November 28, 2001 (Research Reports) - Chronic lymphocytic leukemia accounts for 25 % of new cases of leukemia each year in the United States. In its non-progressive or slowly progressive forms, it often is not treated. There is no curative drug treatment program, although in its progressive phase there are several drugs that can slow the progress of the disease. CLL is very uncommon under 50 years of age and its incidence increases progressively in later decades of life.
A group of oncologists in Barcelona examined the effect of autologous marrow infusion (so-called autologous stem cell transplantation) and of allogeneic stem cell transplantation from a sibling in a group of patients under age 60 and 55 years, respectively. The requirement to use younger patients in transplant studies means that the great majority of patients could not be treated with standard stem cell transplantation as it is currently practiced.
Fourteen patients were treated either with total body radiation and a high dose of a single drug (12 cases) or high doses of four drugs (2 cases) in an effort to eradicate the leukemic cells before rescuing their marrow function by infusing their own stem cells recovered prior to this treatment. Twelve patients were treated with total body radiation before infusing stem cells obtained from matched sibling donors.
An important aspect of this study was the measurement of very small amounts of residual leukemia using special sensitive tests for genetic features of the leukemic cells. Thus, in circumstances in which leukemic cells were not seen by standard blood or marrow tests, a special measurement could be made to determine what is referred to as "minimal residual disease". The importance of this test is that if there is no detectable minimal residual disease experience suggests the leukemia is less likely to grow back.
The results are based on small samples of patients in each group. The patients given the autologous stem cell infusion all showed early improvement in that each had a complete remission but the effects were relatively short-lived. Six had return of clinical disease, most within 18 months and 4 others had reappearance of minimal residual disease. Of the 12 patients given allogeneic transplantation, three died after transplantation and one did not respond to the treatment. Of the remaining eight patients seven ultimately had no evidence of minimal residual disease and the possibility that the diseases had been eradicated.
In this exploratory study, the results indicate that a group of "younger" patients may be curable with allogeneic transplantation. However, there are many limitations to the study. The proportion of CLL patients under 55 years with a matched sibling donor is extremely small. Some patients' life is shortened by transplant complications. There was no direct comparison to other forms of treatment to determine how much better this approach could be measured over many years.
On the positive side, since CLL is very resistant to eradication by drugs, the study supports the potential utility of immunotherapy combined with intensive therapy as a possible curative approach to CLL. This conclusion is based on the likelihood that graft-versus-leukemia, a feature of allogeneic as compared to autologous transplantation, played a role in the long-term disease free survival of 7 of 12 patients treated by allogeneic transplantation. This effect implies that not only did the transplanted stem cells restore the blood cell making function of the recipient's marrow but the donor's immune cells suppressed the leukemic cells of the recipient. Original Article Leukemia vol.15, pp445-451, 2001
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