Contributions
Abstract: PB1638
Type: Publication Only
Background
Patients (pts) with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) in first complete remission (CR) are at risk because chemotherapy alone does not allow long-term survival. Hematopoietic stem cell transplantation (HSCT) is considered the most potent post-remission antileukemic therapy.
Aims
We report in this series results of this procedure in 31 pts with Ph+ ALL.
Methods
From January 2012 to December 2016, 31 pts with Ph+ ALL were treated with HSCT (24 sibling HLA-identical, 06 haplo-identical and 01 syngeneic). Twenty four pts (77%) received a tyrosine kinase inhibitor (TKI) during induction therapy. The disease status at transplant: first CR (23 pts), 2nd CR (07 pts), blast phase (01 pt) of whom 16 pts (51%) were in molecular remission. The median age is 29 years (06-49), of whom 08 (32%) are under 18 years of age. The sex ratio is 1.81. The average of last remission-transplant was 4 months (01-12). All pts received chemotherapy conditioning: BAM12 protocol (13 pts) associating Busilvex (dose according to weight in children, 12.8 mg/kg in adults), Aracytine 12 g/m2 and Melphalan 140 mg/m2; the TUTSHKA-VP16 protocol (10 pts) associating Busilvex, Endoxan 120 mg/kg and Etoposide 15 mg/kg; SANTOS protocol (02 pts) associating Busilvex and Endoxan 200 mg/kg. Six pts beneficied haplo-identical HSCT including 05 pts with a Chinese protocol combining Busilvex 9.6 mg/kg, Aracytine 08 g/m2, Endoxan 3.6 g/m2 and Thymoglobulin 10 mg/kg ; one pt received a TBF protocole combining Busilvex (9.6 mg/kg), Fludarabine (150 mg/m2) and Thiotepa (10 mg/kg). All pts received a peripheral blood stem cell transplant obtained after mobilization with G-CSF alone with the average CD34+ cell count 9.88. 106/kg (4.1-41). An additional bone marrow transplant G-CSF primed was used in the 5 pts in haplo-identical HSCT with an average of nucleated cells 5.67. 108/kg (0.5-10.7). GVHD prophylaxis associated Cyclosporine-Methotrexate for sibling HLA-identical HSCT; Cyclosporine-Methotrexate-Cellcept for haplo-identical HSCT (Chinese protocole); Cyclosporine-Cellcept and post-transplantion cyclophosphamide (TBF protocol) and without prophylaxis (syngeneic HSCT). TKI was instituted as prevention for relapse from 3 months after transplant in 21 pts (76%). At December 2017 the minimal follow-up delay is 6 months and the maximal 60 months.
Results
The median duration of aplasia is 15 days (09-29). Neutrophils engraftment was obtained at day 15 (11-29). Transfusions were required with an average of red blood cells: 2,4 units/pt and Platelets concentrates: 1,8 units/pt. No pt showed rejection, VOD or haemorrhagic cystitis. Acute GVHD was observed in 08 pts (25%), including 07 grade III-IV, and chronic GVHD occurred in 07 pts (29%), of which 03 were extensive. CMV reactivation was observed in 08 pts (25%) on average day 46 (28-69). Relapse occurred in 12 pts (38%) within an average of 11 months (3-32) of which 10 pts was in TKI post-transplantation. At December 2017, 17 pts died, of which 08 related to the procedure (TRM : 25%, GVHA 07 pts, acute pancreatitis 01 pt) and 09 pts of relapse. Fourteen pts are alive in complete remission with a median follow-up of 28 months (06-50), including 13 in molecular remission. Overall survival and event-free survival at 57 months are 26.7% and 24.2% respectively.
Conclusion
Results of HSCT in pts with Ph+ ALL have to be improved. The addition of TKI as a preventive treatment for post-transplant relapses has not been beneficial in our series.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Philadelphia chromosome, Stem cell transplant
Abstract: PB1638
Type: Publication Only
Background
Patients (pts) with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) in first complete remission (CR) are at risk because chemotherapy alone does not allow long-term survival. Hematopoietic stem cell transplantation (HSCT) is considered the most potent post-remission antileukemic therapy.
Aims
We report in this series results of this procedure in 31 pts with Ph+ ALL.
Methods
From January 2012 to December 2016, 31 pts with Ph+ ALL were treated with HSCT (24 sibling HLA-identical, 06 haplo-identical and 01 syngeneic). Twenty four pts (77%) received a tyrosine kinase inhibitor (TKI) during induction therapy. The disease status at transplant: first CR (23 pts), 2nd CR (07 pts), blast phase (01 pt) of whom 16 pts (51%) were in molecular remission. The median age is 29 years (06-49), of whom 08 (32%) are under 18 years of age. The sex ratio is 1.81. The average of last remission-transplant was 4 months (01-12). All pts received chemotherapy conditioning: BAM12 protocol (13 pts) associating Busilvex (dose according to weight in children, 12.8 mg/kg in adults), Aracytine 12 g/m2 and Melphalan 140 mg/m2; the TUTSHKA-VP16 protocol (10 pts) associating Busilvex, Endoxan 120 mg/kg and Etoposide 15 mg/kg; SANTOS protocol (02 pts) associating Busilvex and Endoxan 200 mg/kg. Six pts beneficied haplo-identical HSCT including 05 pts with a Chinese protocol combining Busilvex 9.6 mg/kg, Aracytine 08 g/m2, Endoxan 3.6 g/m2 and Thymoglobulin 10 mg/kg ; one pt received a TBF protocole combining Busilvex (9.6 mg/kg), Fludarabine (150 mg/m2) and Thiotepa (10 mg/kg). All pts received a peripheral blood stem cell transplant obtained after mobilization with G-CSF alone with the average CD34+ cell count 9.88. 106/kg (4.1-41). An additional bone marrow transplant G-CSF primed was used in the 5 pts in haplo-identical HSCT with an average of nucleated cells 5.67. 108/kg (0.5-10.7). GVHD prophylaxis associated Cyclosporine-Methotrexate for sibling HLA-identical HSCT; Cyclosporine-Methotrexate-Cellcept for haplo-identical HSCT (Chinese protocole); Cyclosporine-Cellcept and post-transplantion cyclophosphamide (TBF protocol) and without prophylaxis (syngeneic HSCT). TKI was instituted as prevention for relapse from 3 months after transplant in 21 pts (76%). At December 2017 the minimal follow-up delay is 6 months and the maximal 60 months.
Results
The median duration of aplasia is 15 days (09-29). Neutrophils engraftment was obtained at day 15 (11-29). Transfusions were required with an average of red blood cells: 2,4 units/pt and Platelets concentrates: 1,8 units/pt. No pt showed rejection, VOD or haemorrhagic cystitis. Acute GVHD was observed in 08 pts (25%), including 07 grade III-IV, and chronic GVHD occurred in 07 pts (29%), of which 03 were extensive. CMV reactivation was observed in 08 pts (25%) on average day 46 (28-69). Relapse occurred in 12 pts (38%) within an average of 11 months (3-32) of which 10 pts was in TKI post-transplantation. At December 2017, 17 pts died, of which 08 related to the procedure (TRM : 25%, GVHA 07 pts, acute pancreatitis 01 pt) and 09 pts of relapse. Fourteen pts are alive in complete remission with a median follow-up of 28 months (06-50), including 13 in molecular remission. Overall survival and event-free survival at 57 months are 26.7% and 24.2% respectively.
Conclusion
Results of HSCT in pts with Ph+ ALL have to be improved. The addition of TKI as a preventive treatment for post-transplant relapses has not been beneficial in our series.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Philadelphia chromosome, Stem cell transplant