Minimal Residual Disease Tests Provide an Independent Predictor of Clinical Outcome in Adult Acute Lymphoblastic Leukemia

Mortuza, Forida Y.; Papaioannou, M; Moreira, Ilidia M.; Coyle, Luke; Gameiro, Paula; Gandini, Domenica; Hg, Prentice; Goldstone, Anthony H.; Hoffbrand, A. Victor; Foroni, Letizia

doi:10.1200/jco.20.4.1094

Cited by 126 publications

(68 citation statements)

References 34 publications

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“…In another study, MRD was assessed by a semiquantitative PCR for IgH gene four times during the first 24 months of therapy. MRD positivity was associated with an increased risk of relapse at all time points, but the association was most significant 3 to 5 months after induction and beyond [66]. Bruggemann et al [67] used quantitative PCR in 196 patients with standard-risk ALL to prospectively monitor MRD up to nine times in the first year of treatment.…”

Section: Advances In Monitoring Minimal Residual Diseasementioning

confidence: 97%

Modern treatment programs for adults with acute lymphoblastic leukemia

Ravandi

Kebriaei²,

Kantarjian³

2007

Curr Hematol Malig Rep

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The current treatment programs for adult patients with acute lymphoblastic leukemia are modeled on pediatric regimens. The result has been complete remission rates comparable to those seen in children, but a significant proportion of adult patients relapse. Salvage therapy for patients with acute lymphoblastic leukemia continues to have limited success. Advances in molecular biology have discovered new targets for therapeutic intervention, and the introduction of some targeted agents, such as the new tyrosine kinase inhibitors and monoclonal antibodies, has led to improvements in response and survival in some subsets. The development of techniques for identification and monitoring of minimal residual leukemia has provided possible ways to predict relapse and consider early intervention. It is likely that we will further refine therapeutic approaches and improve patient outcome through the translation of biologic and molecular discoveries into effective and risk-adapted strategies.

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Section: Advances In Monitoring Minimal Residual Diseasementioning

confidence: 97%

Modern treatment programs for adults with acute lymphoblastic leukemia

Ravandi

Kebriaei²,

Kantarjian³

2007

Curr Hematol Malig Rep

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show abstract

“…Moreover, the most appropriate time points and a standard method for measuring residual disease have not been determined. In addition, although PCR is very sensitive at detecting MRD, molecular relapse detected by PCR does not always predict clinical relapse in adults with ALL [51].…”

Section: Minimal Residual Diseasementioning

confidence: 99%

Clinical manifestations and treatment of newly diagnosed acute lymphoblastic leukemia in adults

Landau

Lamanna

2006

Curr Hematol Malig Rep

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Adult acute lymphoblastic leukemia (ALL) is a heterogeneous disease with distinct biologic and prognostic subgroups. The treatment of adults with ALL has evolved largely from the therapy developed for childhood ALL and, despite differences across regimens, can be broadly classified as including induction, consolidation, maintenance, and central nervous system prophylaxis. Although there has been marked improvement in the outcomes for pediatric patients with ALL, the same success has not yet been realized for adult patients. Some of this difference can be attributed to a greater incidence of unfavorable cytogenetic subtypes in adults than in children. In addition, the ability to tolerate intensive regimens likely plays a role. This article reviews the classification, prognostic features, current treatment programs, and new advances as applied to adult patients with newly diagnosed ALL.

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“…High-level MRD prior to conditioning may be overcome in a selected group of children with replete T cell SCT and the occurrence of chronic GVHD [40]. This association is less prominent in adults [41]. Miglino et al [42]described four patterns of MRD kinetics in 23 patients with ALL.…”

Section: Significance and Kinetics Of Mrd In Different Malignanciesmentioning

confidence: 99%

Clinical Implications of Minimal Residual Disease Monitoring for Stem Cell Transplantation after Reduced Intensity and Nonmyeloablative Conditioning

Shimoni¹,

Nagler²

2004

Acta Haematol

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Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for a variety of hematological malignancies; however, relapse and treatment-related toxicities are major obstacles to cure. Nonmyeloablative and reduced-intensity conditioning regimens were designed not to eradicate the malignancy completely, but rather to be immunosuppressive enough to allow engraftment, and to serve as a platform for additional cellular immunotherapy. Minimal residual disease (MRD) typically persists after SCT, and is gradually eliminated with different kinetics typical of each disease. Significant progress has been achieved with technologies for MRD assessment. Quantitative PCR tests are very sensitive in detecting tumor-associated transcripts, allowing serial monitoring. Threshold levels have been established for some malignancies, above which relapse is imminent. Persistent negative tests, a low level or a decreasing MRD level are consistent with continuous remission, whereas high-level MRD or increasing levels predict an incipient relapse. Patients at high risk of relapse are candidates for additional cellular or targeted therapy. Immunotherapy is more effective for MRD than at frank relapse. Timing and dosing of therapy are not yet well established and depend on aggressiveness of the disease, type of conditioning, level and kinetics of MRD.

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Minimal Residual Disease Tests Provide an Independent Predictor of Clinical Outcome in Adult Acute Lymphoblastic Leukemia

Abstract: The association of MRD test results and DFS was independent of and greater than other standard predictors of outcome and is therefore important in determining treatment for individual patients.

Cited by 126 publications

References 34 publications

Modern treatment programs for adults with acute lymphoblastic leukemia

Modern treatment programs for adults with acute lymphoblastic leukemia

Clinical manifestations and treatment of newly diagnosed acute lymphoblastic leukemia in adults

Clinical Implications of Minimal Residual Disease Monitoring for Stem Cell Transplantation after Reduced Intensity and Nonmyeloablative Conditioning

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