Lisa Chodirker

Lenalidomide and metronomic melphalan for CMML and higher risk MDS: A phase 2 clinical study with biomarkers of angiogenesis

Metronomic, low dose chemotherapy may have anti-angiogenic effects and augment the effects of lenalidomide in MDS and CMML. We evaluated the clinical efficacy, tolerability and anti-angiogenic effects of melphalan 2mg and lenalidomide 10mg for 21 days/28 in CMML (n=12) and higher risk MDS (n=8) patients in a prospective phase II study. The primary endpoint was overall response and secondary endpoints included survival, progression-free survival, toxicity and biomarkers of angiogenesis. The median age was 73 years, 55% were pretreated and transfusion dependent. The overall response rate was 3(15%) of 19 evaluable patients but 25% in CMML and 33% in pCMML. Dose reductions and/or delays were common due to myelosuppression. Transient spikes in circulating endothelial cells that declined below baseline were seen in responders and patients with CMML, suggesting anti-angiogenic activity. In conclusion, lenalidomide and metronomic low dose melphalan demonstrate signals of clinical and possible anti-angiogenic activity in patients with pCMML that require future validation. This trial was registered at clinicaltrial.gov under # NCT00744536.

Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient‐related factors and measuring from time of first red blood cell transfusion dependence: an MDS‐CAN analysis

Analyses suggest iron overload in red blood cell (RBC) transfusion‐dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient‐related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient‐related factors. TD International Prognostic Scoring System (IPSS) low and intermediate‐1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease‐modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non‐ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P < 0·0001). By multivariate analysis, not receiving ICT independently predicted inferior OS, (hazard ratio for death 2·0, P = 0·03). In matched pair analysis, OS remained superior for ICT patients (P = 0·02). In this prospective, non‐randomized analysis, receiving ICT was associated with superior OS in lower IPSS risk MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease‐modifying agents. This provides additional evidence that ICT may confer clinical benefit.

Initial transfusion intensity predicts survival in myelodysplastic syndrome

Abstract We evaluated 52 patients with myelodysplastic syndrome (MDS) who had received at least one red blood cell (RBC) transfusion. In the 4-week period following the first transfusion, 24 patients (group 1) required no transfusion, while 28 (group 2) required transfusion of two or more units of RBCs. Survival was greater in group 1 (440 weeks vs. 167 weeks, p < 0.01), even when only international prognostic scoring system (IPSS) low and intermediate-1 risk patients were analyzed (median overall survival 491 vs. 170 weeks, p < 0.05), independent of age, IPSS and progression to acute myeloid leukemia (AML). The intensity of transfusion required in the first few weeks after the first transfusion predicts disease severity and correlates with survival.

Intravascular large B-cell lymphoma presenting as Richter's syndrome with cerebral involvement in a patient with chronic lymphocytic leukemia

Intravascular large B‐cell lymphoma (IVLBCL) is an aggressive non‐Hodgkins lymphoma which can present with B symptoms, rash, and neurological deterioration. Up to 10% of cases of IVLBCL are associated with other hematological neoplasms, including this extremely rare presentation of IVLBCL as Richters transformation in chronic lymphocytic leukemia.

Autologous stem cell transplant and combination immunotherapy of rituximab and interferon-α induces prolonged clinical and molecular remissions in patients with follicular lymphoma

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Iron overload in myelodysplastic syndromes.

The myelodysplastic syndromes (MDSs) comprise a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cellular dys plasia, peripheral cytopenias and an increased risk of transformation to acute myeloid leukemia [1]. Despite the use of erythropoietinstimulating agents and the develop ment of novel therapies to enhance bone marrow function, more than 80% of MDS patients will require chronic red blood cell (RBC) transfusions [2]. In humans, no physiological mechanism exists for iron elimination and, as such, patients with MDS are prone to transfusional iron overload. Eventually, the effects of iron deposition will be seen clinically, causing damage to the heart, liver and endocrine organs [3]. It is a widely held belief, echoed in published treatment guidelines [4–14], that the use of iron-chelation therapy is important in the management of patients with MDS. It remains to be discerned whether iron-chelation therapy results in improved overall survival.