High-dose chemotherapy followed by rescue with blood-forming stem cells may be better than standard chemotherapy for certain lymphoma patients, according to French researchers. Writing in the New England Journal of Medicine (Vol. 350, No.13: 1287-1295), they report that some patients receiving this treatment are more likely to remain free of their disease and live longer.

Chemotherapy for patients with aggressive lymphomas has advanced to the point where about 40% to 50% of patients can be cured. The standard chemotherapy is usually a combination of the drugs cyclophosphamide, vincristine, doxorubicin and prednisone, called CHOP.

The French investigators set out to see if they could improve the cure rate by giving patients higher doses of chemotherapy.

Doctors often classify lymphomas simply by their growth pattern. Some grow slowly and take a long time before becoming life threatening, while others can be very aggressive and can cause death within a year without treatment. The French researchers studied 197 patients under age 60 with this latter type of lymphoma.

Half the patients were treated with the CHOP regimen, while the other half underwent more intensive treatment. The high-dose of chemotherapy destroys the bone marrow and its ability to make blood cells. In order to repopulate the damaged bone marrow, the patients were also given a transfusion of blood-forming stem cells that had been separated from their blood stream and saved earlier.

Overall, patients who received the high-dose therapy had a better outcome. Fifty-five percent were free of lymphoma at 5 years compared with only 37% in the CHOP group. High-dose patients also had a better survival, although the difference wasn't statistically significant.

The best results were seen in patients who had worst outlook. These patients, who had more advanced disease, made up about half of the entire group. Those that received high-dose therapy had a 74% 5-year survival compared to a 44% 5-year survival for the patients treated with CHOP.

Side effects were worse in the high-dose group. They spent many more days in the hospital and were much more likely to develop severe infections. These side effects led the researchers to advise that only the patients with more advanced lymphomas should be given high-dose treatment.

In an accompanying editorial, Andrew Lister, MD, of London's St. Bartholomew's Hospital, says this report proves that intensive chemotherapy is best for patients with these more aggressive lymphomas. But, he also points out that this is toxic therapy and many patients could have been cured with the standard CHOP regimen.

Another issue, according to Lister, is that a new drug, Rituxan, is now being used along with CHOP. This combination is more effective than CHOP alone, and the results using Rituxan may be similar to those seen with the high-dose chemotherapy. But not everyone gets better with this combination and some patients may need more intensive chemotherapy. Doctors just need to be better able to select these patients.

The French authors agree that it is important to select patients who can't be helped by the standard-dose regimens. They point to new genetic methods of separating out lymphoma patients who won't respond well to standard-dose therapy. Once these methods become available, they might be able to identify the best candidates for these intensive chemotherapy regimens.