Contributions
Abstract: PB2432
Type: Publication Only
Background
A sequential conditioning provides promissing results that has not, otherwise, been validated in haploidentical setting. Only 10-20% of refractory acute myeloid leukaemia (AML) achieve complete remission (CR) with another course of chemotherapy, and less than 20% of OS is reached after a year in this high risk population, this approach could be meant to obtain the best outcome. With similar chemotherapy schemes it has been obtained a 40% OS but still unsatisfactory results due to toxicity.
Aims
We show our experience with clofarabine-based sequential chemotherapy in haploidentical SCT followed by TBF reduced intensity conditioning (RIC-TBF) (thiotepa, busulfan, fludarabine) and post transplant cyclophosphamide (PTCy) plus tacrolimus as graft versus host disease prophylaxis (GvHD).
Methods
We collected data retrospectively of 15 cases of refractory/relapsed/progressive haematological malignancies who received clofarabine based sequential conditioning followed by RIC-TBF. As a standard, we have used clofarabine at the dose of 40mg/m2/day from days -13 to -9 (5 doses), alongside cytarabine 2000 mg/m2/day. Once the disease burden was reduced, thiotepa 5 mg/Kg/day on days -5 and -4, fludarabine 50 mg/m2 on days -3 and -2, and busulfan 3.2mg/Kg on day -2 were administered. Only one patient received fludarabine instead of clofarabine for burden mass reducing. As GvHD prophylaxis we combined PTCy 50 mg/Kg/day on days +3 and +4 with tacrolimus in all cases, adding sirolimus in one patient, or mycophenolate mofetil in other two cases.
Given the clinical situation, and because all patients lacked a suitable HLA matched donor, an haploidentical donor was selected with a median age of 36 years old (16-62) and a sex ratio male-female of 60%>40%.
From our N of 15 patients (median age 39 yrs (6-66), male/female 7/8), the underlying conditions were AML 46.6%, ALL 33.3% and MDS 20%, with disease status pre-transplant of refractoriness in 73.3%, 13.3% relapsed and 13.3% progressed. Sorror HCT -CI scoring was 40%, 40% and 20% for 0, 1 and ≥3 respectively. Disease scoring risk of high/very high (86.7%).
Results
With a median follow up among survivor of 19.3 months an estimated OS and RFS at 13 months of 58.2% and 43.6% respectively. A CR at day +90 was achieved in 80% of the cases (12). In two patients, the test could not be assessed due to early death at days +48 and +57.
Four patients (26.7%) relapsed at a median period time of 6 months (range 2-9) and 2 of these died. All together (6 patients) died while 4 of these cases were non leukaemia related. Transplant related mortality of the entire cohort was 26,7%. We had 53.3% of grade ≥3 aGvHD with a median onset at D+55 and cGvHD (at least moderate) in 3 cases (20%) with a median onset of D+302.
Conclusion
With promising results, even though presenting a small N of 15 patients, a significant reduced disease burden and limited toxicity due to RIC with thiotepa T cell replete haplo SCT, allows to show feasibility with significant OS, RFS rates and a good quality of life (QoL) for patients with a presumed very poor outcome.
There are still several challenging goals to achieve, that we need to work on, especially on considering to reduce the incidence of GvHD without incrementing the relapse rate, thus, overall means to improve a QoL, which would be the ultimate target.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Clofarabine, Haploidentical stem cell transplantation, Reduced intensity transplantation, Refractory
Abstract: PB2432
Type: Publication Only
Background
A sequential conditioning provides promissing results that has not, otherwise, been validated in haploidentical setting. Only 10-20% of refractory acute myeloid leukaemia (AML) achieve complete remission (CR) with another course of chemotherapy, and less than 20% of OS is reached after a year in this high risk population, this approach could be meant to obtain the best outcome. With similar chemotherapy schemes it has been obtained a 40% OS but still unsatisfactory results due to toxicity.
Aims
We show our experience with clofarabine-based sequential chemotherapy in haploidentical SCT followed by TBF reduced intensity conditioning (RIC-TBF) (thiotepa, busulfan, fludarabine) and post transplant cyclophosphamide (PTCy) plus tacrolimus as graft versus host disease prophylaxis (GvHD).
Methods
We collected data retrospectively of 15 cases of refractory/relapsed/progressive haematological malignancies who received clofarabine based sequential conditioning followed by RIC-TBF. As a standard, we have used clofarabine at the dose of 40mg/m2/day from days -13 to -9 (5 doses), alongside cytarabine 2000 mg/m2/day. Once the disease burden was reduced, thiotepa 5 mg/Kg/day on days -5 and -4, fludarabine 50 mg/m2 on days -3 and -2, and busulfan 3.2mg/Kg on day -2 were administered. Only one patient received fludarabine instead of clofarabine for burden mass reducing. As GvHD prophylaxis we combined PTCy 50 mg/Kg/day on days +3 and +4 with tacrolimus in all cases, adding sirolimus in one patient, or mycophenolate mofetil in other two cases.
Given the clinical situation, and because all patients lacked a suitable HLA matched donor, an haploidentical donor was selected with a median age of 36 years old (16-62) and a sex ratio male-female of 60%>40%.
From our N of 15 patients (median age 39 yrs (6-66), male/female 7/8), the underlying conditions were AML 46.6%, ALL 33.3% and MDS 20%, with disease status pre-transplant of refractoriness in 73.3%, 13.3% relapsed and 13.3% progressed. Sorror HCT -CI scoring was 40%, 40% and 20% for 0, 1 and ≥3 respectively. Disease scoring risk of high/very high (86.7%).
Results
With a median follow up among survivor of 19.3 months an estimated OS and RFS at 13 months of 58.2% and 43.6% respectively. A CR at day +90 was achieved in 80% of the cases (12). In two patients, the test could not be assessed due to early death at days +48 and +57.
Four patients (26.7%) relapsed at a median period time of 6 months (range 2-9) and 2 of these died. All together (6 patients) died while 4 of these cases were non leukaemia related. Transplant related mortality of the entire cohort was 26,7%. We had 53.3% of grade ≥3 aGvHD with a median onset at D+55 and cGvHD (at least moderate) in 3 cases (20%) with a median onset of D+302.
Conclusion
With promising results, even though presenting a small N of 15 patients, a significant reduced disease burden and limited toxicity due to RIC with thiotepa T cell replete haplo SCT, allows to show feasibility with significant OS, RFS rates and a good quality of life (QoL) for patients with a presumed very poor outcome.
There are still several challenging goals to achieve, that we need to work on, especially on considering to reduce the incidence of GvHD without incrementing the relapse rate, thus, overall means to improve a QoL, which would be the ultimate target.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Clofarabine, Haploidentical stem cell transplantation, Reduced intensity transplantation, Refractory