Risk-Adjusted Combination Chemotherapy in Treating Young Patients With Acute Lymphoblastic Leukemia

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor stem cell transplant may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving combination chemotherapy before the transplant helps stop the growth of cancer cells and stop the patient's immune system from rejecting the donor's stem cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is studying different risk-adjusted combination chemotherapy regimens in treating young patients with acute lymphoblastic leukemia.

Sex

All

Maximum age

18 Years

DISEASE CHARACTERISTICS:

* Cytologically proven acute lymphoblastic leukemia (ALL)
* No relapse of a previously unrecognized ALL
* Patients must meet one of the following risk criteria:

  * Standard-risk (SR) group meeting all of the following criteria:

    * Blasts \< 1,000/μL in peripheral blood (PB) on day 8
    * Aged 1 to \< 6 years
    * Initial WBC \< 20,000/μL
    * M1 (5%) or M2 (≥ 5% to \< 25%) blasts in bone marrow on day 15
    * M1 marrow on day 33
  * Intermediate-risk (IR) group meeting all of the following criteria:

    * Aged \< 1 or ≥ 6 years and/or WBC ≥ 20,000/μL
    * Blasts \< 1,000/μL in PB on day 8
    * M1 or M2 marrow on day 15
    * M3 (≥ 25%) marrow on day 15 OR meets SR criteria but M3 marrow on day 15 and M1 marrow on day 33
  * High-risk (HR) group meeting ≥ 1 of the following criteria:

    * Meets IR criteria and M3 marrow on day 15 (not SR and M3 on day 15)
    * Blasts ≥ 1,000/μL in PB on day 8
    * M2 or M3 marrow on day 33
    * Translocation t(9;22) \[BCR/ABL+\] (Philadelphia chromosome-positive) or t(4;11) \[MLL/AF4+\]
* No secondary ALL

PATIENT CHARACTERISTICS:

* No Down syndrome
* No other major disease that prohibits study treatment (e.g., severe congenital heart disease)
* Not requiring significant therapy modification owing to study therapy-associated complications
* No complications due to other interventions
* No one with missing data that are needed for the differential diagnosis, or for selection of the proper therapy arm

PRIOR CONCURRENT THERAPY:

* No steroids or cytostatic drugs within four weeks prior to start of study therapy

• DERIVEDZuna J, Moericke A, Arens M, Koehler R, Panzer-Grumayer R, Bartram CR, Fischer S, Fronkova E, Zaliova M, Schrauder A, Stanulla M, Zimmermann M, Trka J, Stary J, Attarbaschi A, Mann G, Schrappe M, Cario G. Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia. Br J Haematol. 2016 Jun;173(5):742-8. doi: 10.1111/bjh.13989. Epub 2016 Feb 23. PMID 26913693
• DERIVEDStary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, Gonzalez A, Izraeli S, Janic D, Jazbec J, Konja J, Kaiserova E, Kowalczyk J, Kovacs G, Li CK, Magyarosy E, Popa A, Stark B, Jabali Y, Trka J, Hrusak O, Riehm H, Masera G, Schrappe M. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014 Jan 20;32(3):174-84. doi: 10.1200/JCO.2013.48.6522. Epub 2013 Dec 16. PMID 24344215