Prognostic Factors in Childhood ALL

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Release 22.0, Sept. 2008

The Medical Algorithms Project

Chapter :

ch28. Oncology: Hematologic

Section :

Acute Lymphoblastic Leukemia (ALL)

Prognostic Factors in Childhood ALL

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Overview :

Identification of significant risk factors in a patient helps in selecting the optimum treatment protocol for that patient, permitting a more or less aggressive approach as needed.

Parameters:

(1) age

(2) initial white blood cell count

(3) sex

(4) race

(5) cytogenetics

(6) immunophenotype

(7) FAB morphology

(8) organomegaly

(9) mediastinal mass

(10) lymphadenopathy

(11) hemoglobin

(12) LDL

(13) platelet count

(14) serum immunoglobulins

(15) rapidity of leukemic cytoreduction on induction therapy

(16) response to initial course of induction chemotherapy

Parameter	Finding	Prognosis
age	< 12 months	very poor
	12-23 months	poor (?)
	2 - 10 years	good
	> 10 years	poor
initial white blood cell count	> 200,000 per µL	very poor
	> 50,000 per µL	poor
	< 10,000	good
sex	females	good
	males	poor
race	Blacks	poor
cytogenetics	hyperdiploidy (> 50 chromosomes)	good
	hypoploidy	poor
	t (8;14)	very poor (induction failure and early relapse)
	t (9;22) (Philadelphia chromosome)	very poor (induction failure and early relapse)
	t (4;11)	poor (induction failure and early relapse)
	dicentric translocation involving short arms of 9 and 12	good
	t (1;19) and pre-B immunophenotype (not early pre-B)	poor
	MLL gene rearrangement in infants	very poor
immunophenotype	early pre-B cell (no cytoplasmic immunoglobulin)	good
	pre-B cell (cytoplasmic immunoglobulin)	poor
	mature B cell	very poor
	T cell	poor
	myeloid markers present	poor
FAB morphology	L3	poor
	L2	poor
	L1	good
mediastinal mass	present	poor
organomegaly	hepatomegaly	poor
	splenomegaly	poor
lymphadenopathy	present	poor
hemoglobin level
LDH
platelet count
serum immunoglobulins	low IgM	poor
	low IgG and/or IgA	poor
rapidity of leukemic cytoreduction on induction therapy	residual leukemia on day 14 of induction therapy	poor
response to initial course of induction chemotherapy	failure to achieve complete remission	poor

where:

• The relationship between initial WBC count and prognosis is linear and continuous, with the prognosis inversely related to the count.

• The worse prognosis in males is related to testicular relapse and the higher rate of T cell ALL.

• The worse prognosis in Blacks is associated with an increased frequency of very high initial white blood cell counts, mediastinal mass, and L2 morphology.

• Mediastinal mass, hepatomegaly, splenomegaly and lymphadenopathy reflect high initial tumor burden and correlation with the initial WBC count.

• > 1,000 blasts per µL one week after preliminary treatment with glucocorticoids and intrathecal methotrexate is a poor prognostic finding (Arico et al)

References:

Arico M, Valsecchi MG, et al. Outcome of treatment in children with Philadelphia chromosome-positive Acute Lymphoblastic Leukemia. N Engl J Med. 2000; 342: 998-1006.

Berg S, Poplack DG. Chapter 68: Clinical manifestations of acute lymphocytic leukemia in children. pages 1067-1075 (Table 68-5, page 1072). IN: Hoffman R, Benz EJ Jr, et al (editors). Hematology, Basic Princples and Practice, Second Edition. Churchill Livingstone. 1995.

Crist W, Pullen J, et al. Acute lymphoid leukemia in adolescents: Clinical and biologic features predict a poor prognosis - A pediatric oncology group study. J Clin Oncology. 1988; 6: 34-43.

Hammond D, Sather H, et al. Analysis of prognostic factors in acute lymphoblastic leukemia. Medical Pediatric Oncology. 1986; 14: 124-134.

Hann IM, Jones PHM, et al. Low IgG or IgA: A further indicator of poor prognosis in childhood acute lymphoblastic leukaemia. Br J Cancer. 1980; 41: 317-319.

Kalwinsky DK, Rivera G, et al. Variation by race in presenting clinical and biologic features of childhood acute lymphoblastic leukaemia: Implications for treatment outcome. Leuk Research. 1985; 9: 817-823.

Khalifa AS, Take H, et al. Immunoglobulins in acute leukemia in children. J Pediatrics. 1974; 85: 788-791.

Leikin S, Miller D, et al. Immunologic evaluation in the prognosis of acute lymphoblastic leukemia. A report from Childrens Cancer Study Group. Blood. 1981; 58: 501-508.

Miller DR. Editor's column: Prognostic factors in childhood leukemia. J Pediatrics. 1975; 87: 672-676.

Pui C-h. Childhood Leukemias. N Engl J Med. 1995; 332: 1618-1630. 1995.

Sather HN. Statistical evaluation of prognostic factors in ALL and treatment results. Medical Pediatric Oncology. 1986; 14: 158-165.

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