Changing approaches to transplant conditioning for hematologic malignancy.

Abstract

H E C L A SS IC C O N C E P T R E G A R D IN G BMT in hematologic malignancy holds that myeloablative conditioning is a prerequisite for cure. However, as many as one third of patients may die from complications after this procedure. A preliminary publication in 1985, dealing with 5 cases of accelerated CML using dibromomannitol/ cytarabine/cyclophosphamide preconditioning instead of TBI stated that “ full eradication of leukemia clones in the course of preconditioning does not seem to be a prerequisite for eventual cure” of accelerated CML (1). The role of the graft vs. leukemia effect was considered. Surprisingly, few cases of acute graft vs. host disease, interstitial pneumonitis, and septic infection were seen with this nonmyeloablative preconditioning even among 19 additional patients allotransplanted from identical siblings, reported in 1993 and 1998 (2,3). In these cases, venoocclusive liver disease and severe mucositis were absent. Although only 9 of 33 patients were under 30 years of age and only 10 patients had a history of disease of less than 1 year, the leukemia-free survival was 82% even though 5 patients exhibited accelerated processes. In the entire patient group, there were 8 hematologic relapses. The reduction in post-BMT complications has greatly enhanced the quality of life of such patients. Normal pregnancy occurred in 2 of 4 female patients of childbearing age. The remarkable reduction in certain transplant-related complications showed some advantage as compared with busulfan conditioning. Nurses reported significant reduction of workload, and savings in eliminating the need for irradiation, parenteral nutrition, and antibiotics were also remarkable. Of the Abstracts of the 1998 Annual Meeting of the American Society of Hematology (4), 11 deal with nonmyeloablative clinical stem cell transplantation in children and adult recipients, matched and mismatched, related and unrelated donors, with application of blood stem cells. In these reports, 1‐ 45 patients were treated, and 6 of 11 studies included 10 or more patients. Although the minimum follow-up period in these cases was short (3 weeks‐ 2 months), the longest follow-up was 16 months. In our last series (3), the minimum follow-up period was extended to 3 years, and the longest follow-up period was 7 1/2 years. In 4 of 11 abstracts, including a study of 48 cases, the follow-up period is not included.