Haematology Acute leukemia

Acute lymphoblastic leukemia Dr.Hussein Alatabi

Acute lymphoblastic leukemia (ALL): is amalignant disorder of lymphoblasts occuring as aresult of indefinite clonal proliferation of single lymphoblast that has undergo malignant transformation. This lymphoblastic clonal proliferation leads to overgrowth and the crowding out of normal marrow


Precursors,invasion of non hematopoietic tissues and suppresion of differentiation of normal cells causing in effective heamatopoiesis ALL is the most common cancer of childhood,and the peak incidence occure between 2 and 5 years old,more common in white and boys

causes

* unknown,may be associated with *Genetic predisposition(identical twins ,down syndrom,ataxia telangectasia , bloom syndrom,wiscott-aldrich syndrom ,congenital hypogamaglobul- inemia) *immunodeficiencies(ionizing radiation ,chemical exposure, immunosuppressive therapy.

Complications

Due to disease: Hyperleukocytosis(WBC)>400,000) can lead to stroke. Mediastinal mass(usully T-cell lineage) wich can lead to cardiorespi- ratory arrest Tumor lysis:leads to renal failure and cardiorespiratory arrest(arrhythmias) Sever anemia:can lead to CHF

Coagulopathy: lead tostroke and hemorrhage Hypocalcemia:lead to RF and cardior- espiratory arrest Febrile neutropenia:lead to infection, strock,sepsis

Other compiications;Due to therapy:

Cranial radiation(brian tumors, learnig deficit Growth retardation Vincristne(vcr):SIADH,hair loss L-asparagenase:pancreatitis, cogulo- pathy Adriamycin,Doxorubicin,daunorubicin: cardiac toxicity Cyclophosphamide:hemorrhagic cystitis, sterility Methotraxate(MTX):hepatotoxicity


Prognosis
Remission induction with present therapy is 95% Long term survival approches 80%

Differential Diagnosis

Non malignant conditions: JRA Infectious mononucleosis ITP Acute infectious lymphocytosis Aplastic anemia Pertusis and parapertusis Malignant cnditions: Neuroblastoma Lymphoma Retinoblastoma Rhabdomyosarcoma Acute myeloid leukemia

Clinical features

HistoryBleeding( cutanous and mucocutanous) due to low platlets count and cogulopathyBone pains, arthalgia, limp due to infiltrative disease of boneFatigue and paller due to anemiaStridor, orthopnea, SOB or any respiratory distress due to mediastinal mass, pleural effsionOliguria,anuria( RF due to tumor lysis syndrom)Ocular pain,blurred vision, photophbia due to infiltration of leukemia to orbit,optic n.,….Headache, vomiting, seizures,..due to leuk. Infiltration of CNS

Physical examination

Pallor(anemia) Lymphodenopathy(infiltration with leuke.) HSM(infiltration) Bone tenderness(infiltration) Petechiae,purpura,subconjunctival and retinal hemorrhage(thrombocytopenia) Subcutuneus nodules(leuk. Infiit. To skin) Extermity weakness,numbness or tingling (spinal cord compression)

Laboratory aids

CBC: either increase WBC or neutropenia,thrombocytopenia,low Hb, prepheral smear my show leukemic lymphoblast Bone marrow aspirate(BMA): if more than 25% of leukemic lymphoblast is diagnostic Immunophenotyping and cytogenic studies onBMA for diagnosis and prognosis Biochemical abnormalities(hyperurisemia( CXR CSF exam. With lymphoblast(CNS involv.)

Prognstic factors

Patients with following criteria are at high risk for relapse and require more intensive treatment: Age < 1 year or >10 years of age WBC count > 50,000 Translocation t (9-22), t (4-11) t (1-19) Hypodiploidy ( <46 chromosome)

Therapy

Stratified according to risk groups -risk assesment based on clinical features ,biologic charact. Of lymphoblasts and BM response to initial therapy;(low risk ,stander risk, high and very high risk) -Over all, there are four phases of therapy : *Induction *Consolidation *Delayed intensification *Maintenance

Therapy (cont.)

Induction :to achieve remission (< 5% blast in bone marrow ) -vcr -steriod -L asparginase - doxyrubicine or daunorubicin - intrathecal methotraxate( MTX) Consolidation and CNS prophylaxis: to prevent CNS disease. -itrathecal MTX along with oral( 6 MP);(6 marcaptopurine( and MTX -itrathecal MTX along with cranial radiation,oral 6 MP and MTX

Therapy (cont.)

Delayed intensification : to further decrease leukemic burden -vcr -steriod -L asparginase -doxyrubicin –cyclophosphamide -cytosinearabinoside -6 thioguanine(6 TG) -intrathecal MTXMaintenance :long treatment for 2.5 years in girls and 3 years in boys -Dialy oral 6MP ,weekly MTX and monthly of vcr and steriods with intrathecal MTX every 3 months **CNS leukemia at diagnosis: cranial radiatin and triple intrathecal( MTX, ARA-c, hydrocortison ) in addision to drug above. ***************************************************** End ALL ********************

Acute myeloid leukemiaDr.Hussein Alatabi

Acute myloid leukemia ( AML ) : is block in differentiation and an unregulated proliferation of myeloid progenitor cells.**exact cause unknown, may be aquired risk factors (exposure to benzene, ionizing radiation or therapy induced );it is seventh most common pediatric malignancy. ** classified according to FAB to 7 subtypes (M1,M2,M3,M4,M5,M6,M7)

Complications at Diagnosis

Bleeding Disseminated intravascular coagulation (DIC ) Infection Leukstasis Tumour lysis syndrom Prognosis ** 85% achieve remission with intensive chemotherappy 30-40% achieve long term survival

Clinical features

History : *fever *paller *weight loss\anoroxia *fatigue *bleeding *bone or joint painPhysical examination : *signs of anemia (paller, fatigue, dyspnea, heart murmer,….. *signs of thrombocytopenia (petechiae,brusing,.. *signs of infection (fever,….. *other finding (HM , SM , lymphadenopathy , gingival hyper plasia ,papilledema, cranial nerves or skin manifestation


Laboratory aids
CBC : anemia,thrombocytopenia, increase or decrease WBC, *smear:myeloid may be seen BMA : > 30% of myeloblast is diagnostic Others; eloctrolytes, CSF for cells and cytology

Therapy

Most effective drugs for remission induction in AML are anthracycline as doxorubicin Consolidation with ARA-C and L-asp. Intrathecal ARA-c for CNS prophylaxs Duration of treatment 6-9 months Allogenic BMT may be the best treatment of AML in first remission

Therapy (supportive care)

Hydration Alkalization Blood products support Broad spectrum antiboitic and antifungul,.. Prophylaxis;as trimethoprim\sulfmethoxazole for pneumocystis ca. *****************************************END AML*******************