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CASE CONFERENCE. KAREN ESTRELLA PEDS PGY-2 04/28/2011. 16y/o F comes to ER for abdominal pain for 5 days and “rash”. HPI. Abd pain: 5 days, > in flanks, better when sitting No V, N, D Normal stool No dysuria, no vaginal d/c Went to nurse @ school who noted “hard abdomen”

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Case conference

CASE CONFERENCE

KAREN ESTRELLA

PEDS PGY-2

04/28/2011



HPI “rash”

  • Abd pain: 5 days, > in flanks, better when sitting

    • No V, N, D

    • Normal stool

    • No dysuria, no vaginal d/c

    • Went to nurse @ school who noted “hard abdomen”

  • Rash: small red-purple dot in left breast, later spreading, not painful, not itchy


ROS “rash”

  • Epistaxis

  • Gums bleeding

  • “more tired and weak”

  • Nocturnal sweating

  • Frequent burping

  • No wt loss


PE “rash”

  • VS: T 97.8, HR 106, RR 18 BP 95/62, O2 100% Wt: 46.9kg

  • HEENT: swollen nasal turbinates w/ min bleeding

  • CV: wnl

  • Lungs: wnl

  • Abdomen: + BS, NT, ND, + hard , protuberant upper quadrants, difficult to assess HSM, dull to percusion, no adenopathies

  • Ext: wnl

  • Skin: + petechiae in medial lower quadrant of L breast


Differential dx

Differential Dx “rash”

?


Labs imaging

Labs “rash” Imaging

?


Labs: “rash”

  • CBC: 88.8<5.3/16.2>21, RBC 2.00

  • Coags: 12.1/1.2/27.6

    138 100 7 125 3 25 1.5 372

    4 27 0.7 6.2 72

  • P: 2.6

  • UA: turbid, prot: TR, urobilinogen: 5

  • Monospot: neg

  • EBV: + IgG


Labs “rash”

  • Manual differential:

    • Segm: 3%, Bands: 1%, Lymphs: 89%

    • atypical Lymph: 3%

    • Blasts: 3%

    • RBC morphology: 2+ anysocytosis, hypocromasia

    • WBC: 2+ smudge cells

    • Platelets: markedly decrease

  • Uric Acid: 10.5

  • LDH: 3323


Imaging
Imaging “rash”

  • CXR: normal

  • Abd Xray:


Dx pre b cell all

Dx “rash” :Pre-B cell ALL


All acute lymphoblastic leukemia

ALL “rash” (Acute Lymphoblastic Leukemia)


Definition
Definition: “rash”

  • Malignant disease of BM in which early lymphoid precursors proliferate and replace normal hemotopoietic cells.

    • Anemia, neutropenia, trombocytopenia

    • Prolieration in other organs: lymph nodes, spleen, liver

  • More common cancer in children

    • 2.8 to 10 cases/100000

    • Peak 2-5y/o

    • > blacks

    • > boys

    • Inmunosuppresed sd: Down, ataxia-telangiectasia, neurofibromatosis type 1


Symptoms
Symptoms “rash”

  • Anemia (>75%)

  • Neutropenia (50%), leukocytosis (20%)

  • Thrombocytopenia (75%)

    • Associated with HSM

  • Fever

  • Bone pain: aseptic osteonecrosis

  • Early satiety

  • Hyperuricemia

  • Headache: CNS involvement

  • Lymphadenopathy > 1.5cm

  • Boys: testicular enlargement

  • SOB: mediastinal mass


Workup
Workup “rash”

LABORATORY

  • CBC

  • Blood smear

  • Coags: exclude DIC

  • CMP: LFT

  • Uric acid

  • LDH

  • If febrile: cx

IMAGING

  • CXR

  • CT SCAN

  • EKG


Workup1
Workup “rash”

  • BM biopsy

    • ALL: >20% lymphoblasts (WHO) in BM and/or peripheral blood


  • Morphology: “rash”

    • FAB classification on L1, L2, L3 is no longer valid.

  • Immunophenotype:

    • Based on CD markers identified by flow cytometry

    • 70-80% are preB cell: +CD10, CD19, CD20

    • 15% are preTcell: +CD2, 3, 4, 5, 7, 8

  • Cytogenetics:

    • hyperdiplody-trisomy 4, 10 (>50): good

    • Hypodyploidy (<46): poor prognosis

    • Translocations: t (9;22), t (1;19), t(4;11), and t(8;14)


Prognosis
Prognosis “rash”

  • Cure rate: 80%

    • With a 5y/o survival in high-risk pts of 65-75%

    • With a 75-80% of recent dx who are incorporated on clinical trials


Treatment
Treatment “rash”

  • Induction

  • Consolidation

  • Maintenance

  • CNS


1 induction
1. Induction “rash”

  • Place pt on remission : >90%

  • Drugs:

    • Vincristine: qwk for 3wks

    • Corticosteroids: qd

    • Asparaginase: qd

    • Doxorrubicin

  • Success:

    • Minimal residual disease (MRD) at 2wks and 4 wks (<5% lymphoblasts)

  • Main complication: tumor lysis sd


Tumor lysis syndrome
Tumor Lysis Syndrome “rash”

  • Rapid leukemic cell lysis after chemotherapy can cause overproduction and overexcretion of uric acid. The precipitation of uric acid in the tubules can lead to oliguric or anuric renal failure.

  • Risk factors:

    • Age >10 years

    • Splenomegaly

    • Mediastinal mass

    • Initial white blood cell count >20,000/microL

  • Labs:

    • HyperK, hyperP, hypocalcemia, hyperuricemia


  • 20-25% : + relapse “rash”

    • BM

    • CNS

    • Boys: testes

  • In general: if relapse occurs in <18mo of dx, 5yr prognosis is <21%


2 consolidation intensification
2. Consolidation (intensification) “rash”

  • Soon after MRD.

    • Goals: Prevent leukemic regrowth, reduce residual tumor burden, prevent drug-resistance in the remaining leukemic cells.

    • 4-6months

      • Occasional “pulse therapy”

3. Maintenance

  • 24-36mo

  • Drugs:

    • 6-mercaptopurine + steroids: qd

    • Metotrexate: qwk

  • Higher risk of infections: prophylactic Bactrim


4 cns
4. CNS “rash”

  • Intrathecal chemotherapy:

    • Drugs:

      • Cytarabine

      • Metotrexate

      • hydrocortisone


Long term outcomes
Long term Outcomes “rash”

  • CNS: cognitive impairment, stroke, coordination and fine motor, sensory deficits

  • Decrease linear growth

  • Obesity

  • Cardiotoxicity

  • Hyperglycemia

  • Infertility

  • Increase frequency for secondary malignancies

    • Brain tumor

    • AML


In our patient
In our patient “rash”

BONE MARROW:

Histology:

  • Hypercellular marrow (> 90%) diffusely infiltrated by blasts.

    • few scattered megakaryocytes

    • limited hematopoyesis

    • a reticulin stain shows mild to moderate diffuse increase in reticulin fibers.

      Flow cytometry:

    • 87%: pre B lymphoblasts that express CD9, CD10, CD19, CD22, CD79A, HLA-DR, CD45 and TdT

      • NEG: CD20, CD34

    • 7% mature lymphocytes

    • 3% grabulocytes

      Cytogenetic: 46, XX


Cham course
CHAM course: “rash”

HD1

  • Fever on HD1 : started on Cefepime for 5 days

  • UA: + yeast: fluconazole

  • Abd: normal appearing kidneys and bladder

    HD2:

  • BM bx, PICC, induction therapy

  • s/p platelets and PRBC transfusion

    Treatment:

  • -vincristine, doxorrubicin, leukovorin, metotrexate,

    d/c home with f/u


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