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.