treatment of adult all with an mrd-directed programme.

Conditions: Acute Lymphoblastic Leukemia

Summary: the study aims to optimize the concept of risk-oriented postremission consolidation therapy, by offering (i) standard consolidation-maintenance to patients at lowest risk of relapse as defined by mrd(minimal residual disease) negative status, and (ii) allogeneic stem cell transplantation (related/unrelated donor available) or multicycle high-dose therapy with autologous blood stem cell transplant (no donor) to patients at highest risk of relapse as defined by mrd+ status. the prognostic role of mrd evaluation in unselected patients will be evaluated.

improved outcome of adult all through the application of: * risk-adapted induction (cycle no. 1: ivap i.e idarubicin-vincristine-asparaginase-prednisone, plus fractionated cyclophosphamide in t-all,and imatinib in ph/bcr-abl+ all) * risk stratification (clinical) according to morphology, immunophenotype, cytogentics and molecular biology results. standard risk (sr) is defined by pre-b cd10+ phenotype, ph/bcr-abl- status, and a blast count \<10x10e9/l. all other subgroups are hr (high-risk) except for ph/bcr-abl+ and t(4;11)+ all (vhr, very high-risk) * homogeneous early consolidation programme including both conventional therapy with idarubicin-vincristine-cyclophosphamide-dexamethasone/prednisone(cycles no. 2,3,5,6,8) and high-dose treatemt with mtx/ara-c (cycles no. 4,7) and meningeal prophylaxis (triple intrathecal therapy x8-12, skull irradiation), plus imatinib in ph+ all (phase a). autologous bllo stem cells are mobilized and cryopreserved after cycle no. 4. * serial evaluation of minimal residual disease (mrd) with rq-pct technology, aiming to define in individual patients the rate of reduction during early consolidation. the molecular study was centralized and aimed at obtaining one or more patient-specific probe(s)with a sensitivity of at least 10e-3. patient bone marrow was sampled for mrd analysis at timepoints 13 i.e. after cycles no.3,5, and 7. only patients with a negative result at timepoint 3 and a negative/low positive (\<10e-4) result at timepoint 3 are considered mrd-, all other combinations being regarded mrd+. * phase b therapy according to mrd results and all subset: * mrd- nonph/t(4;11): standard maintenance * mrd+ nonph/t(4;11): allogeneic stem cell transplantation (from sibling/mud) or, alternatively, intensified high-dose therapy (2-4 "hypercycles")with autologous stem cell support and anti cd20 moab (if cd20+), followed by maintenance. each "hypercycle" consists of high-dose mercaptopurine-etoposide-melphalan (cycles no. 1,3) or methotrexate-cytarabine (cycles no. 2,4) * mrd unknown nonph/t(4;11): treatment by clinical risk (sr: maintenance; hr, as per mrd+) * ph/t(4;11)+: allogeneic stem cell transplantation as soon as possible into complete remission; if a transplant is not possible, consolidation is as for hr patients. each cycle is supplemented by imatinib in ph+ all the illustrated strategy aims to optimize postremission consolidation therapy by offering standard treatment "only" to patients at lowest risk of relapse (mrd-), thereby reducing the risks of high dose treatments (expected trm from allogeneic sct 20-30%), while maintaining the latter approach in mrd+ cases and very hr subsets. the prognostic role of mrd evaluation in unselected patients will be evaluated.

Eligibility criteria:
inclusion criteria: * untreated acute lymphoblastic leukemia or lymphoblastic lymphoma (t-cell, precursor b-cell) * age 15-65 years (older patients if biologically fit according to responsible physician) * written informed consent exclusion criteria: * any co-morbidity precluding the administration of intensive chemotherapy for adult all

Keywords: acute lymphoblastic leukemia adult patients minimal residual disease risk-oriented therapy