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Acute Leukemia. Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India. Leukaemia. A 16 year old girl Extreme pallor gum bleeds, Purpura,With Lymphadenopathy and Hepatosplenomegaly. Possible causes: Investigations and treatment.

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Acute leukemia l.jpg

Acute Leukemia

Rakesh Biswas

MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India

Leukaemia


A 16 year old girl extreme pallor gum bleeds purpura with lymphadenopathy and hepatosplenomegaly l.jpg
A 16 year old girlExtreme pallorgum bleeds, Purpura,WithLymphadenopathy and Hepatosplenomegaly


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Possible causes: Investigations and treatment



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During a sunny spring weekend, D would go outside to play, only to return minutes later exhausted, flopping herself onto the sofa to rest


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Leukemia only to return minutes later exhausted, flopping herself onto the sofa to rest

Group of malignant disorders of the hematopoietic tissues characteristically associated with increased numbers of white cells in the bone marrow and / or peripheral blood


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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?"


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Classification lot, she asked,

  • Classified based on cell type involved and the clinical course

  • 1. Acute :

  • ALL

  • AML

    2. Chronic :

  • CLL

  • CML


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Subclassification lot, she asked,

  • ALL

    • Common type( pre-B)

    • B-cell

    • T-cell

    • Undifferentiated


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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.


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Myelomono confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.


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Ref-Harrison’s Principle of Internal Medicine confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.


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CLL confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

B-cell: common

T-cell: rare


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CML confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

Ph +ve

Ph –ve, BCR-abl +ve

Ph –ve, BCR-abl -ve

Eosinophilic Leukemia

Ph: Philadelphia chromosome

BCR: Breakpoint cluster region; abl : Abelson oncogene


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Acute Myeloid Leukemia confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell. ( AML)

  • Malignant transformation of a myeloid precursor cell ; usually occurs at a very early stage of myeloid development

  • Rare in childhood & incidence increases with age


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Etiology confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

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


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Epidemiology confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

  • M > F

  • ALL which predominantly affects younger individuals

  • AML – adults and the elderly

  • Median age gp-65yrs

  • Geographical variation-none


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Clinical features confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

General : Onset is abrupt & stormy

(usually present within 3 months)

  • Bone marrow failure (anemia, infection ,bleeding)

  • Bone pain & tenderness


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Specific: confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

  • 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


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Skin Infiltration with AML confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell. (Leukemia Cutis)


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Diagnosis confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

  • Blood count : WBC usually elevated (50,000- 1,00,000 / cmm ); may be normal or low; often anemia & thrombocytopenia

  • Blood film : (as above) Blast cells


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P. Smear AML confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.


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  • Bone marrow aspirate & trephine confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell. : 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





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Confirmation: positivity in blasts

Immunophenotyping

Molecular genetics

Cytogenetics: Chromosomal abnormalities


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Other Inv positivity in blasts:

  • Coagulation screen, fibrinogen, D- dimer

  • RFT, LFT

  • LDH, Uric acid

  • Urine

  • CXR

  • ECG, ECHO


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Management positivity in blasts

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


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  • Metabolic problems positivity in blasts : Monitoring hepatic / renal / hematologic function; Fluid & electrolyte balance, nutrition Hyperuricemia- hydration, Allopurinol

  • Psychological support


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The white blood cell count in her peripheral blood was about 550,000. Her bone marrow was packed with leukemia blasts."


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The next thing that occurred was a procedure called 550,000. leukopheresis.This procedure lasted 4 hours and cut D’s white blood cell (WBC) count in half--to about 250,000.


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She was administered chemotherapy immediately following the 550,000. leukopheresis procedure. The next day we learned that the chemo had produced an effect as well: The WBC had halved again--125,000.


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SPECIFIC THERAPHY: 550,000.

Chemotherapy :

Induction: (4-6 wks)

vincristine, prednisone,

anthracycline, (idarubicin or daunorubicin)

cyclophosphamide, and L-asparaginase


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Consolidation 550,000. : (multiple cycles of intensive chemotherapy given over a 6 to 9 month period).Cytosine arabinoside, high-dose methotrexate, etoposide anthracycline, (idarubicin or daunorubicin)


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Maintenance phase: 550,000. (18 to 24 months).LPs with intrathecal MTX every 3 months, Monthly vincristine, Daily 6-MP, and weekly MTX.


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At day 29 of the induction protocol D was declared to be in complete remission. We were all relieved with this news.


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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.


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For instance, she would receive an infusion of consolidation therapy. methotrexate for a couple of days and then take 6-MP by mouth for a week. Another cycle included VM-26 (Teniposide) and Ara-C.


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Complete remission consolidation therapy. ( CR): < 5% blast cells in normocellular bone marrow

Autologous BMT : Can be curative in younger patient (< 40-50 yrs)


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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."


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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.


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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…


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…the first 30 days representing Ds' relapse and the induction therapy to obtain a second remission


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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


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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.


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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.


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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.


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III. PALLIATIVE THERAPHY the lab results.

Chemo, RT, Blood product support


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Prognosis the lab results.

  • 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


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Poor prognostic factors the lab results.

  • Increasing age

  • Male sex

  • High WBC count at diagnosis

  • CNS involvement at diagnosis

  • Cytogenetic abnormalities

  • Antecedent hematological abnormalities (eg. MDS)

  • No complete remission


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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."


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Among other things, she wrote: collector of many things, trinket boxes, key rings. "Hair loss is a side effect of chemotherapy, and cancer is a side effect of life."


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Summary; collector of many things, trinket boxes, key rings. Learning Points


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THANK YOU collector of many things, trinket boxes, key rings.


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