Reduced intensity conditioning allows for up-front allogeneic hematopoietic stem cell transplantation after cytoreductive induction therapy in newly-diagnosed high-risk acute myeloid leukemia

Abstract

There is substantial need to improve the outcome of patients with high-risk acute myeloid leukemia (AML). The clinical trial reported here investigated a new approach of up-front allogeneic hematopoietic stem cell transplantation (HSCT), provided a median of 40 days (range 22-74) after diagnosis, in twenty-six consecutive patients with newly-diagnosed high-risk AML characterized by poor-risk cytogenetics (n ¼ 19) or inadequate blast clearance by induction chemotherapy (IC, n ¼ 7). The median age was 49 years (range 17-68). During IC-induced aplasia after the 1st (n ¼ 11) or 2nd (n ¼ 15) cycle, patients received allogeneic peripheral blood stem cells (PBSC) from related (n ¼ 11) or unrelated (n ¼ 15) donors following a fludarabine-based reduced-intensity regimen. Seventeen patients were not in remission before HSCT with a median marrow blast count of 34% (range 6-70). All patients achieved rapid engraftment and went into remission with complete myeloid and lymphatic chimerism. Grades II to IV acute GvHD occurred in 14 (56%) and extensive chronic GvHD was documented in 8 (35%) patients. The probability of disease-free survival was 61% with only three patients relapsing 5, 6 and 7 months after transplantation, respectively. Up-front allogeneic HSCT as part of primary induction therapy seems to be an effective strategy in highrisk AML patients and warrants further investigation.

Early allo-SCT for AML with a complex aberrant karyotype—results from a prospective pilot study

“…In a similar approach, the Dresden Group investigated RIC-HSCT performed in aplasia after induction chemotherapy for high-risk AML. 23 In their study, an impressively short median interval of 40 days between diagnosis and transplantation was achieved by an urgent donor search programme of DKMS (the German bone marrow donor registry), one of the largest stem cell Early allogeneic transplantation for complex karyotype AML C Schmid et al donor registries worldwide. However, it took almost 7 years to include 26 high-risk patients.…”

Feasibility of clofarabine cytoreduction before allogeneic transplant conditioning for refractory AML

“…The feasibility of this strategy has been shown prospectively, both as initial therapy for patients with high-risk disease and for refractory patients with active disease. 10,11 We have given clofarabine with the intent to reduce disease burden immediately before HCT for AML. Clofarabine has significant activity in relapsed leukemia with low morbidity and mortality in the elderly.…”

“…10,11 This cytoreductive chemotherapy 'bridge' has produced promising results in early studies for patients with newly diagnosed high-risk disease and relapsed patients with active disease. We have employed clofarabine salvage for this purpose and present results from 17 consecutive patients.…”

Reduced-intensity conditioning for acute myeloid leukemia: is this strategy correct

“…Table 3 presents the results of 14 relatively recent published experiences of using reduced-intensity conditioning in trials that enrolled at least 15 AML patients. 19,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] In general, most of the trials were conducted during the periods from 1998 through 2004 but the publications reported heterogeneous patients with respect to disease status at transplant (CR1, CR2, relapse, refractory disease). Further, the reports often differed as to whether the studies were retrospective analyses versus prospective trials.…”