Cytoreductive treatment with clofarabine/ara‐C combined with reduced‐intensity conditioning and allogeneic stem cell transplantation in patients with high‐risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome

Abstract

The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

Idarubicin-intensified BUCY2 conditioning regimen improved survival in high-risk acute myeloid, but not lymphocytic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: A retrospective comparative study

“…Some retrospective analysis demonstrated that sequential use of cytoreductive chemotherapy and reduced-intensity conditioning (RIC) was highly effective to eradicate leukemia for high-risk, relapsed, or refractory AML patients undergoing allo-HSCT. The long-term survival reached up to 52%, and even higher at 72.7% for those patients in CR1 [39]. Here in our study, IDA-intensified regimen significantly improved the survival in high-risk AML patients.…”

Low efficacy and high mortality associated with clofarabine treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes

“…Additional studies have also supported use of clofarabine either for cytoreduction or conditioning purposes [23][24][25][26][27][28]. Concerns for increased post-transplant hepatotoxicity in clofarabine-treated patients, given the hepatotoxicity of the drug, have thus far not been substantiated [29].…”

Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome

“…To overcome the limitation of long-lasting myelosuppression but gain the antileukemic effect of pretransplantation induction chemotherapy, some centers have evaluated AML-like induction chemotherapies, such as anthracycline/cytosine, arabinoside/fludarabine, or clofarabine/cytosine arabinoside-based chemotherapy, followed by only 3 days' rest before performing a RIC and subsequent allogeneic SCT. [55][56][57] With those conditioning regimens and matched related or unrelated donors, 2-year OS rates of 69% and 56% can be achieved. 56,57 Newer agents, such as 5-azacytidine or decitabine, which have been shown to be active in MDS, 58,59 may also be used as pretransplantation cytoreductive therapy.…”

“…[55][56][57] With those conditioning regimens and matched related or unrelated donors, 2-year OS rates of 69% and 56% can be achieved. 56,57 Newer agents, such as 5-azacytidine or decitabine, which have been shown to be active in MDS, 58,59 may also be used as pretransplantation cytoreductive therapy. However, the CR rate of approximately 10% is much lower than after conventional induction chemotherapy, and the reported trials confirmed the feasibility without significant survival benefit.…”