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ACUTE LEUKEMIA
| Question | Answer | ||||||
|---|---|---|---|---|---|---|---|
| Acute Leukemias | Acute Lymphoblastic Leukemia (ALL) Acute Myelogenous Leukemia (AML) | AML accounts for 80% of acute leukemias and more common in adults ALL is primarily pediatric and has better survival in kiddos vs adults ALL may manifest as B-cell or T cell (B-Cell is most common) | AML accounts for 80% of acute leukemias and more common in adults ALL is primarily pediatric and has better survival in kiddos vs adults ALL may manifest as B-cell or T cell (B-Cell is most common) | AML accounts for 80% of acute leukemias and more common in adults ALL is primarily pediatric and has better survival in kiddos vs adults ALL may manifest as B-cell or T cell (B-Cell is most common) | |||
| ALL Prognosis | t(9:22) = philadelphia chromosome translocation. This translocation leads to worse outcomes in ALL | ||||||
| ALL risk factors | mostly seen in adults since they've been alive longer and had more exposure | - chemical exposure - previous chemo -genetic disorders | - Chemical exposure examples: pesticides, benzene, petroleum products, hair dyes - Previous chemo: Cyclophosphamide and melphalan. usually occurs after 3-5 years - Genetic Disorders; Downs' syndrome | ||||
| ALL S/Sx | ABRUPT onset - fatigue -fever or infection (leukopenia) - bleeding and bruising (thrombocytopenia) - bone pain and tenderness (more common in kiddos) -Most common cancer where you ge TLS | LABS - WBC maybe increased (>50) or decreased (<10) - Peripheral blast cells - Increased LDH - Increased uric acid | |||||
| ALL Physical Findings | Pallor, petrchiae, mediastinal mass (most common in T-cell ALL), hepatosplenomegaly, msk pain, Lymphadenopathy | ||||||
| Immunophenotyping | - a part of workup/dx - assists in determining lineage (B-cell vs T-cell) | B-cell = CD19, CD20, CD22 T-cell = CD2, CD3, CD5, CD7, CD8 | |||||
| ALL RISK STRATIFICATION | Low - hyperdiploidy: >50 chromos High - Tetraploidy: >82 chromos Very High Hypodiploidy: <45 chromos | Very high chromosomal variations (<45 chromosomes) usually carry a philidelphia chromosome (t9:22) | |||||
| ALL Therapy | Induction (4-6 wks) + Consolidation (20-30 wks) + Maintenance (2+ years) | Cytarabine and Methotrexate given every cycle both parts as CNS prophylaxis | |||||
| Induction in ALL | goal is to rapidly kill most tumor cells and obtain remission | Built around 3-4 drugs - Anthracyclines - Vinecristine - Corticosteroids - Asparaginase Induction therapy we learning: HYPER-CVAD | WHAT DEFINES REMISSION: <5% leukemic blasts in BM, normal blood cells, Absence of tumor cells in blood, Absence of other signs and symptoms of the diseasse | Pt is most likely to have TLS during this time | |||
| HyperCVAD | Used as induction therapy in ALL contains part A and B | PART A: give for several days w/in 21-28 days Cyclophosphamide and Mesna Vincristine IV Doxorubicin (Adriamycin) IV Dexamethasone 40mg x4days | PART B: follows A not done together HIGH DOSE MTX HIGH DOSE Ara-C (Cytarabine) IV | USE LEUVOCORIN TO RESCUE CELLS W MTX | |||
| METHOTREXATE (MTX) | HIGH DOSE TXT: requires hospitalization, rigorous hydration and leucovorin rescue | SIDE EFFECTS: Myelosuppression Severe Diarrhea Mouth Sores Kidney Damage Liver Damage | DDIs Meds that decreases MTX excretion: NSAIDs, Aspirin, Penicillins, PPIs Interfere with folate antagonism- Phenytoin and Bactrim (trimethoprim component) Should NOT be used the day before or the day of therapy w MTX | Take tylenol in place of NSAIDs for pain | |||
| VINCRISTINE (IV) | Max dose of 2 mg generally capped at 2mg | NEVER ADMIN INTRATHECALLY (IT) - can result in death | ADRs: Myelosuppresion Peripheral neuropathy Constipation | ||||
| Consolidation in Adult ALL | Goal is to eradicate residual measurable leukemia cells (further reduce tumor burden) | Using high doses of multi drug chemo: HyperCVA give months 6 & 18 and MTX + L-asparaginase give on months 7 & 19 + Blinatumomab | Asparaginase & Blinatumomab added for consolidation | During consolidation CNS prophylaxis given intathecal the whole time | |||
| Asparaginase Toxicities + Manage | Hypersensitivity: premed steroids, diphenhydramine, acetaminophen, slow the infusion | Thrombosis/Bleeding: Monitor Fibrinogen 2x weekly and replace if low | Hypertriglyceridemia: hold txt if TRI> 1000 | Pancreatitis: DC txt | Hyperammonemia: know as asparaginase blues. monitor ammonia in pts w/ mental status | HyperGlycemia: stop txt till glucose is normal. counsel on glucose monitoring | Hepatotoxicity: prevent with cautious dosing in adults (especially if fat) Hold until Bili <2mg/dL |
| Blinatumomab Toxicities | Needs hospitalization for at least 3 days for first treatment | MAJOR TOX: - Cytokine release syndrome - Neurotoxicity (ICANS) | |||||
| Maintenance in Adult ALL | GOAL to prevent disease relapse | used for pt who are NOT philly positive | POMP Purinethol Oncovin Methotrexate Prednisone | ||||
| Maintenance in PHILLY CHROMO POS PT | pt is high risk if they get an alo-transplant | If Ph+ AND they got a HSCT then pt gets TKI | TKI = imatnib, dasatinib, nilotinib, bosutinib, ponatinib (PICK 1) | NO POMP FOR THESE PT | |||
| Acute Myeloid Leukemia (AML) | most common myeloid malignancy | incurable 50 yrs ago. Now cured in 35 to 40% of adults <60y/o | Older pt median survival of only 5-10 mos bc they can't get intense chemo | can be caused by Topo II Inhibitors and Alkylating agents also chemicals like benzene and pestisides | |||
| AML Diagnosis | Peripheral blasts or BM findings consistent with AML ≥20% blasts | ||||||
| AML Risk Stratification | Pt age comorbidities Treatment related AML/prior hematologic disorders, cytogenetics/molecular mutations | ||||||
| AML Therapy | Induction + Consolidation + Maintenance | Induction = 7+3 Consolidation = HiDAC the transplant | |||||
| Principles of AML therapy | HIGH INTENSITY THERAPY: used ≤60 y/o or >60 but medically fit GOAL = CR - < 5% blasts in marrow - recovery of normal blood count - no disease symptom INTENT IS TO CURE | LOW INTENSITY THERAPY: used for older or medically unfit pt medication continues until disease progression GOAL IS PALLIATION NOT CARE | high intensitiy for > 65 y/o has poor outcomes | ||||
| Induction in healthy patients AML | SOC = 7+3 if FLT3 mutation add midostaurin on day 8 & 21 to 7+3 | 7 Days of continuous Cytarabine 3 days of Donaurubacin or Idarubicin (Anthracycline) If FLT3+ add midostaurin | Day 14: if leukemic cells in marrow perform a reinduction of 7+3, if not leukemic cells continue to post remission | ||||
| AML Consolidation | GOAL: deepen remission/cure after achieving complete remission (CR) consider chemo or allogenic transplant | chemo is done for favorable risk pts. allogenic transplants are done for intermediate or poor risk | SOC: HiDAC (high dose cytarabine +/- gemtuzumab if CD33 positive | ||||
| HiDAC | Cytarabine (Ara-C) 4 cycles days 1,3,5 per cycle | NEUROTOXICITIY IS MAIN CONCERN WITH HiDAC | |||||
| AML Maintenance | YES TO AN ALLOTRANSPLANT: - FLT3 Mutation: Midostaurin No FLT3: No maintenance | NO TO ALLOTRANSPLANT: Azacitadine maintenance | |||||
| AML Low intensity induction | FOR PT WHO CANT TOLERATE CHEMO OR DECLINE IT | - 5-azacitidine + venetoclax - 5-azacitidine + ivosidenib - Low dose cytarabine - Best supportive care | |||||
| Cytarabine toxicities | - severe CNS tox - conjunctivitis | ||||||
| Anthracycline Toxicities | DOSE LIMITING TOXICITY: cardiotoxicity are cummulative doxorubicin dose equivalent. Dose dependent and permanent; delay onset by years | ||||||
| Midostaurin Toxicities | Pulmonary toxicity Nausea Anemia Can increase QTc, don't use if baseline QTc >500 msec |
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