AUTOGRAFTING IN CHRONIC MYELOID-LEUKEMIA WITH CULTURED MARROW - UPDATE OF THE VANCOUVER STUDY

When chronic myeloid leukemia (CML) marrow is set up in long-term cult ure (LTC), Philadelphia chromosome (Ph)-positive (Ph+) cells typically decline and Ph-negative (Ph-) hematopoietic cells often become detect able. In 1987, we initiated a study to evaluate the feasibility of usi ng 10-day cultured marrow autografts to allow intensive treatment of C ML. Patients were selected on the basis of a previous assessment of th e frequencies of normal and leukemic LTC-initiating cells (LTC-IC) rem aining in their marrow after 10 days of LTC. Of the 87 patients evalua ted, 36 (41%) were considered eligible, and 22 (15 in first chronic ph ase [CP], Group 1; and 7 with more advanced disease, Group 2) were aut ografted with 10-day cultured marrow after intensive therapy. Satisfac tory hematological recovery occurred in 16 patients, and of these, onl y Ph cells were detected in 13 (nine in Group 1), with 76-94% Ph- cell s in the other three (two in Group 1). Ph+ cells reappeared between 4 and 36 months post-autograft in all but one of the 13 patients in whom complete (morphological and cytogenetic) remission had been achieved; the remaining patient died in remission. Nine of these twelve patient s were then treated with alpha-interferon (IFN-alpha) 1-3 x 10(6) unit s/m2, 3-7 days/week; four returned to complete remission, three develo ped increasing numbers of Ph+ cells, and two are still too early to ev aluate. Fifteen patients (12 in Group 1) remain alive and well, nine i n hematological remission (eight in Group 1), 9 to 64 months (median 2 8) post-autograft. Another patient (Group 1) remains alive 30 months p ost-autograft but has developed blast phase disease. Four patients (al l in Group 1) continue in complete remission after treatment with IFN- alpha. These results establish the feasibility of using cultured marro w autografts for the treatment of CML.