Prevention of graft-versus-host disease by lymphocyte depletion of the bone marrow graft with use of counterflow centrifugation.
A combination of density flotation centrifugation and counterflow centrifugation (elutriation) allows the elimination of 98% of the T-lymphocytes, present in a marrow aspirate. This reduces substantially the occurrence of graft versus host disease (GvHD) after transplantation without loss of the repopulation capacity. A limitation of the traditional Beckman elutriator rotor is the relatively small size of the elutriation chamber, which makes five to six runs, of one hour each, necessary to process the whole bone marrow graft. We developed a new elutriator rotor, containing four disposable elutriator chamber (Dijkstra BV, Amsterdam, The Netherlands), which allows to complete the lymphocyte elimination from the bone marrow graft within 2 hours. Ninety-nine consecutive patients were transplanted with elutriated MLC-negative bone marrow grafts from histocompatible siblings. Indications for transplantation were: AML (n = 32), ALL (n = 34) and CML (n = 33). The grafts contained after counterflow centrifugation a mean of 12.1 (+/- 2.4)% of the nucleated cells, 1.9 (+/- 1.4)% of the T-lymphocytes, and 93.5 (+/- 59.4)% of the CFU-GM, originally present in the collected bone marrow. Immunoprophylaxis post grafting was given to 97 BMT recipients. Primary graft failure occurred in 5 of 95 evaluable patients (5%). The probability of acute GvHD greater than grade 1 at day 100 after BMT was 16%. The projected 3-year estimate of extensive chronic GvHD was 13%. The low incidence of GvHD was associated with a relatively low transplant related mortality in patients above the age of 40 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Haanen
C
C
Division of Hematology, University Hospital, Nijmegen, The Netherlands.
De Witte
T
T
Plas
A
A
Schattemberg
T
T
D000328:Adult; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D002469:Cell Separation / Q000379:methods*; D002498:Centrifugation / Q000379:methods*; D005069:Evaluation Studies as Topic; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007558:Italy / Q000453:epidemiology; D007938:Leukemia / Q000401:mortality / Q000601:surgery*; D008212:Lymphocyte Depletion; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D015996:Survival Rate
D007166:Immunosuppressive Agents