Autografting in Philadelphia (Ph)+ chronic myeloid leukaemia using cultured marrow: an update of a pilot study

Abstract

Incubation of CML marrow in long-term culture (LTC) conditions may result in selection of normal (Ph−) LTC-initiating cells (LTC-IC) as early as 10 days, and in production of Ph− clonogenic cells and mature end cells within 5 weeks. This was the rationale for using marrow cells from 10-day-old LTC to autograft nine chronic phase CML patients, ineligible for HLA-matched sibling donor transplant, and who were selected on the basis of a pre-transplant screening LTC test. Of the transplanted patients three died; two of graft failure and one of therapy-related toxicity with 97% Ph− cells 16 months following the autograft. The reconstituting haemopoietic cells in the seven engrafted patients were 100% Ph− in four, ⩾ 90% Ph− in two and 71% Ph− in the seventh, with a duration of complete cytogenetic response of 6–12 months. Three patients reverted to chronic phase and 100% Ph+ haemopoiesis 27–36 months post-autograft. The other three patients remain in continuous haematological remission with 22% Ph− cells in one and complete cytogenetic remission in the other two 3–4 years post-autograft. IFN therapy was generally introduced on the first evidence of recurrence of Ph+ cells or of cytogenetic deterioration. Further strategies to modulate immune surveillance in vivo may improve the outcome of cultured marrow autografts which give an initial and rather prolonged bias towards Ph− haemopoiesis.