Prophylactic Infusion of Donor Lymphocytes in Cord Blood Transplantation

Pilot, multicentric, open-label, single-arm, phase I-II clinical trial to evaluate the safety and efficacy of a novel Umbilical Cord Blood Transplantation (UCBT) platform, that consists of a UCBT of the 80 fraction, followed by a Donor Lymphocyte Infusion (DLI) of the 20 fraction (between 60 and 90 days after transplantation).

Sex

All

Maximum age

60 Years

Inclusion Criteria:

At the time of transplantation:

* Patients under 60 years with proposal UCBT according to assistance protocol
* Diagnosis of high-risk acute leukemia with an indication of allogenic transplantation
* Frozen UCB bag split into two bags: one with the 80% of the product and another with the 20%
* Presence of at least 1.2E9 total nucleated cells and\> 1E5 CD34 / kg and\> 6E6 CD34 + in fraction 80%
* 4/6 or better compatibility taking Human Leukocyte Antigen (HLA) HLA-A, HLA-B by antigenic resolution and DRB1 by allelic resolution
* The patient (or legal representative if required) has signed the informed consent

At the time of DLI:

* Documented cord blood engraftment
* The patient has had no Graft Versus Host Disease (GVHD) during the first 60 days post-transplantation or, if present, receives less than 10 milligrams of prednisone at the time of the DLI or \<0.2 mg / kg / day of prednisone for pediatric patients (\<16 years).
* The patient has less than 200 CD4 + cells per microliter on peripheral blood at 60 days (± 7 days) post-transplantation
* The patient (or legal representative if required) has signed the informed consent

Exclusion Criteria:

At the time of transplantation:

* Simultaneous participation in another clinical trial or treatment with other research phase product within 30 days prior to inclusion in the study.
* Pregnant women or those who intend to become pregnant within 12 months after the signing of the informed consent or not taking proper contraceptive measures according to investigator criteria.
* Breastfeeding women
* Other pathologies or circumstances that may compromise the patient's participation in the study according to the criteria of the investigator.

At the time of DLI:

* Grade III-IV GVHD after allogeneic UCB
* Prednisone treatment (\> 10 mg total per day in adults or\> 0.2 mg / kg / day prednisone for pediatric patients)

• BACKGROUNDDohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30. PMID 19880497
• BACKGROUNDCornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM, van Marwijk Kooy M, Wijermans P, Schouten H, Huijgens PC, van der Lelie H, Fey M, Ferrant A, Maertens J, Gratwohl A, Lowenberg B. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007 May 1;109(9):3658-66. doi: 10.1182/blood-2006-06-025627. Epub 2007 Jan 9. PMID 17213292
• BACKGROUNDKoreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, Wadleigh M, DeAngelo DJ, Stone RM, Sakamaki H, Appelbaum FR, Dohner H, Antin JH, Soiffer RJ, Cutler C. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009 Jun 10;301(22):2349-61. doi: 10.1001/jama.2009.813. PMID 19509382
• BACKGROUNDLodewyck T, Cornelissen JJ. Allogeneic stem cell transplantation in acute myeloid leukemia: a risk-adapted approach. Blood Rev. 2008 Nov;22(6):293-302. doi: 10.1016/j.blre.2008.03.008. Epub 2008 May 1. PMID 18455284
• BACKGROUNDMessner HA. How good is allogeneic transplantation for high-risk patients with AML? Best Pract Res Clin Haematol. 2006;19(2):329-32. doi: 10.1016/j.beha.2005.11.007. PMID 16516130
• BACKGROUNDSchlenk RF, Dohner K, Mack S, Stoppel M, Kiraly F, Gotze K, Hartmann F, Horst HA, Koller E, Petzer A, Grimminger W, Kobbe G, Glasmacher A, Salwender H, Kirchen H, Haase D, Kremers S, Matzdorff A, Benner A, Dohner H. Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol. 2010 Oct 20;28(30):4642-8. doi: 10.1200/JCO.2010.28.6856. Epub 2010 Aug 30.