Allogeneic Hematopoietic Cell Transplantation Is a Curative Treatment Option for Advanced-Stage Chronic Myeloid Leukemia in the TKI Era, a Single Institution Retrospective Study of 29 Post AP/BC Cases

BACKGROUND: The prognosis of chronic myeloid leukemia (CML) in advanced stages (accelerated phase or blast crisis) is still poor even with tyrosine kinase inhibitors (TKIs). Allogeneic hematopoietic cell transplantation is the only curative treatment for them. METHOD: Using our database, we retrospectively collected CML patients transplanted at Toranomon Hospital between June 2004 and March 2014, after the introduction of TKIs in Japan. RESULT: Twenty-nine consecutive patients were extracted. The median age was 52 years (range; 16-70). The disease status at diagnosis was chronic phase (CP, n=11), accelerated phase (AP, n=5) and blast crisis (BC, n=13). All patients were treated with TKIs before transplantation including imatinib (n=15), nilotinib (n=1), dasatinib (n=6), imatinib/dasatinib (n=4), nilotinib/dasatinib (n=1) and imatinib/nilotinib/dasatinib (n=2). All of 11 patients in CP at diagnosis progressed into AP/BC in their course and only 3 patients achieved second CP at transplantation. On the other hand, 11 of 18 patients in AP/BC at diagnosis achieved CP at transplantation and the remaining 7 patients did not achieve CHR. (Fig.1) The median HCT-CI and EBMT score at transplantation was 2 (range, 0-5) and 5 (range, 0-7), respectively. Additional cytogenetic abnormalities developed in 19 of 29 patients until transplantation. Point mutations in ABL gene were detected in 9 of 20 patients (45%) in their course. Overall, 14 of 29 (48%) patients underwent transplantation in CP stage. The donors were related PBSC (n=6), unrelated BM (n=4) or unrelated CB (n=19). The conditioning regimens were myeloablative in 20 patients and reduced-intensity in 9. Twenty-seven patients achieved neutrophil engraftment at a median day of 19 (range, 10-34). The cumulative incidence of neutrophil engraftment was 93.1% at day 42 (patients engrafted, n=27; dead before day 19, n=2). At 3 years, the cumulative incidence of relapse and non-relapse mortality was 32.3% and 14.0%, respectively. In 15 patients who did not achieve CP before transplantation, 11 patients (73.3%) achieved CR after transplantation. With a median follow-up of survivors of 1144 days (range, 127-3705), overall survival (OS) and event free survival (EFS) at 3 years was 63.2% and 56.3%, respectively. In univariate analysis, the variables that influenced on OS were disease status at transplantation (CP vs. AP/BC, 85% vs. 42%, p=0.012), karyotype (sole Ph-chromosome vs. additional cytogenetic abnormalities, 90% vs. 47.5%, p=0.042) and conditioning regimen (MAC vs. RIC, 72.7% vs 41.7%, p=0.039). In multivariate analysis, the only variable that influenced on OS was disease status at transplantation (p=0.015). CONCLUSION: We concluded that allogeneic hematopoietic cell transplantation from any cell sources could become a promising option for the patients with CML in advanced stage, especially if they achieved CP before transplantation.