Cancer Data Base

Hodgkin Lymphoma (HL); how can we do better with fewer side effects?

Hodgkin Lymphoma (HL) was one of the earliest cancers to be successfully treated with chemo/radiotherapy. Although successful, in the majority of patients, this form of therapy is associated with significant toxicity. A number of groups are investigating the possibility of reducing therapy, minimizing toxicity and maintaining a good outcome. A group from Koln (abs no333) will present evidence that 2 cycles, instead of 4, of the standard chemotherapy (ABVD) and a lower radiation dose (20Gy instead of 30Gy) are sufficient to achieve a similar rate of remission and prolonged survival with reduced toxicity.

Another study (abs no1628) demonstrates that all four components of the chemotherapy (ABVD) are necessary. Although the majority of patients are cured when diagnosed with early stage HL, a small proportion of patients does not respond and have a poorer outcome. For this subset of patients, an Italian group (abs no 73) using FDG-PET scanning (a way of scanning the cancer and measuring its metabolic activity) after 2 courses' is able to predict outcome. Therefore patients in the non-responsive group may have their treatment intensified to provide cure.

Multiple Myeloma; now a chronic disease

Multiple Myeloma (MM) is the second most common blood cancer with an incidence of approximately 4-5 new cases per 100.000 people per year. In Europe there were estimated to be 31,883 new cases of MM and 21,677 MM-related deaths in 2002.

One of the major complications in MM is bone involvement by the cancer cells leading to pain and a risk of fractures. The Medical Research Council (MRC group from UK) will report on the benefit of the drug Zolendronic acid compared to Clodronate for the delay of bone disease and prolongation of survival.

Proteasomes are intracellular complexes that break down proteins. Proteasome inhibitors are new and potentially effective drugs in MM and the use one of these, Carfilzomib, in patients with relapsed or refractory MM will be discussed. The results of a large international trial employing classic chemotherapy with the addition of Lenalidomide, a class of drugs called immunomodulators (IMIDs), will be updated.

Italian and Dutch groups will discuss the role of genetic markers in predicting the clinical outcome, following specific treatments.

Maintenance therapy after autologous stem cell transplant remains a controversial issue. Data, derived from a large randomized trial, about the role of Thalidomide in this setting, will be presented. Finally the HOVON group will report on their experience with allogeneic stem cell transplant using a new treatment strategy.

New strategies for patients with Lymphoma

In spite of treatments, which include the humanized monoclonal anti-body Rituximab, a number of patients with a form of Lymphoma called Diffuse Large B Cell Lymphoma (DLCBL) will relapse. Gisselbrecht et al (abs No 1059) demonstrate a critical role for autologous stem cell transplantation in the management of patients with relapsed DLBCL whose initial treatment included Rituximab.

Visani et al (abs no 469) demonstrate a potentially important role for a new drug, bendamustine, in patients with relapsed lymphoma. They identify a new, and well-tolerated, transplant regimen for evaluation in patients with high-risk lymphoma.

Ruggeri et al (abs no 1699) provide new data demonstrating an important role for umbilical cord blood transplantation in the management of high-risk acute lymphoblastic leukemia (ALL) in children. This approach may be important in treating children with high-risk ALL who lack a family (sibling) or unrelated stem cell donor.

Stadler et al (abs no 1817) explore the role of delayed donor lymphocyte infusion as a strategy for delivering curative immunotherapy in patients transplanted for high-risk leukemia. Their important study demonstrates an encouraging safety profile and a new approach to treatment.

Stem Cell Transplantation (SCT) and immunotherapy

The factors determining the numbers of stem cells mobilized by the cytokine GCSF in normal donors remain undetermined. Martin-Antonio et al (abs no 2096) have identified polymorphisms (inherited differences) in the stromal adhesion molecule VCAM-1, which has a significant impact on the numbers of CD34+ progenitor cells, collected after administration of GCSF. These data may assist in the identification of new stem cell collection strategies.

Chronic Myeloid Leukemia

Jedema et al (abs no 680) have examined mechanisms of resistance to tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia. Importantly they identify immunotherapeutic mechanism, which may contribute to the eradication of resistant leukemia stem cells, and potential mechanism of resistance.

Galski et al (abs no 1170) have examined mechanisms of resistance to TKIs in patients with chronic myeloid leukemia. They identified a potential role for drugs, which modulate the activity of the multidrug transporter p glycoprotein in overcoming resistance to TKIs and immunotherapeutic killing by NK cells (a type of lymphocyte).

Novel Therapeutic Approaches

Berger et al (abs no 1693) demonstrate clinical activity of a new proteasome inhibitor MLN 9708 in preclinical models of high-risk lymphoma identifying a potentially new treatment modality in this common hematological malignancy in which drug resistance is frequently documented.

Granulocytes (White Cells)

An increased risk of malignant transformation (Myelodysplastic Syndrome, MDS, or Acute Myeloid leukemia, AML) is well documented in patients with congenital neutropenia (CN, people born with an abnormally low white cell count)). Zeidler et al (abs no 1765) identify molecular and clinical factors predicting the likelihood of development of MDS or AML.

Marks et al (abs no 2188) report important data identifying a potential benefit for the use of voriconazole (an anti-fungal drug) as primary prevention of systemic fungal infection in patients undergoing allogeneic stem cell transplantation.