· minimal residual disease (mrd) mrd an excellent prognostic marker pcr assay or flow cytometry...
TRANSCRIPT
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BY Dr SUBHASHINI 1st yr PG
DEPARTMENT OF PEDIATRICS
MANAGEMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA
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Introduction
The management of ALL, the most common childhood malignancy (1/3rd of all malignancy), has been changing over the years.
Multi-agent systemic chemotherapy over a prolonged duration (2–3 years) and adequate CNS-directed therapy, in addition to improved antibiotic and blood product support has improved cure rates from approximately 10% (50 years back) to nearly 90%.
Monitoring of minimal residual disease (MRD) to refine therapy based on risk of relapse to maximize cure and minimize toxicities has improved the outcome.
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DIAGNOSIS: CLINICAL
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DIAGNOSIS: LABORATORY
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DIAGNOSIS: LABORATORY
• Bone marrow:>25% lymphoblastCSF analysis for CNS involvementUSG for testicular involvementECG and ECHO for baseline cardiac statusRFT and LFTCytogenetics
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RISK STRATIFICATION
Risk stratification
Features
Low risk Age 1-9 yrs, WBC count<50,000/cumm, pre-B ALL, trisomy 4 and 10, hyperdiploidy, t(12;21)
Standard risk Age 1-9 yrs, WBC count<50,000/cumm, pre-B ALL, normal cytogenetics
High risk Age<1years and >9 years, WBCcount>50,000/cumm, T-cell ALL, CNS involvement, hypodiploidy
Very high risk t(9;22),t(4;11), induction failure
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MULTIDISCIPLINARY TREATMENT TEAM
Pediatric hemato-oncologistRadiation oncologistNursing teamDieticianMedical social worker
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COMPONENTS OF MANAGEMNT
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SUPPORTIVE THERAPY
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SUPPORTIVE CARE
Blood component therapy to maintain Hb>10gm/dl and TPC >1lkh/cmm before each induction.
Cotrimoxazole prophylaxisFolic acid, vit B12 supplementationImmunization: Hepatitis B, pneumococcal,
meningococcal Oral hygiene
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CHEMOTHERAPY REGIMEN: MCP (841) : 3 PHASES
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REMISSION INDUCTION: 1 (4-6 CYCLES)
Chemotherapy Dose and schedule
Prednisone 40mg/m2 PO days 1-28
Vincristine 1.4mg/m2 IV days 1,8, 15 and 22
Methotrexate 12 mg IT, days 1,8,15 & 22
L-asparaginase 600o μ/m2 IM on alternate days *10 doses, days 2-20
Daunorubicin 30 mg/m2 IV days8,15 &29
• To induce remission (bone marrow blast cell < 5%)
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REMISSION INDUCTION : 2
INDICATION : FAILURE OF INDUCTION 1
CHEMOTHERPY DOSAGES AND SHEDULE
Mercaptopurine 75mg/m2 PO daily 1-7days &15-21days
Cyclophosphamide 750 mg/m2 IV day1& day15
Methotrexate 12mg/m2 IT days 1,8,15&22
Cranial radiation 200cGy daily *9days(total 1800cGy)
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CONSOLIDATION: 14 to 28 weeks
To clear residual or resistant blast cells
Chemotherapy Dose and schedule
CyclophosphamideVincristineMercaptopurine
Cytarabine
Daunorubicin
750 mg/m2 IV day 1 & 151.4 mg/m2 IV days 1 & day 1575 mg/m2 PO daily days 1-7 & days 15-21100mg /m2 SC every 12hrs *6hours on days 1-3 & days 15-1730 mg/m2 IV days 15
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MAINTENANCE THERAPY: 2-2.5 YEAR
Given to prevent relapse.
Chemotherapy
Dose and schedule
PrednisoneVincristineDaunorubicinL-asparaginase
Mercaptopurine
40 mg/m2 PO days 1-71.4 mg/m2 IV on day 130mg/m2 IV on day 16000 μ/m2 IM days 1,3,5 &715 mg/m2 PO once a week, missing every 4th for a total of 12 weeks, begin on day 1575mg/m2 PO daily, 3 weeks out of every 4 for total of 12 weeks, begin on day 15
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TREATMENT OF RELAPSE
Combination chemotherapyTotal body radiation therapyBone marrow transplantation
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NEWER TARGET THERAPY
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ALLOGENIC HSCT
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RADIOTHERAPHY
Indications: Induction failure, CNS and bone marrow relapse
Dose: 200cGY Complication: Neurocognitive deficits, Obesity, Cardiomyopathy, Avascular necrosis, Secondary
leukemia and osteoporosis, Growth hormone deficiency and brain tumors.
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MONITORING
LaboratoryCBCBone marrow StudiesChest x rayUSG RFTLFTECGLDHMRD
Clinical Vital signs Weight Organomegaly Neurocognitive defects Gonads Ophthalmic Growth
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PROGNOSIS
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MINIMAL RESIDUAL DISEASE (MRD)
MRD an excellent prognostic marker
PCR assay or Flow cytometry can detect one leukemic cell in 10,000 to 100,000 normal cells.
MRD at the end of induction
< 0.01%: Favorable prognosis
> 1: Unfavorable prognosis
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OVERALL SURVIVAL IS IMPROVING OVER YEARS
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TREATMENT OF EARLY COMPLICATION
Tumour lysis syndrome: hyperuricimia, hyperkalemia,
hyperphosphatemia.
Rx: Bicarbonate, allopurinal, and dialysis
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CONCLUSION
Management steps include1. Confirmation of diagnosis2. Risk stratification3. Combination Chemotherapy +/- radiotherapy4. Supportive therapy5. Treatment of complications6. Follow up for 5-6 event free years.
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THANK YOU
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