Are we nearer to curing patients with MDS?

Myelodysplastic syndromes (MDS) are a heterogeneous collection of clonal hematopoietic disorders derived from abnormal multipotent progenitor cells. They have been classified by the World Health Organization as myeloid neoplasms with several different subtypes based on morphology and cytogenetics. Because MDS was only recently recognized as a cancer, epidemiological data is tentative and incidence and prevalence will probably increase as reporting improves. Prognosis for MDS patients is calculated using the International Prognostic Scoring System, though this system is currently being revised by several groups. Therapy for MDS varies based on pathobiology, prognosis, and cytogenetics, such as the deletion of 5q. Treatment options range from supportive care, to disease-modifying chemotherapeutic agents, to stem cell transplantation, to therapies that may affect quality of life, improve survival, or even cure the disease.     

Role of autologous stem-cell transplantation in multiple myeloma

Multiple myeloma (MM) is one of the diseases in which the impact of dose intensity has been demonstrated. Consequently, in 2005 MM was the first disease for which autologous stem-cell transplantation (ASCT) was indicated in Europe and the US. However, ASCT is not curative, and most patients relapse in a median of 3 years. The introduction of novel agents such as thalidomide, bortezomib (Velcade) or lenalidomide (Revlimid) was logical to try to improve the high-dose strategy, and promising results have been reported. This article will focus on the current results of ASCT and will discuss the main research area to try to improve this strategy.     

Thromboembolic toxicity observed with concurrent trametinib and lenalidomide therapy

The event-free survival of pediatric low-grade gliomas is poor, and patients often require multiple treatment strategies. While MEK and RAF inhibitors are efficacious in early-phase trials, not all patients respond, and many experience progression following completion of therapy. Evaluating combination therapies that may enhance efficacy or prolong disease stabilization is warranted. We report our institutional experience using concurrent trametinib and lenalidomide in the treatment of primary pediatric central and peripheral nervous system tumors. Two of four patients using this combination therapy experienced severe thromboembolic events, necessitating discontinuation of therapy. This combination requires further investigation, and we urge caution if used.     

A rare case of acute lymphoblastic leukemia in a patient with light chain (AL) amyloidosis treated with lenalidomide

Lenalidomide belongs to a novel class of drugs called Immunomodulators which are now being used for the treatment of plasma cell dyscrasias with variable degrees of efficacy and toxicity. Though Second Primary Malignancies (SPM) have been a concern with its use, the benefits of the treatment outweigh the risks. The leukemogenic risk seems to be potentiated especially when combined with alkylating agents and the SPMs documented are predominantly myeloblastic. To date there are no reported cases of new lymphocytic leukemias in AL amyloidosis, regardless of whether undergone treatment or not. We present a case of AL amylodosis who was treated with lenalidomide and subsequently developed acute lymphoblastic leukemia.     

Relief of intractable pruritus with romidepsin in patients with cutaneous T‐cell lymphoma: A series of four cases

Cutaneous T‐cell lymphomas (CTCL) are a relatively rare and heterogeneous group of non‐Hodgkin lymphomas that typically present in the skin. The majority of patients with CTCL experience pruritus, which can interfere with daily activities, significantly impact quality of life, and is typically uncontrolled by standard anti‐itch therapies. Several lymphoma treatments have reported anti‐pruritic effects including romidepsin, a potent class 1 selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had at least one prior systemic therapy. Here, we describe the cases of four patients with debilitating and refractory pruritus that were resolved with romidepsin. Resolution of pruritus was observed in both clinical responders and nonresponders, and dose modification was used successfully to manage adverse events and for maintenance treatment. The potential for pruritus relief with romidepsin should be considered when treating patients with CTCL.     

Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome

BACKGROUND:

Secondary acute myeloid leukemia (AML) from an antecedent myelodysplastic syndrome (MDS)/myeloproliferative neoplasm is associated with a poor prognosis. The authors evaluated predictive factors in patients with secondary AML treated with anthracycline‐based induction therapy.

METHODS:

This was a retrospective review of secondary AML patients treated with induction therapy. Age, International Prognostic Scoring System, Eastern Cooperative Oncology Group performance status, cytogenetics, duration of MDS/myeloproliferative neoplasm, and prior MDS/myeloproliferative neoplasm treatment were evaluated for their impact on complete response (CR), CR with low platelets, and overall survival (OS).

RESULTS:

The authors evaluated 61 secondary AML patients who received induction chemotherapy; 59% (36 patients) achieved CR/CR with low platelets (95% confidence interval [CI], 46%‐71%), and median OS was 6.5 (95% CI, 3.9‐8.1) months. Three factors were associated with lower CR/CR with low platelets and OS: poor risk cytogenetics, prior treatment with hypomethylating agents or lenalidomide, and longer time to transformation to AML. Of those treated with hypomethylating agents or lenalidomide, 32% achieved CR/CR with low platelets versus 78% in the group not treated with a hypomethylating agent or lenalidomide (odds ratio [OR], 0.13; 95% CI, 0.04‐0.42). Median OS for those treated with a hypomethylating agent or lenalidomide was 3.7 versus 10.5 months for those not treated with a hypomethylating agent or lenalidomide (P < .0001). The CR/CR with low platelets rate for those with intermediate risk cytogenetics was 70% versus 35% for those with poor risk (OR, 4.33; 95% CI, 1.38‐13.6). Those with poor risk cytogenetics had a median OS of 2.8 versus 7.5 months for those with intermediate risk (P = .01).

CONCLUSIONS:

Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy. Cancer 2011. © 2010 American Cancer Society.