Patient Encounter Part 1

RH is a 7-year-old girl who presents to her pediatrician with a 1-week history of runny nose and fever. Her mom has noted a lot of bruising on her lower extremities. Physical examination reveals splenomegaly, multiple petechiae, and pallor. A CBC reveals a normochromic, normocytic anemia with a hemoglobin of 6 g/dL (60 g/L, 3.7 mmol/ L; normal 11.7-15.7 g/dL, 117-157 g/L, 7.3-9.7 mmol/L), hematocrit of 18% (0.18; normal 35-47%, or 0.35-0.47), and WBC of 2.6 x 103/mm3 (2.6 x 109/L). The differential on the WBC reveals 75% (0.75) lymphocytes (normal 20-40%, or 0.2-0.4), 20% (0.2) neutrophils (normal 55-62%, or 0.55-0.62), and 5% (0.05) lymphoblasts (normal 0%). Based on this information, a bone marrow aspirate and biopsy are performed, which reveal 85% (0.85) lymphoblasts and a DNA index of 1.17. A lumbar puncture is also performed, which shows no evidence of leukemia.

What information is suggestive of acute lymphocytic leukemia?

What are the prognostic factors for RH?

What is the goal of induction therapy?

Prognostic Factors in ALL

In both children and adults with ALL, clinical trials have identified several risk factors that correlate with outcome (Table 95-6). Prognostic features include age, WBC, cytogenetic abnormalities, ploidy (DNA content), leukemic cell immunophenotype,

and degree of initial response to therapy (minimal residual disease, MRD). When these factors are combined, they predict groups of patients with varying degrees of risk for treatment failure.

In adults, there is a steady decline in the rate of complete remission (CR) following initial induction therapy with increasing age. When results are corrected for differences in immunophenotype, ALL cells from adults are more resistant to the multiple antileukemic agents than are cells from children in the first decade of life.8 While induction treatment produces 95% CR in children, it declines to no more than 60% in patients older than 60 years of age. This is due in part to decreased tolerance of assertive induction/consolidation regimens in older patients. Other potentially import ant factors relate to a higher incidence of poor prognostic factors such as the presence of Philadelphia chromosome (Ph+) or t(9;22), in older populations.5 BCR-ABL fusions (Ph+) are strongly associated with chemoresistant leukemia in all age groups but are much more prevalent in adults with ALL than in children (30% versus less than 5%).U

Table 95-6 Prognostic Factors in ALL

Risk for Leukemic Relapse

Factor

Low

High

Morphology

L1

L2r L3

Immunologic

Early pre-B cell

Null celLTcell,

phenotype

pre-B cell, B cell

WBC at diagnosis

Less than 10 x 103/

Greater than SO x 10V

mmJ (10 x 107U

mm1 (50 x 1071)

Platelets

Greater than

Less than 30 xlOV

100 x lOVrnrn3

mm1 (30 x 1071)

(100 x 107LJ

Patient aye

3-7 years

Less than 1 year or

greater than i0 years

Cytogenetics

Normal karyotype

t{9;22fcT(4;ll); -7; fS

Myeloid markers

Absent

Present

CN5 leukemia

Absent

Present

Node/liver/spleen

Absent

Massive

enlargemem

Mediastinal mass

Absent

Present

Time to remission

Less than 4 weeks

Greater than 4 weeks

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