Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia.
OBJECTIVE
The molecular analysis of minimal residual disease (MRD) may provide information on the risk of recurrence in patients with acute lymphoblastic leukemia (ALL). The aim of this study was to correlate the kinetics of MRD clearance after allogeneic transplantation with the clinical outcome of adults with ALL.


METHODS
MRD was evaluated by real-time quantitative polymerase chain reaction (RQ-PCR) using probes derived from fusion chimeric genes (BCR/ABL and MLL/AF4) (n=22) or rearrangements of the T-cell receptor or immunoglobulin genes (n=21). Forty-three adult patients with ALL were studied to correlate the kinetics of MRD clearance before and after allogeneic hematopoietic stem cell transplantation.


RESULTS
At 36 months, the overall survival of patients who underwent transplantation in hematologic remission (n= 37) was 80% for those who were PCR-negative before transplantation (n= 12) compared to 49% for PCR-positive patients (n= 25)(p=0.17). For the same patients the cumulative incidence of relapse was 0% and 46%, respectively (p=0.027). Moreover, the relapse rate of patients who were PCR-negative at day +100 after transplantation was remarkably low (7%) compared to that among patients who were PCR-positive (80%, p=0.0006).


CONCLUSIONS
The kinetics of MRD clearance may help to identify patients at high risk of leukemia relapse after allogeneic stem cell transplantation. Patients not achieving an early molecular remission after transplantation require prompt and appropriate pre-emptive treatments such as infusions of donor lymphocytes or new experimental drugs.
Spinelli
Orietta
O
Hematology and Bone Marrow Transplantation Units of Ospedali Riuniti Bergamo, Bergamo, Italy.
Peruta
Barbara
B
Tosi
Manuela
M
Guerini
Vittoria
V
Salvi
Anna
A
Zanotti
Maria Cristina
MC
Oldani
Elena
E
Grassi
Anna
A
Intermesoli
Tamara
T
Micò
Caterina
C
Rossi
Giuseppe
G
Fabris
Pietro
P
Lambertenghi-Deliliers
Giorgio
G
Angelucci
Emanuele
E
Barbui
Tiziano
T
Bassan
Renato
R
Rambaldi
Alessandro
A
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D017353:Gene Deletion; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D007700:Kinetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D051788:Myeloid-Lymphoid Leukemia Protein / Q000097:blood; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000097:blood; D010879:Piperazines / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage; D012074:Remission Induction; D012306:Risk; D016019:Survival Analysis; D015996:Survival Rate; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014178:Translocation, Genetic; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D051792:Basic Helix-Loop-Helix Proteins; D001549:Benzamides; D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl; D000068877:Imatinib Mesylate; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C113855:MLL-AF4 fusion protein, human; C067143:TAL1 protein, human