non-myeloablative stem cell transplantation in hematologic malig nancies: an experience from the hematology-oncology and bmt re search center

background: myeloablative-allogeneic stem cell transplantation is a common way of treating various malignant and nonma-lignant diseases; but, it is associated with hazardous immediate and late complications. the majority of patients are not good candidates for high dose therapy because of old age, medical co-morbidities or previous heavy treatments. the donor stem cells can engraft in the recipient and induce mixed chimerism when we use a less intensive, but sufficiently immunosup-pressive, conditioning regimen, known as mini-transplantation or non-myeloablative allogeneic stem cell transplantation (nm-allo-sct).
methods: the conditioning regimens were the combination of fludarabine and cyclophosphamide or busulfan and atg. prophylaxis against graft versus host disease (gvhd) included cyclosporine a (csa) +/- methotrexate. a multiplex-pcr using short tandem repeats (vntr) was used for chimerism analysis.
results: we report the results of nm-allo-sct from the hla-identical siblings in 20 patients with aml (n=7), cml (n=6), nhl (n=2), mds (n=2), all (n=1) and fanconi anemia (n=2). fourteen males and 6 females with median age of 43 years (range 8-55) underwent nm-allo-sct and were followed up 4-870 days (median 420 days). typical side effect of conventional hsct, such as severe mucositis, vomiting and vod were absent. most of the patients did not become se verely pancytopenic and had relatively short hospitalization. hematological recovery was rapid, a median of 8.5 days. acute gvhd (grade ≥ii) and extensive chronic gvhd was observed in three patients. most of the patients initially had mixed-chimerism, progressing to full-donor-chimerism in 11 patients, after the interruption of the csa therapy, and, in one patient, after dli. nine patients died, six from relapse or disease progression and three from transplantation-related complications (gvhd, infection or secondary malignancy). 14 month overall survival and disease free survival of 55% and 50%, respec tively, was observed.
conclusion: our results confirm that nm-allo-sct is safe and minimally toxic and is a potential new approach for a safer treatment of a large variety of hematologic diseases, especially in patients with aml and cml in remission.