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 complications4- 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 100-200 mg tds to prevent hyperuricemia

3)Correct anemia- Blood Transfusion 4)Psychological preparation of the patient &

family for ttt & complications5) Tell them about the seriousness of disease &

prognosis

Treatment of Complications

Sometimes the patient presents with complications1- 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 3rd generation cephalosporin (Ceftriaxone)+ gentamicin

Persistent fever

Correct antibiotic according to C&SIf feveer persist think of coagulase –ve Staph &

give VancomycinIf fever persisted think of fungal infection & give

amphotericin-B injectionsIf persisted think of viral infections & treat

accordingly

3- DIC

Mostly seen in APL (M3)Give fresh frozen plasma (FFP), Platewlet

concentrate, blood transfusion4- 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>ALLEspecially with hyperleukocytosis > 50000 Manifested as CNS & Pulmonary manifestationDue to sludging of blasts in microcirculationCNS- confusion, cranial nerve palsies, seizure, , meningitis, comaPulm- tachypnea, dyspnea, pulmonary crackles, bilateral

radiological pulmonary infiltrates, hypoxemiattt – hydroxyurea, cranial irradition

TREATMENT

1- COMBINATION CHEMOTHERAPY2- Supportive therapy3- Targeted therapy4- BMT & Stem cell Transplant

ALL treatment

1- Induction CT UKALL or BFM protocol*Anthracyclin (Daunorubicin, Doxorubicin)- antibiotic

cytotoxic given weekly ----i.v infusion /1hS/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/dContinurd for 5 weekly doses

2- Postinduction CT

1- Consolidation giving same doses as induction2- Intensification giving high dose CTShould use new non-cross resistant agentsGiving 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 daily2- methotrexate tab weeklyContinued for 2-3 yearsReinforcement doses given every 3 months

AML

1- Induction “3+7” protocolDaunorubicin or Doxorubicin i.v infusion over 1h

D1-D3Cytosine arabinoside continuous infusion 12

hourly D1-D7Given monthly until CR

2- Postinduction CT

A- Consolidation giving same dosesB- Intensification High dose CT *No maintenance ttt in AML except M3* No CNS prophylaxis except M4,M5

Targeted therapy

1- Imatinib in Ph +ve ALL2- All-trans-retinoic acid (ATRA) a differentiating

agent used in M3 induction & maintenanceS/E retinoic acid syndrome3- 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/µl3- packed RBCs to correct anemia

BMT

1- syngeneic from identical twin2- 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 2nd CR after 1st relapseALL- in 3rd CR after 2nd relapse

Prognosis

ALL better AMLALL 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 PrepreBAML 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