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Michael J. Barnett, Connie J. Eaves, Gordon L. Phillips, Donna E. Hogge, Hans-G Klingemann, Peter M. Lansdorp, Stephen H. Nantel, Donna E. Reece, John D. Shepherd, Heather J. Sutherland, Allen C. Eaves, Allografting in chronic myeloid leukemia with cultured marrow: Update of the vancouver study, Stem Cells, Volume 11, Issue S3, 1993, Pages 64–66, https://doi.org/10.1002/stem.5530110916
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Abstract
When chronic myeloid leukemia (CML) marrow is set up in long-term culture (LTC), Philadelphia chromosome (Ph)-positive (Ph+) cells typically decline and Ph-negative (Ph−) hematopoietic cells often become detectable. In 1987, we initiated a study to evaluate the feasibility of using 10-day cultured marrow autografts to allow intensive treatment of CML. Patients were selected on the basis of a previous assessment of the frequencies of normal and leukemic LTC-initiating cells (LTC-IC) remaining in their marrow after 10 days of LTC. Of the 87 patients evaluated, 36 (41%) were considered eligible, and 22 (15 in first chronic phase [CP], Group 1; and 7 with more advanced disease, Group 2) were autografted with 10-day cultured marrow after intensive therapy. Satisfactory hematological recovery occurred in 16 patients, and of these, only Ph− cells were detected in 13 (nine in Group 1), with 76–94% Ph− cells 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 patients were then treated with α-interferon (IFN-α) 1–3 × 106 units/m2, 3–7 days/week; four returned to complete remission, three developed increasing numbers of Ph+ cells, and two are still too early to evaluate. Fifteen patients (12 in Group 1) remain alive and well, nine in hematological remission (eight in Group 1), 9 to 64 months (median 28) post-autograft. Another patient (Group 1) remains alive 30 months post-autograft but has developed blast phase disease. Four patients (all in Group 1) continue in complete remission after treatment with IFN-α. These results establish the feasibility of using cultured marrow autografts for the treatment of CML.