Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Abstract

Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by realtime PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.

CD34+ lineage specific donor cell chimerism for the diagnosis and treatment of impending relapse of AML or myelodysplastic syndrome after allo-SCT

“…18 Different approaches of monitoring of MRD after allo-SCT for AML patients have been described. 11,20 Cytogenetic analyses are standard methods in the initial diagnostic evaluation and allow the detection of chromosome abnormalities in B55% of adult AML patients. 12 Although this technique provides a very highly specific tool, the sensitivity to detect impending relapse seems to be rather low.…”

The association of level of reduction of Wilms’ tumor gene 1 mRNA transcript in bone marrow and outcome in acute myeloid leukemia patients

“…On the other hand, a predictive marker for outcome available during chemotherapy may be important for the decision on post-remission therapy, including allogeneic stem cell transplantation (SCT). Evaluation of minimal residual disease (MRD) during chemotherapy is considered as one of the predictive markers for acute leukemia [8,9]. Detection of leukemia-specific chimeric genes by real-time quantitative polymerase chain reaction represents the most sensitive method to quantify MRD, but over 50% of AML patients lack suitable leukemia-specific genes and other gene markers for assessing MRD are necessary for a great proportion of AML patients.…”

Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial

“…12, 13, 14, 15, 16 Although determination of MRD by these methods may precede morphologic disease detection by weeks, they are often only applicable in a distinct population of MDS or AML patients with specific molecular markers. 13, 14, 15, 17, 18 Donor chimerism analyses of whole blood or bone marrow cells harbor a low sensitivity.…”