Acute Leukemia Treatment

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

Preparation--steps 1) Adequate hydration i,v fluids 2-3 L/d of glucose water or normal saline 2) Allopurinol 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

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

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

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.

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

6- Leukostasis In AML>ALL Especially with hyperleukocytosis > 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

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

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 mg/d Continurd for 5 weekly doses

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)

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

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

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

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

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

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

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)

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

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

Acute Leukemia Treatment