Pretransplant imatinib can improve the outcome of nonmyeloablative stem cell transplantation without increasing the morbidity in Philadelphia chromosome-positive chronic myeloid leukemia [3]

Indications:10 patients with Philadelphia chromosome-positive chronic myeloid leukemia (chronic phase [CP] 3 and accelerated phase 7).

Patients:20 patients were studied. Pre-NST Glivec group: 10 patients, 4 male and 6 female, aged 27 to 54 years. The median time to the last follow-up was 18 months. No Glivec group: 10 patients, 7 male and 3 female, aged 31 to 55 years; 4 patients were subsequently treated with Glivec. The median time to the last follow-up was 20 months.

TypeofStudy:This study described the impact of a long-term pre-transplant treatment with Glivec on engraftment following nonmyeloablative stem cell transplantation (NST), transplant-related morbidity and mortality (TRM), graft-versus-host disease (GVHD), relapse, and survival in patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML).

DosageDuration:Initially 400-600 mg daily orally; doses were adjusted according to dosing guidelines. Dosing was continued until complete cytogenetic response (CCR) or the major response for more than 6 months was achieved and was stopped 10 days before starting the conditioning regimen for NST. Duration: 6-12 months (median, 9.5 months).

Results:After a median Glivec treatment of 9.5 months, 9/10 patients achieved a CCR and 1/10 patient returned to CP at a transplant. No differences in the engraftment and morbidity were observed between the two groups. In the pre-NST Glivec group, 1/10 patient developed a cytogenetic relapse after transplant, and received Glivec. Following Glivec treatment of more than 6 months, all 10 pre-NST Glivec patients were successfully engrafted. In addition, there were no significant differences in the period of cytopenia between the 2 groups. At present, all have maintained a CCR and are alive. In the no Glivec group, 4/10 patients developed a hematological relapse after transplant, and received Glivec. 2/10 patients died from multi-organ failure and relapse, respectively. Overall, 8 patients are alive including 6/8 patients in CCR. In the pre-NST Glivec group, only 1 patient who was in CP at the transplant demonstrated a high transcript level ≥ 0.01 and 5 patients showed the transcript level ≥ 0.001 at 3 months. From 3 to 6 months, only 2/9 MRD-assessable patients had a mild increase in the transcript level within 1 log. Overall, 7 patients maintained a molecular remission (MR). In the no Glivec group, although the transcript level increased only in 1/9 assessable patients during the early 3 months, 4/9 patients demonstrated a high transcript level ≥ 0.01 and 7/9 patients showed the transcript level ≥ 0.001 at 3 months. An increasing transcript level was observed in 6/9 patients between 3 and 6 months. Overall, 2/10 patients sustained an MR. The MR rates were significantly different between the 2 groups (83.3 vs. 40%). A lower frequency and lower intensity of the acute GVHD were observed in pre-NST Glivec group; only 2/10 patients had acute GVHD with a grade I intensity (vs. 3/9 patients in no Glivec group). However, chronic GVHD (6/10 patients and 5/9 patients in the pre-NST Glivec and no Glivec groups, respectively) occurred with similar frequency in other conventional NST studies. Overall, the incidence of GVHD between the 2 groups was similar. All the 5 patients who were treated with Glivec for a post-transplant relapse showed no recurrence of the GVHD.

AdverseEffects:No adverse events were mentioned.

AuthorsConclusions:In conclusion, this study suggests that pre-transplant imatinib can lead to a durable engraftment and elimination of molecular evidence of the disease with minimum toxicity. As a small number of patients were involved in this study, prospective randomized trial with a larger number of patients would be required to confirm these clinical observations.

FreeText:All 20 patients received fludarabine-based regimens and the cyclosporine or the tacrolimus used for GVHD prophylaxis was tapered during or after the third month post-transplant according to the minimal residual disease (MRD) status and the evidence of GVHD. Tests: conventional cytogenetics, nested reverse transcriptase polymerase chain reaction (RT-PCR), and quantitative real time RT-PCR, bone marrow aspiration, and BCR-ABL transcript.