Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.

The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low-intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches.

Myelodysplastic syndromes, version 2.2015.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) comprise a heterogeneous group of myeloid disorders with a highly variable disease course that depends largely on risk factors. Risk evaluation is therefore a critical component of decision-making in the treatment of MDS. The development of newer treatments and the refinement of current treatment modalities are designed to improve patient outcomes and reduce side effects. These NCCN Guidelines Insights focus on the recent updates to the guidelines, which include the incorporation of a revised prognostic scoring system, addition of molecular abnormalities associated with MDS, and refinement of treatment options involving a discussion of cost of care.

A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.

Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) may respond to treatment with epigenetic-modifying agents. Histone deacetylase inhibitors may synergize with hypomethylating agents. This phase 1 dose-escalation study was designed to determine the maximum tolerated dose, recommended phase 2 dose, safety and tolerability of vorinostat plus decitabine in patients with relapsed/refractory AML, newly-diagnosed AML, or intermediate- to high-grade MDS. Thirty-four patients received concurrent therapy with decitabine plus vorinostat and 37 received sequential therapy with decitabine followed by vorinostat. Twenty-nine patients had relapsed/refractory AML, 31 had untreated AML and 11 had MDS. The target maximum administered dose (MAD) of decitabine 20 mg/m(2) daily for 5 d plus vorinostat 400 mg/d for 14 d was achieved for concurrent and sequential schedules, with one dose-limiting toxicity (Grade 3 QTc prolongation) reported in the sequential arm. Common toxicities were haematological and gastrointestinal. Responses were observed more frequently at the MAD on the concurrent schedule compared with the sequential schedule in untreated AML (46% vs. 14%), relapsed/refractory AML (15% vs. 0%) and MDS (60% vs. 0%). Decitabine plus vorinostat given concurrently or sequentially appears to be safe and well-tolerated. Concurrent therapy shows promising clinical activity in AML or MDS, warranting further investigation.

The role of interferon-alpha in the treatment of chronic myeloid leukemia.

Biological agents have long been used in the treatment of cancer, and interferon-alpha was the first human cytokine to be widely studied in this setting. Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder for which interferon-alpha has demonstrated substantial activity. In the 1980s interferon-alpha became first-line therapy for patients with chronic-phase CML, not eligible for allogeneic stem cell transplantation. Following the discovery of the leukemic oncogene BCR/ABL and its causal association with CML, the potent BCR/ABL tyrosine kinase inhibitor imatinib mesylate was developed. Imatinib proved to be superior to interferon-alpha in all outcome measures, making imatinib the new standard of care for patients with CML. There is both clinical and laboratory evidence suggesting imatinib therapy alone is not curative in CML, whereas IFN has induced a low but reproducible curative effect in some patients. This unique activity may be the basis for the reincorporation of IFN into the management of CML. These observations may be best explained by imatinib's negligible activity against the leukemic stem cell (LSC) population. This review discusses the history of interferon-alpha in the treatment of CML, the evolution of molecularly targeted therapies, and some of the lessons we have learned from years of informative research in CML. It also explores the new challenge of managing minimal residual disease in the imatinib era, and addresses the promising role for LSC-directed therapies in the future treatment of CML.

A 5-drug regimen maximizing the dose of cyclophosphamide is effective therapy for adult Burkitt or Burkitt-like lymphomas.

Burkitt lymphoma (BL) and Burkitt-like lymphomas (BLL) are clinically and biologically aggressive B-cell malignancies. Brief-duration, high intensity multidrug regimens with central nervous system (CNS) prophylaxis have proven to be effective, with published series of adult patients documenting complete response (CR) rates of 80 to 100 percent and 2-year event-free survival (EFS) rates ranging from 60 to 90 percent. Based upon the known sensitivity of BL to cyclophosphamide and favorable results reported from the Dana Farber Cancer Center using high-dose CHOP in diffuse aggressive lymphomas, we tested a regimen designed to maximize the administered dose of cyclophosphamide while eliminating other agents commonly used in BL protocols. Eleven patients with Burkitt or Burkitt-like lymphoma were treated with 4 cycles of a 5-drug regimen, called high-dose CHOP, which contains a cyclophosphamide dose of 4 gm/m2 with each cycle. Intrathecal methotrexate and midcycle high-dose methotrexate were added as CNS prophylaxis. Ten patients achieved a complete response (91 percent) and with a median follow up of 38 months, the 3-year EFS is 64 percent and the 3-year overall survival (OS) is 72 percent. Three patients recurred after the achievement of a CR. Treatment-related toxicities included myelosuppression, neutropenic fevers/infections, and tumor lysis syndrome requiring hemodialysis in 2 patients. There were no treatment-related deaths and none of the patients had to discontinue therapy secondary to toxicity. In conclusion, the high-dose CHOP with midcycle methotrexate regimen produces response rates and EFS rates comparable to other regimens, with an acceptable toxicity profile. Utilization of high dose cyclophosphamide may eliminate the need for several other agents in Burkitt lymphoma regimens.