The immunophenotype in infant acute lymphoblastic leukaemia: correlation with clinical outcome. An Italian multicentre study (AIEOP)

Abstract

A detailed analysis of immunophenotype of 112 infants aged less than 18 months with acute lymphoblastic leukaemia (ALL) was performed. Patients were divided into three groups on the basis of age at presentation (under 6 months: group 1: 6-12 months: group 2; 13-18 months: group 3). There were three cases of T-ALL (2.6%). The proportion of other subtypes was: common ALL in 59 patients (52.68%), pre-B ALL in 15 patients (13.3%), pre-pre-B ALL in 27 (24.1%) and acute undifferentiated leukaemia (AUL) in eight patients (7.14%). In non-T ALL, positivity to CD10 (corresponding to C-ALL and pre-B ALL) was distributed in the three age groups as follows: 38.88% (group I) 65.38% (group II) and 86.36% (group III). Conversely, immature phenotypes (pre-pre-B and AUL) were found more often in the younger patients of groups I and II, as well as anomalous phenotypes, such as the presence of myeloid antigens (MyAg) and of CD7. Prognostic significance was evaluated as event-free survival (EFS) by statistical analysis. A better outcome in CD10-positive ALL than in CD10-negative ones (48% v. 25% of long-term survivors) was demonstrated in all infants. Similarly, EFS was significantly better in MyAg-negative than in MyAg-positive cases. These results were confirmed also when adjusting for white blood cell count. This allowed the identification of CD10-negative, MyAg-positive ALL, which were relatively more frequent in infants and had a poorer clinical outcome with the current therapies. This study stresses the prognostic relevance of the immunological study in infant leukaemias and its utility in choosing different therapeutic modalities for poor risk phenotypes.

Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group

“…In 12 cases, testing did not include the entire triad of cytogenetics, Southern blot, and RT-PCR. In these 12, the sample was inadequate for Southern blot testing, and cytogenetics were either inadequate (2) or normal (10). In 10 of these 12 cases, RT-PCR was completed and was negative for the 3 11q23 translocations for which testing was done.…”

“…Infants without CD10 expression have a reported EFS of 21% to 40% at 4 to 6 years, with an EFS of 45% to 73% at 4 to 6 years in infants with CD10 ϩ blasts. [1][2][3]5,6,10 CD10 positivity is therefore correlated with better outcome.…”

“…7,8 The blast cells most commonly lack CD10 expression 9 and frequently coexpress lymphoid and myeloid antigens. 10,11 Cytogenetic 11q23 abnormalities, most commonly t(4;11)(q21;q23), and molecular genetic rearrangement of the MLL gene at chromosome band 11q23 have been associated with infant ALL. 8,12 Correlation between various clinical and laboratory characteristics and outcomes has been studied in the context of a number of clinical trials.…”

Analysis of Infectious Complications in Infants With Acute Lymphoblastic Leukemia Treated on the Children's Cancer Group Protocol 1953

“…[3][4][5][6][7][8][9][10] When compared with children >1 year of age, infants present with a significantly increased incidence of unfavorable features such as high white blood cell count, hepatomegaly, splenomegaly, and central nervous system (CNS) disease. 8 Additionally, 48% to 65% of cases lack CD10 expression, 3,5,7,9,11 and 67% to 81% contain MLL gene rearrangements. 10,[12][13][14][15] Failure in this group of patients has historically been related to early relapse.…”

Bone Marrow

“…Loss or weak expression of CD45 is associated with an improved prognosis. 181,182 Loss of CD10 is generally a poor prognostic indicator in precursor B-cell ALL, 183,184 and loss of CD10 with aberrant CD15 expression is seen commonly in ALL of infants and therapy-related ALL of adults and is usually associated with 11q23 abnor- malities in both patient groups. Rare cases of precursor Bcell ALL express both TdT and surface immunoglobulin light chains.…”