Molecular Monitoring in Acute Myeloid Leukemia Patients Undergoing Matched Unrelated Donor - Hematopoietic Stem Cell Transplantation: Single Center Experience.

INTRODUCTION: Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) cases is a complex, multi-modality process and, though much of its clinical implications at different points are extensively studied, it remains even now a challenging area. It is a disease the biology of which governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. On the other hand, relapse is considered as the leading cause of treatment failure in AML patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). MATERIALS AND METHODS: Since November 2018 until June 2020, 10 AML patients underwent matched unrelated donor (MUD) HSCT at the University Clinic of Hematology-Skopje, Republic of North Macedonia. Molecular markers were identified in a total of 4 patients; 3 patients expressed chimeric fusion transcripts; two RUNX-RUNX1T1 and one for CBFB-MYH11. One patient harbored mutation in the transcription factor CCAAT/enhancer binding protein α (CEBPA). Post-transplant MRD kinetics was evaluated by using quantitative polymerase chain reaction (RT-qPCR) or multiplex fluorescent-PCR every three months during the first two years after the transplantation. RESULTS: MRD negativity was achieved in three pre-transplant MRD positive patients by the sixth month of HSCT. They sustained hematological and molecular remission for 19, 9 and 7 months, respectively. The fourth patient died due to transplant-related complications. CONCLUSION: According to our experience, when molecularly-defined AML patients undergo HSCT, regular MRD monitoring helps predict impending relapse and direct future treatment strategies.

Multivariable model consisting of clinical and biological markers for time to first treatment in CLL patients: Preliminary results from single centre experience.

INTRODUCTION: The clinical course for patients with chronic lymphocytic leukaemia (CLL) is extremely heterogeneous; one of the most important challenges in the clinical management of these patients is the decision on initiating their treatment, but there is no available prognostic system that will resolve this issue. Usually, criteria for active disease are used to initiate therapy. Recently, some authors have proposed prognostic models, scoring systems involving a set of clinical and biological risk factors and estimates of individual patient survivals. Here, we report our initial results from a study designed to evaluate the statistical association of the distinct clinical and biological parameters with the prognosis and time to initiating treatment for patients with CLL. MATERIAL AND METHODS: Our study incorporated 100 consecutive, treatment naive CLL patients. In each patient all traditional laboratory, clinical and biological prognostic factors were evaluated at their first visit to our Institution. We then combined the following independent characteristics: age, ß-2 microglobulin, absolute lymphocyte count, sex, Rai stage, and number of involved lymph node groups, which are included in some of the already published CLL prognostics index, in association with the CD38 expression and mutational status of the immunoglobulin heavy chain gene variable region (IGVH). Further, we correlated those factors by multivariable analysis with time to first treatment. This multivariable model was used to develop a nomogram-a weighted tool to calculate 5- and 10-year survival probability and estimate median time to first treatment (TFT). RESULTS: According to the prognostic index, a classification tree was built that identified three subsets of patients whose scores were 1-3 (low risk - 32 pts - 32%), 4-7 (intermediate risk - 48 pts - 48%) and > 8 (high risk - 20 pts - 20%). Estimated median survival in the low risk subset of patients is 141 years, and 10.7 and 4.6 years respectively in the intermediate and high risk subsets of patients. Projected survival in respectively low, intermediate and high-risk groups are 100%, 100%, 25%, and 43%, 34%, 25% at 5 years and 10 years, respectively. Also, statistical analyses showed that among other things CD38 expression and unmutated IGHV mutation status are associated with a shorter time to first treatment. CONCLUSION: Our prognostic model that combines and correlates the distinct clinical and biological markers of CLL patients enables identification of patients who are at high risk of progression. This prognostic model may facilitate the clinical decision for initiating treatment.