Search

Introduction: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Unfortunately, it is still associated with a significant risk of relapse due to mechanisms of escape from the control of alloreactive T cells. Repetitive adjuvant donor lymphocyte infusion (DLI), termed prophylactic DLI (proDLI), as an effective strategy in preventing relapse is still debated. Methods: We performed a retrospective multicenter study to evaluate the efficacy of proDLI in allografted AML and MDS. We identified 56 patients treated with proDLI (DLI planned in full chimeras without any sign of disease relapse) and matched them to 167 patients in control group, (DLI performed for mixed chimerism or positive minimal residual disease) based on similar age, initial disease, cytogenetic prognosis, and conditioning intensity. Results: In univariate analysis, the incidence of severe aGVHD at 100 days and incidence of all grades of chronic GVHD 1 year after allo-HSCT were similar in the two groups. We also observed a trend of higher 3-year RI (52.61% [95% confidence interval 25.99–79.23]) in the proDLI group versus the control group (29.31% [20.28–38.34], p = 0.067). However, 3-year overall survival (p = 0.892), progression-free survival (p = 0.239), and nonrelapse mortality (p = 0.343) were similar between the two groups. In multivariate analysis, the only factor influencing overall and progression-free survival was anti-thymocyte globulin administration during the conditioning regimen. Conclusion: The proDLI strategy had an acceptable toxicity profile but did not improve patient outcomes compared to the pre-emptive strategy. [ABSTRACT FROM AUTHOR]

Background: The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT). Methods: Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221‐C‐001 trial and SoC outcomes obtained from a real‐world chart review of patients in France. Results: Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61–1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47–0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72–13.24) and 4.76 months for SoC (95% CI, 3.81–8.21). Results remained robust across all sensitivity analyses conducted. Conclusions: PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern. [ABSTRACT FROM AUTHOR]

They rather identified six Ph+AML patients harboring I NPM1 i mutations and outlined some criteria, in which I NPM1 i mutation, to discriminate Ph+AML from BP-CML. Subsequently, using the oncomine myeloid research assay panel of ThermoFisher Scientific SP ® sp (3% sensitivity for point mutations and 5% for indels), the NGS analysis singled out the I NPM1 i type A mutation with variant allele frequency at 42-6% on the diagnostic bone marrow sample. Does eventually NPM1 mutation in blast phase chronic myeloid leukemia (BP-CML) exist? The prognostic value of a I NPM1 i mutation in BP-CML and Ph+AML cannot be determined because of the scantiness of case reports. [Extracted from the article]

Abstract: Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing until the resolution of fever. We found that bacteremia did increase PCT levels above 0.5ng/mL and these levels predicted bacteremia at day 15 of chemotherapy. This finding may be relevant in the decision to alter antibiotic regimens to decrease toxicity and cost when patients remain febrile at day 15. [Copyright &y& Elsevier]