title: Prospective monitoring of minimal residual disease in acute myeloid leukemia with inversion(16) by CBFbeta/MYH11 RT-PCR: implications for a monitoring schedule and for treatment decisions.
abstract: Minimal residual disease in patients with acute myeloid leukemia (AML) with inversion(16) can be monitored by CBFbeta/MYH11 RT-PCR. While the association between molecular remission (MR) in bone marrow (BM) and peripheral blood (PB) and long-term clinical remission (CR) seems to be established, there are insufficient data on the kinetics of CBFbeta/MYH11. We have performed a prospective study in order to generate a reasonable and sufficient schedule for PCR-monitoring. 11 patients with AML and inversion (16) in complete hematological remission have been prospectively monitored by CBFbeta/MYH11 RT-PCR in their BM and PB during an observation period of 7 to 67 months (median 32 months). Patients were followed during consolidation chemotherapy with repetitive cycles of high-dose Ara-C and after autologous or allogeneic stem cell transplantation in 2nd CR or refractory AML. MR never coincided with achievement of CR but occurred between 2 and 8 months after hematological remission. All patients in continuous CR were PCR-negative after 1-8 (median 4) months. Two patients relapsed despite MR for 10 to 15 months. Molecular relapse preceded hematological relapse by 3 to 5 months. Three out of four patients who were not in MR after 8 months relapsed. Allogeneic stem cell transplantation was able to eradicate minimal residual disease in 4/4 patients. In 2 patients a temporary reconversion to PCR-positivity was reversed by reduction of immunosuppression. 1 patient did not become PCR-negative until compete withdrawal of immunosuppression. We suggest that BM and PB should be examined after the last consolidation treatment. In case of MR, PB should be examined every 1 to 2 months and BM examination should be done only in case of PCR-positivity in PB in order to confirm the molecular relapse and to identify an impending cytogenetic and/or hematological relapse. CBFbeta/MYH11 RT-PCR monitoring is able to predict relapse 3 to 5 months prior to overt hematological relapse, offers a window of opportunity for preemptive therapy of molecular relapse and confers implications for immunotherapy in the setting of allografting.
authors.affiliation: Department of Medicine I, University of Vienna, Austria. Klaus.Laczika@akh-wien.ac.at
authors.forename: K
authors.initials: K
authors.lastname: Laczika
authors.forename: G
authors.initials: G
authors.lastname: Mitterbauer
authors.forename: M
authors.initials: M
authors.lastname: Mitterbauer
authors.forename: P
authors.initials: P
authors.lastname: Knöbl
authors.forename: I
authors.initials: I
authors.lastname: Schwarzinger
authors.forename: H T
authors.initials: HT
authors.lastname: Greinix
authors.forename: W
authors.initials: W
authors.lastname: Rabitsch
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: U
authors.initials: U
authors.lastname: Jaeger
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001769:Blood / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion