Autologous Stem Cell Transplantation with PCR-Negative Graft Would Be Associated with a Favorable Outcome in Core-Binding Factor Acute Myeloid Leukemia

Abstract

Although core-binding factor acute myeloid leukemia (CBF-AML) is generally considered to be a low-risk form of AML, the survival rate is still 50% to 60%. To evaluate the effectiveness of autologous stem cell transplantation (ASCT) with a PCR-negative graft we analyzed a series of consecutive CBF-AML patients. Between 1997 and 2006, 18 patients aged<60 years were referred under a diagnosis of CBF-AML. Peripheral blood stem cells (PBSC) were collected after a second or further course of postremission therapy. When >2.0x10(6)/kg CD34-positive cells with minimal residual disease (MRD) undetectable by nested polymerase chain reaction (PCR) had been collected, ASCT was performed with busulfan, etoposide, and cytarabine combined with granulocyte colony-stimulating factor. Event-free survival (EFS) and complications of ASCT were then assessed. Fourteen of the 18 patients received ASCT. The median observation period was 4.4 years. The 5-year EFS was 93% for ASCT patients, despite the presence of adverse factors. In 8 of 10 patients who had detectable MRD in the bone marrow before ASCT, MRD became undetectable after ASCT. Neutrophils recovered promptly within 2 weeks, but platelets recovered relatively slowly. Half of the patients suffered from varicella zoster virus infection. Although 1 case of myelodysplastic syndrome occurred, there was no case of relapse. ASCT with a PCR-negative graft was associated with excellent EFS. For patients with CBF-AML, especially with adverse factors or remnant MRD in the bone marrow, this strategy is the treatment of choice.

Prognostic value of CD34+ peak in peripheral blood during mobilization in intermediate-risk AML patients treated in first CR by autologous or allogeneic transplantation

“…17 Good cytogenetic risk patients can also have excellent results after auto-SCT. 18 Based on our work, the pattern of CD34 þ cell mobilization could CD34 peak in AML G Milone et al also be useful in selecting the patients for auto-SCT. However, a direct comparison of the value of these different assays is needed, as well as determining their reproducibility in different clinical settings.…”

The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential

“…Patients with high levels of PB CD34+ cells have a high relapse rate and shorter disease-free and overall survival. Our results might pave the way towards achieving better results with ASCT [15] by more accurate identification of patients who can be cured by ASCT. High levels of CD34+ cells may be used to identify patients who should receive additional therapy, but not necessarily ASCT.…”

Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia

“…In addition, we have previously shown the utility of SCT using autologous disease-free peripheral blood stem cells in the first remission period of t(8;21) AML, including cases of c-kit mutations at initial presentation. 31 This result is intriguing because it suggests that autologous peripheral blood stem cells without residual disease are useful against t(8;21) AML with c-kit mutations. Taking the above into consideration, future studies should investigate stratification of SCT indications during the first remission period according to genetic mutations such as ckit mutations and Flt3 ITD for t(8;21) AML, similar to current investigations for normal karyotype AML.…”

“…PCR amplification of c-kit and Flt3 ITD was performed as previously described. 31,32 Mutational analysis of the extracellular domain (exons 8 and 9), transmembrane domain (exon 10), juxtamembrane domain (exon 11) and the second intracellular kinase (TK) 2 domain (exons 17 and 18) of the c-kit gene was carried out with PCR followed by direct sequencing. Specific sequences of primers used for PCR and sequencing are available on request.…”