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• An oral RIF plus ATRA chemotherapy-free protocol is highly efficacy in APL. • Oral RIF plus ATRA regimen is well-tolerated in postremission therapy for APL. • A home-based model is feasible for APL even in high-risk patients. Realgar-Indigo naturalis formula(RIF)is an oral form of arsenic developed for treatment of acute promyelocytic leukemia (APL). We retrospectively evaluated the efficacy and safety of a novel RIF combined with all-trans retinoic acid (ATRA) based chemotherapy-free approach in newly diagnosed APL patients. Patients received oral ATRA (25 mg/m2/day in 2 divided doses) plus intravenous arsenic trioxide (0.15 mg/kg/day) or oral RIF (60 mg/kg/day in 3 divided doses) as induction chemotherapy, followed by 2 consolidations with ATRA plus RIF and maintenance therapy with intermittent ATRA and RIF. From January 2015 to December 2017, 40 subjects were enrolled. Eighteen subjects were male. Median age was 42 years (range, 14–77 years) and 10 subjects were ≥ 60 years. All subjects achieved a complete morphologic remission after initial induction. Molecular complete remission achieved 100% after second RIF plus ATRA consolidation. Median follow-up of survivors was 27 months (range, 7–43 months). The 2-year event-free survival (EFS) and overall survival (OS) were both 100%. Adverse events were modest and all patients needed only outpatient care during postremission therapy. Compared to our historical RIF plus ATRA with chemotherapy regimen (the Chinese APL07 trial), the inpatient treatment duration was greatly reduced by the RIF plus ATRA regimen. Our data indicates that early switching to RIF plus ATRA based chemotherapy-free approach has yielded encouraging outcomes and might be considered a practicable option to treat patients with newly diagnosed APL. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) is a medical emergency. In order to evaluate the usefulness of initial coagulation parameters in the predictive value of APL diagnosis, 1304 consecutive newly diagnosed acute leukemia patients, including APL (n = 211), non-APL acute myeloid leukemia (n = 781) and acute lymphoblastic leukemia (n = 312) were retrospectively evaluated between January 2011 and May 2015. The area under curve (AUC) of fibrinogen was the largest among the coagulation markers based on receiver operating characteristic (ROC) analysis. The optimum cutoff value of fibrinogen was 1.87 g/L (AUC = 0.912, sensitivity 80.1% and specificity 88.8%). The optimum cutoff value of D-dimer was 2191 μg/L (AUC = 0.786, sensitivity 81.1% and specificity 67.8%). The AUC difference between the fibrinogen and D-dimer was significant (P < 0.001). Other coagulation markers showed less predictive power. Importantly, in the analysis of high white blood cell count (over 10 × 10 9 /L) subgroup, a low fibrinogen level could efficiently discriminate APL patients from controls (AUC = 0.983, sensitivity 96.4% and specificity 94.4%) with a criterion value ≤1.71 g/L. Thus, our results suggest that a low fibrinogen level could be a key marker in early prediction of APL diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Currently, there are few studies that address the prognostic significance of baseline additional chromosomal abnormalities (ACAs) in newly diagnosed acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO) as the front-line therapy. A series of 271 consecutive APL patients has been cytogenetically investigated between 2004 and 2011 in our institution. The incidence of ACAs was 27% (46/172) in APL cases with t(15;17). Trisomy 8 was the most recurrent abnormality, accounting for 30% (14/46) of patients with ACAs, followed by +21 (7%, 3/46) and −7/7q (7%, 3/46). Nine cases (14.1%) were found to have additional balanced translocation aberrations, most of them are new and non-recurrent. Treatment protocols consisted of all-trans retinoic acid (ATRA) and chemotherapy with or without the ATO therapy. Overall, patients with and without ACAs had similar complete remission (CR) rates (94% and 98%, respectively, P =0.344). With a median follow-up of 41 months, univariate analysis showed that ACAs did not show any prognostic significance in relapse-free survival (RFS) and overall survival (OS). In addition, ATO treatment was an independent favorable predictor for RFS. Thus, this data provides insights into cytogenetic features of APL, and suggests that ATO-based combination therapy improved RFS in de novo APL patients, while ACAs had no impact on prognosis. [Copyright &y& Elsevier]

Prognostic factors for patients with acute promyelocytic leukemia (APL) treated in the context of arsenic trioxide (ATO)-based frontline regimes have not been established clearly. We retrospectively analyzed the clinical features, immunophenotypes, Fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), and outcomes of 184 consecutive newly diagnosed APL patients treated by intravenous ATO-based therapy. The median age was 40 years (14–77 years). The early death rate was 4.9% (9/184 patients). With a median follow-up time of 36 months (9–74 months), the 3-year relapse-free survival (RFS) and overall survival (OS) were 93.3% and 92.2%, respectively. Interestingly, there was no meaningful association between 3-year RFS and initial white blood cell count, FLT3-ITD status, or type of PML–RARA isoforms. In multivariable analysis, the CD56 expression was the only independent risk factor in terms of RFS (hazard ratio, 4.70; P = 0.005). These results suggested that ATO-based therapy may ameliorate the unfavorable influence of previously known high-risk features; moreover, CD56 expression remains to be a potentially unfavorable prognostic factor in APL patients. [ABSTRACT FROM AUTHOR]

Abstract: Musashi-2 (MSI2) expression of 116 adult B-cells acute lymphoblastic leukemia (B-ALL) patients was measured by real-time PCR. Kaplan–Meier analysis showed that patients with high MSI2 expression had inferior overall survival (OS) (P =0.004), event free survival (EFS) (P =0.001) and relapse free survival (RFS) (P =0.018) in BCR-ABL-negative B-ALL. Multivariate models revealed that, besides WBC more than 30×109/L and IK6 variant of IKZF1, high MSI2 expression was also an independent prognostic factor for adult BCR-ABL-negative B-ALL. Our data suggest that high MSI2 expression could indicate poor prognosis and facilitate risk and treatment stratification in adult BCR-ABL-negative B-ALL. [Copyright &y& Elsevier]

Abstract: We conducted a retrospective study to evaluate the efficacy of combining arsenic trioxide (ATO) with all-trans-retinoic acid (ATRA) based induction therapy, followed by 3 courses of consolidation chemotherapy and 2-year sequential ATO/ATRA maintenance therapy in acute promyelocytic leukemia (APL). 137 patients were enrolled in the study. The complete remission (CR) rate was 93.4%. All the 9 (6.6%) induction failures were due to early death. With a median follow-up of 35months, 5 relapses (4%) in CR patients were recorded, including 3 isolated CNS relapses. By using the Kaplan–Meier analysis, the 5-year overall survival and relapse-free survival of the low/intermediate risk group and high-risk group was 98.9% versus 97.4% and 98.7% versus 87.9%, respectively. The results indicated that ATO based first-line protocol is highly effective for treatment of newly diagnosed APL. [Copyright &y& Elsevier]