This preview shows page 1. Sign up to view the full content.
Unformatted text preview: Acute Leukemia
MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India A 16 year old girl Extreme pallor gum bleeds, Purpura,With Lymphadenopathy and Hepatosplenomegaly Possible causes: Investigations and treatment Only a week later, D was ill again, with a fever, severe headache, and extreme lethargy. During a sunny spring weekend, D would go outside to play, only to return minutes later exhausted, flopping herself onto the sofa to rest Leukemia
Group of malignant disorders of the hematopoietic tissues characteristically associated with increased numbers of white cells in the bone marrow and / or peripheral blood Once inside the van and on our way out of the clinic parking lot, she asked, "Dad, what is leukemia?" "Can I die from this?" Classification Classified based on cell type involved and the clinical course 1. Acute : ALL AML 2. Chronic : CLL CML Subclassification
Common B-cell T-cell Undifferentiated type( pre-B) After the oncologist performed a bone marrow aspiration to confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell. Myelomono AML
French-American-British (FAB) Classification M0: Minimally differentiated leukemia M1: Myeloblastic leukemia without maturation M2: Myeloblastic leukemia with maturation M3: Hypergranular promyelocytic leukemia M4Eo: Variant: Increase in abnormal marrow eosinophils M4: Myelomonocytic leukemia M5: Monocytic leukemia M6: Erythroleukemia (DiGuglielmo's disease) M7: Megakaryoblastic leukemia
Ref-Harrison's Principle of Internal Medicine CLL
B-cell: common T-cell: rare CML Ph +ve Ph ve, BCR-abl +ve Ph ve, BCR-abl -ve Eosinophilic Leukemia Ph: Philadelphia chromosome BCR: Breakpoint cluster region; abl : Abelson oncogene Acute Myeloid Leukemia Malignant transformation of a myeloid precursor cell ; usually occurs at a very early stage of myeloid development ( AML) Rare in childhood & incidence increases with age Etiology
Unknown / De-novo !! In majority
Predisposing factors: Ionizing radiation exposure Previous chemotherapy : alkylating agents Occupational chemical exposure : benzene Genetic factors: Down's Syndrome, Bloom's, Fanconi's Anemia Viral infection ( HTLV-1) Immunological : hypogammaglobulinemia Acquired hematological condition -Secondary Epidemiology
M >F ALL which predominantly affects younger individuals AML adults and the elderly Median age gp-65yrs Geographical variation-none Clinical features
Onset is abrupt & stormy (usually present within 3 months)
Bone marrow failure (anemia, infection ,bleeding) pain & tenderness Bone Specific: M2 : Chloroma:-presents as a mass lesion `tumor of leukemic cells' M3 : DIC M4/M5 : Infiltration of soft tissues, gum infiltration, skin deposits ,Meningeal involvement-headache, vomiting, eye symptoms Skin Infiltration with AML (Leukemia Cutis) Diagnosis Blood count : WBC usually elevated (50,0001,00,000 / cmm ); may be normal or low; often anemia & thrombocytopenia film : (as above) Blood Blast cells P. Smear AML Bone marrow aspirate & trephine: Hypercellular, blast cells ( > 20%), presence of Auer rods - AML type Cytochemistry : Special stains to differentiate AML from ALL ; Positivity with Sudan black & Myeloperoxidase (MPO) in AML Jemshidi trephine & Salah aspiration needle Auer Rods in Leukemia cells MPO (right) & Sudan black (left) showing intense localised positivity in blasts Confirmation: Immunophenotyping Molecular genetics Cytogenetics: Chromosomal abnormalities Other Inv: Coagulation screen, fibrinogen, D- dimer RFT, LFT LDH, Uric acid Urine CXR ECG, ECHO Management
I. Supportive care :
Anemia red cell transfusion Thrombocytopenia platelet concentrates Infection broad spectrum IV antibiotics Hematopoietic growth factors : GM-CSF, G-CSF Barrier nursing Indwelling central venous catheter Metabolic problems : Monitoring hepatic / renal / hematologic function; Fluid & electrolyte balance, nutrition Hyperuricemia- hydration, Allopurinol
Psychological support The white blood cell count in her peripheral blood was about 550,000. Her bone marrow was packed with leukemia blasts." The next thing that occurred was a procedure called leukopheresis. This procedure lasted 4 hours and cut D's white blood cell (WBC) count in half--to about 250,000. She was administered chemotherapy immediately following the leukopheresis procedure. The next day we learned that the chemo had produced an effect as well: The WBC had halved again--125,000. SPECIFIC THERAPHY: Chemotherapy :
Induction: (4-6 wks) vincristine, prednisone, anthracycline, (idarubicin or daunorubicin) cyclophosphamide, and L-asparaginase Consolidation: (multiple cycles of intensive chemotherapy given over a 6 to 9 month period). Cytosine arabinoside, high-dose methotrexate, etoposide anthracycline, (idarubicin or daunorubicin) Maintenance phase: (18 to 24 months). LPs with intrathecal MTX every 3 months, Monthly vincristine, Daily 6-MP, and weekly MTX. At day 29 of the induction protocol D was declared to be in complete remission. We were all relieved with this news. Step two was the next phase of treatment called consolidation therapy. This entailed multiple combinations of drugs administered on a rotational basis (on various weeks) for the next six months. For instance, she would receive an infusion of methotrexate for a couple of days and then take 6MP by mouth for a week. Another cycle included VM-26 (Teniposide) and Ara-C. Complete remission ( CR): BMT : < 5% blast cells in normocellular bone marrow Autologous Can be curative in younger patient (< 40-50 yrs) Exactly 5 months since her diagnosis, and 16 weeks of remission... "We're at the clinic. D has relapsed. Her white count is 27,000." The Consolidation protocol had been dropped and replaced with a new induction protocol.
After the bone marrow aspiration to determine the extent of the leukemia relapse, she was given doxirubicin, vincristine and L-asparaginase. For several days following D`s discharge from the bone marrow transplant unit, all of us loaf around the house and recuperate from our 90 day marathon... ...the first 30 days representing Ds' relapse and the induction therapy to obtain a second remission Back in fighting form, D proceeds directly to the final 30 days of the marathon--the actual bone marrow transplant. BMT patients are in a delicate condition following discharge Looking back, the nine weeks or so--the post BMT discharge period--was a sublime time for us. D was home and was feeling pretty good. As D's hair began to grow again, we rubbed her head every night at the dinner table, wondering what color it was going to be or if it was going to be curly or straight. We never found out. On Monday, March 1, 1999 we went to clinic and waited for the lab results. The results came back as we feared. D had relapsed. Her white count was 47,000. We were devastated. III. PALLIATIVE THERAPHY
RT, Blood product support Chemo, Prognosis Median survival without treatment is 5 weeks 30% 5-yr survival in younger patients with chemotherapy Disease which relapses during treatment or soon after the end of treatment has a poor prognosis Poor prognostic factors Increasing Male age sex High WBC count at diagnosis CNS involvement at diagnosis Cytogenetic abnormalities Antecedent hematological abnormalities (eg. MDS) No complete remission Two things that I will always remember about D: She was a collector of many things, trinket boxes, key rings. But she was first and foremost a collector of "FRIENDS." Among other things, she wrote: "Hair loss is a side effect of chemotherapy, and cancer is a side effect of life." Summary; Learning Points THANK YOU ...
View Full Document
This note was uploaded on 02/23/2012 for the course SCI 310 taught by Professor Staff during the Fall '10 term at Rutgers.
- Fall '10