Reduced-intensity conditioning followed by unrelated umbilical cord blood transplantation for advanced hematologic malignancies: rapid engraftment in bone marrow.

Abstract

Reduced-intensity (RI) conditioning followed by cord blood transplantation (CBT) is a new treatment modality, but failure to engraft is a major concern. We describe 12 patients with advanced hematologic malignancies who underwent RI conditioning and CBT with a conditioning regimen consisting of 200 mg/m(2) fludarabine (Flu), 50 mg/kg cyclophosphamide (CY), and 3 Gy total body irradiation (TBI). Cyclosporin A and/or methotrexate were used for graft-versus-host disease prophylaxis. Cord blood grafts were not mismatched for more than 2 serologically defined HLA alleles but were later found by high-resolution DNA typing to be mismatched for 2 to 4 alleles in most cases. Short tandem repeat analysis of bone marrow cells at day 14 showed complete donor chimerism in 6 of the patients and mixed chimerism in 5, indicating rapid engraftment in the bone marrow, whereas the remaining patient experienced graft rejection. Neutrophil recovery was achieved at a median of day 17 (range, days 11-24) in 10 of the 11 patients with marrow chimerism at day 14. Of these 10 patients, however, transplantation-related mortality within 100 days occurred in 4 patients who showed failed platelet recovery and a lack of durable engraftment. Overall survival and disease-free survival rates were 41.7% and 33.3%, respectively. These results show that CB mismatched at 2 to 4 HLA alleles and transplanted with the Flu/CY/3 Gy TBI regimen is able to engraft in the bone marrow as early as day 14.

• Authors: Mahito Misawa, Shunro Kai, Masaya Okada, Toshiyuki Nakajima, Kaori Nomura, Takeshi Wakae, Akinari Toda, Hisayuki Itoi, Hiroyuki Takatsuka, Takeyoshi Itsukuma, Keisuke Nishioka, Yoshihiro Fujimori, Hiroyasu Ogawa, Hiroshi Hara
• Journal: International journal of hematology (Int J Hematol) Vol. 83 Issue 1 Pg. 74-9 (Jan 2006) ISSN: 0925-5710 [Print] Japan
• PMID: 16443557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Myeloablative Agonists
• Cyclosporine
• Cyclophosphamide
• Vidarabine
• fludarabine
• Methotrexate

Topics

• Adult
• Bone Marrow
• Cord Blood Stem Cell Transplantation (methods, mortality)
• Cyclophosphamide (administration & dosage)
• Cyclosporine (administration & dosage)
• Disease-Free Survival
• Female
• Graft Survival (drug effects, radiation effects)
• Graft vs Host Disease (prevention & control)
• Hematologic Neoplasms (mortality, therapy)
• Humans
• Immunosuppressive Agents (administration & dosage)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Myeloablative Agonists (administration & dosage)
• Transplantation Chimera
• Transplantation Conditioning (methods, mortality)
• Treatment Outcome
• Vidarabine (administration & dosage, analogs & derivatives)
• Whole-Body Irradiation (methods, mortality)