Adolescence has been claimed since the seventies to be associated to a a bad prognosis in childhood ALL. Out of 4658 patients with ALL, 258 adolescents (15–20 year old)(5.5%) were treated in the successive FRALLE 83, FRALLE 87–89, FRALLE 92 (pilot phase), FRALLE 93 and FRALLE 2000 protocols. The main characteristics were: a sex ratio of 1.8 (M/F), a B-lineage in 71% of the cases vs T lineage in 29%, and a median WBC of 12 G/L (9–1000). Translocation and fusion transcripts were searched for in 120 evaluable BCP-ALL: t(9;22)/BCR-ABL, 8 pts (6%); t(1;19)/E2A-PBX1, 12 pts (10%); t(4;11)/MLL-AF4, 4 pts (3%). Out of 75 evaluable pts t(12;21)/TEL-AML1 was found in only 4 pts (3%). 242 out of 258 adolescents were in CR at the end of induction therapy(EOI)(94%) without any significant difference according to the era. Nevertheless a major difference in the 3y and 5y EFS was found:

Number of ptsCR at EOI (%)3y EFS (%)5y EFS (%)10y EFS (%)
*: p=.04; **: p=.04 
Eighties (F83, F87–89) 100 93 42 +/− 5 35 +/− 5 35 +/− 5 
Nineties (F92, F93) 84 93 71 +/−5* 67 +/− 5** 67 +/− 5 
2000– (F2000) 74 96 86 +/−5* 86 +/− 10** NYA 
Number of ptsCR at EOI (%)3y EFS (%)5y EFS (%)10y EFS (%)
*: p=.04; **: p=.04 
Eighties (F83, F87–89) 100 93 42 +/− 5 35 +/− 5 35 +/− 5 
Nineties (F92, F93) 84 93 71 +/−5* 67 +/− 5** 67 +/− 5 
2000– (F2000) 74 96 86 +/−5* 86 +/− 10** NYA 
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The main modification introduced in the nineties was the adoption of a double delayed intensification for the good early responders. Autologous BMT or allogenic BMT were indicated in bad early responders (D8 poor prednisone response, D21 marrow M3 response) and/or unfavourable cytogenetics. The better results of the 2000 protocol can mainly be explained by the further intensification of chemotherapy between induction and delayed Intensification 1 and before delayed Intensification 2. These better results were obtained despite decreasing the indications of BMT (6 performed vs 20 in the nineties) and of CNS irradiation (100% in the nineties vs 35% in the current era, including the TBI for BMTs).

Conclusions:

  1. excellent results can now be achieved in adolescents with ALL

  2. this study emphasizes again the need to treat adolescents with ALL according to pediatric intensive protocols and not “adult-type” protocols, as we recently suggested (Boissel et al, J Clin Oncol 2003).

  3. Whether this could also be applied to young adults remains to be demonstrated but seems appealing.

Topics:
acute lymphocytic leukemia, adolescent, chemotherapy regimen, brachial plexus neuritis, bcr-abl tyrosine kinase, leukemia, lymphocytic, acute, childhood, neoadjuvant therapy, prednisone, translocation (genetics), young adult

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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