1. 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, (4,52 – 10,70)
CD3+ (x 108/kg)
1,15 (0,35 - 2,42)
2, (0,64 – 3,53)
CD3-/CD56+ (x107/kg)
0,94 (0,50 - 1,55)
2, (1,30 – 3,10)
CD34+ (x 106/kg)
3,29 (1,42 - 6,58)
6, (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:
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:
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
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