[Autogeneic peripheral blood hemopoietic stem cell transplantation for chronic myeloid leukemia with imatinib mesylate-induced negative Philadelphia chromosome].

Objective: To study the possibility of curing chronic myeloid leukemia with autogeneic hemopoietic stem cell transplantation in patients with negative Philadelphia (Ph) chromosome induced by imatinib mesylate (STI 571) treatment.

Methods: Two patients with chronic myeloid leukemia in chronic phase, who had 90% Ph chromosome-positive cells and bcr/abl fusion gene-positive cells as shown by interphase fluorescence in situ hybridization (I-FISH), failed to respond favorably to interferon-alpha therapy in the treatment courses of 7 and 8 months, respectively. Treatment with STI 571 at a daily dose of 300 to 400 mg for 5 months to 8 months was subsequently implemented, after which the Ph chromosome and bcr/abl fusion genes became normal in detection for 3 times. Peripheral blood haemopoietic stem cell mobilization was then initiated by intravenous injection of cytarabine (2.0 g/d) for 3 days, etoposide (0.2 g/d) for 3 d and cyclophosphamide (1.0 g/d) for one day. When the white blood cell was below 1.0x10(9)/L, the G-CSF (300 microg/d) was administered subcutaneously for 5 or 6 d, and the peripheral blood mononuclear cells were collected by CS3000 Plus blood cell separator. The percentage of bcr/abl fusion gene-positive cells among CD34(9) cells enriched by MiniMAC ranged from 11% to 14%. After 3 or 4 weeks, the patients received total body irradiation at 9 Gy given in 2 fractions, with intravenous injection of cyclophosphamide (60 mg/kg daily) and etoposide (300 mg/d) for 2 d. On the day of transplantation, the collected mononuclear cells were 4.17x10(8)/kg and 3.9x10(8)/kg, with CD34(+)/ cells reaching 4.89x10(6)/kg.b.w and 4.89x10(6)/kg. CsA was also used since day -1 to day +13 of the transplantation for prevention of graft-versus-host disease. G-CSF was administrated daily at the dose of 300 microg subcutaneously from day +3 to +12.

Results: After the transplantation, the absolute neutrophil count (ANC) took a mean of 11 d to exceed 0.5x10(9)/L in these two patients, and 19 and 21 d, respectively, were needed for the platelet count to exceed 20x10(9)/L. The two patients showed cytogenetic relapse at 120 and 300 d after the transplantation, respectively.

Conclusion: Autogeneic peripheral blood stem cells transplantation after Ph chromosome is negative in patients with chronic myeloid leukemia, who receive STI 571 treatment, may also relapse, and more radical elimination of Ph chromosome-positive cells is needed.