Correspondence

Treatment of Acute Lymphoblastic Leukemia in a Second Remission

N Engl J Med 1995; 332:823-824March 23, 1995

Article

To the Editor:

Barrett et al. (Nov. 10 issue)1 conclude that for children with acute lymphoblastic leukemia (ALL) in a second remission, bone marrow transplants from HLA-identical siblings result in fewer relapses and longer leukemia-free survival than does chemotherapy. This conclusion was based on a comparison of children whose cases were reported to the International Bone Marrow Transplant Registry and children treated with chemotherapy by the Pediatric Oncology Group. Their report arouses some concern.

The comparison does not take into account possible differences between the two groups with respect to race or ethnic background, financial and nutritional status, and type of medical center. Race or ethnic group and malnutrition are independent prognostic factors, confounded by financial status. Children from low-income families, with inadequate nutrition, and of African or Mexican ancestry have less favorable outcomes with leukemia therapy than others.2,3 Such patients tend to be underrepresented in transplantation programs and to have inferior outcomes.4,5 The children who undergo transplantation are treated in major hematology centers, whereas those receiving chemotherapy are treated both in major centers and in satellite facilities.

An alternative conclusion of the study by Barrett et al. might therefore be that children with ALL in a second remission have fewer relapses and longer leukemia-free survival if they are of European ancestry, well nourished, from families with good health insurance and incomes, and treated in major hematology centers.

The lesson to be learned from this controversy is that we need to conduct randomized, prospective clinical trials comparing promising new treatments with conventional treatment before clinical impressions take over, particularly when the methods are as hazardous and the level of emotion as high as they are with leukemia therapy.

Donald Pinkel, M.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX 77030

5 References

1. 1

   Barrett AJ, Horowitz MM, Pollock BH, et al. Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. N Engl J Med 1994;331:1253-1258
   Full Text | Web of Science | Medline

2. 2

   Pinkel D. Ethnicity and survival in children with acute lymphoid leukemia. Leukemia 1993;7:Suppl 2:S146-S147
   Web of Science | Medline

3. 3

   Viana MB, Murao M, Ramos G, et al. Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis. Arch Dis Child 1994;71:304-310
   CrossRef | Web of Science | Medline

4. 4

   Durbin M. Bone marrow transplantation: economic, ethical, and social issues. Pediatrics 1988;82:774-783
   Web of Science | Medline

5. 5

   Pinkel D. Bone marrow transplantation in children. J Pediatr 1993;122:331-341
   CrossRef | Web of Science | Medline

To the Editor:

In their large multi-institutional study, Barrett et al. concluded that for children with ALL in a second remission, bone marrow transplants from HLA-identical siblings result in longer leukemia-free survival than does chemotherapy. In our single-institution study of similar children, all chemotherapy recipients died within 3 years, whereas 8 of 24 patients who received marrow grafts were alive after 3.5 to 6.75 years.1,2 We concluded that marrow grafting after intensive therapy offered the best chance of long-term remission and possible cure.

Now, 10 years after our last report, all bone marrow recipients remain in remission, six with a Karnofsky performance score of 100, one with a score of 90, and one, who had undergone cranial irradiation before transplantation, with leukoencephalopathy and a performance score of 40. We are pleased that the study of Barrett et al. confirms our earlier observations.

F. Leonard Johnson, M.D.
University of Chicago, Chicago, IL 60637

E. Donnall Thomas, M.D.
Fred Hutchinson Cancer Research Center, Seattle, WA 98104

2 References

1. 1

   Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med 1981;305:846-851
   Full Text | Web of Science | Medline

2. 2

   Johnson FL, Thomas ED. Treatment of relapsed acute lymphoblastic leukemia in childhood. N Engl J Med 1984;310:263-263
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Our analyses of leukemia-free survival among children with ALL in a second remission showed no association with race or performance score (a surrogate for nutritional status) in either the chemotherapy group or the transplantation group. Although we did not analyze financial status, transplantation results from European countries with socialized medicine were similar to those in the United States. Although race or ethnic origin and financial status may affect the rate of relapse after initial chemotherapy, these are not important prognostic factors for children beyond the first remission, since this group includes children from all racial and ethnic groups who did not respond to treatment.

Although randomized trials are a good method for comparing alternative therapies, we pointed out in our article that no such study has been feasible because of the limited numbers of patients and the logistic difficulties.

A. John Barrett, M.D.
National Institutes of Health, Bethesda, MD 20892

Brad H. Pollock, Ph.D.
University of Florida College of Medicine, Gainesville, FL 32610

George R. Buchanan, M.D
University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235

Citing Articles (2)

Citing Articles

1. 1

   Lawson, Harrison, Richards, Oakhill, Stevens, Eden, Darbyshire, . (2000) The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the Medical Research Council UKALLR1 study. British Journal of Haematology 108:3, 531-543
   CrossRef

2. 2

   Pierre Bordigoni, Helene Esperou, Gerard Souillet, JosE Pico, Gerard Michel, Brigitte Lacour, Josy Reiffers, Alain Sadoun, Pierre Rohrlich, Jean-Pierre Jouet, Noel Milpied, Patrick Lutz, Emmanuel Plouvier, Guy Cornu, Jean-Pierre Vannier, Virginie Gandemer, HervE Rubie, Nicole Gratecos, Guy Leverger, Jean-Louis Stephan, Patrice Boutard, Jean-Paul Vernant. (1998) Total body irradiation-high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation from HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Societe Francaise de Greffe de Moelle study. British Journal of Haematology 102:3, 656-665
   CrossRef