Blood, 15 April 2002, Vol. 99, No. 8, pp. 3070-3071
CORRESPONDENCE
To the editor:
Treatment options in chronic myelogenous leukemia
The perspective "Chronic myelogenous leukemia: current
treatment options"1 provides a succinct, direct, and
evenhanded approach to a complex topic, for which I congratulate the
authors. I have a lone concern with the final aspect of the review, the dependence on age to determine the recommended treatment option.
As the authors state, scoring systems devised by Sokal and Hasford can
be used to predict survival for individual patients receiving
nontransplant therapy. Similarly, Gratwohl's scoring system estimates
survival after allotransplantation; the reliability of this scoring
system was recently confirmed by the International Bone Marrow
Transplant (IBMT) Registry.2 Advanced age is a poor
prognostic factor for all patients, whether they undergo transplantation or receive nontransplant therapies. The other variables
used in these scoring techniques are necessary to estimate outcome.
Recipient age may influence outcome in adults undergoing allogeneic
transplantation for chronic myelogenous leukemia (CML) to a lesser
degree than is commonly thought. Bolwell recently summarized relevant
data and concluded that the inclusion of pediatric patients (grouped
with young adults) in many studies has led to the impression that older
adults fare far more poorly with transplantation than do younger
adults.3 He found only a slightly higher risk of
transplantation-related mortality in older compared to younger adults.
Data from Seattle4 and our own center,5 among
others, indicate that conventional allogeneic transplantation can be
performed safely in older patients. Data from the same institutions
suggest that transplantation less than 6 months4 and 3 months5 from diagnosis can further improve results,
including in older patients.
Thomas et al's original report of allogeneic transplantation in CML
found a direct relationship between mortality rate and interval from
diagnosis to transplantation and an association between older age and
longer interval from diagnosis to transplantation.6 Delaying transplantation in older patients contributes to a higher mortality rate. The fact that every study does not demonstrate a
significant influence of this interval on outcome does not prove a lack
of influence any more than studies that fail to demonstrate an adverse
influence of older age prove the absence of an adverse affect. These
studies are not appropriately designed to detect the absence of such differences.
Last, results at specific institutions, often with large patient
numbers, are clearly better than overall IBMT Registry results. Many studies with favorable results have included large numbers of
patients and have utilized similar approaches. Using targeted busulfan and cyclophosphamide, the Seattle group reports one-year transplantation-related mortality rates of approximately 10% and rare
relapses. Institutions with poor results should consider referring
patients to centers consistently achieving favorable results.
We can all agree that the decision can best be made by a well-informed
patient; that patient depends on clinicians to provide an accurate,
fair, and complete description of his or her options.
Edward A. Copelan
Correspondence: Ohio State University, 315-B Starling-Loving
Hall, 320 W 10th Ave, Columbus, OH 43210
References
1.
Goldman JM, Druker BJ.
Chronic myeloid leukemia: current treatment options.
Blood.
2001;98:2039-2042[Abstract/Free Full Text].
2.
Passweg J, Walker I, Sobocinski K, et al.
Validation of the EBMT risk score for recipients of allogeneic hematopoietic stem cell transplants for chronic myelogenous leukemia (CML) [abstract].
Blood.
2001;98:349a.
3.
Bolwell BJ.
Is bone marrow transplantation appropriate in older patients? In:
Bolwell BJ, ed.
Current Controversies in Bone Marrow Transplantation. Totowa, NJ: Humana Press, Inc; 2000:29-40.
4.
Applebaum FR, Clift R, Radich J, Anasetti C, Buckner CD.
Bone marrow transplantation for chronic myelogenous leukemia.
Seminars in Oncol.
1995;22:405-411[Medline]
[Order article via Infotrieve].
5.
Copelan EA, Penza SL, Theil KS, et al.
The influence of early transplantation, age, GVHD prevention regimen, and other factors on outcome of allogeneic transplantation for CML following BuCy.
Bone Marrow Transplantation.
2000;26:1037-1043[CrossRef][Medline]
[Order article via Infotrieve].
6.
Thomas ED, Clift RA, Fefer A, et al.
Marrow transplantation for the treatment of chronic myleogenous leukemia.
Ann Int Med.
1986;104:155-163.
7.
Radich RP, Gooley T, Clift R, Bryant E, Flowers MED, Appelbaum FR.
Allogeneic-related transplantation for chronic phase chronic myeloid leukemia (CML) using a targeted busulfan and cytoxan preparative regimen [abstract].
Blood.
2001;98:778a.
Response:
Age and chronic myelogenous leukemia treatment algorithm
Our recent perspective tried to balance the benefits and risks
of treatment with STI571 (imatinib mesylate) against the benefits and
risks of early allogeneic stem cell transplantation (SCT) for patients
with chronic myelogenous leukemia in chronic phase. Dr Copelan feels
that we have ascribed undue importance to age in guiding
decision-making. Regarding transplantation, he refers to published and
unpublished data from single centers in which the
transplantation-related mortality (TRM) does not differ greatly between
younger and older patients.
As noted, in both the Sokal and Hasford systems for estimating
survival with nontransplant therapy, older age is a negative prognostic factor. Thus, older patients would more likely fall into
their intermediate- and high-risk categories. According to our
algorithm, we would tend to favor transplantation options for
these patients.
In all published series of unrelated allogeneic SCTs, including
single-institution studies, age is indisputably the most
important factor in predicting survival. In the Seattle experience, age over 50 years was associated with a greater than 60% mortality rate at
2 years after transplantation.1 In patients under
age 50 receiving transplants within the first year of diagnosis, the 5-year survival rate was 74%. The HLA sibling transplantation experience is a bit more complicated and may relate in part to the
conditioning regimen. In particular, the use of busulfan and cyclophosphamide, as opposed to cyclophosphamide and total body irradiation, may have a lower mortality rate. Whether this will also
apply to unrelated transplantations is unknown. But this may account
for some of the variability reported by individual centers.
Despite this, even sibling transplantations carry a significant
mortality rate in the first 2 years following transplantation. For a
Sokal or Hasford low-risk patient of older age, for whom median
survival with nontransplantation therapy may approach 10 years,
we would be less likely to consider transplantation as initial
therapy. Ultimately of course, the final decision will be the
patient's.
John M. Goldman and Brian J. Druker
Correspondence: Brian J. Druker, Oregon Health and Science
University, Division of Hematology and Medical Oncology, 3181 SW Sam
Jackson Park Rd, L592, Portland, OR 97201-3098
References
1.
Hansen JA, Gooley TA, Martin PJ, et al.
Bone marrow transplantation from unrelated donors for patients with chronic myeloid leukemia.
New Engl J Med.
1998;338:962-968[Abstract/Free Full Text]
