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Acute Lymphoblastic Leukemia: Acute Lymphoblastic Leukemia: IncidenceIncidence
ALL is the most common malignancy in ALL is the most common malignancy in childrenchildren
1/31/3rdrd of all pediatric cancers of all pediatric cancers
The annual incidence of ALL is about 30 The annual incidence of ALL is about 30 cases per million peoplecases per million people
ALL accounts for 75-85% of acute ALL accounts for 75-85% of acute
leukemias in childrenleukemias in children
ALLALL
Sex: M> F (1.3:1)Sex: M> F (1.3:1)
Race: more frequently in Caucasians than in Race: more frequently in Caucasians than in African AmericansAfrican Americans
Age: peaks age 2-5 years Age: peaks age 2-5 years
AetiologyAetiology
Mostly unknownMostly unknown
Many environmental factors - exposure to Many environmental factors - exposure to ionizing radiation and electromagnetic fields)ionizing radiation and electromagnetic fields)
Post-chemo for other malignanciesPost-chemo for other malignancies
PesticidesPesticides
Infectious agentsInfectious agents
Papilloma virus—aggressive T-Cell leukaemia in Papilloma virus—aggressive T-Cell leukaemia in young adultsyoung adults
Risk FactorsRisk Factors
Single Gene Defects:Single Gene Defects:
Fanconi's anaemiaFanconi's anaemia
NeurofibromatoisType 1NeurofibromatoisType 1
X-Linked AgammaglobulinaemiaX-Linked Agammaglobulinaemia
Osteogenesis ImperfectaOsteogenesis Imperfecta
PKUPKU
Marfan's Syndrome, Marfan's Syndrome, AchondroplasiaAchondroplasia
Risk FactorsRisk Factors
Chromosomal: -Chromosomal: -
Down, TurnerDown, Turner
Immunedeficiency: -Immunedeficiency: -
Wiscott Aldrich, EBV Wiscott Aldrich, EBV
Identical Twin 20% chance < 5yearsIdentical Twin 20% chance < 5years
Acute Lymphoblastic Leukemia: Acute Lymphoblastic Leukemia: PathogenesisPathogenesis
A A lymphoid progenitor celllymphoid progenitor cell becomes becomes genetically altered > dysregulated genetically altered > dysregulated proliferation > clonal expansionproliferation > clonal expansion
Altered expression of genes > Altered expression of genes > development of abnormal B cells and T development of abnormal B cells and T cellscells
Recent data : suggest that leukemia arises Recent data : suggest that leukemia arises from the stem cell from the stem cell
ALL: Clinical featuresALL: Clinical featuresS/S reflects bone marrow infiltration and S/S reflects bone marrow infiltration and extramedullary diseaseextramedullary disease
Features of BM failure: -Features of BM failure: -
1. Anaemia—pallor, irritable, dec activity, 1. Anaemia—pallor, irritable, dec activity, fatigue fatigue
2. Thrombocytopenia —bleeding mainly 2. Thrombocytopenia —bleeding mainly superficial—petechiae, ecchymosis, DICsuperficial—petechiae, ecchymosis, DIC
3. Infections—dec functional WBC 3. Infections—dec functional WBC neutropenia. —fever, localization not neutropenia. —fever, localization not present, quick disseminationpresent, quick dissemination
ALL: Clinical featuresALL: Clinical features
RE System InfiltrationRE System InfiltrationLymphadenopathyLymphadenopathyHepatosplenomegalyHepatosplenomegaly
Involvement of other sites— Involvement of other sites— CNS, Testes, CNS, Testes, Thymus, GIT, Cardiac, Pulmonary, OcularThymus, GIT, Cardiac, Pulmonary, OcularBone PainBone PainWeight lossWeight loss
ALL: Clinical features ALL: Clinical features
CNS involvement CNS involvement - headache, nausea, vomiting, lethargy, - headache, nausea, vomiting, lethargy,
irritability, nuchal rigidity, papilledema irritability, nuchal rigidity, papilledema
Cranial nerves mostly involved – 7Cranial nerves mostly involved – 7thth ,3 ,3rdrd ,4 ,4thth 66thth cranial nerves cranial nerves
Intracranial or spinal mass - leading to nerve Intracranial or spinal mass - leading to nerve compression/ICSOL features compression/ICSOL features
C/F of Chronic leukemiaC/F of Chronic leukemia
Common in CGLCommon in CGL -Anemia, splenomegaly, -Anemia, splenomegaly,
fatigue ,weight lossfatigue ,weight loss
Less common -Less common - Hemorrhagic Manifestations Hemorrhagic Manifestations
(Bruising)(Bruising)
Occasional - Occasional - Abdominal, bones, joints pain Abdominal, bones, joints pain
Neurologic symptomsNeurologic symptoms
Disturbance of vision or hearingDisturbance of vision or hearing
Differential diagnosis: ALLDifferential diagnosis: ALL
Acute Myelocytic Leukemia Acute Myelocytic Leukemia
Aplastic anemiaAplastic anemia
Juvenile Rheumatoid Arthritis Juvenile Rheumatoid Arthritis
Lymphoma Lymphoma
ITPITP
Neuroblastoma Neuroblastoma
HSPHSP
ITPITP
Menincococcal septicemiaMenincococcal septicemia
ALL: Investigations ALL: Investigations
Blood counts:Blood counts:
1.1. Hemoglobin -reduced (3-8gm/dl)Hemoglobin -reduced (3-8gm/dl)
2.2. WBC-20,000-50,000/cumm.of blood.May WBC-20,000-50,000/cumm.of blood.May exceed 100,000/cummexceed 100,000/cumm
3.3. Platelets – DecreasedPlatelets – Decreased
ALL: Investigations ALL: Investigations
1.1. Blood film: Blood film:
A) RBC-Microcyitc or normocytic, moderate to A) RBC-Microcyitc or normocytic, moderate to marked anisopoikilocytosis, nucleated RBC marked anisopoikilocytosis, nucleated RBC fewfew
B) WBC-30-90% atypical or typical blast cells B) WBC-30-90% atypical or typical blast cells
C) Platelets – Decreased C) Platelets – Decreased
- Reticulocytes count-Increased upto 5%- Reticulocytes count-Increased upto 5%
Invasive Invasive
Lumbar puncture/CSF analysis Lumbar puncture/CSF analysis
Bone marrow aspiration Bone marrow aspiration
- > 30% Blast cells- > 30% Blast cells
- FAB classification (L1, L2, L3)- FAB classification (L1, L2, L3)
is generally usedis generally used
Histologic Findings:Histologic Findings:3 groups based on morphology. 3 groups based on morphology.
– L1: Cells are usually small, with scant L1: Cells are usually small, with scant cytoplasm and inconspicuous nucleoli. cytoplasm and inconspicuous nucleoli.
accounts for 85%accounts for 85% of cases of of cases of childhood ALLchildhood ALL
– L2: Cells are larger in size, with L2: Cells are larger in size, with prominent nucleoli, and abundant prominent nucleoli, and abundant cytoplasm. cytoplasm.
accounts for 14%accounts for 14% of all childhood of all childhood ALLs. ALLs.
Histologic Findings:Histologic Findings:
–L3: Cells are large and notable for L3: Cells are large and notable for their deep cytoplasmic basophilia their deep cytoplasmic basophilia and prominent cytoplasmic and prominent cytoplasmic vacuolation vacuolation
accounts for 1%accounts for 1% of childhood of childhood ALLsALLs
ALL: Investigations ALL: Investigations
Imaging studies Imaging studies –CXR : mediastinal involvementCXR : mediastinal involvement
–Testicular sonographyTesticular sonography
ALL: InvestigationsALL: Investigations
Serum biochemistrySerum biochemistry–Uric acid, Uric acid,
–Potassium, Potassium,
–Phosphorus, and calcium, Phosphorus, and calcium,
–Lactate dehydrogenase (LDH) Lactate dehydrogenase (LDH)
–Coagulation studies can be helpfulCoagulation studies can be helpful
ALL: Investigations ALL: Investigations
ImmunophenotypingImmunophenotyping– B cellB cell
Poor prognosis, L 3 typePoor prognosis, L 3 type
Lymphomatous masses in abdomen Lymphomatous masses in abdomen head & neckhead & neck
– pre B cell, early pre B cellpre B cell, early pre B cell
Better prognosis , L 1 & 2Better prognosis , L 1 & 2
80 % of all childhood ALL80 % of all childhood ALL
ALL: InvestigationsALL: Investigations
– T cell origin T cell origin Poorer prognosisPoorer prognosisHigh WBC countsHigh WBC countsCNS involvementCNS involvement
Cytogenetic analysis - PCR, southern blotCytogenetic analysis - PCR, southern blot
Chromosomal translocations / gene fusions Chromosomal translocations / gene fusions - - BCR-ABL (t 9;22) BCR-ABL (t 9;22) > poor prognosis> poor prognosis
– E2A-PBX1(t 1:19) > E2A-PBX1(t 1:19) > poor prognosispoor prognosis– TEL-AML1 (t 12;21) > TEL-AML1 (t 12;21) > good prognosisgood prognosis
Treatment : considerationsTreatment : considerationsBased on risk stratificationBased on risk stratification
Different protocols are used by different centers but Different protocols are used by different centers but phase of treatment is same phase of treatment is same Phases : Phases : – InductionInduction– ConsolidationConsolidation– Maintenance -Maintenance -interim maintenanceinterim maintenance - delayed intensification - delayed intensification - continue maintenance- continue maintenance
Duration Duration
Treatment of relapseTreatment of relapse
Molecular targeted therapy Molecular targeted therapy
Supportive TherapySupportive Therapy
Transfusions—Packed cells, PlateletsTransfusions—Packed cells, Platelets
Treat infections—do culture, IV AntibioticsTreat infections—do culture, IV Antibiotics
Counseling of familyCounseling of family
Moral and financial supportMoral and financial support
Metabolic support—to prevent Tumour Lysis Metabolic support—to prevent Tumour Lysis syndrome—Alkalinize the Urine, Allopurinol syndrome—Alkalinize the Urine, Allopurinol (100mg/M2)-24 hrs before starting atileukemic (100mg/M2)-24 hrs before starting atileukemic therapy and continue for 14 days , IV Fluidstherapy and continue for 14 days , IV Fluids
MCP 841 protocol for ALLMCP 841 protocol for ALL
Induction Consists of 3-4 drugs given for 6 weeksInduction Consists of 3-4 drugs given for 6 weeksGoal – achieve remission or <5% blasts in the bone Goal – achieve remission or <5% blasts in the bone marrow marrow
Induction 1:Induction 1:
Prednisolone - Prednisolone - PO DayPO Day 1-28 1-28
Vincristine - Vincristine - IV days 1,8,15,22 & 29 (weeklyIV days 1,8,15,22 & 29 (weekly ) )
L Asparaginase - L Asparaginase - IM 10 doses days 2-20 IM 10 doses days 2-20 Anthracycline (Daunorubicin) – 8,15,29Anthracycline (Daunorubicin) – 8,15,29MTX – IT days 1,8,15,22MTX – IT days 1,8,15,22
Induction 2Induction 2
6- Mercaptopurine –PO days 1-7 & 15-216- Mercaptopurine –PO days 1-7 & 15-21
Cyclophosphamide – IV days 1 & 15Cyclophosphamide – IV days 1 & 15
MTX – IT days 1,8,15 & 22MTX – IT days 1,8,15 & 22
Cranial irradiation – 9 daysCranial irradiation – 9 days
Repeat induction :Repeat induction :
Same as Induction 1Same as Induction 1
Induces complete remission in more than Induces complete remission in more than
98% of patients.98% of patients.
ConsolidationConsolidationTo further reduce the leukemic cell burden To further reduce the leukemic cell burden
The drugs given at doses higher than The drugs given at doses higher than those used during induction, or the patient those used during induction, or the patient is given different drugs is given different drugs – 6-mercaptopurine (6-MP) –PO days 1-7 & 6-mercaptopurine (6-MP) –PO days 1-7 &
days 15-21days 15-21– Cyclophpsphamide – IV days 1&15Cyclophpsphamide – IV days 1&15– Vincristine – IV days 1 & 15 Vincristine – IV days 1 & 15 – Cytosine arabinoside – S/C 12hrly x 6 doses Cytosine arabinoside – S/C 12hrly x 6 doses
day 1-3 & day 15-17day 1-3 & day 15-17
Maintenance Maintenance
In interim maintenance, oral medications are In interim maintenance, oral medications are administered to maintain remission and allow the administered to maintain remission and allow the bone marrow to recoverbone marrow to recover
This occurs for 4 weeks and is followed by delayed This occurs for 4 weeks and is followed by delayed intensification, which is aimed at treating any intensification, which is aimed at treating any remaining resistant leukemia cellsremaining resistant leukemia cells
The last phase of treatment is continue The last phase of treatment is continue maintenancemaintenance
Treatment Cont…Treatment Cont…3. Maintanance – 6 cycles3. Maintanance – 6 cycles - - aimed at treating any aimed at treating any
remaining resistant leukemia cellsremaining resistant leukemia cells
Prednisolone—1- 7 days every 4 weeksPrednisolone—1- 7 days every 4 weeks
Vincristine – IV every 4 weeks day 1Vincristine – IV every 4 weeks day 1
Daunorubicin— IV day 1Daunorubicin— IV day 1
L- Asparaginase – IM day 1,3,5,7L- Asparaginase – IM day 1,3,5,7
6 – mercaptopurine – PO daily 3 wks out of every 6 – mercaptopurine – PO daily 3 wks out of every 4wk for total 12 wks begin on day 154wk for total 12 wks begin on day 15
MTX – PO once a week missing every 4MTX – PO once a week missing every 4 thth for total of for total of 12 wks begin on day 1512 wks begin on day 15
Continue Maintenance Continue Maintenance
To maintain remission and allow the bone To maintain remission and allow the bone marrow to recover -This consists of LPs with marrow to recover -This consists of LPs with intrathecal MTX every 3 months, monthly intrathecal MTX every 3 months, monthly vincristine, daily 6-MP, and weekly MTXvincristine, daily 6-MP, and weekly MTX
Phase last-for 2-3 years Phase last-for 2-3 years 6 Mercaptopurine(6MP) PO, daily OD 6 Mercaptopurine(6MP) PO, daily OD MTX- PO, IV - weekly MTX- PO, IV - weekly Intrathecal MTX every 3 months, Intrathecal MTX every 3 months, IV Vincristine – monthlyIV Vincristine – monthlyMethylprednisolone -monthlyMethylprednisolone -monthly
Continue MaintenanceContinue Maintenance
Co-trimoxazole (900mg/M2 from beginning of Co-trimoxazole (900mg/M2 from beginning of wk 5 to end of maintanance therapywk 5 to end of maintanance therapy
Bone Marrow Transplant with HLA matched Bone Marrow Transplant with HLA matched donordonor
CNS preventive therapyCNS preventive therapyTriple IT therapy - IT Therapy Instead of Triple IT therapy - IT Therapy Instead of cranial irradiation cranial irradiation
Methotrexate (mtx) +Methotrexate (mtx) + Cytosine Cytosine Arabinoside (Ara C) + Hydrocortisone Given Arabinoside (Ara C) + Hydrocortisone Given every week for 6 cyclesevery week for 6 cycles
To treat patients with high-risk diseaseTo treat patients with high-risk disease
Also improve the long-term survival of Also improve the long-term survival of patients with standard-risk diseasepatients with standard-risk disease
High-risk patients: High-risk patients:
Optimal treatment for patients with very high-risk Optimal treatment for patients with very high-risk ALL has not been found. ALL has not been found.
Many institutions treat these patients with Many institutions treat these patients with allogeneic stem-cell transplantation (SCT) soon allogeneic stem-cell transplantation (SCT) soon after first remission is achieved. after first remission is achieved.
For patients without a matched family donor, For patients without a matched family donor, transplantation of marrow from an unrelated transplantation of marrow from an unrelated donor is a reasonable treatment option. donor is a reasonable treatment option.
Molecular targeted therapyMolecular targeted therapyThe best example is imatinib mesylate, a The best example is imatinib mesylate, a selective selective BCR-ABLBCR-ABL tyrosine kinase inhibitor. tyrosine kinase inhibitor.
Imatinib mesylate has demonstrated significant Imatinib mesylate has demonstrated significant anti-leukemic activity and is now a standard anti-leukemic activity and is now a standard frontline treatment for Ph-positive chronic myeloid frontline treatment for Ph-positive chronic myeloid leukemia (CML). leukemia (CML).
Imatinib mesylate is also effective in Ph-positive Imatinib mesylate is also effective in Ph-positive ALL, and combination regimens with imatinib ALL, and combination regimens with imatinib mesylate and conventional chemotherapy or SCT mesylate and conventional chemotherapy or SCT have been evaluated in trials. have been evaluated in trials.
Duration of therapyDuration of therapy
B-cell ALL - 2 to 8 month course of B-cell ALL - 2 to 8 month course of intensive therapyintensive therapy
B-precursor and T-cell ALL - 2-2.5 years of B-precursor and T-cell ALL - 2-2.5 years of continuation therapy continuation therapy
Most protocols - include a continuation Most protocols - include a continuation phase based on weekly parenteral MTX phase based on weekly parenteral MTX given with daily oral 6-MP interrupted by given with daily oral 6-MP interrupted by monthly pulses of vincristine and a monthly pulses of vincristine and a glucocorticoidglucocorticoid
Complete Remission: -Complete Remission: -
Blood ANC > 1500Blood ANC > 1500 APC > 100,000APC > 100,000 No Blast cellsNo Blast cells
Bone Marrow > 20% CellularityBone Marrow > 20% Cellularity< 5% Blast cells< 5% Blast cells
Relapse: -Relapse: -Most common site—Bone MarrowMost common site—Bone MarrowMost serious CNS, TestesMost serious CNS, Testes
RelapseRelapse
Relapsed ALL – resistant to exposed Relapsed ALL – resistant to exposed chemotherapy drugs chemotherapy drugs
Treatment of relapse is intensive and often Treatment of relapse is intensive and often including SCT and new drugs. (e.g, including SCT and new drugs. (e.g, Clofarabine, Nelarabine )Clofarabine, Nelarabine )
The outcome of relapse is poorThe outcome of relapse is poor
Complications and treatmentComplications and treatmentTumor lysis syndromeTumor lysis syndrome
Immediately admit patient who is neutropenic- Immediately admit patient who is neutropenic- IV broad-spectrum antibioticsIV broad-spectrum antibiotics
Pneumocystis prophylaxis: All patients should be Pneumocystis prophylaxis: All patients should be on TMP-SMZ to prevent PCP.on TMP-SMZ to prevent PCP.
Fungal prophylaxis: Patients should be given Fungal prophylaxis: Patients should be given oral nystatin or clotrimazole oral nystatin or clotrimazole
Mouth care: chlorhexidine (Peridex) or Mouth care: chlorhexidine (Peridex) or antibacterial enzymatic mouthwash (Biotene)4 antibacterial enzymatic mouthwash (Biotene)4 times a day.times a day.
PrognosisPrognosis
More than 80% of children with ALL now can More than 80% of children with ALL now can be curedbe cured
Treatment failure in 20% children -unknown Treatment failure in 20% children -unknown
PrognosisPrognosis
Criteria Criteria Standard RiskStandard Risk High RiskHigh Risk
SexSex FemaleFemale MaleMale
AgeAge 1-9 yrs1-9 yrs <1yr or > 10yr<1yr or > 10yr
WBCWBC < 50,000< 50,000 >50,000>50,000
Ph Ph ChromosomeChromosome
AbsentAbsent PresentPresent
PrognosisPrognosisCriteria Criteria Standard RiskStandard Risk High RiskHigh Risk
Adenopathy Adenopathy NegativeNegative PositivePositive
HepatosplenomegalyHepatosplenomegaly Absent or<3cmAbsent or<3cm >3cm>3cm
HbHb >10 gm>10 gm < 7 gm< 7 gm
PlateletsPlatelets > 100,000> 100,000 100,000 100,000
Poor response to Poor response to initial presnisolone initial presnisolone
______ ++++++
PrognosisPrognosis
Criteria Criteria Standard RiskStandard Risk High RiskHigh Risk
LDHLDH NormalNormal IncreasedIncreased
Med mass Med mass AbsentAbsent PresentPresent
Chr anomalyChr anomaly hyperdiploidy = hyperdiploidy = good prognosisgood prognosis - -
t(9:22),t(4:11)t(9:22),t(4:11)
poorpoor
Criteria Criteria Standard RiskStandard Risk High RiskHigh Risk
Response to inductionResponse to induction
mass mass
5% blast cells 5% blast cells 25% 0n day 25% 0n day 1414
Type of Blast cells Type of Blast cells L 1 L 1 L 2,3L 2,3
Septicemia Septicemia NoNo YesYes
Criteria Criteria Standard RiskStandard Risk High RiskHigh Risk
T-cell ALLT-cell ALL ______ ++++++
Type of Blast cells Type of Blast cells L 1 L 1 L 2,3L 2,3
CNS /Testes involvementCNS /Testes involvement NoNo YesYes
Septicemia Septicemia NoNo YesYes
Congenital LeukaemiaCongenital Leukaemia
Onset : -within 1st monthOnset : -within 1st monthType—mostly MyeloidType—mostly MyeloidCl features—marked extramedullary involvementCl features—marked extramedullary involvement
Massive hepatosplenomegalyMassive hepatosplenomegaly Skin nodulesSkin nodules
CNS involvementCNS involvementBl picture—marked Leukocytosis and Bl picture—marked Leukocytosis and ThrombocytopeniaThrombocytopeniaPrognosis: -PoorPrognosis: -Poor
AMLAML
20% of all Leukaemias20% of all LeukaemiasM>FM>FClinical FeaturesClinical FeaturesAs for ALL— As for ALL— In addition: In addition: Gum hypertrophy Gum hypertrophy Chloroma—localised mass of Leukaemic Chloroma—localised mass of Leukaemic cells- may herald Leukaemia. Seen in cells- may herald Leukaemia. Seen in Orbital/Epidural site Orbital/Epidural site
DiagnosisDiagnosis
> 30% Blast cells in Marrow> 30% Blast cells in MarrowTreatment:Treatment:Vigorous Induction: During induction Vigorous Induction: During induction patient is very ill - 10% die.patient is very ill - 10% die.AnthracyclinesAnthracyclines Daunorubicin Daunorubicin Cytosine Arabinoside Cytosine Arabinoside Supportive care: - same as ALLSupportive care: - same as ALL
Treatment:Treatment:
Induction takes > 6weeksInduction takes > 6weeks
CNS IT TherapyCNS IT Therapy
BMT –Allogenic Stem Cell transplant with a BMT –Allogenic Stem Cell transplant with a matched sibling –70% curematched sibling –70% cure
Interleukin 2—to produce ImmunomodulationInterleukin 2—to produce Immunomodulation
AML with Relapse—very poor prognosis.AML with Relapse—very poor prognosis.
CMLCML
3-5% of all Leukaemias3-5% of all LeukaemiasJuvenile Type < 5 yrs of ageJuvenile Type < 5 yrs of ageM>FM>FCl features: - Cl features: -
Suppurative lymphadenopathySuppurative lymphadenopathy hepatosplenomegalyhepatosplenomegaly
Erythematous rashErythematous rash EczemaEczema
PurpuraPurpura Pulmonary infiltratesPulmonary infiltrates
CMLCML - Diagnosis: - Diagnosis:
Anaemia, dec plateletsAnaemia, dec platelets
WBC inc > 60,000WBC inc > 60,000
Inc monocytes/ granulocytes in BMInc monocytes/ granulocytes in BM
Hb F increased in > 50%Hb F increased in > 50%
Only Trt: - BMT/ SCT—50% failureOnly Trt: - BMT/ SCT—50% failure
Prognosis: - poor- Death within 9monthsPrognosis: - poor- Death within 9months
CMLCML
Adult Type: - More commonAdult Type: - More common
Ph Chromosome presentPh Chromosome present
Older children: -lassitude, weight loss, Older children: -lassitude, weight loss, bone pain, inc in size of abdomen.bone pain, inc in size of abdomen.
Blood: - WBC > 100,000Blood: - WBC > 100,000
Platelets N or inc Platelets N or inc
AnaemiaAnaemia
BM hyperplasiaBM hyperplasia
CMLCML
3 Phases—3 Phases—1.Chronic—years-well controlled by 1.Chronic—years-well controlled by
ChemotherapyChemotherapy2.Accelerated – Months, decreased 2.Accelerated – Months, decreased
responseresponse3.Blast Crisis—days—3.Blast Crisis—days—
Myeloid—common does not respond to Myeloid—common does not respond to treatmenttreatmentLymphoid –responds briefly to Lymphoid –responds briefly to treatmenttreatment
TreatmentTreatment
Hydroxyurea 1500-3000 mg/mHydroxyurea 1500-3000 mg/m22 4-6 4-6 weeklyweekly
BusulphanBusulphan
Alpha InterferonAlpha Interferon
Allogenic BMT/ SCT—80% survival if Allogenic BMT/ SCT—80% survival if Identical HLA matched siblingIdentical HLA matched sibling
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