IS PRE-TRANSPLANT THERAPY A KEY FACTOR IN INFLUENCING POST TRANSPLANTATION RELAPSE INCIDENCE IN EXCESS BLAST (EB) MYELODYSPLASTIC SYNDROMES? A SINGLE CENTRE EXPERIENCE
(Abstract release date: 05/18/17)
EHA Library. BERTANI G. 05/18/17; 182645; PB1931
Giambattista BERTANI
Contributions
Contributions
Abstract
Abstract: PB1931
Type: Publication Only
Background
The importance of pre-transplant disease burden in myelodysplastic sindromes (MDS) as a factor influencing post hematopoietic cell transplantation (HCT) outcome is an important argument of debate. It has been reported that relapse rate (RR) after transplant is reduced in patients entering HCT with a blast cell count < 5%. However, the effect of a pre-transplant debulking therapy in reducing RR has not been clearly demonstrated.
Aims
Here we review our data to evaluate if the intensity of pre-transplant therapy may have influenced post transplant RR.
Methods
In our Institute, we treat all patients with a blast cell count of 10% or higher with a debulking therapy pre-transplant. This is usually an AML-like, cytarabine and anthracycline based, intensive chemotherapy (I.C.). In selected cases fludarabine and cytarabine containing regimens are also used. In the last ten years, in the context of a clinical trial, a series of patients have received a less intensive, hypometilating therapy (repeated courses of 5-azacytidine 75 mg/m2 subcutaneously for 7 days), as bridge to transplant.
Conditioning regimen used in MDS patients is busulfan based in younger patients (Bu-Flu, BU-Cy); in the elderly or less fit patients a RIC regimen (thiotepa 5 mg/kg e.v., fludarabine mg/m2 x 3 and L-PAM 100 mg/m2) is administered.
Results
In the last ten years we performed 14 HCT (between June 2008 and september 2016) in patients with MDS with excess blasts. Median patients age was 63,5 years (range: 49-69), male/female ratio was 9/5. According to IPSS, 12 out of 14 patients were high/ int-2 (2 int-1), 11/14 had > 10% blast cells (EB-2).
According to our centre protocol, we treated 11 patients with EB-2 and 1 patient with EB-1 (with hypercellular bone marrow) with a debulking therapy. This was I.C. in 6 patients and 5-AZA in 6 patiens. Two patients with EB-1 did not receive any therapy pre-transplant. However, both of them are not evaluable, due to early mortality. Transplant conditioning was RIC in 11/14 patients, myeloablative in 3 cases. The donor was a sibling in 9/14, MUD in 5/14.
Four out of six patients treated with I.C. achieved a pre-transplant CR (67%), compared to one out of six in the 5-Aza cohort (17%).
Four patients experienced a relapse post HCT, after a median of 8,5 months (4-11). With a median follow up of 21 months (6-68), post transplant RR was 4/12 (33,3%) and was not influenced by debulking therapy (I.C. vs 5-Aza, p=0,54), nor by pre-transplant disease state (CR vs noCR, p=0,22). In fact, 3 out of 6 patients treated with I.C., but only 1 out of 6 treated with 5-Aza relapsed after transplant. Three out of four patients who subsequently relapsed had recived RIC transplant; type of transplant was not assocaited with relapse (P=1,0) The only variable that showed a trend for reduced RR was MUD transplant (p=0,08).
Conclusion
Extreme caution must be used in considering our data, given the very small patients number. In our cohort, pre-transplant intensive debulking chemotherapy, although obtained an high rate of CR, showed no effect in preventing relapse. Larger studies are necessary to assess the real utility of I.C. in this subset of frail patients.
Session topic: 10. Myelodysplastic syndromes - Clinical
Keyword(s): Stem cell transplant, Myelodysplasia, chemotherapy
Abstract: PB1931
Type: Publication Only
Background
The importance of pre-transplant disease burden in myelodysplastic sindromes (MDS) as a factor influencing post hematopoietic cell transplantation (HCT) outcome is an important argument of debate. It has been reported that relapse rate (RR) after transplant is reduced in patients entering HCT with a blast cell count < 5%. However, the effect of a pre-transplant debulking therapy in reducing RR has not been clearly demonstrated.
Aims
Here we review our data to evaluate if the intensity of pre-transplant therapy may have influenced post transplant RR.
Methods
In our Institute, we treat all patients with a blast cell count of 10% or higher with a debulking therapy pre-transplant. This is usually an AML-like, cytarabine and anthracycline based, intensive chemotherapy (I.C.). In selected cases fludarabine and cytarabine containing regimens are also used. In the last ten years, in the context of a clinical trial, a series of patients have received a less intensive, hypometilating therapy (repeated courses of 5-azacytidine 75 mg/m2 subcutaneously for 7 days), as bridge to transplant.
Conditioning regimen used in MDS patients is busulfan based in younger patients (Bu-Flu, BU-Cy); in the elderly or less fit patients a RIC regimen (thiotepa 5 mg/kg e.v., fludarabine mg/m2 x 3 and L-PAM 100 mg/m2) is administered.
Results
In the last ten years we performed 14 HCT (between June 2008 and september 2016) in patients with MDS with excess blasts. Median patients age was 63,5 years (range: 49-69), male/female ratio was 9/5. According to IPSS, 12 out of 14 patients were high/ int-2 (2 int-1), 11/14 had > 10% blast cells (EB-2).
According to our centre protocol, we treated 11 patients with EB-2 and 1 patient with EB-1 (with hypercellular bone marrow) with a debulking therapy. This was I.C. in 6 patients and 5-AZA in 6 patiens. Two patients with EB-1 did not receive any therapy pre-transplant. However, both of them are not evaluable, due to early mortality. Transplant conditioning was RIC in 11/14 patients, myeloablative in 3 cases. The donor was a sibling in 9/14, MUD in 5/14.
Four out of six patients treated with I.C. achieved a pre-transplant CR (67%), compared to one out of six in the 5-Aza cohort (17%).
Four patients experienced a relapse post HCT, after a median of 8,5 months (4-11). With a median follow up of 21 months (6-68), post transplant RR was 4/12 (33,3%) and was not influenced by debulking therapy (I.C. vs 5-Aza, p=0,54), nor by pre-transplant disease state (CR vs noCR, p=0,22). In fact, 3 out of 6 patients treated with I.C., but only 1 out of 6 treated with 5-Aza relapsed after transplant. Three out of four patients who subsequently relapsed had recived RIC transplant; type of transplant was not assocaited with relapse (P=1,0) The only variable that showed a trend for reduced RR was MUD transplant (p=0,08).
Conclusion
Extreme caution must be used in considering our data, given the very small patients number. In our cohort, pre-transplant intensive debulking chemotherapy, although obtained an high rate of CR, showed no effect in preventing relapse. Larger studies are necessary to assess the real utility of I.C. in this subset of frail patients.
Session topic: 10. Myelodysplastic syndromes - Clinical
Keyword(s): Stem cell transplant, Myelodysplasia, chemotherapy
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