Per microtrasplantation

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Presentation transcript:

Per microtrasplantation HLA-PARTIALLY MATCHED CELLULAR THERAPY (STEM-CELL MICROTRANSPLANTATION) IN ACUTE MYELOID LEUKEMIA AND MYELODISPLASTIC SYNDROMES M. E Martínez-Muñoz, R. Forés, C. Regidor, J. L Bueno, Y. Gutiérrez, M. García, G. Bautista, A. de Laiglesia, C. Vilches, R. de Pablo, N. Dorado, J. García-Marco, E. Ojeda, A. Morales, G. Anze y J. R. Cabrera. Hospital Universitario Puerta de Hierro Majadahonda (Madrid) . Spain. BACKGROUND MATERIALS & METHODS DONORS No. donors * 11 Relationship Son /daughter (8) Sibling (2) Grandson (1) Gender (DR) M  M (7) M  F (1) F  M (3) HLA Haploidentical (9) Partially compatible (2) NK alloreactivity No (3) D  R (3) R  D (3) D R and R  D (2) PATIENTS Microtransplants 11 No. patients 9 Age (years) 64 – 72 Male / Female 8 / 1 Diagnosis - AML (de novo) (3) 1 - AML post-MDS (1) - AML post-ET (1) 2 - AML (2nd relapse) (1) - CMML (2) - RAEB (1) 2nd microtransplant - AML (1st relapse) 1 AML(post-ET 1st relapse) 2 Comorbidity (Sorror) 0 (3), 1 (4), 2 (0), 3 (2) Patients AML 1. AML de novo aza-IA HA  HA  1.AML de novo 1 aza-MEC  aza  aza  2. AML de novo IA HA  HA  3. AML post-MDS aza-IA  aza  aza  4. AML post-ET IA HA HA  HA  4. AML post-ET 2 deci-MEC  deci  deci  5. AML 2nd Relapse aza-MEC HA  HA  9. AML de novo aza-IA aza  aza  HA  Non-engraftment alloreactive cellular therapy has been proposed as a treatment for acute myeloid leukaemia (AML). A host-versus-tumour effect induced by graft-rejection has been suggested. OBJECTIVES MDS 6. CMML aza-MEC  aza  - 7. RAEB-1 aza-MEC  aza  8. CMML aza-MEC  - To evaluate: Feasibility and safety of the microtransplantation in AML and myelodisplastic syndrome (MDS) Response rate Infections incidence Development of acute or chronic graft-versus-host disease (GVHD) and alloreactivity . * One or two apheresis of related donor peripheral mononuclear cells were collected after G-CSF mobilization. Patients received each PM-DLI ( DLI) following a conventional chemotherapy cycle or hypomethylant agent course. (aza: Azacitidine, deci: Decitabine, IA: Idarubicin+ AraC , HA: High dose AraC, MEC: Mitoxantrone, Etoposide, AraC) INFUSIONS Microtransplants 11 Total PM-DLI ° 25 No. PM-DLI per patient 1 (1) 2 (6) 3 (4) Per course Per microtrasplantation procedure CMN (x 108/kg) 3,16 (1,37 - 5,51) 6,20 (4,52 – 10,70) CD3+ (x 108/kg) 1,15 (0,35 - 2,42) 2,73 (0,64 – 3,53) CD3-/CD56+ (x107/kg) 0,94 (0,50 - 1,55) 2,20 (1,30 – 3,10) CD34+ (x 106/kg) 3,29 (1,42 - 6,58) 6,01 (3,49 – 15,65) ° HLA-partially matched donor leukocyte infusions (PM-DLI) Median and range infused cells. CONCLUSIONS RESULTS 1. Microtransplantation is a well tolerated procedure, infectious complications are insignificant and the remission rates are encouraging, in the absence of engraftment or GVHD. 2. Patients can undergo a second microtransplantation from a different donor. 3. Leukocyte infusions can be safely administered following a hypomethylant agent course instead of conventional chemotherapy. 4. Larger patient cohorts are necessary to assess the efficacy of this novel therapeutic strategy for hematologic malignancies. The procedure was well tolerated. A mild and transient “haploimmunostorm syndrome” was observed (Fig. 1) - Corticosteroid therapy 2 (CMML) Early infusional reaction 1 - Donor engraftment (chimerism tests ) 0 - Acute o chronic GVHD 0 - Significant infections 0 UPN Fig. 1 AML/CMML/MDS Complete remission 6/0/1 Relapse * 4 /-/0 Retransplantation ** 2 /-/0 Exitus 1/2/0 Currently alive in complete remission 2/0/1 REFERENCES Months Guo M, Hu KX, Yu CL, et al. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood, 2011, 117: 936-941 Guo M, Hu KX, Liu GX et al. HLA-mismatched stem-cell microtransplantation as postremission therapy for acute myeloid leucemia: long-term follow-up. J Clin Oncol, 2012, 30: 4084-90. Currently, with a median follow-up of 11 months (range 1-25 months), six patients are alive and three died (one with CMML during the induction treatment and two due to leukemia progression). * At 7, 9, 10 and 15 months after the infusion. ** With a second sustained complete remission Contact Information Copy and paste your text content here, adjusting the font size to fit.