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Central nervous system (CNS) involvement worsens the prognosis of hematologic neoplasms since cerebrospinal fluid (CSF) represents a sanctuary for malignant cells. Thus, it is evident that without the use of FCM we would have missed 17% and 40% of patients with CNS involvement at diagnosis and relapse respectively. Two patients (40%), who were not screened at diagnosis for CNS disease, resulted at relapse CC SP - sp /FCM SP + sp (15 and 40 events) (Table 1). [Extracted from the article]

The absence of measurable residual disease (MRD) in morphologic complete remission (CR) represents a favorable prognosticator in acute myeloid leukemia (AML) [[1]]. At the diagnostic evaluation, patients were defined as LSCs negative (LSC-0) in case of undetectable LSCs count, LSC SP low sp and LSC SP high sp when LSCs were detected below or above a threshold of 0.03%, respectively [[4]]. Indeed, patients with a high LSC burden at diagnosis have an unfavorable outcome unless LSCs are cleared by chemotherapy. [Extracted from the article]

Azacitidine (AZA) prolonged overall survival (OS) in the AZA-AML-001 trial. However, few subjects were randomized to AZA or intensive chemotherapy (IC). The Medical Research Council (MRC) and the Leukemia Research Foundation (LRF) developed a score for older AML patients receiving IC or non-intensive regimens, whereas the E-ALMA study validated a score for survival and response in elderly patients receiving AZA in daily practice. Both identified three groups with different risk estimates. This analysis evaluates the efficacy of frontline AZA in older AML patients (N = 710) unfit for IC from different national registries (E-ALMA + series) stratified by the MRC/LRF risk score. Median OS of patients categorized as good, standard and poor-risk groups by the MRC/LRF score was 13.4 (95% CI, 10.8-16), 12.4 (95% CI, 9.9-14.8), and 8.1 months (95% CI, 7-9.1), respectively (p = .0001). In conclusion, this is the largest retrospective cohort of older AML patients treated with AZA. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the effectiveness of hypomethylating agent (HMT) 5-azacytidine in treating chronic myelomonocytic leukemia (CMML) patients. Topics explored include the cytogenetic evaluation of the patients involved in the study, the prognostic factors recorded including platelet count, transfusion dependence, and overall response to treatment, and the overall patient survival recorded following HMT treatment.

In chronic lymphocytic leukemia (CLL), inhibition of spontaneous apoptosis determines a worse prognosis and increasing evidences show that disease progression relies also upon cycling CLL cells. We investigated bcl-2, as measure of apoptosis, and CD71, as measure of proliferation, by flow cytometry in 265 patients with CLL. Combining bcl-2 with CD71 values, we defined three subgroups: (1) bcl2 − CD71−; (2) bcl2 + CD71+; and (3) bcl2 + CD71− or bcl2− CD71+. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ ( p < 0.00001) and in patients with bcl2 + CD71+ ( p < 0.00001 and p = 0.02). The patients with discordant in bcl2 + CD71− and bcl2− CD71+ showed an intermediate outcome. Noteworthy, patients with bcl2 + CD71+ showed a shorter PFS within ZAP-70 negative subgroup ( p = 0.00009). In multivariate analysis of PFS, age ( p = 0.005), beta-2 microglobulin (B2-M) ( p = 0.003), bcl-2 ( p = 0.004), CD49d ( p = 0.001), and ZAP-70 ( p < 0.001) resulted to be significant prognostic factors. The independent prognostic significance of B2-M ( p = 0.009) and bcl-2 ( p = 0.03) was confirmed within ZAP-70 negative patients. Bcl-2 and CD71 can be considered as interesting progression indicators, which should be validated in an independent cohort of patients, to take timely therapeutic decisions in CLL. [ABSTRACT FROM AUTHOR]

Major advances have been made in our understanding of the biology and opportunities for treatment of chronic lymphocytic leukemia in recent times. Newer treatment regimens incorporating purine nucleoside analogs have increased the rate of successful remission induction in chronic lymphocytic leukemia patients. Moreover, recent combination chemoimmunotherapy regimens have produced more frequent complete molecular remissions, and early evidence seems to suggest that this could result in prolonged duration of responses, although this association remains to be clearly demonstrated. This review will summarize recent advances in the biology and the management of chronic lymphocytic leukemia, including prognostic factors, pointing mainly on combination chemotherapy based on nucleoside analogs and monoclonal antibodies. In our opinion, in the future a significant improvement of clinical benefits in chronic lymphocytic leukemia will be obtained through the administration of cocktails of monoclonal antibodies combined with chemotherapy in different modalities. [ABSTRACT FROM AUTHOR]

The primary cause of treatment failures in acute myeloid leukemia (AML) is the emergence of both resistant disease and early relapse. Among the most frequent agents of these phenomena are defects in the mitochondrial-mediated apoptotic pathway. This pathway is regulated by bcl-2 family of anti-apoptotic (bcl-2, bcl-xl, mcl-1) and pro-apoptotic proteins (bax, bad, bak). In particular, bcl-2 dimerizes with several members of bcl-2 family of proteins, altering the threshold of cell death. The flow cytometric quantitative measurement of bcl-2 and bax expression for the determination of bax/bcl-2 ratio provided crucial clinical information in AML: in our hands, lower bax/bcl-2 ratio conferred a very poor prognosis with decreased rates of complete remission (CR) and overall survival (OS). Moreover, striking correlations were found between lower bax/bcl-2 ratio and higher progenitor marker expression, such as CD34, CD117 and CD133 antigens, confirming the link between this apoptotic index and the maturation pathways. However, the capacity of bax/bcl-2 ratio to clearly identify patients with different prognosis with regard to CR and OS within the CD34+, CD117+ and CD133+ subgroups implies that other mechanisms, such as proliferation and/or cell cycle dysregulation may be involved to explain its clinical significance. Finally, small molecules that target both the receptor- and mitochondrial-mediated pathway of apoptosis are providing encouraging results in patients with relapsed and/or refractory disease (i.e. CDDOMe, bcl-2 antisense oligonucleotides, CEP-701, etc), confirming the key role of apoptotic mechanisms on the outcome of AML patients. [ABSTRACT FROM AUTHOR]

The term minimal residual disease (MRD) describes the situation in which, after chemotherapy for acute leukemia (AL), a morphologically normal bone marrow (BM) can still harbor a relevant amount of residual malignant cells. Several techniques are now amenable to investigate MRD, and all together they have designated a new era in which a re-definition of the current criteria of complete remission (CR) is required. Depending upon the measured level of MRD we can distinguish a variety of clinical situations ranging from a potentially cured disease to short-term remission. In the context of this spectrum of conditions there would be room for different therapeutic strategies ranging from no further therapy to pre-emptive therapy to treat early relapses (immunologic and/or molecular relapses). This review will focus on the state of art of MRD detection in acute myeloid leukemia (AML) using multidimensional flow cytometry (MFC), and will cover the laboratory and clinical aspects of this approach. [ABSTRACT FROM AUTHOR]