2. DEFINITION
• THE LEUKEMIAS MAY BE DEFINED AS A GROUP OF MALIGNANT DISEASES IN
WHICH GENETIC ABNORMALITIES IN A HEMATOPOIETIC CELL GIVE RISE TO AN
UNREGULATED CLONAL PROLIFERATION OF CELLS.
• THE PROGENY OF THESE CELLS HAVE INCREASE RATE OF PROLIFERATION AND
DECREASE RATE OF APOPTOSIS.
• THE RESULT IS A DISRUPTIONOF NORMAL MARROW FUNCTION AND ULTIMATELY
MARROW FAILURE.
3. • THE LEUKEMIAS ARE THE MOST COMMON MALIGNANT NEOPLASMS
IN CHILDHOOD,ACCOUNTING FOR APPROXIMATELY 31% OF ALL
MALIGNANCIES THAT OCCUR IN CHILDREN YOUNGER THAN 15 YEARS
OF AGE.
• PERCENTAGE OF DIFFERENT LEUKEMIAS IS AS FOLLOWING;
• ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)…………….77%
• ACUTE MYELOGENOUS LEUKEMIA (AML)…………….11%
• CHRONIC MYELOGENOUS LEUKEMIA (CML)…………2-3%
• JUVENILE MYELOMONOCYTIC LEUKEMIA (JMML)..1-2%
4. ACUTE LYMPHOBLASTIC LEUKEMIA
EPIDEMIOLOGY;
• PEAK INCIDENCE AT 2-3 YR OF AGE.
• OCCUR MORE IN BOYS THAN IN GIRLS AT ALL AGES.
• DISEASE IS MORE COMMON IN CHILDREN WITH CHROMOSOMAL
ABNORMALITIES.
• AMONG IDENTICAL TWINS,THE RISK TO THE SECOND TWIN IF 1ST TWIN DEVELOPS
LEUKEMIA IS GREATER THAN THAT IN THE GENERAL POPULATION.
ETIOLOGY;
• ETIOLOGY OF ALL IS UNKNOWN, ALTHOUGH SEVERAL GENETIC AND
ENVIRONMENTAL FACTORS ARE ASSOCIATED WITH CHILDHOOD LEUKEMIA.
• IN CERTAIN DEVELOPING COUNTRIES THERE IS AN ASSOCIATION BETWEEN B-
CELL ALL AND EPSTEIN-BARR VIRAL INFECTION.
6. CELLULAR CLASSIFICATION
• THE CLASSIFICATION OF ALL DEPEND ON CHARACTERIZING THE MALIGNANT CELLS IN
THE BONE MARROW TO DETERMINE MORPHOLOGY,PHENOTYPE (AS MEASURED BY
CELL MEMB MARKERS),CYTOGENETIC AND MOLECULAR GENETIC FEATURES.
• MORPHOLOGY IS USUALLY ADEQUATE ALONE TO ESTABLISH DIAGNOSIS BUT OTHER
STUDIES ARE ESSENTIAL FOR DISEASE CLASSIFICATION WHICH CAN HAVE INFLUENCE
ON PROGNOSIS AND CHOICE OF THERAPY.
• THE CURRENT SYSTEM USED IS WHO CLASSIFICATION OF LEUKEMIAS.
• PHENOTYPICALLY,SURFACE MARKERS SHOW 85% CASES OF ALL ARE CLASSSIFIED AS B-
LYMPHOBLASTIC LEUKEMIA,15% ARE T-LYMPHOBLASTIC LEUKEMIA AND 1% ARE
DERIVED FROM MATURE B CELLS.
• THE RARE LEUKEMIA OF MATURE B CELLS IS TERMED AS BURKITT LEUKEMIA,MOST
RAPIDLY GROWING,REQUIRING DIFFERENT THERAPY THAN OTHER SUBTYPE OF ALL.
7. • CHROMOSOMAL ABNORMALITIES ARE USED TO SUBCLASSIFY ALL INTO
PROGNOSTIC GROUPS,MANY GENETIC ALTERATIONS,INCLUDING INACTIVATION
OF TUMOR SUPPRESSOR GENES AND MUTATIONS THAT ACTIVATE THE NOTCH1
OR RAS PATHWAYS,HAVE BEEN DISCOVERED.
• ANOREXIA,FATIGUE,MALAISE,IRRITABILITY,INTERMITTENT LOW GRADE
FEVER,BONE OR JOINT PAIN PARTICULARLY IN LOWER EXTREMITIES,JOINT
SWELLING.
• BONE PAIN IS SEVERE AND WAKE THE PATIENT AT NIGHT.
• AS DISEASE PROGRESSES,SIGN AND SYMPTOMS OF BONE MARROW FAILURE
BECOME OBVIOUS WITH OCCURRENCE OF PALLOR,FATIGUE,EXERCISE
INTOLERANCE,BRUISING,EPISTAXIS AS WELL AS FEVER.
CLINICAL MANIFESTATIONS
8. • ORGAN INFILTRATION CAN CAUSE
LYMPHADENOPATHY,HEPATOSPLEENOMEGALY,TESTICULAR
ENLARGEMENTS,CENTRAL NERVOUS SYSTEM INVOLVEMENT (CRANIAL
NEUROPATHIES,HEADACHE,SEIZURES).
• RESPIRATORY DISTRESS MAY BE DUE TO SEVERE ANEMIA OR MEDIASTINAL NODE
COMPRESSION OF THE AIRWAYS.
• RARELY,INCREASE INTRACRANIAL PRESSURE THAT INDICATE LEUKEMIC
INVOLVEMENT OF CNS,THESE INCLUDE PAPILLEDEMA,RETINAL HEMORRHAGES
AND CRANIAL NERVE PALSIES.
• T-ALL ALSO USUALLY HAS A HIGHER LEUKOCYTE COUNT.
• B-LYMPHOBLASTIC LEUKEMIA IS THE MOST COMMON
IMMUNOPHENOTYPE,WITH ONSET AT 1-10 YEARS OF AGE.THE MEDIAN
LEUKOCYTE COUNT AT PRESENTATION IS 33,000/MICRO LITER,ALTHOUGH 75%OF
PATIENTS HAVE COUNT <20,000/MICRO LITER,THROMBOCYTOPENIA IN 75% pts.
9. DIAGNOSIS
• DIAGNOSIS OF ALL IS STRONGLY SUGGESTED BY PERIPHERAL BLOOD FINDINGS
THAT INDICATE BONE MARROW FAILURE.
• ANEMIA AND THROMBOCYTOPENIA ARE SEEN IN MOST PATIENTS.
• MANY PATIENTS WITH ALL PRESENT WITH TOTAL LEUKOCYTE COUNTS OF
<10,000/MICRO LITER,IN SUCH CASES LEUKEMIC CELLS OFTEN REPORTED
INITIALLY TO BE ATYPICAL LYMPHOCYTES.
• WHEN THE RESULTS OF ANALYSIS OF PERIPHERAL BLOOD SUGGEST POSSIBILITY
OF LEUKEMIA,THE BONE MARROW SHOULD BE EXAMINED PROMPTLY TO
ESTABLISH DIAGNOSIS.
• BONE MARROW ASPIRATION AND BIOPSY,FLOW CYTOMETRY,CYTOGENETICS AND
MOLECULAR STUDIES ALSO PERFORMED TO CONFIRM DIAGNOSIS AND CLASSIFY
TYPE OF LEUKEMIA.
10. • ALL DIAGNOSED BY BONE MARROW EVALUATION THAT SHOWS >25% OF BONE
MARROW CELLS AS HOMOGENEOUS POPULATION OF LYMPHOBLAST.
• IF LYMPHOBLASTS ARE FOUND AND CSF LEUKOCYTE COUNT IS ELEVATED,CNS OR
MENINGEAL LEUKEMIA IS PRESENT .THIS FINDING REFLECTS WORSE STAGE,THEN
STAGING LUMBAR PUNCTURE MAY BE PERFORMED.
• INCREASE LACTATE DEHYDROGENASE IS OFTEN CLUE TO DIAGNOSIS OF ALL.
11. • WHEN ONLY PANCYTOPENIA IS PRESENT,APLASTIC ANEMIA AND MYELOFIBROSIS
SHOULD BE CONSIDERED.
• FAILURE OF SINGLE CELL LINE (AS SEEN IN ERYTHROBLASTOPENIA OF
CHILDHOOD,IMMUNE THROMBOCYTOPENIA AND NEUTROPENIA)IS RARELY
PRESENTING FEATURE OF ALL.
• INFECTIOUS MONONUCLEOSIS
• JUVENILE IDIOPATHIC ARTHRITIS
• AML AND OTHER MALIGNANT DISEASES THAT INVADE BONEMARROW
(INCLUDING NEUROBLASTOMA ,RHABDODOMYOSARCOMA,EWING SARCOMA
AND RETINOBLASTOMA)
DIFFERENTIAL DIAGNOSIS
12. TREATMENT
• AGE BETWEEN 1-10 YEARS AND LEUKOCYTE COUNT OF <50,000/MICRO LITER
ARE USED BY NATIONAL CANCER INSTITUTE TO DEFINE STANDARD
RISK.CHILDREN WHO ARE YOUNGER THAN 1 YEAR OR OLDER THAN 10 YEARS OF
AGE OR WHO HAVE INITIAL LEUKOCYTE COUNT OF >50,000/MICRO LITER ARE
CONSIDERED TO BE HIGH RISK.
• CHARACTERISTICS THAT ADVERSELY EFFECT OUTCOME INCLUDE T-CELL
IMMUNOPHENOTYPE,SLOW RESPONSE TO INITIAL THERAPY,CHROMOSOMAL
ABNORMALITIES INCLUDE HYPODIPLOIDY,PHILADELPHIA CHROMOSOME,MLL
GENE REARRANGEMENT PORTEND POOR OUTCOME.
• FAVORABLE CHARACTERISTICS INCLUDE RAPID RESPONSE TO
THERAPY,HYPERDIPLOIDY,TRISOMY OF SPECIFIC CHROMOSOME(4,10,17) AND
REARRANGEMENT OF ETV6-RUNX1 GENES.
13. • INITIAL THERAPY……….REMISSION INDUCTION
• IT IS DESIGNED TO ERADICATE LEUKEMIC CELLS FROM BONE MARROW.
• REMISSION INCLUDE <5%BLAST CELLS IN THE MARROW AND RETURN OF
NEUTROPHIL AND PLATELET COUNTS TO NEAR NORMAL LEVELS AFTER 4-5
WEEKS OF TREATMENT.
• DURING THIS PHASE,THERAPY IS GIVEN FOR 4 WEEKS,CONSIST OF VINCRISTINE
WEEKLY,A CORTICOSTEROID (DEXAMETHASONE OR PREDNISONE),AND SINGLE
DOSE OF LONG ACTING ASPARAGINASE PREPARATION.
• PATIENT AT HIGHER RISK ALSO RECEIVE DAUNOMYCIN AT WEEKLY INTERVALS.
• INTRATHECAL CHEMOTHERAPY IS ALWAYS GIVEN AT START OF TREATMENT AND
AT LEAST ONCE MORE DURING INDUCTION.
• WITH THIS APPROACH ,98%OF PATIENTS ARE IN REMISSION.
14. • SECOND PHASE………..CONSOLIDATION
• IT FOCUSES ON INTENSIVE CNS THERAPY IN COMBINATION WITH CONTINUED
INTENSIVE SYSTEMIC THERAPY .
• INTRATHECAL CHEMOTHERAPY GIVEN REPEATEDLY BY LUMBAR PUNCTURE.
• PATIENTS WITH HIGH RISK OF CNS RELAPSE RECEIVE IRRADIATION TO BRAIN IN
LATER PHASES OF THERAPY.
• MANY REGIMES PROVIDE 14-28 WEEKS OF THERAPY,WITH DRUGS AND
SCHEDULES USED VARYING DEPENDING ON RISK GROUP.
• THIS PERIOD OF TREATMENT IS OFTEN TERMED INTENSIFICATION AND INCLUDES
PHASES OF AGGRESSIVE TREATMENT (DELAYED INTENSIFICATION) AS WELL AS
RELATIVELY NONTOXIC PHASES OF TREATMENT (INTERIM MAINTENANCE).
• MULTIAGENT CHEMOTHERAPY INCLUDE MEDICATIONS AS
CYTARABINE,METHOTREXATE,ASPARAGINASE AND VINCRISTINE TO REMOVE
RESIDUAL DISEASE.
15. • FINALLY…………MAINTENANCE PHASE
• IT LAST FOR 2-3 YEARS,DEPENDING ON THE PROTOCOL USED.
• PATIENTS ARE GIVEN DAILY MERCAPTOPURINE,AND WEEKLY ORAL
METHOTREXATE,USUALLY WITH INTERMITTENT DOSES OF VINCRISTINE AND
CORTICOSTEROID.
• PATIENTS WITH POOR PROGNOSTIC FEATURES MAY UNDERGO BONE MARROW
TRANSPLANTATION DURING THE FIRST REMISSION.
16. TREATMENT OF RELAPSE
• BONEMARROW RELAPSE
• OCCURS IN 15-20% OF PATIENTS.
• INTENSIVE CHEMOTHERAPY WITH AGENTS NOT PREVIOUSLY USED FOLLOWED BY
ALLOGENIC STEM CELL TRANSPLANTATION CAN RESULT IN LONG TERM
SURVIVAL.
• CNS RELAPSE
• OCCURS IN <5% OF PATIENTS.
• TREATMENT INCLUDE INTRATHECAL MEDICATION AND CRANIAL OR
CRANIOSPINAL IRRADIATION.
• SYSTEMIC CHEMOTHERAPY ALSO MUST BE USED BECAUSE THESE PATIENTS ARE
AT HIGH RISK FOR BONE MARROW RELAPSE.
17. TESTICULAR RELAPSE
OCCURS IN LESS THAN 2% OF PATIENTS.
SUCH RELAPSE OCCURS AS PAINLESS SWELLING OF 1 OR BOTH TESTES.
DIAGNOSIS IS CONFIRMED BY BIOPSY OF AFFECTED TESTIS.
TREATMENT INCLUDE SYSTEMIC CHEMOTHERAPY AND LOCAL IRRADIATION.
18. SUPPORTIVE CARE
• CLOSE ATTENTION TO THE MEDICAL SUPPORTIVE CARE NEEDS OF PATIENTS IS
ESSENTIAL.
• PATIENT WITH HIGH WBC COUNTS ARE ESPECIALLY PRONE TO TUMOR LYSIS
SYNDROME.
• THE KIDNEY FAILURE ASSOCIATED WITH VERY HIGH LEVEL OF SERUM URIC ACID
CAN BE PREVENTED OR TREATED WITH ALLOPURINOL OR URATE OXIDASE.
• CHEMOTHERAPY OFTEN PRODUCES SEVERE MYELOSUPPRESSION,WHICH
REQUIRE ERYTHROCYTE AND PLATELET TRANSFUSION.
• ANTIMICROBIAL THERAPY FOR SEPSIS IN FEBRILE CHILDREN WITH NEUTROPENIA.
• PATIENT MUST RECEIVE PROPHYLACTIC TREATMENT FOR PNEUMOCYSTIS
JIROVECI PNEUMONIA DURING CHEMOTHERAPY AND FOR SEVERAL MONTHS
AFTER COMPLETING TREATMENT.
19. PROGNOSIS
• CURRENT DATA SHOWING OVERALL 5 YEAR SURVIVAL ARROUND 90%.
• HOWEVER,SURVIVORS ARE MORE LIKELY TO EXPERIENCE SIGNIFICANT CHRONIC
MEDICAL CONDITIONS INCLUDING MUSCULOSKELETAL,CARDIAC AND
NEUROLOGICAL CONDITIONS.
20. ACUTE MYELOGENOUS LEUKEMIA
• EPIDEMIOLOGY
• THE RELATIVE FREQUENCY OF AML INCREASES IN
ADOLESCENCE,REPRESENTING 36% CASES OF LEUKEMIA IN 15-19 YEAR OLDS.
• ONE SUBTYPE ACUTE PROMYELOCYTIC LEUKEMIA (APL) IS MORE COMMON IN
CERTAIN REGIONS OF THE WORLD.
• SEVERAL CHROMOSOMAL ABNORMALITIES ASSOCIATED WITH AML HAVE BEEN
IDENTIFIED,BUT NO PREDISPOSING GENETIC OR ENVIRONMENTAL FACTORS CAN
BE IDENTIFIED IN MOST PATIENTS.
• RISK FACTORS INCLUDE
• IONIZING RADIATION,CHEMOTHERAPEUTIC AGENTS (ALKYLATING
AGENTS,EPIPODOPHYLLOTOXIN),ORGANIC SOLVENTS,PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA AND CERTAIN SYNDROMES.
21. CELLULAR CLASSIFICATION
• THE CHARACTERISTIC FEATURE OF AML IS THAT >20% OF BONE MARROW CELLS
ON BONE MARROW ASPIRATION OR BIOPSY SHOWS HOMOGENEOUS
POPULATION OF BLAST CELLS,WITH FEATURES SIMILAR TO THOSE THAT
CHARACTERIZE EARLY DIFFERENTIATION STATES OF MYELOID-MONOCYTE-
MEGAKARYOCYTE SERIES OF BLOOD CELLS.
• THE WHO HAS PROPOSED A NEW CLASSIFICATION SYSTEM THAT INCORPORATES
MORPHOLOGY, CHROMOSOME ABNORMALITIES AND SPECIFIC GENE
MUTATIONS.
• THIS SYSTEM PROVIDES SIGNIFICANT BIOLOGIC AND PROGNOSTIC
INFORMATION.
22. CLINICAL MANIFESTATIONS
• PATIENTS WITH AML CAN PRESENT WITH ANY OR ALL OF THE FINDINGS
ASSOCIATED WITH MARROW FAILURE IN ALL.
• IN ADDITION ,PATIENTS WITH AML ALSO PRESENTS,
SUBCUTANEOUS NODULES OR BLUEBERRY MUFFIN LESION (ESPECIALLY IN
INFANTS)
INFILTRATION OF GINGIVA.
DISSEMINATED INTRAVASCULAR COAGULATION (ESPECIALLY INDICATIVE OF APL)
DISCRETE MASSES CALLED CHLOROMAS OR GRANULOCYTIC SARCOMAS.
• CHLOROMAS ALSO MAY BE SEEN IN THE ORBIT AND EPIDURAL SPACE.
23. DIAGNOSIS
• ANALYSIS OF BONE MARROW ASPIRATION AND BIOPSY SPECIMENS SHOWS
HYPERCELLULAR MARROW CONSISTING OF MONOTONOUS PATTERN OF CELLS.
• FLOW CYTOMETRY AND SPECIAL STAINS ASSIST IN IDENTIFYING
MYELOPEROXIDASE-CONTAINING CELLS,THUS CONFIRMING BOTH
MYELOGENOUS ORIGIN OF LEUKEMIA AND DIAGNOSIS.
24. PROGNOSIS AND TREATMENT
• AGGRESSIVE MULTIAGENT CHEMOTHERAPY IS SUCCESSFUL IN INDUCING
REMISSION IN 85-90% OF PATIENTS.
• TARGETING THERAPY TO GENETIC MARKERS MAY BE BENEFICIAL.
• UPTO 5% OF PATIENTS DIE OF EITHER INFECTION OR BLEEDING BEFORE A
REMISSION CAN BE ACHIEVED.
• MATCHED-SIBLING BONE MARROW OR STEM CELL TRANSPLANTATION AFTER
REMISSION ACHIEVES LONG TERM DISEASE FREE SURVIVAL.
• CONTINUED CHEMOTHERAPY FOR PATIENTS WHO DO NOT HAVE MATCHED
SIBLING DONOR IS LESS EFFECTIVE THAN MARROW TRANSPLANTATION.
• FOR SELECTED PATIENTS WITH FAVORABLE PROGNOSTIC FEATURES
[t(8;21);t(15;17);inv(16);APL] AND IMPROVED OUTCOME WITH
CHEMOTHERAPY,MATCHED SIBLING STEM CELL TRANSPLANTATION IS
RECOMMENDED ONLY AFTER RELAPSE
25. • HOWEVER,PATIENTS WITH UNFAVORABLE PROGNOSTIC FEATURES
(e.g,MONOSOMIES 7 AND 5) WHO HAVE INFERIOR OUTCOME WITH
CHEMOTHERAPY MIGHT BENEFIT FROM MATCHED UNRELATED DONOR STEM
CELLS TRANSPLANT IN FIRST REMISSION.
• APL,CHARACTERIZED BY GENE REARRANGEMENT INVOLVING THE RETINOIC ACID
RECEPTOR IS VERY RESPONSIVE TO all-trans-retinoic acid COMBINED WITH
ANTHRACYCLINES AND CYTARABINE,ARSENIC TRIOXIDE IS AN EFFECTIVE
NONCYTOTOXIC THERAPY FOR APL.
• INCREASE SUPPORTIVE CARE IS NEEDED IN PATIENTS WITH AML BECAUSE THE
INTENSIVE THERAPY THEY RECEIVE PRODUCES PROLONGED BONE MARROW
SUPPRESSION WITH SERIOUS INFECTIONS,ESPECIALLY STREPTOCOCCAL VIRIDANS
SEPSIS AND FUNGAL INFECTIONS.
26. CHRONIC MYELOGENOUS LEUKEMIA
• CML IS CLONAL DISORDER OF THE HEMATOPOIETIC TISSUE THAT ACCOUNTS FOR
2-3% OF ALL CASES OF CHILDHOOD LEUKEMIA.
• IN 99% CASES,SPECIFIC TRANSLOCATION ,t(9;22),KNOWN AS PHILADELPHIA
CHROMOSOME,RESULTING IN BCR-ABL FUSION PROTEIN.
• THE PRESENTING SYMPTOMS OF CML ARE NONSPECIFIC INCLUDE
FEVER,FATIGUE,WEIGHT LOSS, ANOREXIA AND SPLENOMEGALY.
• THE DIAGNOSIS IS SUGGESTED BY HIGH WBC COUNT WITH MYELOID CELLS AT
ALL STAGES OF DIFFERENTIATION IN PERIPHERAL BLOOD AND BONE
MARROW,AND IS CONFIRMED BY CYTOGENETIC AND MOLECULAR STUDIES THAT
SHOWS PHILADELPHIA CHROMOSOME AND BCR-ABL GENE REARRANGEMENT.
27. • THE DISEASE IS CHARACTERIZED BY AN INITIAL CHRONIC PHASE IN WHICH
MALIGNANT CLONE PRODUCES AN ELEVATED WBC COUNT WITH
PREDOMINANCE OF MATURE FORMS BUT WITH INCREASED NO OF IMMATURE
GRANULOCYTES.
• IN ADDITION TO LEUKOCYTOSIS,BLOOD COUNT CAN REVEAL MILD ANEMIA AND
THROMBOCYTOSIS.
• CHRONIC PHASE TERMINATES 3-4 YEARS AFTER ONSET,WHEN CML MOVES INTO
ACCELERATED OR “BLAST CRISIS” PHASE,AT THIS POINT BLOOD COUNTS RISE
DRAMATICALLY AND CLINICAL PICTURE IS INDISTINGUISHABLE FROM ACUTE
LEUKEMIA.
• ADDITIONAL MANIFESTATIONS INCLUDING NEUROLOGIC SYMPTOMS FROM
HYPERLEUKOCYTOSIS,WHICH CAUSES INCREASED BLOOD VISCOSITY WITH
DECREASED CNS PERFUSION.
• IMATINIB ,AN AGENT DESIGNED TO INHIBIT BCR-ABL TYROSINE KINASE.WHILE
WAITING FOR RESPONSE TO TYROSINE KINASE INHIBITOR,THREATENING SIGN
AND SYMPTOMS DURING CHRONIC PHASE CAN CONTROLLED BY HYDROXYUREA,
28. WHICH GRADUALLY RETURNS LEUKOCYTE COUNT TO NORMAL.
• CURE IS ENHANCED BY HUMAN LEUKOCYTE ANTIGEN-MATCHED FAMILY DONOR
ALLOGENIC STEM CELL TRANSPLANT.
• IT IS CLONAL PROLIFERATION OF HEMATOPOIETIC STEM CELLS THAT TYPICALLY
AFFECTS CHILDREN YOUNGER THAN 2 YEAR OF AGE.
• PATIENTS WITH THIS DISEASE DO NOT HAVE PHILADELPHIA CHROMOSOME THAT
IS CHARACTERISTIC OF CML.
• PATIENT WITH JMML PRESENT WITH RASHES,LYMPHADENOPATHY,
SPLENOMEGALY AND HEMORRHAGIC MANIFESTATIONS.
JUVENILE MYELOMONOCYTIC LEUKEMIA
29. • ANALYSIS OF PERIPHERAL BLOOD OFTEN SHOWS AN ELEVATED LEUKOCYTE
COUNT WITH INCREASE MONOCYTES,THROMBOCYTOPENIA AND ANEMIA WITH
PRESENCE OF ERYTHROBLASTS.
• MOST PATIENTS WITH JMML HAVE BEEN FOUND TO HAVE MUTATIONS THAT
LEAD TO ACTIVATION OF RAS ONCOGENE PATHWAY.
• STEM CELL TRANSPLANTATION OFFERS BEST OPPORTUNITY FOR CURE.
