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69 Cards in this Set
- Front
- Back
Types of lung Cancer
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1) Non-Small Cell Lung Cancer (NSCLC)
2) Small Cell Lung Cancer (SCLC) |
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Non-Small Cell Lung Cancer (NSCLC)
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1) slower growing
2) surgery is 1st line in early stages 3) lower sensitivity to chemo 4) better survival 5) presents in lung periphery |
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Small Cell Lung Cancer (SCLC)
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1) very aggressive
2) very chemo and XRT sensitive 3) clear relationship to smoking 4) Death occurs in 2-4 months without treatment 5) presents centrally |
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NSCLC histologic subtypes
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1) non-squamous: most common in non-smokers, lung periphery
2) Squamous cell carcinoma: slower growing, smoking, bleeding |
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Risk Factors for Lung Cancer
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1) Smoking
2) asbestos (synergistic with smoking) 3) Radon (2nd leading cause) 4) Occupational carcinogens 5) Diet 6) Co-existing lung disease 7) genetic/familial factors |
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EGFR Mutations
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1) common in Asians and Caucasians
2) patients with this mutation should receive EGFR inhibitor first line 3) PREDICTIVE biomarker |
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KRAS mutations
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1) associated with cigarette smoking
2) associated with shorter survival, poor prognosis 3) lack of benefit from platinum or vinorelbine chemo 4) prognostic and predictive biomarker |
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EML4-ALK Mutation
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1) seen in younger men, non-smokers
2) drives cancer cell growth and proliferation 3) patients with this mutation should receive crizotinib as first line 4) Predictive biomarker |
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Clinical Presentation of Lung Cancer
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1) Persistent cough
2) Dyspnea 3) Chest Pain/discomfort 4) Hemoptysis 5) Hoarseness 6) Generalized weakness 7) Weight Loss 8) clubbing |
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Clinical Presentation of SCLC --Regional Metastases
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1) evident tumor at diagnosis
2) distal atelctasis (collapse lung) or post obstructive pneumonia 3) pleural or pericardial effusions 4) hoarseness/dysphasia |
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Clinical Presentation of SCLC -- Distant Metastases
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1) tendency for early metastases
2) CNS preferential site (headache, double vision) |
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Paraneoplastic Syndromes in lung cancer
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**clinical S/Sx that develop at other sites in the body not associated with tumor; more common in SCLC**
1) SIADH: (SCLC) - euvolemic, hypo-osmolar hyponatremia w/ normal kidney & adrenal function Treatment: free water restriction & demeclocycline 2) Hypercalcemia: (NSCLC) - due to parathyroid hormone like substance Treatment: fluids, IV bisphos |
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NSCLC Staging
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TNM
T: tumor size N: nodal involvement M: metastasis |
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SCLC Staging
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Limited Disease (confined to 1 hemithorax and regional lymph nodes; curative intent)
Extensive Disease (extends beyond, rarely curable) |
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Prognosis of Lung Cancer
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1) Stage
2) Performance status 3) Gender (females more favorable) 4) Age (<60) 5) CNS involvement 6) Weight loss |
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Goals of Treatment of NSCLC
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Early Stage Disease: cure, using chemo and radiation
Advanced Stage Disease: Palliative |
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Treatment of Stage I NSCLC
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Surgical resection - TREATMENT OF CHOICE
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Treatment of Stage II & III (locally advanced)
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Treatment dependent on ability to resect tumor and surgical margins
may use neoadjuvant/adjuvant chemo and/or radiation |
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Chemo option for NSCLC Stage IA and IB
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not recommended
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Chemo option for NSCLC Stage II and IIIA
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adjuvant cisplatin-based chemo
Cisplatin & Vinorelbine Carboplatin/Paclitaxel (intolerant to cisplatin) |
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Drugs that can be used with Cisplatin/Carboplatin in NSCLC
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1) Etoposide
2) Vinblastine 3) Docetaxel 4) Gemcitabine 5) Irinotecan 6) Pemetrexed |
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Chemo Options for NSCLC Stage IIIB (unresectable)
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Platinum based chemo + radiation
1) Cisplatin + Etoposide 2) Cisplatin + Vinblastine |
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Treatment of Advanced Stage Disease (Stage IV NSCLC)
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*not curable - prolong survival*
*not resectable if disseminated Platinum based doublet regimen |
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Drugs that can be used with Cisplatin/Carboplatin in Advanced Stage NSCLC
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1) Etoposide
2) Vinorelbine 3) Paclitaxel/Docetaxel 4) Gemcitabine 5) Irinotecan 6) Vinblastine |
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Monoclonal Antibodies used in Advanced Stage NSCLC
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1) Bevacizumab - added to normal regimens
2) Cetuximab - added to cisplatin + vinorelbine |
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Oral Targeted Therapy - EGFR mutations
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1) erlotinib
2) Afatinib |
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Oral Targeted Therapy - ALK rearrangements
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crizotinib
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Treatment of Limited Disease SCLC
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Goal: cure using chemo and thoracic radiation
EP: etoposide + cisplatin EC: etoposide + carboplatin |
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Treatment of Extensive Disease SCLC
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EP: etoposide + cisplatin
EC: etopside + carboplatin CI: cisplatin + irinotecan |
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Cisplatin ADRs and dosing
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1) nephrotoxicity
2) Electrolyte wasting 3) Delayed N/V 4) ototoxicity Dose: based on BSA |
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Carboplatin ADRs and dosing
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1) thrombocytopenia
2) neutropenia 3) N/V Dose: calvert equation D=(CrCl + 25) x target AUC |
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Second line agents for recurrent disease of SCLC
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1) ifosfamide
2) paclitaxel/docetaxel 3) gemcitabine 4) topotecan/irinotecan 5) vinorelbine 6) CAV (cyclophosphamide, doxorubicin, vincristine) 7) enroll in clinical trial (PREFERRED) |
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Relapse with SCLC <2-3 months
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1) ifosfamide
2) paclitaxel/docetaxel 3) topotecan 4) irinotecan 5) gemcitabine |
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Relapse with SCLC >2-3 months
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1) Topotecan
2) Irinotecan 3) CAV (cyclophosphamide, doxorubicin, vincristine) 4) Gemcitabine 5) Paclitaxel/Docetaxel 6) oral Etopaside 7) Vinorelbine |
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Relapse with SCLC > 6 months
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may repeat original regimen
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Pemetrexed (Alimta)
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MOA: antifolate antimetabolite that inhibits thymidylate synthase & dihydrofolate reductase
USE: non-squamous cell histology (NSCLC) *locally advanced or metastatin non-squamous NSCLC* ADRs: rash, neutropenia, stomatitis, N/V |
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Pretreatment with Pemetrexed
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1) Folic Acid 400-1000mcg given 1-3 weeks prior and 1-3 weeks after
2) Vitamin B12 1000mcg IM given 1-3 weeks prior and given every 9 weeks 3) Dexamethasone 4mg PO day before, day of, and day after to prevent rash |
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Bevacizumab (Avastin)
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MOA: targets VEGF
USE: in combo with platinum based doublet as 1st line therapy for advanced non-squamous cell NSCLC ADRs: HTN, proteinuria, hemorrhage, decreased wound healing, VTE |
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Cetuximab (Erbitux)
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MOA: targets EGFR
USE: with any histologic type of NSCLC but NOT FDA approved ADRs: infusion related reactions, acneiform rash, malaise, diarrhea, N/V |
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Erlotinib (Tarceva)
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MOA: EGFR inhibitor for patients with EGFR mutation
USE: first line therapy for Stage IV non-squamous NSCLC with a known EGFR mutation ADRs: rash, diarrhea, N/V, fatigue, pruritis, conjunctivitis, infection, dry skin **Take on EMPTY stomach** |
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Drug interactions and should be avoided with Erlotinib
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Avoid H2 blockers and PPIs
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Crizotinib (Xalkori)
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MOA: selectively inhibits ALK which reduces proliferation of cells expressing this genetic alteration
USE: first line therapy in locally advanced or metastatic NSCLC that is ALK positive ADRs: edema, diarrhea, nausea, vision disorders, QT prolongation **take with or without food** |
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Afatinib (Gilotrif)
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MOA: potent and irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4
USE: second line therapy for patients with EGFR mutation and progressed past 1st line ADRs: diarrhea, acneiform rash, stomatitis, dry skin, decreased appetite **take on EMPTY stomach** |
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Leukemias
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hematologic malignancies characterized by an uncontrolled increase and accumulation of immature abnormal blood forming cells
Acute or Chronic |
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Pathogenesis of Leukemias
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Myeloid stem cell OR lymphoid stem cell
monoclonal |
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Acute Myeloid Leukemia
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Median age of diagnosis: 66 years (disease of elderly)
Males > Females Causes: 1) Chemical exposure (benzene, pesticides) 2) Environmental Exposure (hair dyes, smoking) 3) Prior chemo (alkylating agents, Topo II inhibitors) 4) Prior radiation 5) Genetic disorders |
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Clinical Presentation of AML
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**Non-specific signs/symptoms***
1) Anemia (fatigue, weakness) 2) Neutropenia (infection) 3) Thrombocytopenia (bleeding/bruising) 4) Leukemic infiltration (cutaneous/gingival infiltration of leukemic cells) 5) Leukostasis |
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Diagnosis of AML
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presence of >/= 20% abnormal blasts in bone marrow
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Prognostic Factors (Better)
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1) younger age
2) not MDS or chemo induced 3) better risk of cytogenetic abnormalities |
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Induction Therapy for AML
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1st cycle to eradicate all signs of leukemia
destroys all bone marrow (pancytopenia) |
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Consolidation Therapy for AML
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further chemo after complete remission
eradicates any remaining leukemia and prevent relapse |
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Induction therapy used in AML
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7+3 treatment
Cytarabine + Anthracycline Day 14 bone marrow biopsy |
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Consolidation Therapy used in AML
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High Dose Cytarabine
Allogeneic hematopoietic stem cell transplant |
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Refractory AML
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failed induction chemo (didn't achieve CR)
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Relapse AML
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achieve CR after induction, sometime later
disease comes back |
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Acute Promyelocytic Leukemia (APL)
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characterized by t(15,17) chromosomal translocation
fusion protein (PML-RAR alpha) - prevents maturation of promyelocytes in normal neutrophils known to have fatal coagulopathy (DIC) |
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DIC (fatal coagulopathy) in APL
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Increasing clotting & increase bleeding
Need to treat APL to resolve |
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Induction treatment of APL
HIGH Risk (WBC >10,000) Tolerates Anthracyclines |
ATRA (all trans-retinoic acid)
+ (7+3) daunorubicin + cytarabine |
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Induction treatment of APL
HIGH Risk (WBC >10,000) Doesn't tolerate anthracyclines |
ATRA (all trans-retinoic acid)
+ ATO (Arsenic Trioxide) |
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Induction Treatment APL
LOW/INTERMEDIATE risk (WBC <10,000) Tolerates Anthracyclines |
ATRA (all trans-retinoic acid)
+ Anthracyclines |
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Consolidation Treatment for APL
HIGH Risk (WBC >10,000) |
ATRA (all trans-retinoic acid)
+ 7+3 (daunorubicin + cytarabine) |
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Consolidation Treatment for APL
LOW/INTERMEDIATE risk (WBC <10,000) |
ATRA (all trans-retinoic acid)
+ ATO (Arsenic Trioxide) |
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All Trans-Retinoic Acid (ATRA) for APL
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MOA: overwhelms PML-RAR alpha fusion protein to accelerate differentiation of malignant promyelocytes to mature neutrophils
ADRs: leukostasis, APL differentiation syndrome |
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APL Differentiation Syndrome
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Fever, Hypoxia, Weight Gain, rapidly rising WBC, pleural effusions
Treatment: Dexamethasone 10mg q12h x 3-5 days |
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Arsenic Trioxide (ATO)
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MOA: induces apoptosis of abnormal cells and causes partial differentiation of abnormal cells to normal neutrophils
ADRs: fluid retention, APL differentiation syndrome, EKG abnormalities Rx: verify Mg >2, K>4, normal EKG |
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Acute Lymphoid Leukemia (ALL)
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Proliferation and expansion of immature lymphoid cells in the bone marrow, blood, and other organs
Effects B, T, and NK cells Bimodal: children ~5yrs, late adulthood ~50yrs |
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Causes of ALL
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**Exact is unknown**
Chemical Exposure Genetic predisposition (Trisomy 21, Fanconi's anemia) Infections (Epstein Barr, HIV) |
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Clinical Presentation of ALL
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**Non-specific Symptoms**
1) Anemia - fatigue 2) Neutropenia - increased infection 3) Thrombocytopenia - increased bleeding/bruising 4) CNS manifestations 5) B Symptoms 6) Joint and bone pain |
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Prognostic Factors (better prognosis)
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1) T-cell
2) BC < 30,000 3) < 30 years 4) Female 5) Achieve CR after 1 cycle 6) Normal cytogenetics |