Plasma cell myeloma following a prior diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.

A 69-year-old man presented with plasma cell myeloma (PCM) 4 years after the treatment of chronic lymphocytic leukemia (CLL). Light chain expressions in the two tumors were different suggesting unrelated cell of origin clonality. Few reports have been added to the literature describing synchronous CLL and PCM in a patient.

Patterns of Ruxolitinib Therapy Failure and Its Management in Myelofibrosis: Perspectives of the Canadian Myeloproliferative Neoplasm Group.

Ruxolitinib improves splenomegaly and other disease-related symptoms in patients with myelofibrosis, but over time, many patients lose this benefit. It is difficult to determine whether this is due to resistance or intolerance to the drug; thus, we have used the more inclusive term of ruxolitinib failure. The survival of patients with myelofibrosis after ruxolitinib failure is poor but varies significantly by the pattern of the failure, underlining the need for a clinically appropriate classification. In this review, we propose diagnostic guidance for early recognition of the pattern of ruxolitinib failure and we recommend treatment options. The most frequent patterns of ruxolitinib failure are loss or failure to obtain a significant reduction in splenomegaly or symptom response, and the development or persistence of clinically significant cytopenias. Ruxolitinib dose modification and other ancillary therapies are sometimes helpful, and splenectomy is a palliative option in selected cases. Stem-cell transplantation is the only curative option for these patterns of failure, but its restricted applicability due to toxicity highlights the importance of ongoing clinical trials in this area. Recent approval of fedratinib by the US Food and Drug Administration provides an alternative option for patients with suboptimal or loss of spleen response. The transformation of myelofibrosis to accelerated or blast phase is an infrequent form of failure with an extremely poor prognosis, whereby patients who are ineligible for transplantation have limited treatment options.

How we treat paroxysmal nocturnal hemoglobinuria: A consensus statement of the Canadian PNH Network and review of the national registry.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by intravascular hemolysis, thrombophilia, and marrow failure. Its phenotype is due to absent or reduced expression of GPI-linked complement regulators and subsequent sensitivity of hematopoietic cells to complement-mediated damage and lysis. Introduction of the terminal complement inhibitor eculizumab drastically improved outcomes in PNH patients; however, despite this improvement, there remain several challenges faced by PNH patients and physicians who care for them. One of the most important is increasing awareness of the heterogeneity with which patients can present, which can lead to significant delays in recognition. Data from the Canadian PNH Registry are presented to demonstrate the variety of presenting symptoms. In Canada, geography precludes consolidation of care to just a few centers, so management is distributed across academic hospitals, linked together as the Canadian PNH Network. The Network over the last several years has developed educational programs and clinical checklists and has worked to standardize access to diagnostics across the country. Herein, we address some of the common diagnostic and therapeutic challenges faced by PNH physicians and give our recommendations. Gaps in knowledge are also addressed, and where appropriate, consensus opinion is provided.

Evolving Therapeutic Options for Polycythemia Vera: Perspectives of the Canadian Myeloproliferative Neoplasms Group.

Polycythemia vera (PV) is a clonal stem cell disorder characterized by erythrocytosis and associated with burdensome symptoms, reduced quality of life, risk of thrombohemorrhagic complications, and risk of transformation to myelofibrosis and acute myeloid leukemia. The discovery of the JAK2 V617 mutation marked a significant milestone in understanding the pathophysiology of the disease and subsequently the diagnostic and therapeutic approaches. The current diagnostic criteria for PV are based on hemoglobin level and presence of the JAK2 V617 mutation. The treatment is geared toward prevention of thrombotic events, normalization of blood counts, control of disease-related symptoms, and potential prolongation of survival. Cytoreductive therapy is indicated in patients at increased risk of thrombosis. Hydroxyurea (HU) remains the most commonly used first-line cytoreductive therapy and is superior to phlebotomy in reducing risk of arterial and venous thrombosis. Interferon (IFN) is used either at failure of HU or in selected patients as first-line therapy. The results of pegylated IFN in phase 2 studies appear encouraging, with molecular responses occurring in some patients. Ongoing phase 3 studies of HU versus pegylated IFN will define the optimal first-line cytoreductive therapy for PV. A recent phase 3 trial has shown the superiority of the JAK1/2 inhibitor ruxolitinib in comparison to best available treatment in HU-intolerant or -resistant patients. The therapeutic landscape of PV is likely to change in the near future. In this report, we assess the potential impact of the changing landscape of PV management on daily practice.

Cytomegalovirus colitis following azacitidine therapy.

The present report describes the first recognized case of cytomegalovirus (CMV) colitis following azacitidine therapy. A 66-year-old woman with myelodysplastic syndrome developed CMV colitis, which responded to treatment with ganciclovir. Currently, patients receiving azacitidine do not undergo CMV testing, or receive prophylaxis or CMV-free blood products; however, this policy needs to be revised.

Iron overload in myelodysplastic syndromes: a Canadian consensus guideline.

In December 2005, 11 Canadian hematologists met to develop an evidence-based clinical practice guideline that would address the diagnosis, monitoring, management, and rationale for the treatment of transfusional iron overload in patients with myelodysplastic syndromes (MDS). This Expert Panel consisted of hematologists from across Canada, each with an active practice in a major population centre or a rural area. Based on an extensive literature search and years of clinical experience, their mandate was to address common clinical practice questions, particularly why treat, whom to treat, when to initiate treatment, and how to treat iron overload in patients with MDS.

A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7.

The effectiveness of melphalan plus dexamethasone (M-Dex) with melphalan plus prednisone (MP) as induction therapy and dexamethasone with observation as maintenance therapy was compared in 585 older patients with multiple myeloma. Randomization to the M-Dex arm was stopped as a result of an analysis performed which met a predetermined event-related criterion. Of 466 patients randomised to MP or M-Dex, no differences were detected in the respective median progression-free survivals (PFS) [1.8 vs. 1.9 years; Hazard Ratio (HR) = 0.88, 95% CI 0.72-1.07; P = 0.2] or overall survivals (OS) (2.5 vs. 2.7 years; HR = 0.91, 95% CI 0.74-1.11; P = 0.3). Of the initial 585 patients, 292 remained evaluable for maintenance therapy. Patients randomised to maintenance dexamethasone had a superior median PFS (2.8 years vs. 2.1 years; HR = 0.61, 95% CI 0.47-0.79; P = 0.0002). No difference in median OS was detected (4.1 years vs. 3.8 years; HR = 0.88, 95% CI 0.65-1.18; P = 0.4). The maintenance therapy results were robust when analysed by using two additional methodologies. Dexamethasone did not improve clinical outcome when combined with melphalan during induction; maintenance dexamethasone improved PFS, but this did not translate into a detectable survival advantage.