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Vaccine for Chronic Myelogenous Leukemia Shows Promise

According to the results of a study recently reported in the Lancet, researchers from Italy have reported that a new vaccine may eradicate residual leukemia cells left in the bone marrow after treatment with Gleevec® or interferon for chronic myeloid leukemia (CML).

Chronic myelogenous leukemia (CML) is a blood disease characterized by excess production of white blood cells. This disease is associated with a chromosomal abnormality called the Philadelphia chromosome. Some patients have what is called a BCR-ABL-derived p210 fusion protein which can be recognized by the body as non-self and can potentially be a target for immune therapies. For the past several years, all newly diagnosed patients have been treated with a drug called Gleevec® (imatinib), which results in clinical remissions and disappearance of the Philadelphia chromosome in most cases.

There is also evidence that Gleevec® improves survival over the previous best therapy, which was interferon. However, most patients treated with Gleevec® still have residual leukemia as detected in a molecular test called polymerase chain reaction (PCR). Younger patients who fail Gleevec® therapy are usually treated with an allogeneic stem cell transplant, which is the only treatment that truly eradicates the leukemic clone. However, this is a risky procedure and researchers are seeking alternative immune therapies for patients with CML.

In this recent study, researchers investigated the role of a vaccine as a targeted treatment for CML. In order to be eligible for this study, patients had to have specific histocompatibility (HLA) types and have the type of CML targeted by the vaccine. Sixteen patients diagnosed with CML were enrolled. Each patient was determined to have stable disease and had completed a minimum of 12 months of treatment with Gleevec® or 24 months of treatment with interferon, and had no further reduction in residual disease within six months of enrollment. All participants were treated with six injections of a protein-based vaccine that was target-specific for CML. Response was measured by evaluating the patients immune response, as well as the disease response.

Ten of the patients in this study had been treated with Gleevec®, nine of whom had an average of 10 months of stable disease and one patient started the study with a stable, complete clinical response. All patients who had been treated with Gleevec® showed an improvement at the cellular level after receiving the six vaccinations, with five patients reaching a complete clinical response. Interestingly, three of the five were found to have undetectable levels of disease by PCR.

These authors reportred that all 10 Gleevec® and 5 of 6 interferon patients had decreased numbers of Philadelphia chromosome positive cells after treatment. The complete cytogenetic response rate was 7 of 16 and 4 had complete molecular remissions as tested by PCR. Toxicities associated with the vaccines were considered minimal. Eleven of the 16 patients had a positive skin test to the vaccine indicating successful vaccination.

A discussion among the researchers and other colleagues reveals that the success of this study, along with the lack of toxicity, supports the development of immune strategies for the treatment of CML. The current thinking is that cure of CML will be associated with complete eradication of the CML clone as measured by sensitive PCR testing. Immune therapies appear to be the best approach for eradication of minimal residual disease. Patients with CML who have not had a complete molecular remission to Gleevec® should seek out experimental treatments designed to eradicate the last leukemia cell.

References:

Wong K, Chatterjee S. Vaccine Development for Chronic Myelogenous Leukemia. Lancet. 2005; 365: 631-632.

Bocchia M, Gentili S, Abruzzese E. et al. Effect of a p210 Multipeptide Vaccine Associated With Imatinib or Interferon in Patients with Chronic Myeloid Leukemia and Persistent Residual Disease: a Multicenter Observational Trial. Lancet 2005; 365: 657-662.

MDS Clinical Trials Announcement

MD Anderson Cancer Center, Houston, TX. Phase II study of combination of Thymoglobulin and cyclosporine in patients with newly diagnosed aplastic anemia or with hypoplastic myelodysplastic syndromes. The purpose of this study is to determine the efficacy of the combination of thymoglobulin, methylprednisone, cyclosporine and G-CSF in achieving response and to assess the effect of treatment on transfusion requirements and overall survival. Eligible patients must have a diagnosis of severe aplastic anemia or MDS with bone marrow cellularity less than 30%, two of three peripheral counts low with ANC less than 500/mL, Plt less than 20,000/mL or reticulocyte count less than 40,000/mL.

Patients with MDS who have received prior biological therapy (not chemotherapy), age 15 or greater, adequate renal and hepatic function, no other investigational therapy in the past 14 days, able to comply with the need for contraception during the entire study period. Exclusion criteria include active and uncontrolled pulmonary, cardiac, neurological or other medical illness that would interfere with study treatment, pregnant or breast-feeding, HIV positive or active and uncontrolled infection.

Treatment Plan is as follows: 1. thymoglobulin to be given intravenously for 4 days, 2. Methylprednisone to be given intravenously for 4 days; methylprednisone to be given before each dose of thymoglobulin. Oral prednisone will then be started daily and will be tapered over a three-week period. 3. Cyclosporin A orally, daily for 6 months; to start after completion of thymoglobulin 4. G-CSF to be given subcutaneously daily for up to 3 months; start after completion of thymoglobulin. 5. Prophylactic broad-spectrum antibiotics.

Contact: Farhad Ravandi, MD. Phone: 713-745-0394 or call The MDS Foundation at 800-MDS-0839 for more information.

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