Search

The optimal high-dose methotrexate (HDMTX)-based combination therapy for primary central nervous system lymphoma is unknown. We report our experience with rituximab, HDMTX, procarbazine and lomustine (R-MPL) given as first-line treatment in our center. Fifty-two patients between 2006 and 2019 were included. Eighteen patients proceeded to autologous transplant or two cycles of intermediate-dose cytarabine. The median age was 62 y (range 28–94) and the Eastern Cooperative Oncology Group performance status (ECOG-PS) was ≥2 in 62% (32/52). The overall/complete response rates were 79% (41/52) and 52% (27/52), respectively. The median progression-free/overall survival was 19 m/84m, respectively. Grade 3–4 adverse events included infections (17%) and kidney injury (13%). Ten patients (19%) discontinued therapy for toxicity. There were no treatment-related deaths. In summary, in a cohort enriched in frail patients, R-MPL achieved good responses and OS and was safe for all ages. The PFS was sub-optimal, possibly explained by a low proportion of consolidation. This regimen should be evaluated prospectively. [ABSTRACT FROM AUTHOR]

Data from 11 Israeli centers, where venetoclax was used for relapsed/refractory AML after intensive chemotherapy, were retrospectively collected. During 2016–2019, forty patients were identified. Median age was 67 years (21–82), 60% males, median of 2(1–4) prior lines of treatment and 42% relapsed after allogeneic transplant. 62.5% of the patients received the venetoclax with hypomethylating agents and 22.5% with low dose cytarabine. Median follow-up was 5.5 months. Of the 29 patients who survived for more than two cycles of therapy, 22 (76%) achieved neutrophil recovery and 59% (n = 17) recovered also their platelet count. In 15 (52% of those who survived > 2 months), CR/CRi was confirmed by bone marrow examination. The median OS from venetoclax initiation of all the patients and of those who survived more than 2 months was 5.5 and 6.5 months, respectively. In conclusion, this study demonstrates that venetoclax is safe and active also in AML patients with advanced disease. [ABSTRACT FROM AUTHOR]

The optimal tyrosine kinase inhibitor for any individual patient with chronic myeloid leukemia (CML) is not predictable. Pharmacogenetic parameters and trough levels of imatinib (IM) have each been independently correlated with response. We therefore studied the human organic cation transporter (h OCT1) and multidrug resistance ( MDR1) single nucleotide polymorphisms (SNPs) and correlated these with IM levels and major molecular response (MMR) (3-log reduction) in 84 patients with CML, the first such study performed in Caucasians. We studied MDR1 G2677T and C3435T, and for h OCT1, C480G and A1222G. IM levels varied significantly with dose (< or > 400 mg/day) ( p = 0.038) and were significantly lower in 20 patients who lost MMR ( p = 0.042). Adjusting for dose, trough IM levels were not significantly correlated with SNPs. Patients with MDR1 3435 TT had significantly longer times to MMR compared to CC/CT genotypes ( p = 0.047). Genotypes did not predict treatment failure when controlling for IM levels. We conclude that IM levels, but not the SNPs studied here, determine IM failure. [ABSTRACT FROM AUTHOR]

Recent studies suggest that anti-platelet agents are not equally effective in all individuals. We have developed a new method to evaluate the effect of anti-platelet drugs using the cone and plate(let) analyzer (CPA) test. The method is based on the ability of activators to reduce platelet adhesion under flow conditions. Treatment of a blood sample with arachidonic acid (AA) or ADP in vitro significantly decreased platelet deposition to a surface coverage (SC) of 2.1?±?0.4 and 1.3?±?0.6%, respectively, compared with the basic SC of 12.3?±?6.8%. The effect of AA was prevented by aspirin (SC 8.1?±?3.8%) and that of ADP was reduced by 2-methylthio-AMP, a P2Y12 ADP receptor inhibitor (SC 4.8?±?2.0%). Pre-incubation with AA of whole blood samples from untreated healthy volunteers resulted in a marked decline of SC (from SC 9.8?±?2.2 to 0.6?±?0.3%). In contrast, in volunteers treated with 100, 300, and 500?mg aspirin per day, AA (but not ADP) decreased SC only to 3.5?±?1.3, 4.4?±?1.7, and 4.1?±?2.0%, respectively ( P <0.001 versus SC with AA before treatment). A good correlation was observed between the modified CPA and aggregometry ( R 2 ?=?0.55). In conclusion, the modified CPA test is a useful tool to evaluate the efficacy of anti-platelet therapy. [ABSTRACT FROM AUTHOR]

Bleeding is a common complication during initial induction treatment for acute promyelocytic leukemia (APL). Administration of all-transretinoic acid (ATRA), which is in routine use for APL in the past decade improves the bleeding tendency dramatically. Nevertheless, thrombotic events have still been reported in a small proportion of APL patients treated with ATRA. Here we describe a case of splenic infarction and life threatening thrombosis in a young patient with APL treated with ATRA. We review the relevant literature and discuss the pathophysiology, risk factors and treatment of this complication occurring during therapy, for APL. [ABSTRACT FROM AUTHOR]