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Welcome to clinical presentation

Presented by…

Dr. Nazia Sharmin

Resident, Phase B

Dept of haematology

BSMMU.

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Acute Lymphoblastic Leukemia..

  • Acute lymphoblastic leukemia (ALL) is a neoplastic disorder that is rapidly fatal if untreated.

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  • In children, ALL is the most common malignancy and cure is mostly evitable.

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  • Historically, treatment outcomes in adults have not been as favorable.

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  • Incidence in the US in 2018 (based on SEER data) 1.7 per

100 000 per year.

  • Deaths is 0.4 per 100 000.
  • Slight male predominance.
  • Median age at diagnosis 15 years with a peak between of 2 and 5.
  • Median age of death 56 years and highest percent of deaths (15.8%) among people aged 65 to 74 years.

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Presentation:

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Fever/infection

3-56%

Bleeding

33%

Lymphadenopathy

40-57%

Hepatomegaly

24-47%

Splenomegaly

31-56%

Mediastinal mass

10-15%

Central nervous system

1-7%

Pleura

2.9%

Pericardium

1.0%

Retina

1.0%

Skin

0.6%

Tonsil

0.6%

Testes

0.3%

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  • Initial assessment:

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  • Clinical assessment
    • Full history
    • Physical examination including CNS
    • Height, weight and body surface area
    • Performance status.

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  • Investigations:

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    • Full blood count and film
      • Normocytic normochromic anaemia
      • WBC i.Increased (59%), very elevated >100 (15%), very occasionally >500 ii.Normal (14%) iii.Decreased (29%)
      • Thrombocytopenia- <50*10*9/L (1/3rd)
    • Urinalysis
    • Coagulation profile- fibrinogen, D-dimer, PT, APTT
    • TLS profile- uric acid, potassium, calcium, phosphorus
    • Biochemistry, LDH, urate level, LFT
    • Blood culture if febrile
    • G6PD test if rasburicase is used
    • Pregnancy test for women with child bearing age
    • HBV, HCV, HIV, CMV Ab serology
  • Infection screening

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  • Bone marrow aspirate- hypercellular with infiltration with lymphoblast >25% nucleated cells, majority of cases >50%.
    • Morphology
    • Flow cytometry
    • Cytogenetics (G-banding and FISH)
    • Molecular diagnosis
  • MRD evaluation
  • Lumbar puncture for CSF study
  • Examination of CSF for blast by cytospin
  • CSF flow cytometry
  • Chest X ray
  • Echocardiogram, cardiac nuclear scan
  • CT head, neck, thorax, abdomen, pelvis if extranodal disease
  • Tissue typing of patient and siblings.

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  • Frequencies of Common Genetic Aberrations in Childhood and Adult Acute Lymphoblastic Leukemia
    • Hyperdiploidy (>50 chromosome) 6-7%
    • Hypodiploidy (<45 chromosomes) 2%
    • t(1;19)(q23;p13.3) [TCF3-PBX1] 2-3%
    • t(9;22)(q34;q11.2) [BCR-ABL1] 25–30%
    • t(4;11)(q21;q23) [MLL-AF4] 3-7%
    • t(8;14)(q23;q32.3) 4%
    • t(12;21)(p13;q22) [ETV6-RUNX1] 0-3%
    • NOTCH1 mutations 15%
    • HOX11L2 overexpression 13%
    • LYL1 overexpression 15%
    • Abnormal 9p 6–30%
    • Abnormal 12p 4–6%
    • del(7p)/del(7q)/monosomy 6–11%
    • +8 10–12%

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  • Adverse Prognostic Factors in Adult Acute Lymphoblastic Leukemia-

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    • Age (years)* >35
    • Leukocyte count >30×10^9/L)
    • Immunophenotype Pro-B (CD10–)
    • Genetics
      • t(9;22) [BCR-ABL1]
      • t(4;11) [MLL-AF4]
      • Hypodiploidy?
    • Treatment response
      • Delayed remission (>4 weeks)
      • Minimal residual disease >10 -4 after induction

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CASE: 1�

  • A 16-year-old female presented with-

Fever

G. weakness for 20 days

H/O 3 units of BT (last 20 days)

O/E: anemia, lymphadenopathy

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  • Hb : 9.1 g/dl
  • WBC: 24× 10^9/L
  • PLATELET: 50×10^9/L
  • Blast: 80%
  • BMS & biopsy: B-ALL
  • Immunophenotyping: B ALL

CD19,CD20,CD10,CD79a, aberrant CD7,13

  • BCR-ABL + ve

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  • Rx-

BFM 2002 Induction

Imatinib

Vincristine+Steroid

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CASE: 2

  • A 35-years-old male presented with-

Fever and

generalized weakness for 1 month.

O/E- Anaemia, LN

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  • Hb: 8.4g/dl
  • WBC: 41×10 ^9/µl
  • PLATLET: 40×10^3/ µl
  • Blast: 70%
  • BM: ALL

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  • Immunophenotyping:
  • B-ALL,

CD10,CD19,CD22,CD79a,

  • BCR –ABL +ve
  • BFM induction , Consolidation completed
  • Now received high dose MTX protocol

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ASH case study

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Case1 : Younger patients with no comorbidity

  • 45-year-old male,presented with fatigue-

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Hb

11.7 g/dl

WBC

153×10^9/L, 60% blast,

PLATELET

26× 10^9/L

BM

B - ALL

immunophenotyping

CD19+,CD20-CD10+,CD22+,CD34+,TdT+

RT –PCR for BCR/ABL

+ ve

Cytogenetics

t(9;22)(q34;q 11.2)

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Hyper-CVAD

Dasatinib 100mg

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BM D21- Complete Remission

BM 3M- complete molecular remission.

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allo-HCT from an HLA identical sibling,

etoposide and total body irradiation preparative regimen

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After the transplant patient continue

Dasatinib 100mg daily for 100 days

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Dasatinib 50mg daily

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Dasatinib 20mg daily

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  • He remain in remission for more than 7 years while continuing maintenance low dose Dasatinib

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Case2:younger patients without allo-HCT

  • A 23-year-old male patient presented with RTI

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Hb

8.8 gm/dl

WBC

0.2×10^9/L

PLATLET

54×10^9/L

BM

B-ALL

immunophenotyping

CD19, CD10,CD33, CD34,CD22,CD79a,TDT,HLA-DR

Cytogenetics

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t(9;22)(q34;q 11.2)

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RT –PCR for BCR/ABL

+ ve

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Started hyper- CVAD plus Dasatinib

Achieved CR after one cycle of therapy & CMR after completed 7 cycles of therapy

Maintainance therapy: Dasatinib 100mg daily plus monthly steroid and vincristine.

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After 2 yrs – Rt sided pleural effussion,which responded to Steroid and reduction of dose to 50mg daily

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Patient remained in CR for 11 years

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CASE4: use of newer TKI

  • A 67-year-old man presented with fatigue,fevers and sinus congestion.

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Hb

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WBC

Pancytopenia

PLATLET

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BM

47% blast

immunophenotyping

CD34,CD10,TDT,CD19,CD38,CD22,CD52,HLA-DR

Cytogenetics

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RT –PCR for BCR/ABL

+ve

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Hyper –CVAD with ponatinib 45mg daily

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Achieve morphological CR as well as CMR after 1cycle of therapy.

Ponatinib 45 mg continued with further cycle of the regimen.

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Dose of ponatinib was reduced to 15 mg daily due to ponatinib related cardiovasculer risk.

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He continued to remain in CMR and remained adherent to ponatinib 15 daily for 3 years.

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Then he developed chest pain

Coronary angiogram revealed multivassel coronary artery disease requiring percutaneous balloon dilatation and stent placement.

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Ponatinib discontinued and he was initiated on maintenance imatinib 400mg daily continued to date while remains in CMR.

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CASE 5: relapsed disease

  • A 43-year-old man presented with fatigue

Hb

7.9g/dl

WBC

52.2× 10^9/l, 79% blast

PLATLET

43×10^9/l

BM

B- ALL,82% blast

BCR-ABL 1

+ve

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He was treated with hyper- CVAD plus dasatinib and achieved CR after 1 cycle of therapy.

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allo-HCT was not possible, patient declined a haplo- identical transplant.

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He continued to receive 7 consolidation cycles of chemotherapy with continuous dasatinib 70 mg daily without major complications.

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Received maintenance therapy with monthly vincristine and prednisolone while continuing dasastinib at 100mg daily.

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He completed 1 year of maintenance followed by dasatinib monotherapy at 100 mg daily till 5 years

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Moleculer relapse

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A BM examination showed frank morphological relapse with 68% blast.

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Then he received salvage therapy with combination of bosutinib plus inotuzumab and achieved complete remission

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But the therapy was discontinued because of suspected veno-occlusive disease of the liver.

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He was then initiated on the combination of blinatumomab and ponatinib ,and after one cycle of therapy achieved a second CMR.

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NCCN guideline

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