Vidyya Medical News Servicesm
Vidyya, from the Sanskrit "vaidya," a practitioner who has come to understand the science of life.

Volume 2 Published - 14:00 UTC    08:00 EST    28-March-2001      
Issue 87 Next Update - 14:00 UTC 08:00 EST    29-March-2001      

Vidyya Home  Vidyya

Home Of Our Sponsor, Vidyya.  Vidyya. Home

Vidyya Archives  Vidyya Archives

Search Vidyya  Search Vidyya

Visit Our Library  Ex Libris

Subscribe To Our News Service  Subscriptions

All About Us  About Vidyya



















Back To Vidyya High Response Rate Of Hairy Cell Leukemia Patients To Immunotoxin Treatment Raises Hopes

Clinical Trial At NCI Reports That 11 Of 16 Patients With Chemotherapy-Resistant Hairy Cell Leukemia Had Complete Remissions For Up To 18 Months

An ongoing Phase I clinical trial at the National Cancer Institute (NCI) reports that 11 of 16 patients with chemotherapy-resistant hairy cell leukemia (HCL), an uncommon form of B-cell cancer, had complete remissions lasting up to 18 months, most without major side effects, when treated with a new immunotoxin-based drug. The Phase I trial was presented at a minisymposium during the American Association for Cancer Research's annual meeting in New Orleans, 24-28 March 2001. The unusually high response rates lead researchers to have high hopes for the use of this drug in HCL, and possibly in other patients.

"Phase I clinical trial response rates are usually very low," said Robert Kreitman, M.D., the lead investigator. "If the Phase I results can be reproduced in a Phase II trial, we may be able to proceed to applying for FDA (Food and Drug Administration) approval." The Phase I trial has been extended to include more patients and Kreitman and his colleagues are already planning a Phase II clinical trial for this drug that will include centers across the country.

The drug, a recombinant immunotoxin, is one of several new agents that have been developed in the Laboratory of Molecular Biology by Ira Pastan, M.D., David Fitzgerald, Ph.D., Kreitman, and colleagues. The immunotoxins are designed to link cell-killing toxins to antibodies, biologically active molecules that guide the toxin to the cancer cell like a bomb in a missile. This immunotoxin, BL22, is created by cloning portions of antibodies to portions of a toxin excreted by the bacteria Pseudomonas. "Recombinant DNA techniques allow cloning part of the antibody and part of the toxin to make a smaller recombinant immunotoxin that gets into the tumor faster and reduces the toxicity to the body," explained Kreitman.

The antibody portion of BL22 specifically binds to the CD22 receptor, which is found in abundance on the surface of many types of leukemia cells. CD22 is also found, in lower amounts, on the surface of normal B cells. Therefore, it seems likely that BL22 would bind to and destroy both leukemic cells and normal B cells. Because stem cells–the progenitors of normal B cells–do not have CD22, any B cells lost in the short-term treatment should be replaced by the patient's untouched stem cells. And, in fact, Kreitman and his colleagues did not detect a decrease in normal B cells of patients.

Kreitman added, "Malignant stem cells– the progenitors of the leukemic cells--may be CD22-positive as well and be lost, too. But only further follow-up will determine if this is correct." Therefore, it is thought that this treatment may not only clear the body of malignant circulating cells but may remove the source of the cells, the malignant stem cells.

The most serious side effect of BL22 immunotoxin treatment was a decrease in platelet and red blood cell counts. This decrease suggests clotting and breaking up of red blood cells in the kidney, which can cause kidney failure. However, both patients experiencing the side effect completely recovered and had complete remissions of HCL. Taking the drug with large quantities of fluid, investigators hope, will make the drug more safe. They plan to test that theory during the extended Phase I trial.

It is possible that the BL22 immunotoxin will prove to be useful in treating more than just hairy cell leukemia. The Phase I trial includes patients with other types of leukemia and, while Kreitman and his colleagues saw the most dramatic response in HCL, a significant benefit was seen in the other types, including chronic lymphocytic leukemia. These leads are being followed up by the researchers. "The hairy cell leukemia cells have more CD22 receptors and therefore respond faster and more thoroughly than the other cancers being investigated," Kreitman explained.


Vidyya. Home |  Ex Libris |  Vidyya  | 
Subscription Information |  About Vidyya |  Vidyya Archives | 
Editor: Susan K. Boyer, RN
© Vidyya. All rights reserved.