Acute Lymphoblastic Leukaemia Committee (ALL)

Committee Chairman:

Ajay Vora

Committee Members:

A.Baruchel, Y.Benoit, Y.Bertrand, A.Biondi, M.Campbell, A.Colombini, V.Conter, L.Dalla Pozza, S. Elitzur, Mats Heyman, M. Kato, C.Kiss, G.Kovacs, F.Locatelli, G.Mann, A.Moericke, F.Niggli, R.Pieters, C.Rizzari, M.Schrappe, J. Moppett, S. Rives, S. Samarasinghe, Kjeld Schmiegelow, B.Stark, J.Stary, R.Sutton, T. Trahair, M.Taskinen, , M.G.Valsecchi, A.Vora, M.Zimmermann

Clinical Trials:

Open:

INTERFANT-06: Randomized clinical trial for ALL under 1y*
ALLIC-BFM 2002 (2002-2009 ): Randomized clinical protocol for ALL in countries with limited resources
ALL-SCT BFM 2003: HSCT* in VHR ALL
AIEOP-BFM ALL 2009: Randomized clinical trial for ALL (age 1-18y) Germany
ALL IC-BFM 2009
*web-based trials

Completed:

IDH (1991-1995): SR ALL
Pulses (1995-2000): MR ALL
HSCT in VHR ALL (1995-2000)
AIEOP-BFM ALL (2000-2006): ALL
Interfant-99 (1999-2006): ALL below the age of one year (ALL<1y)
EsPhALL* (2004-2009): ALL positive for the t(9;22) translocation

Activities/Projects:

  1. The Committee continues to focus on recent findings from ongoing studies and collaboration with other I-BFM-SG Committees.
  1. The interim meeting was held in Milan on January 25, 2016 and was combined with the B&D committee meeting. Peter Hoogerbrugge attended on behalf of the Resistant Disease committee. Topics discussed were T-cell ALL biology (joint with B&D), asparaginase TDM and toxicity and indications for immunotherapy/SCT. Except UK, all groups are adjusting asparaginase doses based on therapeutic drug monitoring but whether this will translate into an EFS benefit remains to be seen. There was discussion about the benefit of asparaginase intensification and it was agreed that this is likely to vary by treatment backbone. Most groups are planning to test the benefit of immunotherapy for refractory patients with some prioritising Blinatumomab (AIEOP-BFM) and others CART cells (ALLtogether group). Although recent studies have provided much new information on T-cell biology, this has yet to find a clinical application.
  1. The Down syndrome ALL collaborative has agreed a registry proposal which will start to collect data this year.
  1. The amended EsPhALL Imatinib study and the Dasatinib BMS study CA 180372 have closed. Discussions are continuing on an intercontinental study to replace both these trials which will test de-escalation of chemotherapy for MRD good responders.
  1. The INTERFANT-06 study continues to recruit. An outline international protocol has been agreed between Japanese, European and US groups to replace Interfant 06 in 2016. It will incorporate epigenetic modifiers and blinotumumab randomisations for high and medium risk groups.

Recent Publications:

  1. Alexander S, Pole JD, Gibson P et al. Classification of treatment-related mortality in children with cancer: a systematic assessment. Lancet Oncol 2015;16(16):e604-e610.
  2. Boer JM, van d, V, Rizopoulos D et al. Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: an international collaborative study. Leukemia 2015.
  3. Conter V, Valsecchi MG, Buldini B et al. Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis. Lancet Haematol 2016;3(2):e80-e86.
  4. Driessen EM, De LP, Campbell M et al. Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant-99 protocol. Leukemia 2015.
  5. Fischer U, Forster M, Rinaldi A et al. Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. Nat Genet 2015;47(9):1020-1029.
  6. Henriksen LT, Harila-Saari A, Ruud E et al. PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol. Pediatr Blood Cancer 2015;62(3):427-433.
  7. Hough R, Rowntree C, Goulden N et al. Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003. Br J Haematol 2015.
  8. Jenkinson S, Kirkwood AA, Goulden N, Vora A, Linch DC, Gale RE. Impact of PTEN abnormalities on outcome in pediatric patients with T-cell acute lymphoblastic leukemia treated on the MRC UKALL2003 trial. Leukemia 2015.
  9. Lennard L, Cartwright CS, Wade R, Vora A. Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics. Br J Haematol 2015;169(2):228-240.
  10. Lennard L, Cartwright CS, Wade R, Vora A. Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003. Br J Haematol 2015;170(4):550-558.
  11. Moricke A, Zimmermann M, Valsecchi MG et al. Dexamethasone vs. prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood 2016.
  12. Moriyama T, Nishii R, Perez-Andreu V et al. NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat Genet 2016.
  13. Pui CH, Yang JJ, Hunger SP et al. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol 2015;33(27):2938-2948.
  14. Tiphaine AB, Hjalgrim LL, Nersting J et al. Evaluation of a pediatric liquid formulation to improve 6-mercaptopurine therapy in children. Eur J Pharm Sci 2016;83:1-7.
  15. Toft N, Birgens H, Abrahamsson J et al. Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia. Eur J Haematol 2016;96(2):160-169.
  16. van der Sluis IM, Vrooman LM, Pieters R et al. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica 2016;101(3):279-285.
  17. Vicente C, Schwab C, Broux M et al. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia. Haematologica 2015;100(10):1301-1310.
  18. Vora A, Andreano A, Pui CH et al. Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy. J Clin Oncol 2016.

Meetings:

Recent:

January 22-23, 2018, Milan, Italy

Next:

January, 2019, Milan, Italy

Contact

Ajay Vora    Ajay.Vora@gosh.nhs.uk