

›Coding reference

›ICD-10-CM D47.4: Osteomyelofibrosis (primary myelofibrosis)

›ICD-10-CM D75.81: Myelofibrosis (general/secondary)

Learn More: Myelofibrosis→

Comprehensive Clinical Review

Structured, evidence-informed, long-form analysis for deeper understanding.

Evidence & Review

Reviewed by SymptomDx Medical Team · Last reviewed August 18, 2026

SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.