Autologous Stem Cell Transplantation in Acute Myeloid Leukemia; A Single Centre “Real Life” Study

Background.

Autologous stem cell transplant is a consolidation treatment for standard risk acute myeloid leukemia (AML). Traditional preparative regimens, most of all Busulphan (Bu) based, have been widely used, but the relapse risk is high and extra hematologic toxicity is a concern. Even if the combination of Busulphan intravenous formulation in association with cyclophosphamide has shown lower toxicity and suggests favorable safety and efficacy, new drugs associations are continuously explored.

Methods.

Since April 2004 to January 2013, 39 consecutive patients (20 males, 19 females ) entered this study. Median age at transplant was 51 years (range 21-79). Cytogenetic risk classification at diagnosis was good in 4, intermediate in 29 and poor in 6. At transplant time thirty-six patients were in first complete remission, one in partial remission and two in second complete remissions. Mean number of induction chemotherapy courses received was 2.2.

Conditioning consisted of oral Busulfan/Cyclophosphamide in 13, intravenous once-daily infusion Busulphan/Cyclophosphamide in 11, intravenous Busulfan/Fludarabine in 8, intravenous Busulphan /Melphalan in 3, Treosulfan/Cyclophosphamide in 3 and Treosulfan /Melphalan in 1. In all patients aged less than 70 years an extended patient and family HLA typing was performed at diagnosis to eventually plane a salvage allogeneic transplant since the beginning of the therapy course.

Cytogenetic risk, status of disease, age, number of chemotherapy courses, conditioning regimens have been analyzed. Primary objective was evaluation of overall survival, disease free survival, transplant related mortality and relapse. Comparison analyses were performed with chi square test. All analyses were intention to treat.

Results:

Of the 39 patients studied one patient (2.5%) died for intracranial haemorrhage during the period of aplasia. All the other engrafted. Of the latter all but one had sustained long-term engraftment. Fourteen patients (36%) did not relapse; all but one are alive and well in continuous complete remission. The only patient who died in remission had lethal infection after salvage allogeneic transplant performed for persistent cytopenias. Twenty-four patients (61%) relapsed

Of the 24 relapsed patients eleven (46%) received a second allogeneic transplant after re-induction chemotherapy (all but one from alternative donors: 8 from a matched unrelated donor, 1 from an aplo-identical family member and one from an unrelated cord blood donor). Of them six have died by transplant related mortality and 5 are alive (4 in complete remission).

Overall nineteen over 39 patients (49%) are alive after a median follow up of 60 months (range 18-120); seventeen (44% of the entire cohort) in complete remission and two with persistent disease.

As regard the 13 patients who didn’t relapse all were transplanted in first complete remission; cytogenetic risk was good in 2, intermediate in 10 and poor in 1; leukemia chemotherapy induction was standard Daunoblastina- Cytarabine (3+7 schedule) in all; transplant conditioning regimens were oral Busulphan/Cyclophosphamide in 6 and intravenous once-daily dose Busulphan in association with cyclophosphamide or Fludarabine in 7.

In our analyses the only risk factor impacting on patients’ outcome was patient age at transplant time. Age impacted overall survival and disease free survival. Median age was 61years (range 21-79 ) in patients who died versus 36 years (range21-68) in patients alive (P = 0.03 ) and 64 years ( 21-79) in patients with relapse versus 36 years (21-60) in patients who didn’t relapse (P = 0.04). No other factor had impact on outcome.

Conclusion.

This limited, single centre experience, confirms that autologous hematopoietic stem cell transplant is an efficient consolidation treatment for AML in remission. Relapse still remains the major problem even if some selective patients may be rescued by allogeneic transplant after a re-induction strategy. A complete HLA family study and preliminary unrelated research should be early performed in all patients for optimal treatment plan and decision.