Inzidenz, klinische Merkmale und prognostische Bedeutung immunologischer Subtypen der akuten lymphoblastischen Leukämie (ALL) im Kindesalter: Erfahrungen der Therapiestudien ALL-BFM 83 und 86

Abstract

In the therapy studies ALL-BFM 83 and 86, immunophenotyping of ALL by monoclonal antibodies was performed in a total of 1162 protocol patients (ALL-BFM 83 n = 578; ALL-BFM 86 n = 584). Both studies yielded similar results with respect to the incidence of immunological subtypes: CD10-negative pre-pre-B ALL (ALL-BFM 83: 3.6%; ALL-BFM 86: 5.3%), common ALL (80.1%; 77.9%), B-ALL (1.9%; 2.8%), pre-T/T-ALL (13.9%; 13.5%). Leukemic cells of 3 patients in the ALL-BFM 83 study lacked lymphoid and myeloid antigens (acute unclassifiable leukemia, 0.5%), and 3 patients in the ALL-BFM 86 study exhibited different blast populations with expression of either myeloid or lymphoid features (acute mixed-lineage leukemia, 0.5%). Coexpression of myeloid antigens (CD13 and/or CD33 and/or CDw65) on lymphoblasts (My-positive ALL) was identified in 35 of the 570 (6.1%) protocol patients prospectively analyzed in the ALL-BFM 86 study. The following associations were observed between the immunological subtype and the clinical risk factors: median age (years)-pre-pre-B 3.0, common 4.3, B- 7.9, pre-T/T-ALL 8.5 (pre-pre-B, common vs. pre-T/T-ALL p = 0.05); median leukocyte counts (x 10(9)/l)-pre-pre-B 80, common 9.1, B- 12.3, pre-T/T-ALL 68.1 (common, B- vs. pre-pre-B, pre-T/T-ALL p less than 0.05). The prognostic relevance of the immunophenotype was evaluated on the basis of the therapeutic results obtained in the ALL-BFM 83 study. A significant difference in the remission rate was only recognizable between patients with common ALL (99.1%) and those with pre-T/T-ALL (93.7%, p less than 0.001). After a median follow-up of 54 months, the probability of event-free survival is 71% for pre-pre-B ALL, 67% for common ALL, 56% for pre-T/T-ALL and 27% for B-ALL (common vs. B-, pre-T/T-ALL p less than 0.001), the prognosis in patients with pre-pre-B and common ALL being markedly influenced by the initial leukocyte counts and the age.

Durchflußzytometrische Charakterisierung von Reifungsvorgängen und stammzellnahen Zellpopulationen bei der B-Vorläuferzell-ALL im Kindesalter

“…This suggests that the CD34 +CD19 1o cells were part of the leukemic clone and~hat the CD34+CD38-CD19-cells may represent.resldual normal primitive hematopoietic cells. In c~n.c1uslOn, f10w cytometry allowed identification of pri-mitIve CD34 + cell populations in children with ALL which~an now .be functionally characterized by transp Einleitung Die Charakterisierung von Oberflächenantigenen auf leukämischen Blasten mit Hilfe der Durchflußzytometrie besitzt in der Diagnostik der akuten lymphatischen Leukämien (ALL) einen zentralen Stellenwert, da sie es in den meisten Fällen ermöglicht, die leukämischen Blasten einer Zellreihe zuzuordnen und damit eine eindeutige Diagnose zu stellen (17,21). Darüberhinaus konnten in den letzten Jahren deutliche Fortschritte in der Charakterisierung der Oberflächenantigene von normalen stammzellnahen hämatopoetischen Zellpopulationen erzielt werden (1,7,8,18,20,25,28).…”

Paediatric oncology in developing countries

“…T-ALL appears to be particularly frequent in children of low socio-economic groups [68,85]. The rarity of common-ALL, which in the West accounts for 80% of all ALL [51] explains the absence of the early age peak in developing countries [3,24,52]. Different centres report ag many as 20%-30% of their patients with lymphomas/leukaemias as unclassified.…”

“…Primary gastrointestinal involvement is rare, with the B-cell type predominating [51]. In developing countries, lymphomas are mostly of the Burkitt and non-Burkitt types and are predominantly located in the abdomen; they are of Bcell lineage.…”

“…In the West, T-cell ALL in children accounts for about 14% of all ALL [51]. In many developing countries such as sub-Saharan Africa [24,85] there is a relative predominance of T-ALL.…”

Transplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission: A Report from the Center for International Blood and Marrow Transplant Research

“…2–4 Historically, T-ALL portended a worse prognosis compared to B-ALL (75.2% versus 83.7% 5-year event-free survival (EFS)), 5, 6 but treatment with intensive, high-dose, multi-agent chemotherapy resulted in significantly improved outcomes (5-year EFS ~80%). 7 Recent pediatric ALL trials using a Berlin-Frankfurt-Munster (BFM) based backbone and/or intensified therapy with high-dose methotrexate have further improved outcomes for children with T-ALL, but have plateaued around 85% EFS.…”