CD19-CAR Immunotherapy for Childhood Acute Lymphoblastic Leukemia (ALL)

Inclusion Criteria Pre-emptive arm Children (18 years or younger) with CD19+ precursor B cell ALL fulfilling one of the following criteria who are undergoing an allogeneic stem cell transplant from an EBV-seropositive donor: In first remission, if at least one of the following criteria are met: * t(9;22) and MRD positive (BCR-ABL/ABL ratio \> 0.01%) after HR3 block of EsPhALL or pre-HSCT or * Infant ALL age \< 6 months at diagnosis with MLL gene rearrangement and either presenting wcc \>300 x 10\^9/L or poor steroid early response (i.e circulating blast count \>1x10\^9/L following 7 day steroid pre-phase of Interfant 06) or * Resistant disease (\> 30% blasts at end of induction treatment day 28-33) in subsequent morphological CR or * High level bone marrow MRD (\> 1 in 1000) at week 12 ALL-BFM 2000/AIEOP BFM ALL 2009/EORTC 58951 protocols, week 12-15 of FRALLE A or at week 14 of UKALL2011 Relapsed patients if at least one of the following criteria are met: * Very early (\< 18 months from diagnosis) bone marrow or extramedullary relapse in second CR or * Early (within 6 months of finishing therapy) isolated bone marrow relapse with bone marrow MRD \> 1 in 100 at day 35 of reinduction in second CR or * Early (within 6 months of finishing therapy) bone marrow or combined relapse with high level bone marrow MRD (\> 1 in 1000) at the end of consolidation therapy (week 12-13 UKALL R3/INTREALL and COOPRALL protocols, prior to protocol M in BFM relapse protocol (ALL-REZ BFM 2002) and after Protocol II-IDA in AIEOP LLA Rec 2003)or * Any relapse of infant or Philadelphia-positive ALL in morphological complete remission * Any patient being transplanted in 3rd or greater CR These patients have a high (\> 50%) risk of relapse and will be monitored for evidence of MRD in bone marrow aspirates (monthly for months 1-6, 6 weekly months 7.5-12 post HSCT) for the first year post-transplant. Patients who become MRD +ve in the marrow at a level minimum 5 x 10-4 (or BCR-ABL/ABL ratio 0.05% in Ph+ve ALL patients with no IgH MRD marker) but are in morphological remission (\<5% blasts in BM) will be eligible to be treated pre-emptively with CD19ζ transduced CTL Prophylaxis arm Additionally, any patient (≤ 18 years) with ALL relapsing in the bone marrow (isolated or combined) after myeloablative allogeneic HSCT who achieves morphological remission after re-induction and who is a candidate for second HSCT at one of the participating centres is eligible to receive CD19ζ transduced CTL prophylactically * Stem cell donors must be EBV sero-positive and HLA-matched (8/8 HLA A,B,C and DR at medium resolution typing) or a single antigenic/allelic (7/8) mismatch with the recipient * A life expectancy of at least 12 weeks * Karnofsky score of \>60% if \>10 years old or Lansky performance score of \>60 if ≤ 10 years old * Patients must have transduced donor-derived EBV-specific CTLs with 15% or higher expression of CD19ζ determined by flow-cytometry which meet the specified release criteria * Informed written consent indicating that patients are aware this is a research study and have been told of its possible benefits and toxic side effects Exclusion Criteria * Patients with CD19 negative precursor B cell ALL * EBV seronegative or \> single antigenic/allelic HLA-mismatched donor * Active acute GVHD overall Grade 2 or higher or significant chronic GVHD requiring systemic steroids at the time of scheduled infusion of transduced CTL will be excluded until the patient is GVHD-free and off steroids * Pre-existing severe lung disease (FEV1 or FVC \< 50% predicted) pre-HSCT or an oxygen requirement of \>28% O2 supplementation or active pulmonary infiltrates on chest X-ray at the time scheduled for transduced CTL infusion * Serum bilirubin \>3 times the upper limit of normal or an AST or ALT \> 5 times the upper limit of normal * Serum creatinine \>3 times upper limit of normal * Active severe intercurrent infection at the time of transduced CTL infusion (if present consult with Chief investigator). * Patients in whom transduced donor-derived EBV-specific CTLs don't meet release criteria * Serologically positive for Hepatitis B, C or HIV pre-HSCT * Females of childbearing age with a positive pregnancy test * Known allergy to DMSO