1. Acute Leukemia Treatment

2. PREPARATION 1- Acute leukemia should be regarded as an emergency & needs treatment within 48h of Dx 2- Patient should be prepared for treatment to avoid complications 3- Stabilization of patient & ttt of complications 4- Taking consent of patient or family

3. Preparation--steps 1) Adequate hydration i,v fluids 2-3 L/d of glucose water or normal saline 2) Allopurinol 100-200 mg tds to prevent hyperuricemia 3)Correct anemia- Blood Transfusion 4)Psychological preparation of the patient & family for ttt & complications 5) Tell them about the seriousness of disease & prognosis

4. Treatment of Complications Sometimes the patient presents with complications 1- Hemorrhage should be stopped – correct thrombocytopenia by platelet transfusion. Correct hypovolemia. 2- Fever is regarded due to infection. Never regarded due to leukemic process. Infection due to neutropenia. Usually due to G-ve bacilli such as Klebsiella, Escherichia, Pseudomomnas, Proteus. Treated after taking samples for C&S don’t wait the results. Give emperically a 3 rd generation cephalosporin (Ceftriaxone)+ gentamicin

5. Persistent fever Correct antibiotic according to C&S If feveer persist think of coagulase –ve Staph & give Vancomycin If fever persisted think of fungal infection & give amphotericin-B injections If persisted think of viral infections & treat accordingly

6. 3- DIC Mostly seen in APL (M3) Give fresh frozen plasma (FFP), Platewlet concentrate, blood transfusion 4- Hyperuricemic nephropathy – it is prevented better than treated. It causes renal failure treated by dialysis.

7. 5- Tumor lysis syndrome Manifested as hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia It is prevented by preparation & adequate hydration

8. 6- Leukostasis In AML>ALL Especially with hyperleukocytosis > 50000 Manifested as CNS & Pulmonary manifestation Due to sludging of blasts in microcirculation CNS- confusion, cranial nerve palsies, seizure,, meningitis, coma Pulm- tachypnea, dyspnea, pulmonary crackles, bilateral radiological pulmonary infiltrates, hypoxemia ttt – hydroxyurea, cranial irradition

9. TREATMENT 1- COMBINATION CHEMOTHERAPY 2- Supportive therapy 3- Targeted therapy 4- BMT & Stem cell Transplant

10. ALL treatment 1- Induction CT UKALL or BFM protocol *Anthracyclin (Daunorubicin, Doxorubicin)- antibiotic cytotoxic given weekly ----i.v infusion /1h S/E myelosuppression pancytopenia dilated cardiomyopathy, mucositis *Vincristine i.v diluted bolus weekly– antitubulin agentS/E PNP senory> motor, extravasation causes severe necrosis of skin & subcut tissues Not myrlosuppressive *PDN 60-100 mg/d Continurd for 5 weekly doses

11. 2- Postinduction CT 1- Consolidation giving same doses as induction 2- Intensification giving high dose CT Should use new non-cross resistant agents Giving L-Asparaginase that depletes blasts from asparagine essential amino acid ( especially useful in children)

12. 3- CNS prophylaxis 1- Intrathecal Methotrexate or cytosine arabinoside & hydrocrtisone given weekly 2- Cranial irradiation giving 2400 rad to cranium to prevent CNS relapse 3- High dose methotrexate crosses BBB

13. 4- Maintenance treatment 1- 6mercaptopurine tab daily 2- methotrexate tab weekly Continued for 2-3 years Reinforcement doses given every 3 months

14. AML 1- Induction “3+7” protocol Daunorubicin or Doxorubicin i.v infusion over 1h D1-D3 Cytosine arabinoside continuous infusion 12 hourly D1-D7 Given monthly until CR

15. 2- Postinduction CT A- Consolidation giving same doses B- Intensification High dose CT *No maintenance ttt in AML except M3 * No CNS prophylaxis except M4,M5

16. Targeted therapy 1- Imatinib in Ph +ve ALL 2- All-trans-retinoic acid (ATRA) a differentiating agent used in M3 induction & maintenance S/E retinoic acid syndrome 3- Gemtuzumab/ozagamycin moAb M3 * Arsenic trioxide in M3 relapse

17. Supportive therapy 1- Stimulating factors (G-CSF, GM-CSF) to correct neutropenia in myelosuppression 2- Plat conc keep plat > 20000/µl 3- packed RBCs to correct anemia

18. BMT 1- syngeneic from identical twin 2- Autologous from pt during CR (high risk of relapse, less GVHD) 3- Allogeneic from HLA-matched related or un related donor ( less relapse, Gvleukemia effect, moreGVHD)

19. Indications AML – in 2 nd CR after 1 st relapse ALL- in 3 rd CR after 2 nd relapse

20. Prognosis ALL better AML ALL L1 better than L2 better than L3 Children better than adults (2-9y) female better than male T cell worse than B cell worse than PrepreB AML M3 worse in acute stage but better longterm M4 M5 bad M4E better than M4 M7 bad secondary leuk worse than deNovo

29. Acute Leukemia Treatment